Release of brain-specific creatine kinase and neuron-specific enolase into cerebrospinal fluid after hypothermic and normothermic cardiopulmonary bypass in coronary artery surgery.

BACKGROUND: Coronary artery bypass (CABG) surgery is successfully managed with normothermic cardiopulmonary bypass (CPB) using warm blood cardioplegia. The lack of the protective effect of hypothermia, however, might make the central nervous system vulnerable. METHODS: Thirty-six patients were randomized into normothermic CPB (36-37 degrees C) (NTCPB group, n=18) and hypothermic CPB (28 degrees C) (HTCPB group, n=18) in order to examine whether normothermic or hypothermic CPB induces the release of the intracellular brain enzymes, creatine kinase (CK), its brain-specific isoenzyme (CK-BB), and neuron-specific enolase (NSE) into cerebrospinal fluid (CSF). In addition, clinical neurologic examination and neuropsychologic assessment were done preoperatively, 5 d and 11-23 mo postoperatively. RESULTS: One patient in each group suffered a stroke after surgery. Two patients in the normothermic group had minor neurologic complications. The cognitive decline after operation was similar in the NTCPB and HTCPB groups. CSF enzymes from normothermic and hypothermic CABG patients without gross neurologic complications were not significantly higher than CSF enzymes from orthopaedic reference patients. CABG patients with neurologic complications had higher enzyme concentrations. Cognitive decline after the operation correlated statistically significantly with CSF enzyme concentrations in the NTCPB group, but not in the HTCPB group. CONCLUSION: CABG operation without major neurologic complication does not induce the release of CK, CK-BB or NSE enzymes into CSF, irrespective of whether the CPB is normothermic or hypothermic.

Serum antioxidants and risk of non-insulin dependent diabetes mellitus.

OBJECTIVE: To examine whether serum levels of alpha-tocopherol, beta-carotene and retinol were associated with risk of non-insulin dependent diabetes mellitus (NIDDM). DESIGN AND SUBJECTS: The study design was a nested case-control study within a longitudinal population study. Serum levels of antioxidants were determined in 106 incident cases with non-insulin dependent diabetes mellitus detected on follow-up and 201 controls matched for sex, age and study region. RESULTS: The incident cases had lower serum alpha-tocopherol and beta-carotene levels than controls. The relative risk between the highest and lowest tertiles of serum alpha-tocopherol was 0.61 (95% confidence interval (CI) 0.32-1.15), between the highest and lowest tertiles of serum beta-carotene 0.45 (CI 0.22-0.92). Although the relative risk of highest compared with lowest tertile of serum alpha-tocopherol was not statistically significant the inverse trend through the tertiles was (P < 0.05). The decreasing risk of diabetes was particularly evident in the elderly, women, nonsmokers and the obese. However, adjustment for serum cholesterol, obesity, smoking and hypertension abolished the associations. The adjusted relative risks in relation to serum alpha-tocopherol and beta-carotene (between highest and lowest tertiles) were 1.25 (CI 0.54-2.90) and 0.94 (CI 0.38-2.32), respectively. No associations were observed relating to serum retinol. CONCLUSIONS: High levels of alpha-tocopherol and beta-carotene were found to be associated with decreased risk of non-insulin dependent diabetes mellitus, but the association disappeared after adjustment for cardiovascular risk factors.

Serum antioxidants and risk of rheumatoid arthritis.

OBJECTIVES: Oxygen free radicals have been implicated as mediators of tissue damage in patients with rheumatoid arthritis (RA). Thus it is possible that several micronutrients acting as antioxidants and free radical scavengers provide protection against RA. Serum alpha-tocopherol, beta-carotene, and selenium were studied for their associations with the risk of RA. METHODS: A case control study was nested within a Finnish cohort of 1419 adult men and women. During a median follow up of 20 years, 14 individuals initially free of arthritis developed RA. Two controls per each incident case were individually matched for sex, age, and municipality. Serum alpha-tocopherol, beta-carotene and selenium concentrations were measured from stored serum samples. An antioxidant index was calculated as the product of the molar concentrations of these three micronutrients. RESULTS: Elevated risks of RA were observed at low levels of alpha-tocopherol, beta-carotene and selenium, but none of the associations were statistically significant. A significant association, however, was observed with a low antioxidant index (p for trend = 0.03), the relative risk of RA between the lowest tertile and the higher tertiles of its distribution being 8.3 (95% confidence interval 1.0-71.0). CONCLUSIONS: The results of the present study are in line with the hypothesis that a low antioxidant level is a risk factor for RA.

Dietary determinants of serum beta-carotene and serum retinol.

The relationship of major dietary carotenoids, preformed and total vitamin A, and different foods to serum beta-carotene and serum retinol levels was studied among 224 male and 117 female adults taken from the Finnish Mobile Clinic Health Examination Survey. Serum nutrients were analysed after 10-15 years of storage at -20 degrees C. Dietary data were collected by a quantitative dietary history interview method. Intakes of nutrients were calculated based on analysed data on Finnish foods. The positive gradient between beta-carotene intake and serum level, being highly significant in women and non-significant in men, was concentrated in non-smokers. Other major dietary carotenoids tended to be positively correlated with serum beta-carotene in parallel with dietary beta-carotene. Carrot intake was the most specific single food predictor for serum beta-carotene. Serum retinol levels were not significantly associated with dietary variables and were not affected by current smoking. In women, serum beta-carotene values were higher, but serum retinol levels lower, compared with men. The results support earlier findings that smoking modifies the association between dietary beta-carotene and serum beta-carotene, and suggest that despite the long storage of serum samples beta-carotene determinations had some value as a biological marker for beta-carotene in the diet.

Serum antioxidant vitamins and risk of cataract.

OBJECTIVE: To investigate serum concentrations of alpha tocopherol, beta carotene, retinol, and selenium for their prediction of end stage cataract. DESIGN: A case-control study, nested within a cohort study, based on the linkage of records of subjects aged 40-83 from a health survey with those from the national Finnish hospital discharge register. SUBJECTS: 47 patients admitted to ophthalmological wards for senile cataract over 15 years and two controls per patient individually matched for sex, age, and municipality. MAIN OUTCOME MEASURE: Concentration of serum micronutrients, development of cataract according to whether operation was performed. RESULTS: Low serum concentrations of antioxidant vitamins predicted the development of senile cataract, the odds ratio between the lowest third and the two higher thirds of the distribution of serum concentrations of alpha tocopherol and beta carotene being 1.9 (95% confidence interval 0.9 to 4.1) and 1.7 (0.8 to 3.8), respectively. Patients with both alpha tocopherol and beta carotene concentrations in the lowest third had an odds ratio of 2.6 (1.0 to 6.8) of cataract compared with subjects in the top two thirds. The associations were strengthened by adjustment for potential confounding factors such as occupation, smoking, blood pressure, serum cholesterol concentration, body mass index, and diabetes. No association was found between the serum concentrations of selenium, retinol, and retinol binding protein and the risk of cataract. CONCLUSIONS: Low serum concentrations of the antioxidant vitamins alpha tocopherol and beta carotene are risk factors for end stage senile cataract. Controlled trials of the role of antioxidant vitamins in cataract prevention are therefore warranted.

Serum ceruloplasmin level and the risk of myocardial infarction and stroke.

The associations between serum ceruloplasmin level and the subsequent incidence of myocardial infarction and stroke were studied in a nested case-control study in Finland (baseline examination 1968-1972). Ceruloplasmin levels were measured in stored serum samples from 104 myocardial infarction or stroke cases occurring during a median follow-up of about 11 years and from 104 individually matched controls. High serum ceruloplasmin levels were significantly associated with higher future odds of myocardial infarction but not of stroke. The odds ratios for myocardial infarction and stroke comparing the highest and lowest tertiles of serum ceruloplasmin, adjusted for smoking, serum cholesterol, body mass index, hematocrit, hypertension, and diabetes, were 3.1 and 0.7, respectively. The results of the present study support the hypothesis that a high serum ceruloplasmin level is a risk factor for myocardial infarction.

Herpes simplex virus type 2 infection and cervical cancer: a prospective study of 12 years of follow-up in Finland.

This study was initiated to investigate the role of past herpes simplex virus type 2 (HSV-2) infection, as determined by serum antibody analysis, in the etiology of cervical neoplasia. Two Finnish registers, the registry of the Social Insurance Institution's Mobile Clinic Survey and the Finnish Cancer Registry, were linked. About 40,000 blood samples were drawn in 1968-72 and stored by the Social Insurance Institution. According to the Cancer Registry, 32 cases of cervical carcinoma or carcinoma in situ for which serum samples were available were diagnosed in this cohort during a follow-up of 12 years (1968-81). The serum samples of these individuals and age matched controls (2:1) from the cohort were analyzed for HSV-2 antibodies. HSV-2 infection as determined by the best available HSV-2 type-specific antibody assay, glycoprotein gG2-ELISA, was not related to cervical neoplasia, i.e., the risk of cervical neoplasia among the HSV-2 positive women was not higher than that among the negative ones (smoking-adjusted relative risk = 0.5, 95 percent confidence interval = 0.2-1.6). The results do not support the hypothesis that HSV-2 is an etiologic agent for cervical neoplasia.

Tumour antigens CA 195 and CA 19-9 in pancreatic juice and serum for the diagnosis of pancreatic carcinoma.

OBJECTIVE: To see if tumour associated antigens CA 195 and CA 19-9 were able to differentiate between patients with pancreatic carcinoma, and those with chronic pancreatitis or stones in the common bile duct. DESIGN: Prospective, open, clinical study. SETTING: 47 patients with histologically confirmed pancreatic adenocarcinoma, 38 with chronic pancreatitis diagnosed by endoscopic retrograde cholangiopancreatography (ERCP), and 26 with stones in the common bile duct diagnosed and treated by ERCP. INTERVENTIONS: Samples of serum taken from all patients just before ERCP, and samples of pancreatic juice obtained from 18, 11, and 12 patients, respectively during ERCP. RESULTS: Assay of the two tumour markers in pancreatic juice failed to differentiate between patients with benign and malignant disease. When assayed in serum, however, CA 195 detected those with carcinoma with a sensitivity of 72% and a specificity of 92%, and CA 19-9 with a sensitivity of 81% and a specificity of 88%. The patients with unresectable tumours had significantly higher concentrations of both markers in serum than patients with resectable tumours (p less than 0.05). CONCLUSIONS: CA 195 and CA 19-9 concentrations in serum are equally successful in differentiating between benign and malignant pancreatic disease. Assay of markers in pancreatic juice does not provide useful diagnostic information.

Serum ceruloplasmin and the risk of cancer in Finland.

The relationship between serum ceruloplasmin level and cancer incidence was investigated in a case-control study nested within a longitudinal study of 39,268 Finns participating in the Social Insurance Institution's Mobile Clinic Health Examination Survey carried out in 1968-1972. During a median follow-up of 8 years, 766 cancer cases were identified. Ceruloplasmin levels were determined from stored serum samples collected at the baseline from these cancer cases and from two matched controls per case. The overall incidence of cancer was positively associated with serum ceruloplasmin level. The association was strongest for lung cancer and other cancers related to smoking and, consequently, in males. The smoking-adjusted relative risk of lung cancer among men was 4.3 (95% confidence interval (CI) = 1.8-10.6) in the highest quintile of serum ceruloplasmin as compared with that in the lowest quintile. The corresponding relative risks for cancers related to smoking combined, and for cancers not related to smoking were 3.9 (CI = 1.9-8.4) and 0.9 (CI = 0.6-1.5), respectively. The elevated risk of lung cancer at high concentrations of serum ceruloplasmin persisted after further adjustment for several potential confounding factors such as serum levels of vitamins A and E and selenium. The risk was stronger during the first 6 years of follow-up than later, and strongest during the first 2 years. The most likely explanation of the present results thus is that high serum ceruloplasmin levels in lung cancer are mainly due to occult cancer.

Serum micronutrients and risk of cancers of low incidence in Finland.

The associations between serum alpha-tocopherol, beta-carotene, retinol, retinol-binding protein, and selenium levels and the subsequent occurrence of different cancers of low incidence were investigated in a nested case-control study of 39,268 men and women participating in the Social Insurance Institution's Mobile Clinic Health Examination Survey in Finland. During follow-up from the baseline in 1968-1972 to the end of 1977, a total of 115 cancers of the lip, oral cavity, pharynx, larynx, esophagus, liver, gallbladder, kidney, urinary bladder, brain, and skin were reported to the nationwide Finnish Cancer Registry. Alpha-tocopherol, beta-carotene, retinol, retinol-binding protein, and selenium concentrations were determined from stored serum samples collected from these cancer cases and matched controls at baseline. Several sites indicated an elevated risk of cancer at low levels of the serum variables, although only a few of these associations were statistically significant. Only melanoma patients had significantly lower serum alpha-tocopherol and beta-carotene levels than corresponding controls. Since the numbers of cancer cases were small, no firm conclusions can be drawn from these results until they have been confirmed in studies based on larger cohorts or on pooled data from several small samples.

Vitamin E and cancer prevention.

Some animal experiments and human studies suggest that vitamin E may protect against cancer. Serum alpha-tocopherol concentration was studied for its prediction of cancer in a cohort of 36,265 adults in Finland. During a mean follow-up of 8 y, cancer was diagnosed in 766 persons. The levels of serum alpha-tocopherol were determined from stored serum samples (at -20 degrees C) taken from these cancer patients and from 1419 matched control subjects. Individuals with a low level of alpha-tocopherol had about a 1.5-fold risk of cancer compared with those with a higher level. The strength of the association between serum alpha-tocopherol level and cancer risk varied for different cancer sites and was strongest for some gastrointestinal cancers and for the combined group of cancers unrelated to smoking. The association was strongest among nonsmoking men and among women with low levels of serum selenium. The findings agree with the hypothesis that dietary vitamin E in some circumstances protects against cancer.

Serum vitamin A and subsequent risk of cancer: cancer incidence follow-up of the Finnish Mobile Clinic Health Examination Survey.

From 1968 to 1977, the association between the level of vitamin A in serum and the subsequent incidence of cancer was examined in a longitudinal study of 36,265 persons initially aged 15-99 years in 25 population groups in Finland. During a mean follow-up of 8 years, 766 cancers were diagnosed. Serum retinol, retinol-binding protein, and beta-carotene levels were measured from frozen serum samples (stored at -20 degrees C) drawn from these persons before the start of follow-up and from 1,419 controls matched for sex, age, and place of residence who did not develop cancer during follow-up. The mean level of serum retinol among the cancer cases was 645 micrograms/liter for men and 587 micrograms/liter for women. The corresponding levels in the controls were 3.3% and 2.8% higher. There was an inverse gradient between serum retinol level and the occurrence of cancer among men. This association was, however, mainly concentrated in the first 2 years of follow-up. The mean level of serum beta-carotene was 72.3 micrograms/liter among male cases and 119.5 micrograms/liter among female cases. The corresponding levels of the controls were 14.0% and 5.5% higher. The differences were particularly clear with regard to lung cancer. These findings suggest that the association between retinol and cancer may be due to preclinical cancer and that there may be an association between beta-carotene and cancer.

Serum selenium and subsequent risk of cancer among Finnish men and women.

The association between the serum selenium level and the subsequent incidence of cancer was investigated in a longitudinal study of 39,268 men and women participating in the Social Insurance Institution's Mobile Clinic Health Examination Survey in Finland. The baseline examinations, including the collection of blood samples, were performed in 1968-1972. During a median follow-up of 10 years, 1,096 new cancer cases were identified from the files of the Finnish Cancer Registry. Selenium concentrations were measured from the stored serum samples collected from these cancer cases and from two controls per case, matched for sex, municipality, and age. The mean serum selenium level was 59.1 micrograms/L among all male cancer cases and 62.5 micrograms/L among controls. The difference was statistically significant (P less than .001). Corresponding values among women were 63.6 and 63.9 micrograms/L, respectively. Low serum selenium levels were associated with an increased risk of developing cancer at several sites, especially cancers of the stomach and lung among men. The relative risk of lung cancer between the highest and lowest decile of serum selenium was 0.11, and it differed significantly from unity (P less than .001). These findings are in agreement with the hypothesis that low selenium intake may increase the risk of some cancers among men.

Serum CA 125 in acute pelvic inflammatory disease.

Serum levels of CA 125 and other selected tumour markers were measured in 31 patients with proven pelvic inflammatory disease (PID). Ten (32%) of the patients had elevated CA 125, one (4%) had elevated CEA, and none had elevated CA 15-3, AFP or beta 2-microglobulin. Compared to patients with normal CA 125, patients with elevated CA 125 were older, more often users of intrauterine contraceptive devices, had longer duration of symptoms, higher erythrocyte sedimentation rates, and more often had an adnexal mass on pelvic examination. There was a correlation between CA 125 levels and the severity of adnexal inflammation as defined by laparoscopy. Isolation of specific micro-organisms from the upper genital tract was not associated with elevated CA 125. In most women serum levels of CA 125 decreased during treatment. PID should be considered as a major cause of positive CA 125 findings among young women.

Serum vitamin E, serum selenium and the risk of gastrointestinal cancer.

The association between levels of alpha-tocopherol and selenium in serum and subsequent risk of gastrointestinal cancer was investigated in a longitudinal study based on 36,265 Finnish men and women, aged 15-99 and initially free of cancer. Serum alpha-tocopherol and serum selenium levels at entry into the study were measured from stored serum samples of 150 incident gastrointestinal cancer cases diagnosed during a follow-up of 6-10 years and for 276 controls who were matched for sex, age and place of residence. Subjects with a low level of alpha-tocopherol or selenium had an elevated subsequent risk of cancer of the upper gastrointestinal tract. This association persisted among men after adjustment for various confounding factors and after the exclusion of those with cancer diagnosed during the first 2 years of follow-up. The relative risk of cancer of the upper gastrointestinal tract among men who fell in the lowest quintile of serum selenium was 3.3 (95% confidence limits, 1.3 and 9.1) while among those who fell in the 3 lowest quintiles of alpha-tocopherol it was 2.2 (95% confidence limits 0.9 and 5.6) compared with those in the higher quintiles. Serum levels of selenium or alpha-tocopherol in general were not inversely associated with colorectal cancer risk. These findings indicate that high selenium intake and possibly also high vitamin E intake, especially among men, may provide protection against cancer of the upper gastrointestinal tract but not against colorectal cancer.

Determinants of serum alpha-tocopherol in Finnish adults.

The relationship between serum alpha-tocopherol level and many of its possible determinants was studied in 1,373 cancer-free Finnish men and women age 40-79 years. Dietary data were available from a subsample of 301 persons. The mean alpha-tocopherol level in the serum samples stored at -20 degrees C was 8.6 mg/liter among men and 10.5 mg/liter among women. Intake of margarine, vegetable oils, and green vegetables predicted the serum level of alpha-tocopherol. Altogether six food groups accounted for about 10% of the variation. The levels also varied with age, geographical area, type of population, occupation, socioeconomic status, and marital status. They were positively correlated with serum cholesterol and serum vitamin A in both sexes, and with body mass index and serum selenium in men. Altogether these variables accounted for over 40% of the variation in alpha-tocopherol levels. The level of serum alpha-tocopherol, which is associated with the dietary intake of vitamin E, is dependent upon living conditions.

Serum CA 15-3 assay in the diagnosis and follow-up of breast cancer.

Serum CA 15-3 values were determined in 177 patients with primary breast cancer and in 41 with non-malignant breast disease. Increased preoperative serum CA 15-3 values (greater than 38 U ml-1) were observed in 7%, 17%, 64% and 67% of patients with stage I, II, III and IV disease, respectively and in none of the patients with benign breast disease. Patients with elevated serum CA 15-3 values had poor 3-year cumulative survival (27%). In the postoperative follow-up 9% of patients with no clinical evidence of disease, 33% with a single metastasis and 67% with two or more metastases had elevated values. Increasing or decreasing serum CA 15-3 values correlated with the clinical outcome in 26 out of 27 cases (96%), whereas serum values remaining in the reference range had no predictive value. At the time of recurrence elevated serum CA 15-3 values were also observed in patients with normal preoperative values. Increased serum CA 15-3 values preceded the clinical detection of tumour recurrence by up to 13 months. In conclusion, serum CA 15-3 levels had prognostic value in breast cancer, reflected the extent of clinically detectable disease and the presence of occult metastatic disease. Further research is warranted on the benefits of CA 15-3 assays in relation to adjuvant chemotherapy as well as the earlier detection and treatment of metastatic disease.

Serum vitamin E and risk of cancer among Finnish men during a 10-year follow-up.

The association between serum alpha-tocopherol levels and the subsequent incidence of cancer was investigated in a longitudinal study of 21,172 men initially aged 15-99 years in six geographic areas in Finland. The baseline examination was conducted in 1968-1972, and during the follow-up of 6-10 years, 453 cancers were diagnosed. The serum alpha-tocopherol levels were measured from stored serum samples from these men and from 841 male controls, matched for municipality and age, who did not develop cancer during the follow-up. The mean levels of serum alpha-tocopherol among the cancer cases and controls were 8.02 and 8.28 mg/liter, respectively. A high serum alpha-tocopherol level was associated with a reduced risk of cancer. The relative risk of cancer in persons in the two highest (threshold 8.70 mg/liter) quintiles of serum alpha-tocopherol was 0.64 (95 per cent confidence interval = 0.49-0.85) in comparison with those in the three lowest quintiles. The association was strongest for the combined group of cancers unrelated to smoking and varied between subgroups of the study population as well as between different cancers. The association persisted when adjusted for serum cholesterol, serum vitamin A, serum selenium, and various confounding factors. It also persisted when subjects with possible signs of cancer at the time when the blood samples were drawn or with cancers diagnosed during the first two years of follow-up were excluded. These findings agree with the hypothesis that high vitamin E intake protects against cancer.

Carcinoembryonic antigen levels in sera drawn 1 to 12 years before diagnosis of cervical malignancy.

We determined serum CEA and beta-HCG levels in women who developed cervical carcinoma 1 to 12 years after the serum samples were drawn. Only 32 diagnostic sera CEA and beta-HCG levels were found. However, the serum CEA levels of the carcinoma patients differed significantly from those of their matched controls, who remained cancer free during the following 8 to 12 years after serum withdrawal. The difference in CEA levels between cases and controls did not depend on the lag period between serum withdrawal and cancer diagnosis, the severity of underlying cervical disease, or smoking habits.