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In order to examine the postprandial blood concentrations of insulin-independent carbohydrates after gastric surgery oral galactose test (1.65 g/kg body weight in water, 33%, w/v) was performed in 55 symptomatic patients and in 5 healthy subjects. There were patients after total gastrectomy (TG) (n = 17), gastric resection with (GRS, n = 17) or without (GR; n = 12) selective vagotomy, and after proximal selective vagotomy (PSV, n = 9). The patients had immediately after drinking the test solution a 2- to 5-fold higher blood galactose concentration than the healthy subjects. The TG patients had the most rapid, the healthy subjects the slowest and the GR and GRS patients an intermediate rapid, immediate increase of blood galactose concentration. The TG patients showed a plateau 40-60 min and a decrease 60-90 min after the start of the test. The PSV patients showed a plateau 60-90 min after the commencement of the test. The GR and GRS patients and the healthy subjects had a continuous increase in blood galactose concentration during the whole test period, but the maximal point 90 min after the drinking of the solution was lower in the GRS than in the GR patients and lowest in the healthy subjects. The PSV patients had a lower blood galactose curve than the TG, GRS and GR patients but higher than the healthy subjects except the plateau 60-90 min postprandially.(ABSTRACT TRUNCATED AT 250 WORDS)

Nuclear debris may significantly interfere with the analysis of S-phase fraction (SPF) from paraffin-embedded tumors. We used a background subtraction algorithm to compensate for the effects of slicing of tumor cell nuclei during preparation of paraffin-embedded specimens. DNA histograms were analyzed from 88 node-negative breast and from 78 prostatic carcinomas. Median SPFs corrected for nuclear slicing were lower than uncorrected ones in both breast cancer (7.6% vs. 5.7%) and prostate cancer (6.7% vs. 4.2%). The median SPF value in each group was used as a cut-off point in survival studies. As compared with the uncorrected SPFs, corrected SPF levels resulted in a more significant survival difference between breast cancer patients with above and below median SPF (p = 0.0014 vs. p = 0.014) and in a higher relative risk (RR) of death (4.5 vs. 3.1). The same was true for prostate cancer survival (p less than 0.0001 vs. p = 0.002) and RR (5.3 vs. 3.1). Compared with the exponential background subtraction method, the sliced nuclei correction was more reproducible and could be applied in all evaluable histograms without the risk of overcompensation. In conclusion, our results support the use of background correction with the sliced nuclei model in DNA flow cytometric studies of archival tissues.

A new biological alcohol marker, the ratio between the acetaldehyde-induced haemoglobin fraction HbA1ach and the glycated haemoglobin fraction HbA1c (HbA1ach/HbA1c), was studied in association with data obtained in a questionnaire, the Malmö modified Michigan alcoholism screening test (Mm-MAST), completed by 270 consecutive middle-aged men participating in a voluntary health screening. None of them had earlier alcoholic health or alcohol-dependent social problems. The nine-question Mm-MAST correlated positively with the ratio of HbA1ach/HbA1c (r = 0.272, P less than 0.001). In the three drinker groups defined according to the questionnaire, HbA1ach/HbA1c values were significantly higher among heavy drinkers (mean = 40, S.E.M. = 1) than among teetotallers (mean = 32, S.E.M. = 2, P less than 0.01) or social drinkers (mean = 35, S.E.M. = 1, P less than 0.01). In the groups formed according to the respondents' own alcohol anamnesis there was no significant difference between the marker values, but the Mm-MAST score was significantly higher in both social (P less than 0.001) and heavy drinkers' (P less than 0.001) groups as compared with teetotallers. This shows that the questionnaire detected heavy drinkers better than the self-given anamnesis. The correlation of HbA1ach/HbA1c and the questionnaire means that the biological marker studied represents a new possibility to identify heavy drinkers before alcoholic health problems or social consequences have appeared.

We developed a sensitive cation exchange liquid chromatographic method for analysis of acetaldehyde binding with hemoglobin. When human hemolysates were incubated in vitro with micromolar concentrations of acetaldehyde without reducing agents, HbA0 was found to form two new fractions. One of them was eluated with HbA1c, whereas a novel, previously undescribed fraction was detected between HbF and HbA1c. This new fraction was termed HbA1ach. The mean within-assay variation for the different hemoglobin fractions varied from 0.45 (HbA0) to 8.2% (HbA1ach) and the between-assay variation from 0.6 to 19.3%, respectively. After incubation with [1,2(14)C]acetaldehyde the specific radioactivity of HbA1ach was about 10 times higher than that of HbA0 and twice as high as the activity of the HbA1c fraction. The reaction kinetics of the formation of hemoglobin adducts were studied in vitro by incubation of hemolysates with various acetaldehyde concentrations. Acetaldehyde caused both short-term and permanent changes in hemoglobin. Even low acetaldehyde concentrations from 10 to 100 mumol/liter caused detectable changes in hemoglobin. During incubation the amount of HbA1ach and HbA1c fractions increased rapidly within the first 10 min and decreased slowly during the next hr but did not return to the initial levels. This suggests that only the part of binding of acetaldehyde with hemoglobin is irreversible and the changes can be already detected after incubation with physiological acetaldehyde concentrations.

The suitability of the nine-question Malmö modified Michigan Alcoholism Screening Test (Mm-MAST) was tested on 133 40-year-old men and 140 45-year-old men attending a voluntary population health screening in a typically week-end-drinking society. With a cut-off level of two 'yes' answers 29% of the middle-aged male population has been reported to give a positive result in this questionnaire. In our study alcoholics were excluded. The amount and type of alcohol consumed per week was asked. The subjects were divided into three groups: (1) social drinkers (0 or 1 'yes' answer), (2) suspect abusers (two 'yes' answers), and (3) abusers (three or more 'yes' answers or drinking at least 280 g absolute alcohol per week). Group 2 reported drinking more than group 1, but according to biological markers they belonged better to group 1 than group 3. With the originally recommended cut-off level of two 'yes' answers 50.8% of 40-year-old men and 36.5% of 45-year-old men in our study proved positive. With the three 'yes' answer criterion the corresponding percentages were 28.5 and 24.0. Forty- and 45-year-old men in group 2 gave many positive answers in the question concerning week-end drinking and avoidance of alcohol for a time, as did 40-year-old men in the question concerning bad conscience after drinking. Beer and spirits were the most popular beverage combination and week-end drinking was the commonest drinking habit. The number of positive answers correlated well with the announced amount of alcohol.(ABSTRACT TRUNCATED AT 250 WORDS)

Consecutive sections from 33 paraffin-embedded human breast carcinomas without intratumor heterogeneity were sent for flow cytometric (FCM) DNA analysis in two experienced laboratories. FCM instruments, run conditions, and tumor disaggregation procedures were different in the two laboratories. In four cases (12%) the laboratories reported a different DNA ploidy and DNA index (DI). These variations were due to analytical reasons, differences in the detection rates of near-diploid and tetraploid DIs, not due to interpretation of data or the criteria used for aneuploidy. There was a significant correlation between S-phase fractions (SPF) obtained in the two laboratories (r = 0.90, p less than 0.0001) if only cases with concordant DI were included. Discordant DI usually led to very different SPF values.

Surgical biopsy specimens of 179 breast carcinoma were studied by steroid-binding and immunohistochemical assays or oestrogen and progesterone receptors (ER, PR) in order to explore reasons for discordant results between the two assay types. Receptor statuses in 18% of ER assays and 30% of PR assays were in disagreement. Immunohistochemistry-positive steroid-binding-negative status predominated among the discordant ER assays, while the discordant PR assays displayed the opposite situation. In discordant assays receptor concentration was significantly more often close to the cut-off (10-50 fmol mg-1) than in the concordant ones. Low binding affinity (high Kd) was also significantly associated with disagreeing assay results. These observations clearly indicate that immunohistochemical ER and PR assays measure high-affinity binding components (i.e. type I receptors) in steroid-binding assays. ER but not PR assays in premenopausal women disagreed more often than those in post-menopausal women. Such factors as histological type, specimen size in steroid-binding assay, grade of malignancy and tumour necrosis were statistically unrelated to agreement or disagreement of receptor assays.

Serum triglycerides, high density lipoprotein (HDL) cholesterol, and total cholesterol were measured in 698 patients examined by angiography. The ratio of HDL cholesterol to total cholesterol was significantly lower in patients with single, double, and triple vessel disease than in patients without disease. The serum concentration of triglyceride was significantly higher in patients with single, double, and triple vessel disease than in those without coronary artery disease. Similar proportion of patients with coronary artery disease and without had serum cholesterol concentrations of greater than or equal to 6.5 mmol/l, but total cholesterol was significantly higher in patients with single, double, and triple vessel disease than in those without. HDL cholesterol (less than 1.0 mmol/l), triglycerides (greater than 2.0 mmol/l), and the ratio of HDL cholesterol to total cholesterol (less than 0.20) were significantly better than total cholesterol as indicators of coronary risk.

N-acetyl-beta-D-glucosaminidase (NAG; EC 3.2.1.30) activity was measured in sera of 23 patients admitted for elective surgery. Cholecystectomy increased serum NAG activity (by 62%) (p less than 0.004), whereas other types of operations (minor or major abdominal surgery, inguinal hernias and leg varices) had no regular effect. In cholecystectomy patients, the increase of serum NAG activity was associated with parallel changes in liver enzymes suggesting that manipulation of liver may liberate NAG into the circulation. Surgical trauma per se does not provoke any significant liberation of NAG.

A recommendation for basic urinalysis and urine culture is published as an attempt to improve the clinical value of urinary tests and to create a system that utilizes laboratory work as sensibly as possible. More clinical background information is needed when basic urinalysis and urine culture is performed in stages. Collection and storage of urine specimens are standardized in addition to used equipment and bacterial culture. Cytological supravital stain improves qualitative and quantitative findings of urine sediment cytology. A close cooperation between central hospital district is necessary and stressed for further bacterial cultures in more complicated microbiological findings.

A recommendation concerning basic urine examinations and bacteriological cultures was published in 1983 in Finland including three clinical indication groups with different screening strategies. Close cooperation between laboratory experts and clinicians as well as much training in urine sediment cytology were essential before the new principle became widely accepted. Decreased workload in laboratories in clinically less significant cases was shown with the use of the full capacity and qualities of complete urinalysis when needed. Standardized test procedures combined with sediment staining improved the clinical efficiency of urine microscopy.

The serum activities of two lysosomal enzymes, beta-N-acetylglucosaminidase (EC 3.2.1.30) and beta-glucuronidase (EC 3.2.1.31) were analyzed for 28 silicosis and 34 asbestosis patients. The enzyme activities of the patients were compared with those of age-, sex- and exposure-matched controls with no radiological signs of pneumoconiosis, and with an additional reference group of blood donors. The serum activity of beta-N-acetylglucosaminidase was higher in the silicosis patients (32.5 +/- 11.7 U/l) than in the asbestosis patients (21.7 +/- 7.9 U/l, p less than 0.001), in the silica exposed controls (27.1 +/- 6.7 U/l, p less than 0.05) or in the blood donors (24.8 +/- 6.3 U/l, p less than 0.05). No significant differences were found in the serum activity of beta-glucuronidase in the studied groups. Although the mechanisms causing different levels of serum beta-N-acetylglucosaminidase activity in silicosis and asbestosis patients remain unresolved, they may be related to the different mechanisms of action of the two dusts on lung (10).

Paraffin-embedded tumor samples from 157 ovarian cancer patients were analyzed by DNA flow cytometry. Tumor ploidy had prognostic significance in both early and advanced ovarian cancer. After adjusting for stage, residual tumor mass, histopathologic type, treatment, and age of patient in a Cox regression analysis, the relative risk of death was two-fold higher in single DNA-aneuploid and sixfold higher in DNA-multiploid tumors as compared to DNA-diploid tumors (P less than 0.0001). A tetraploid DNA index was associated with a relatively low risk ratio, whereas hypertetraploid tumors were highly malignant. S-phase fraction (SPF) had prognostic value especially in DNA-diploid tumors. The simultaneous evaluation of DNA index, the number of aneuploid cell clones, and SPF gave more prognostic information than the determination of tumor ploidy alone. On the basis of these parameters we have developed a classification of tumor DNA histograms for better prognostic assessment of ovarian cancer.

A rapid and simple immunochemical method for fibrinogen determination is described. The method is based on measuring the turbidity caused by antigen-antibody complexes with an enzyme analyser using diluted antiserum as a starting reagent. This immunoturbidimetric method correlates well with the immunodiffusion method and with two of the thrombin methods. Its correlation with the precipitation method according to Low was a little weaker.

The effects of long-term aurothiomalate and D-penicillamine treatments on renal function and the urinary excretion of prostanoids were studied in 20 patients with classic or definite rheumatoid arthritis. Twelve-hour urine was collected overnight, on the following day blood samples were taken in the morning and 12-hour urine was collected during the following day. Albumin excretion into the urine was determined by a sensitive quantitative method. Beta-2-microglobulin (B2MIGLO) and N-acetyl-beta-glucosaminidase (NAG) serum concentrations and excretions into the urine were measured to detect possible tubular or glomerular damage, respectively. The excretions of prostaglandin E2 (PGE2), thromboxane B2 and 6-keto-PGF1 alpha into urine were determined. In the aurothiomalate group, albumin excretion ranged 1-16 mg/12 h, and in the penicillamine group 0.8-31 mg/12 h. In the penicillamine group, but not in the aurothiomalate group, total protein, B2MIGLO and PGE2 excretions were higher (p less than 0.05) during the daytime than during the night. The daytime excretion of PGE2 was higher (p less than 0.01) in the penicillamine than in the aurothiomalate group. In the penicillamine group B2MIGLO excretion into urine correlated (p less than 0.01) with PGE2 excretion in the daytime. According to the results, not even long-term aurothiomalate treatment affects renal prostanoid excretion, while penicillamine increases urinary PGE2 excretion. This could be related either to the cofactor-like activity of penicillamine in the prostanoid synthesis or to damage in tubular cells. The role of prostanoids in maintaining blood flow and filtration may be more important in patients with renal damage than in normal conditions.

An organized mammographic screening program covered 8,690 women from selected birth cohorts (aged 50-59) in the Tampere University Central Hospital district. Forty-four breast cancer cases were detected in the first round of mammographic screening, which is 3.7 times the expected annual number of new cases in this population. To evaluate the proliferative kinetics and biological properties of these cancers, DNA flow cytometric analysis was carried out in 37 of the screen detected cancers (SDCs) using 60 clinically detected stage I-II cancers and 30 screen-detected benign lesions as reference. DNA aneuploidy was observed in 17/37 (46%) of the SDCs as compared to 41/60 (68%) in the clinical controls (p less than 0.05), while all the benign lesions were DNA-diploid. The median S-phase fraction (SPF) in the SDCs was significantly (p less than 0.001) lower (3.5%) than in the clinical controls (9.6%). Differences in SPF persisted in subgroups defined by DNA ploidy and histological type. In stage-I SDCs the median SPF value (2.5%) approached that of benign tumors (1.9%). Our epidemiological and biological data indicate that the first round of mammography predominantly detects prevalent preclinical lesions, some of which are of very low malignant potential. At present such patients may often receive too extensive treatment. DNA flow cytometry could help in the identification of cases which could be treated, for example, by breast-conserving methods.

The automated continuous alpha-amylase assay using p-nitrophenyl-alpha-D-maltoheptaoside (Boehringer Mannheim) as substrate on the Hitachi 705 clinical chemical analyzer, was compared with the Phadebas Kinetic Amylase Assay (Pharmacia Diagnostics) on the Hitachi 705. The two methods showed good correlation. The precision varied from 1.0 to 2.5% (CV) within-day and from 1.1 to 5.6% (CV) day-to-day. The substrate, p-nitrophenyl-alpha-D-maltoheptaoside, was also applied to an automated isoamylase assay. The amylase inhibitor from wheat was used to determine the ratio of pancreatic and salivary amylase activities of serum. About 80% of salivary type amylase was inhibited up to an activity level of 1000 U/l, while inhibition of pancreatic type amylase activity was only 10-15%. Ratios of pancreatic to salivary amylase from 0.1 to 10 can be evaluated in serum with wheat inhibitor. The precision of the isoamylase determination by the Boehringer amylase method was acceptable.

The glucose metabolism of diabetes mellitus during maintenance haemodialysis treatment was studied in four patients with endstage renal failure. There was a large day-to-day variation in the predialysis blood glucose levels, which it was difficult to control by adjusting the insulin dose. In spite of very high blood glucose levels, blood lactate and beta-hydroxybutyrate were not elevated. Triglycerides were markedly and constantly elevated, in no apparent association with the predialysis blood glucose level. The patients were shown to release moderate amounts of glucose, beta-hydroxybutyrate and lactate into the dialysate during the dialysis period. A technique of continuous blood glucose monitoring during the haemodialysis period was applied. With this technique blood sugar levels were accurately determined during the whole dialysis period. A rapid drop in the blood glucose level was found in apparent association with an aggravation of symptoms. A very marked tendency to hypoglycaemia was also revealed. It is concluded that the technique is a valuable aid in the proper management of diabetes in these cases.

In order to study the association between haemostatic-fibrinolytic balance during late pregnancy and retarded foetal growth, 22 mothers with suspected intrauterine growth retardation were studied by blood haematocrit and platelet count, plasma fibrinogen and serum fibrinogen degenerating products (FDP) in late pregnancy. Fifteen mothers with undisturbed foetal growth served as controls. No statistical differences could be found between these two groups of mothers in any of the studied blood parameters. It is thus concluded that a defect in the haemostatic-fibrinolytic balance seems not to play any very important role in the etiology of intrauterine growth retardation.

The serum concentrations of CA 125 and placental alkaline phosphatase were analyzed in 16 patients with ovarian cancer. Increased serum levels of CA 125 and placental alkaline phosphatase were observed in 75% and 50% of the cancer patients, respectively. The serum levels of these tumor markers were not correlated, supporting their distinct antigenic nature. CA 125 seems to be a more promising tumor marker for ovarian cancer than placental alkaline phosphatase.

Sixty-one consecutive patients were examined to determine the current mode of presentation of primary hyperparathyroidism (pHPT). Of these patients, 37.7% were asymptomatic, and the initial indication of pHPT was hypercalcemia, which was found unexpectedly on biochemical screening of the serum in elderly patients. Hypertension was twice as common among patients with pHPT as in the general population (36.1%). The next most common presentations were urinary calculi (18%) and mental depression (18%). The most useful discriminant laboratory tests were serum calcium, phosphorus, chloride, and parathormone (PTH). The calculated coefficient of correlation of PTH to land weight was high (r = 0.571, p less than 0.001). There was very significant correlation between PTH and seriousness of bone disease (r = 0.620, p less than 0.001). After parathyroidectomy, 3.3% of patients remained hypercalcemic, 93% were normocalcemic, and 1.6% were hypocalcemic.

Concentrations of progesterone and oestradiol in peripheral serum and tumour cyst fluid were measured in 42 post-menopausal women with epithelial ovarian tumours (17 cancer, 6 borderline malignant, 19 benign tumours) and in 19 post-menopausal women without ovarian neoplasms. The hormonal response of the endometrium was assessed, progestogen and oestrogen receptor content in the tumour tissue case recorded, and tumour deoxyribonucleic acid (DNA) ploidy was measured by flow cytometry. No significant differences were found between the mean serum steroid levels in patients with malignant, borderline or benign tumours, but the mean serum levels of oestradiol in patients with malignant or benign ovarian tumours were higher than those in the controls. Endometrial hormonal activity was seen in 19% of the samples studied. Malignant and benign mucinous epithelial tumours were the types most frequently associated with hormonal activity. Increased levels of sex steroids were seen in the cyst fluid of serous malignant and borderline malignant tumours, while benign tumours were inactive. The steroid receptor content of the various tumour types did not vary significantly. Ten (59%) out of 17 ovarian carcinomas were found to be aneuploid and 41% diploid as measured by flow cytometry. No significant differences in serum levels of progesterone and oestradiol were found between aneuploid and diploid ovarian carcinomas. These results contribute to our knowledge of the hormonal activity of epithelial ovarian tumours in post-menopausal women.

The nuclear mitochondrial and synaptosomal fractions of rat brain were each found to contain some 25-30% of the total aldehyde dehydrogenase activity. The cytoplasmic fraction had a very low total aldehyde dehydrogenase activity. There were differences in the distribution of the activity when different aldehydes were used as substrates, suggesting the presence of isoenzymes in the various subcellular compartments. When rats were treated intracisternally with 6-hydroxydopamine there was no change in brain aldehyde dehydrogenase activity, although the noradrenaline content and the activities of tyrosine hydroxylase and dopamine-beta-hydroxylase were markedly decreased. Treatment with 6-hydroxydopamine also had no significant effect on the aldehyde dehydrogenase activity in retinal homogenates. The results suggest that the aldehyde dehydrogenase activity in rat brain is predominantly outside the catecholaminergic nerve terminals.

We determined nuclear DNA content from 308 archival paraffin-embedded malignant breast tumours and evaluated the survival of the patients by univariate and multivariate statistical analyses. The overall 8-year survival rate of stage I-III breast cancer patients was 74.3% in DNA-diploid and 51.2% in DNA-aneuploid tumours (P less than 0.0001). DNA ploidy had prognostic significance in both node-negative and node-positive breast cancer, primarily in cases with steroid receptor-positive tumours. In a Cox multivariate analysis DNA ploidy (P = 0.001), primary tumour size (P = 0.0007), nodal status (P = 0.04) and the content of progesterone receptors (P = 0.0008) emerged as significant independent prognostic factors, whereas oestrogen receptor status, age and menopausal status of the patients had no significant independent prognostic value. If the histological grade of ductal carcinomas was also included in the Cox model, both grade and DNA ploidy had independent prognostic effect. In conclusion, our results indicate that the analysis of DNA ploidy is a useful adjunct in the assessment of prognosis for breast cancer patients.

A rapid immunochemical method for transferrin determination is described. The method is based on measuring turbidity caused by antigen-antibody complexes with an enzyme analyser using diluted antiserum as a starting reagent. This immunoturbidimetric method correlates well with TIBC (r=0.979; n=36). A comparison with the radial immunodiffusion method gave the correlation coefficient 0.984 and the regression line y=1.20x-0.54 (n=36).

The usefulness of a simple fluorometric assay for serum heat-stable alkaline phosphatase (HSAP) in the diagnosis and follow-up of ovarian cancer patients was evaluated. 50 percent of the patients with malignant ovarian tumors had serum HSAP-activities above the upper reference range. Active production of this tumor marker in malignant but not in benign ovarian tumors was demonstrated by analysing serum HSAP-activities in ovarian vein blood. After operation, serum HSAP-activities decreased in all cancer patients with elevated preoperative values. Our results suggest that fluorometric serum HSAP-assay may be a useful alternative method for the determination of this tumor marker especially in a clinical laboratory.

Eleven invasive and five non-invasive primary vaginal carcinomas were studied by DNA flow cytometry using archival paraffin-embedded tissue as starting material. Overall frequency of DNA aneuploidy in the invasive carcinomas was 8/11 (73%). DNA aneuploidy occurred in all four advanced stage (III-IV) and in 4/7 (57%) of the early stage (I-II) carcinomas. Among the squamous cell carcinomas aneuploid DNA content was also associated with non-keratinizing tumor type. Invasive vaginal carcinomas showed a high median S-phase fraction (SPF) (18.4%, range 6.9-31.8%). High SPF values were associated with advanced stage and non-keratinizing tumors. Corrected 5-year survival rate in invasive vaginal cancer was 44%, with no significant relation to DNA ploidy or SPF. In situ carcinomas were almost as often DNA-aneuploid (3/5, 60%) as the invasive carcinomas and had comparable median SPF value (13.4%, range 5.5-24.6). One in situ carcinoma with a high DNA-index and SPF relapsed, but overall 5-year survival rate was 100%. In conclusion, both invasive and in situ vaginal carcinomas frequently contain DNA-aneuploid stemlines and show a high SPF. Although DNA aneuploidy and high SPF correlate with advanced stage and non-keratinizing tumor type, they do not have much prognostic relevance in vaginal neoplasia.

We studied the effect of one haemodialysis treatment on the plasma concentrations of intact parathyroid hormone (PTH), total immunoreactive PTH (determined with an antibody against the mid-molecular part of the hormone), and ionised calcium in 25 patients on maintenance dialysis for chronic renal failure. During dialysis the calcium concentration in the external fluid was 1.75 mmol/l, which led to an increase in the plasma ionised calcium concentration from 1.23 +/- 0.07 mmol/l (mean +/- SD) at commencement of dialysis to a final 1.35 +/- 0.07 mmol/l (P less than 0.001). The plasma concentration of intact PTH decreased from 27.4 +/- 26.3 pmol/l to 13.0 +/- 19.1 pmol/l (P less than 0.001) during the treatment. Total immunoreactive PTH did not change, reflecting poor dialysability of PTH and PTH fragments. We also compared the dialysis-induced changes in the plasma concentrations of intact PTH and ionised calcium with those induced by a calcium infusion test. We conclude that in the majority of dialysis patients, one haemodialysis treatment with a relatively high external fluid calcium concentration can be used to assess the suppressibility of secondary hyperparathyroidism.

We have studied the method for the determination of human erythrocyte insulin receptor concentrations using tyrosine-A-14-monoiodoinsulin as the labelled ligand with increasing amounts of unlabelled insulin in a saturation assay. An overnight incubation at 0-+4 degrees C was found to give the highest receptor concentrations and highest affinities for the ligand. Insulin receptor concentrations were found to be very low and lower in erythrocytes from normal females than from normal male subjects (7.0 +/- 1.9 and 10.5 +/- 1.6 receptors per erythrocyte, respectively). Our results suggest that an initially homogenous class of insulin binding sites upon exposure to insulin can appear in different forms with different binding affinities for the ligand. This was deduced from the changes in the forms of Scatchard plots when the saturation assay was performed at different times at low temperature. Variability in the forms of Scatchard plots (linear to biphasic or vice versa) in samples obtained on different occasions from the same subjects also support this view. The apparent dissociation constants (mean values) were 150 and 550 pmol/l for the linear components of the biphasic plots and 300 pmol/l for the linear plot. These values lie well within the normal plasma concentrations of insulin. Addition of spermine to the incubation mixture was shown to further accentuate the high affinity part of the Scatchard plot. The high and low affinity forms of the receptor could provide an ideal means to rapidly regulate the response to insulin.

The quality control of insulin radioreceptor assay for human erythrocytes is based on the storage of erythrocyte preparations in Hepes buffer of pH 8.0, containing 10 g/l of albumin and 20 mmol/l of glucose. The change of erythrocytes into spherocytes and crenated cells reduces the apparent number of insulin receptors in a relatively constant way by less than 8% a week after 10 days of storage. At the same time the dissociation constants of the insulin-receptor complex increase rapidly. Thus the use of a preparation must be limited to controlling the determination of the insulin binding sites of erythrocytes, and not to the measurement of the affinities of the receptors. When mono-125I-Tyr-A14-insulin gets old, a slow decrease in the insulin binding sites can be measured, but the dissociation constants of the insulin receptor complex are not affected.

Properties of the phenobarbital induced cytoplasmic aldehyde dehydrogenase (EC 1.2.1.3) have been studied in rat liver. 7-12-Fold higher levels were seen in the cytoplasmic activities after phenobarbital treatment in reactor compared to non-reactor animals with high concentrations of acetaldehyde (18 mM) and propionaldehyde (9 mM). No difference was found with 0.12 mM acetaldehyde, 2 mM glycolaldehyde, 6 mM formaldehyde or 0.5 mM betaine aldehyde. The reactor group also had slightly higher activity in the mitochondrial fraction with the high acetaldehyde and propionaldehyde concentrations. In the microsomal fraction, the activities showed no differences at any substrate concentration. An induced aldehyde dehydrogenase was purified 70-fold by chromatographic techniques. It had different molecular and enzymic properties than the main high-Km enzyme normally present in rat liver cytoplasm. The pI of the induced enzyme was about 7.0 as measured by isoelectric focusing. It was active with several aliphatic and aromatic aldehydes but not with formaldehyde, glycolaldehyde or D-glyceraldehyde. The Km-values for propionaldehyde and acetaldehyde were in the millimolar range. Millimolar concentrations of aromatic aldehydes caused a strong substrate inhibition. The enzyme was inhibited by submicromolar concentrations of disulfiram. Estrone, deoxycorticosterone, progesterone and diethylstilbestrol also affected the enzyme activity.

The serum activities of two lysosomal enzymes, beta-N-acetylglucosaminidase (EC 3.2.1.30, NAG) and beta-glucuronidase (EC 3.2.1.31, GLU), were determined in 41 insulin-dependent diabetics, 27 age-matched non-diabetic first-degree relatives of the diabetics and 103 age-matched non-diabetic blood-donors. The diabetics were divided into three groups on the basis of ophthalmoscopy: (1) no retinal abnormalities; (2) non-proliferative retinopathy; and (3) proliferative retinopathy. The activities of both serum enzymes were higher in diabetics (NAG 21.39 +/- 5.99; GLU 2.19 +/- 1.01) than in their relatives (NAG 17.22 +/- 3.99; GLU 1.62 +/-0.61). The diabetics with non-proliferative retinopathy had higher serum enzyme levels (NAG 24.05 +/- 6.26; GLU 2.60 +/- 1.06) than diabetics without retinopathy (NAG 17.88 +/- 3.00; GLU 1.69 +/ 0.64), whereas no statistically significant difference was found in patients with the proliferative form of retinopathy (NAG 18.67 +/- 6.28; GLU 1.99 +/- 1.04). In diabetics a positive correlation was found between serum beta-N-acetylglucosaminidase activity and blood glucose (p < 0.01), but not between beta-glucuronidase and blood glucose. Furthermore, the activities of both enzymes in diabetics correlated with the plasma triglyceride level (p < 0.05 for both correlations). No correlation was found between the enzyme levels and signs of other diabetic late complications.

The induction of rat liver cytoplasmic aldehyde dehydrogenase by some xenobiotics and phenobarbital are compared. An acute and a chronic treatment with polycyclic hydrocarbons and with TCDD produce a similar pattern of induced enzymes in isoelectric focusing. The result is clearly different from induction with phenobarbital in the genetically selected rat strain. Another main activity in cytoplasm consists of three different isoenzyme patterns which evidently are normal enzyme types. The induced enzyme of liver cytoplasm after chronic AAF-treatment was purified to homogeneity. The enzyme had a molecular weight of 90000 and a subunit molecular weight of 45000. It had Km-values in the millimolar range for aliphatic aldehydes and in the micromolar range for aromatic aldehydes. Both NAD and NADP were coenzymes of the purified aldehyde dehydrogenase.

Twenty-four patients with acute severe pancreatitis were randomised to receive total parenteral nutrition for 7 days with one of two isocaloric (35 kcal/kg/day) and isonitrogenous (0.16 g/kg/day) programmes containing either a low (15.5% w/w (control group)) or a high (57%) content of branched chain amino acids (BCAA (BCAA group)). During treatment, the nitrogen balance was similar in both groups. The concentrations of serum protein, albumin, prealbumin and retinol-binding protein did not differ between the groups. The plasma concentrations of BCAA measured 2 h after discontinuation of amino acid infusions rose in the BCAA group. In urine, only the concentrations of valine increased as compared with those of control patients. Serum glucose levels were higher in the BCAA group than in the control group, although the BCAA group received slightly more insulin than the control group in order to keep the blood glucose concentration below 10 mmol/l. The results suggest that BCAA-enriched solutions may stimulate gluconeogenesis without affecting catabolism.

Peripheral serum concentrations of progesterone were measured in 27 postmenopausal women with malignant, borderline, or benign ovarian tumor and in 10 women without ovarian neoplasm. The progesterone levels were significantly higher in all ovarian tumor groups as compared with the controls. There was no difference between malignant and benign tumors. Patients with a tumor volume over 1 000 ml had higher progesterone levels than patients with smaller tumors, in both peripheral and ovarian venous blood. Mucinous ovarian tumors were associated with the highest progesterone levels, compared with other histologic types of ovarian tumor. The results indicate that mucinous ovarian tumors are able to secrete progesterone and that the stage of malignancy has no effect on this hormonal activity.

The serum levels of antigen CA 125 expressed by epithelial ovarian carcinoma were measured in 27 postmenopausal women with ovarian tumours and in 16 controls. Increased serum levels of CA 125 were found in nine (75%) out of 12 patients with ovarian cancer; in three with stage I disease levels were not elevated. No significant difference was found in the concentration of CA 125 detected in peripheral or ovarian venous blood. Decreased antigen levels were found 6-30 weeks after radical operation and cytostatic chemotherapy in the ovarian cancer group. The results indicate the value of measuring CA 125 as a tumour marker in the follow-up of ovarian cancer.

Parameters of calcium metabolism were thoroughly examined in 28 adolescents with long-term (over 6 years) anticonvulsant therapy (phenytoin, carbamazepine or combination) and in 10 normal controls in September and in March. The adolescents did not receive any vitamin D supplementation during the study. Serum calcium, inorganic phosphorus, parathyroid hormone and alkaline phosphatase levels in the anticonvulsant group did not differ from those of the control group. Serum 25(OH)D and 24,25(OH)2D levels were in all groups consistently higher in September than in March, but no seasonal variation was found in the 1,25(OH)2D levels in any group. The serum 25(OH)D levels in the phenytoin group in March were the lowest among the three groups treated with anticonvulsants, but the levels in the anticonvulsant groups did not differ significantly from each other or from the control group in the same season. The 24,25(OH)2D and 1,25(OH)2D levels in the anticonvulsant groups did not differ significantly from those of control group in September or in March. There was no correlation between anticonvulsant serum free fraction levels and vitamin D metabolites. The bone mineral content in the distal radius was not significantly decreased in the epileptic patients. In conclusion, the long-term anticonvulsant therapy did not induce the so-called "anticonvulsant rickets" in this ambulatory adolescent material. Our data do not indicate that anticonvulsant drugs alter significantly the vitamin D metabolism. Thus, routine vitamin D supplementation does not appear to be indicated in children on anticonvulsant therapy.