Transvaginal ultrasound and lactate dehydrogenase isoenzyme activity profile in uterine aspirate for diagnosis of endometrial carcinoma in women with postmenopausal bleeding.

Postmenopausal patients with vaginal bleeding (n = 72) were evaluated with the combination of transvaginal ultrasonography (TVS) and analysis of the lactate dehydrogenase (LD) isoenzyme activity profile in uterine fluid aspirates. TVS evaluation of the endometrium was classified as <5 mm, > or =5 mm, or poorly defined. The LD isoenzyme activity profile was characterized as abnormal or normal. Pathologic findings were further evaluated with diagnostic curettage. TVS found the endometrium to be > or =5 mm or poorly defined in 44 patients (61%). Endometrial carcinoma was found in 6 of 72 patients (8%). They appeared in the TVS groups endometrium >5 mm (n = 2) and endometrium poorly defined (n = 4) but not in the endometrium <5 mm. The LD isoenzyme activity profile was abnormal in the six malignant cases and in ten benign cases. Thus, the need for further evaluation with hysteroscopy and curettage was reduced to 16 cases. Since TVS had 100% sensitivity but only 42% specificity, it is suitable for first-level examination in patients with postmenopausal bleeding. The second-level method should have similarly high sensitivity but much higher specificity. The LD isoenzyme activity profile in uterine fluid aspirates had 100% sensitivity and 85% specificity. Another important feature is that the method is not sensitive to endometrial thickness, amount of sample, sampling device, or dilution. Thus, it is more reliable than aspiration histology. For every hysteroscopy or curettage that can be replaced by LD analysis, the cost is reduced by approximately EUR 720 or 540, respectively.

Diagnosis of endometrial cancer in patients with postmenopausal bleeding by analysis of the lactate dehydrogenase isoenzyme activity profile in uterine fluid.

OBJECTIVES: We have previously shown that high activity of lactate dehydrogenase (LD) isoenzymes 4 and 5 in terine aspirates is a marker for endometrial carcinoma. The purpose of this study was to identify an abnormal activity profile of LD2-5 using LD1 as an internal standard, thereby being able to dispense with measurement of the total LD activity. The profile was subsequently tested for diagnostic power in clinical settings. METHODS: We used data from 11 cases of endometrial cancer. Each isoenzyme was estimated relative to the activity of LD1 (LD1 = 1.0). Based on the lowest level found for each of LD2-5 in the 11 cases, the cut-off levels for an "abnormal profile" were identified. The abnormal profile was subsequently tested for diagnostic power in a group of postmenopausal women at risk for endometrial cancer, that is, they had experienced vaginal bleeding (n = 100). A second group of asymptomatic postmenopausal women (n = 366) had endouterine aspiration performed as part of a regular gynecologic check up to evaluate the prevalence of an abnormal LD isoenzyme profile. RESULTS: In the group of postmenopausal women who had experienced vaginal bleeding, abnormal profile was found in 27 cases: 14 with adenocarcinoma and 13 with benign histology. All cases with normal profile had benign histology. Thus, sensitivity as well as the negative predictive value was 100%. In the group of asymptomatic women, abnormal LD isoenzyme profile was found in 15 cases (4.1%). All had benign histology. CONCLUSIONS: The LD isoenzyme profile detects endometrial malignancy with high accuracy, and equally important, a normal profile excludes malignancy. The profile, which uses relative rather than absolute activity levels, based on LD1 as an internal standard, has the great advantage of being independent of both the dilution factor and the aspiration technique. Larger studies comparing the LD isoenzyme activity profile with ultrasonographic evaluation and biopsy histology are needed.

Lactate dehydrogenase and its isoenzymes in vaginal fluid in vaginitis/vaginosis cases and in healthy controls.

The objective of the study was to measure the lactate dehydrogenase (LD) activity in vaginal lavage fluid of women with vaginitis/vaginosis and in healthy pre- and post-menopausal controls. Also to analyse the LD isoenzyme patterns in such samples and compare the influence on the LD activity by different storage and sampling methods. Twenty of the women studied, who had no signs of inflammation as evidenced from vaginal wet smears, were pre-menopausal and 8 post-menopausal. Fifty-eight non-pregnant patients with vaginitis/vaginosis or non-inflammatory gynaecological conditions were analysed for LD isoenzyme patterns. The LD activity was correlated to vaginal pH. Furthermore, the LD activity was determined in another 100 women screened for Chlamydia trachomatis. Finally, the influence on the LD activity when sampling was made by a cytological brush vs vaginal lavage and analysed after different storage periods, as studied. The LD activity was elevated, i.e. >2 micro kat/L, in all but two of the women with leucorrhoea. Only women with bacterial vaginosis (BV) without leucorrhoea, had an increased LD activity. An increased vaginal pH correlated to the LD concentration. The LD activity was elevated in cases with vulvovaginal candidiasis, trichomoniasis, chlamydial cervicitis and senile colpitis. Storage of samples for up to six hours had no influence on the test outcome. Brush and lavage fluid samples did not differ with regard to the rate of positive LD tests. In healthy women, the LD activity is low and predominated by slow-migrating isoenzymes, i.e. LD 4 and 5. The LD activity is generally increased in cases of vaginitis and in women with BV and chlamydial cervicitis. In trichomoniasis, particularly high concentrations of LD 5, are found.

Effect of anticoagulation on renal function and protein excretion in experimental acute ischemic renal failure.

Female Sprague-Dawley rats underwent right nephrectomy and 40 min left renal artery occlusion (RAO). After 15 min of reflow, polyethylene glycol 1000 (PEG1000) was infused to induce osmotic diuresis and to enable glomerular filtration rate (GFR) measurements. Urine was collected during a 90 min period, and the concentrations of PEG1000, albumin, IgG, IgM and fibrin(ogen)/degradation products (FIB) were assessed both in plasma and urine by radial immuno diffusion technique Groups of rats were subjected to saline + RAO, warfarin + RAO or sham-operation. GFR as measured by PEG1000 clearance averaged 0.61, 0.036 and 0.094 mL/min/100g BW/kidney in sham-operated, saline + RAO and warfarin + RAO rats, respectively. Urinary excretion of albumin and IgG increased substantially in both ischemic groups. IgM was not detected in any of the urine samples. FIB excretion was lowest in the saline + RAO group, possibly due to retention of FIB-containing obstructions in the tubules. Rats subjected to warfarin + RAO had significantly higher excretion of FIB. This result suggests that warfarin does not prevent the glomerular sieving of macromolecules in the glomerular filter, but reduces tubular obstruction by preventing fibrin formation, which may explain its positive effect on GFR.

Hepatocyte growth factor (HGF) in patients with pneumonia: a comparison between survivors and non-survivors.

Hepatocyte growth factor (HGF) is a multifunctional growth factor. After lung injury HGF is secreted in the lung and promotes reconstruction of the damaged organ. We measured, retrospectively, the serum HGF concentrations collected on admission in 55 patients with bacterial pneumonia, using an enzyme-linked immunosorbent assay (ELISA). The patients were divided into 3 groups: Group 1 was survivors with normal liver function (n = 14), Group 2 was survivors with abnormal liver function (n = 31) and Group 3 was non-survivors (n = 10). Median concentrations of HGF were elevated in Groups 1 and 2; and no statistically significant difference between these 2 groups was found. Group 3 had a median HGF concentration within the reference range, significantly lower than both Group 1 and Group 2. In addition LDH was significantly higher in non-survivors as compared with survivors. The combination of LDH and HGF concentrations discriminated between survivors and non-survivors (sensitivity 0.90 and specificity 0.96). The results support the hypothesis that increased levels of HGF might be a natural part of the healing process of lung injury, irrespective of liver involvement, and that patients without increased HGF levels, especially those with concomitant liver function impairment, may have a poor prognosis.

Glycosylation of alpha1-acid glycoprotein in inflammatory disease: analysis by high-pH anion-exchange chromatography and concanavalin A crossed affinity immunoelectrophoresis.

High-pH anion-exchange chromatography with pulsed amperometric detection is a highly sensitive technique that can be used for detecting changes in sialylation and fucosylation, as well as different branching patterns of N-linked oligosaccharides in glycoproteins. We examined the N-glycans of alpha1-acid glycoprotein obtained from twelve patients with various inflammatory conditions with this technique, as well as traditional concanavalin A crossed affinity immunoelectrophoresis. We found the chromatographic profiles of N-glycans in all patients with rheumatoid arthritis to be very similar, but significantly different from normal controls. N-glycans from patients with ulcerative colitis also showed specific alterations in their chromatographic profiles. However, some heterogeneity was found between these patients, perhaps reflecting changes in glycosylation secondary to certain states of the disease, or to medical treatment. We conclude that this technique is useful for detailed mapping of glycosylation changes in alpha1-acid glycoprotein in clinical samples, and that it may be used to further increase our knowledge about glycosylation changes in response to inflammatory disease.

Effect of ultrasound guided core biopsy of prostate on serum concentration of prostate specific antigen and acid phosphatase activity.

Forty-three patients had their serum concentrations of prostate specific antigen and activity of tartrate inhibited acid phosphatase measured before and after digital rectal examination, transrectal ultrasonography and transrectal core biopsy. Transrectal core biopsy significantly increased the values for both tumor markers but rectal examination and ultrasonography without biopsy had no such effect. The measurements returned to normal within one week of biopsy in all but four patients who still had slightly increased concentrations of prostate specific antigen. We recommend that the concentration of prostate specific antigen and activity of tartrate inhibited acid phosphatase are checked before biopsy of the prostate is carried on.

Selective deficiency of pancreatic amylase.

Two patients with specific pancreatic amylase deficiency are described. The greatly reduced pancreatic amylase activity was not due to an enzymatically inactive amylase molecule but to an almost complete absence of the molecule itself. The findings are of diagnostic importance as they show that low pancreatic amylase activity in serum or duodenal aspirates, or both, does not necessarily represent chronic exocrine pancreatic disease such as chronic pancreatitis, carcinoma of the pancreas, or cystic fibrosis but may be an isolated finding. In one of our patients a familial occurrence was shown, indicating a congenital deficiency.

Pancreatic disease in dyspepsia.

Determination of the serum activity of pancreatic isoamylase was performed in 30-65-year-old men seeking primary health care centers for dyspepsia. Of 36 consecutive patients 7 had abnormal pancreatic isoamylase activity in serum. This figure indicates dyspepsia to be commonly associated with pancreatic disease such as chronic pancreatitis.

Screening for endometrial carcinoma by endouterine aspiration cytology with analysis of tumor markers in the aspirates. Development and application of a new screening technique.

A new endometrial aspiration technique for office screening of endometrial carcinoma without an anesthesia was studied. In patients without apparent signs of cervical canal stenosis, all of whom were 50 years of age or older, the aspiration attempt was successful in 96%. The aspirates were used for cytologic study and tumor marker assays. The results indicate that screening for endometrial carcinoma should be based on the determination of biochemical tumor markers in the uterine fluid. Lactate dehydrogenase (LD) is recommended as a primary marker, determined as total LD and as LD isoenzyme activity. Endometrial cytology is recommended as a supplementary screening technique in selected cases.

Amylase in human milk from mothers of preterm and term infants.

Amylase activity and isoenzyme pattern were determined in preterm human milk from 25 mothers during the first 55 days after delivery and from 25 mothers delivered at term. The diurnal variation in amylase activity and the variation during a feeding were studied in two mothers. There is a high amylase activity in preterm colostrum, which slowly decreases during the first 2 months. The individual variation in amylase activity is considerable. There is no difference in amylase activity in preterm and term human milk. The isoamylase of preterm milk is of the salivary type, just as in term milk. There is no great variation in amylase activity during a feeding or from one feeding to another.

Additional lactate dehydrogenase (LDH) isoenzymes in normal testis and spermatozoa of adult man.

Adult human testicular tissue contains up to six previously undescribed lactate dehydrogenase (LDH) isoenzymes in addition to the five LDH isoenzymes normally found and the sixth found in spermatogenic cells and spermatozoa, LDH-X. Additional LDH isoenzymes were also found in spermatozoa but not in seminal fluid or in serum. After electrophoresis one additional LDH isoenzyme of testicular tissue was localized between LDH-1 and LDH-2, two between LDH-2 and LDH-3, two between LDH-3 and LDH-4, and two between LDH-4 and LDH-5. These localizations indicate that the additional LDH isoenzymes are tetramers combining the A and B subunits of the five normal LDH isoenzymes and the C subunit of LDH-X. The additional LDH isoenzymes may be important in the metabolism of spermatogenic germ cells and spermatozoa.

Serum lactate dehydrogenase (S-LDH) and S-LDH isoenzymes in patients with testicular germ cell tumors.

The activities of serum lactate dehydrogenase (S-LDH) and S-LDH isoenzymes were determined in 252 patients with a history of testicular germ cell tumors (TGCT). Fifteen of 37 patients with TGCT lesions and seven of 215 without had raised levels of S-LDH (above 8.0 mukat/l (480 U/l)). Of the patients with TGCT lesions, four had only raised S-LDH-1 levels, one only raised S-LDH-2 (and normal S-LDH), two only raised S-LDH-3 (one with normal S-LDH), and 10 had five combinations of raised levels of S-LDH isoenzymes with a predominance of S-LDH-1. S-LDH and S-LDH-1 correlated significantly with the total tumor volume in the patients with TGCT lesions, especially pronounced in those with lesions from seminoma. Of 34 patients with TGCT metastases, 13 with raised S-LDH levels lived significantly shorter lengths of time than 21 with normal S-LDH. Similarly, 11 with raised S-LDH-1 (above 3.0 mukat/l (180 U/l) lived significantly shorter times than 23 with normal S-LDH-1. S-LDH is a valuable tumor marker in patients with TGCT, especially in those with seminoma. Routine determination of S-LDH isoenzymes in addition to S-LDH in patients with TGCT is not recommended. In patients with a history of TGCT and an unexplained elevation of S-LDH levels, a raised S-LDH-1 level indicates the presence of TGCT lesions.

Serum lactate dehydrogenase and its isoenzymes in men with maldescended testes.

Serum lactate dehydrogenase and lactate dehydrogenase isoenzymes were determined as a screen for testicular germ cell neoplasia in 130 men with maldescended testes. A testicular tumor was found on clinical examination in 1 patient, which was revealed to be embryonal carcinoma, teratoma, yolk sac tumor and carcinoma in situ on orchiectomy. Subclinical testicular germ cell neoplasia was found on testicular biopsy in 3 men (1 with microinvasive seminoma and 2 with carcinoma in situ). These 4 patients had normal serum lactate dehydrogenase and serum lactate dehydrogenase isoenzymes. Elevated serum lactate dehydrogenase was noted in 3 men without testicular germ cell neoplasia: 1 had predominantly increased serum lactate dehydrogenase isoenzymes 1 to 3 and 2 had slightly increased serum lactate dehydrogenase isoenzymes 3 and 4. Serum lactate dehydrogenase and lactate dehydrogenase isoenzymes were not sensitive to detect testicular germ cell tumors in a subclinical stage.

Amylase in human milk.

Amylase activity and isoenzyme pattern were determined in human milk from various stages of lactation and were compared with that in duodenal juice. The activity is high in colostrum and somewhat lower in milk from day 15 to day 90 after delivery. In this period of lactation, human milk contains higher amounts of amylase than duodenal juice from infants aged 1 to 6 months. Low activity was found in milk from 90 days or more after delivery. The amylase is of the salivary type. A pH of 5.3 does not inactivate the amylase; there is considerable human milk amylase activity in duodenal juice after a meal of human milk. Human milk amylase could thus contribute to the breast-fed infant's ability to digest starch.