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The purpose of this prospective study was to elucidate the characteristics of adult patients with acute abdomen admitted to a Finnish university hospital. A total of 639 patients entered the study. The most common cause of acute abdomen was non-specific abdominal pain (NSAP) (33.0%) followed by acute appendicitis (23.3%) and acute biliary disease (8.8%). The male:female ratio was 47:53 in the whole study population, but there were differences in the age and sex distributions when studied by diagnosis. NSAP was mainly presented in young women, but also in patients over 75 years of age. Acute appendicitis was most frequently found in young men, and biliary disease was most common in elderly women. A male predominance was noted in cases of alcoholic pancreatitis and gastritis, renal stones and peptic ulcer. Young women and elderly patients were slightly over-represented in the study population when compared with the whole population residing within the study area. 43% of the patients were operated on, and surgery was most common in patients aged 55-64 years and 15-24 years. Altogether 15% of the patients were discharged without hospitalisation. Twelve patients (1.9%) died of various causes, the most common of which was malignancy (four patients). In conclusion, a considerably large proportion (one third) of cases with acute abdomen remained without any specific explanation. Further, age and gender seem to be important factors when the most probable cause of acute abdomen is to be considered. Operative treatment is necessary in almost half of cases, and mortality for acute abdomen is low.

A prospective study of 277 patients with benign (n = 212) and malignant (n = 65) hepatopancreatobiliary disease was carried out to evaluate the value of six serum tumour markers (CEA, CA 50, CA 242, TPA, TPS, TATI) and 16 conventional laboratory tests in the distinction between benign and malignant diseases. In univariate analysis, all tumour marker tests except TATI showed significantly (p < 0.001) higher serum values in the patients with malignant disease than in the patients with benign disease. Among the conventional laboratory tests serum bilirubin, alkaline phosphatase and leucine aminopeptidase showed significantly. (p < 0.001) higher values in the patients with malignant disease, whereas serum protein and amylase levels were significantly (p < 0.01) higher in the patients with benign disease. In a multivariate analysis, serum bilirubin (p < 0.001), antithrombin III (p < 0.01) and blood hemoglobin (p < 0.05) were the most significant independent predictors of hepatopancreatobiliary malignancy. To sum up the contributions of the best tests a diagnostic score (DS) was developed. The sensitivity of DS in detecting malignancy was 73% with a specificity of 82% and an efficiency of 79%. In conclusion, our results speak against the use of multiple tumour marker tests, and rather suggest the use of a relatively limited amount of conventional laboratory tests in the distinction between benign and malignant hepatopancreatobiliary disease.

1. We have shown earlier that pilocarpine strongly inhibits mouse and human liver coumarin 7-hydroxylase activity of CYP 2A and pentoxyresorufin O-deethylase activity of CYP 2B in vitro. Since pilocarpine, like coumarin, contains a lactone structure we have studied in more detail its inhibitory potency on mouse and human liver coumarin 7-hydroxylation. 2. Pilocarpine was a competitive inhibitor of coumarin 7-hydroxylase in vitro both in mouse and human liver microsomes although it was not a substrate for CYP 2A5. Ki values were similar, 0.52 +/- 0.22 microM in mice and 1.21 +/- 0.51 microM in human liver microsomes. 3. Pilocarpine induced a type II difference spectrum in mouse, human and recombinant CYP 2A5 yeast cell microsomes, with Ka values of 3.7 +/- 1.6, 1.6 +/- 1.1 and 1.5 +/- 0.1 microM, respectively. 4. Increase in pH of the incubation medium from pH 6 to 7.5 increased the potency of inhibition of coumarin 7-hydroxylation by pilocarpine. 5. Superimposition of pilocarpine and coumarin in such a way that their carbonyls, ring oxygens and the H-7' of coumarin and N-3 of pilocarpine overlap yielded a common molecular volume of 82%. 6. The results indicate that pilocarpine is a competitive inhibitor and has a high affinity for mouse CYP 2A5 and human CYP 2A6. In addition the immunotype nitrogen of pilocarpine is coordinated towards the haem iron in these P450s.

The aim of the present prospective study was to evaluate the clinical value of a new serum tumour marker small intestinal mucin antigen (SIMA) in the diagnosis of colorectal cancer. The serum SIMA values were measured in a prospective series of patients with colorectal cancer (n = 73) and patients with benign gastrointestinal disease (n = 87). SIMA values were determined using two different techniques. The cut-off levels (90 % specificity) determined for each test were 12.0 U/ml for SIMA I (Delphia), 9.8 U/ml for SIMA II (PCA-Delphia), 2.5 ng/ml for CEA, 17 U/ml for CA 50 and 17 U/ml for CA 242. The diagnostic sensitivity of the SIMA I test was 0.27, of the SIMA II test it was 0.19, of the CEA test it was 0.63, of the CA 50 test it was 0.30 and 0.30 for the CA 242 test in detecting colorectal cancer. The correlation coefficients (Pearson's r) in colorectal cancer patients between SIMA I and SIMA II measurements were 0.99, 0.71 between CEA and CA 50, 0.70 between CEA and CA 242 and 0.96 between CA 50 and CA 242 measurements. The correlation coefficients in colorectal cancer patients between other serum markers were non-significant. All marker tests were entered in a multivariate analysis to find the best combination of independent predictors of colorectal cancer. The most important predictor of colorectal cancer was SIMA I. In order to calculate the contributions of tumour marker tests, a diagnostic score (DS) was developed. The sensitivity of the DS in detecting colorectal cancer was 0.33 with a specificity of 0.90 and an efficiency of 0.65. In conclusion, the results indicate that the diagnostic sensitivity of a new tumour marker SIMA is equal to CA50 and CA 242, but inferior to the diagnostic sensitivity of the CEA test. However, multivariate discriminant analysis suggests some diagnostic value for SIMA I test because of its independent discriminant value.

Objective: To examine the associations between potential risk factors and fractures in perimenopausal women., Subjects: A total of 3,140 women (mean age 53.4 +/- 2.8 (s.d.) years) were followed-up for 2.4 years after axial bone densitometry (lumbar spine and femoral neck) with regard to the occurrence of fractures., Results: In all, 5.6% of the women sustained a fracture. There were 169 low energy fractures (falling on a level surface) in 157 women after the exclusion of 18 fractures caused by a high energy trauma. The wrist was the most frequent site of fracture (n = 46). Lumbar bone mineral density was 5.8% lower and femoral bone mineral density 4.6% lower among fracture cases compared with non-fracture cases (p < 0.0001). History of a fracture during 1980-1989 elevated the risk of all fractures 2.83-fold (95% confidence interval (CI) 1.95-4.10) and the risk of a first wrist fracture 2.25-fold (95% CI 1.10-4.62). The amount of weekly alcohol intake was higher among fracture cases than among non-fracture cases yielding an age-adjusted odds ratio (OR) of 1.45 (95% CI 1.05-2.02). Past or present use of hormone replacement therapy was protective against fractures (age-adjusted OR 0.70, 95% CI 0.50-0.96). If bilateral oophorectomy had been carried out under the age of 45 years, the risk of fracture was 3.64-fold (95% CI 1.01-13.04) compared with women operated upon after the age of 45 years. Age at menarche, parity, lactation and smoking history did not differ between the fracture and non-fracture groups., Conclusions: A former history of fractures, low baseline bone mineral density (BMD) and use of alcohol are predisposing factors associated with perimenopausal fractures, while hormone replacement therapy is protective in this respect.

This investigation was undertaken in order to analyse the expression of tumor associated antigen CA 242 in normal pancreas, in chronic pancreatitis and in pancreatic ductal adenocarcinoma, and to find out if the expression of CA 242 in carcinoma specimens would have prognostic significance. The expression of CA 242 was examined in the tissue specimens by the avidin-biotin-immunoperoxidase technique. According to our results, normal pancreas showed no or only weak staining for CA 242, whereas chronic pancreatitis samples stained somewhat intensely. Five out of 39 adenocarcinomas were negative for CA 242, 5 showed weak staining and 29 showed intermediate or intense staining. Positive staining was found mostly in the ductal cells as well as in intraluminal contents. We found no statistically significant difference of CA 242 expression between different grades. The staining intensity and survival had no clear statistical correlation but all carcinoma patients whose survival time was more than twelve months showed an intense staining for CA 242. The results suggests that the expression of tumour associated antigen CA 242 may have prognostic significance in pancreatic adenocarcinoma.

Objective: To evaluate the effects of intra-abdominal surgical emergency on breathing pattern and gas exchange and compare it with the changes induced by elective abdominal surgery., Design: Prospective clinical study., Setting: Abdominal surgical departments in a university hospital., Patients: Patients operated for intra-abdominal emergency (n = 10, EAS), elective upper abdominal (n = 19, UAS)., Measurements and Results: Breathing pattern and gas exchange were measured with a respiratory inductive plethysmograph and a gas exchange monitor. EAS patients had pre-operatively a classical rapid shallow breathing pattern and increased ventilatory demand due to increased energy expenditure. The operation improved the breathing to normal pattern (frequency, 26 +/- 5/min and 17 +/- 3/min, p < 0.01; tidal volume, 439 +/- 128 ml and 541 +/- 165 ml, NS., before and after surgery, respectively). Sighing was absent before and after EAS and strictly reduced after elective surgery (p < 0.01 for UAS). The operation restricted the abdominal-diaphragmatic breathing movement which was reflected as increased contribution of the rib cage to VT (%RC: from 37% +/- 15 to 57% +/- 15 for UAS p < 0.001; from 47% +/- 16 to 61% +/- 14 for EAS NS.). After EAS and UAS hypoxemia was common (p < 0.001) with frequent radiological pathology. We conclude that intra-abdominal surgical emergencies increase the ventilatory demand and challenge the respiratory system to marked adaptive changes both pre- and post-operatively.

We determined broadband ultrasound attenuation (BUA) of the calcaneus, and bone mineral density (BMD) of the spine, proximal femur and radius in 137 healthy subjects (79 women and 58 men) and in 56 women with Colles' fracture. The repeated measurements on 9 healthy subjects indicated a short-term reproducibility (coefficient of variation) of 4 percent for BUA. There was a small (7 percent) but significant difference in BUA between normal men and women. The age-dependence in normal subjects was weak. When all the study subjects were pooled, modest correlations between BUA of the calcaneus and BMD at all measured skeletal sites were found (rs values 0.3-0.4). However, it was not possible to make an accurate prediction of the axial BMD, using BUA. BUA values were 13 percent lower in the wrist fracture patients than in the age-matched normals. In general, BUA could discriminate the fracture patients from normals as effectively as BMD. As suggested by the physical theory of ultrasound attenuation, our results support the idea that BUA reflects not only the bone density but also other factors related to the structural properties of bone.

Several prospective studies have shown that the bone mineral density (BMD) measured in the appendicular or axial skeleton has an inverse relationship with the risk of subsequent fractures. However, most of these studies have concentrated on relatively old age groups, and the usefulness of measuring BMD at the time of menopause has not been established. In the present study, BMD was measured at the lumbar spine and femoral neck by dual X-ray absorptiometry (DXA) in a random stratified population sample of 3222 perimenopausal women (mean age 53.4 years, range 47-59 years). These women were followed for fractures over a period of 2 years. The fractures reported by a postal inquiry were verified from medical records. Fractures sustained in motor vehicle accidents were excluded from the analyses. During a mean follow-up of 2.4 years, 183 fractures occurred in 168 women. Wrist (n = 47), ankle (n = 31), and rib (n = 28) were the most common sites of a fracture. Women in the lowest quartile of spinal BMD had a 2.9 times greater risk of fracture than those in the highest quartile. The respective risk increased 2.2 times from the lowest to the highest quartile of femoral BMD, respectively. The relative risk for suffering from any fracture per one SD decrease in BMD was 1.50 (95% CI; 1.27-1.76) for the spine and 1.41 (1.21-1.64) for the femoral neck. The present study demonstrates that bone mass is important in the pathogenesis of fractures even in perimenopausal women. We conclude that the axial BMD measurement at the time of menopause can be of use in predicting subsequent fracture risk.

The relationship between gynecological history and bone mineral density (BMD) of the lumbar spine and femoral neck was studied in 3126 perimenopausal women. The study population was a random, stratified sample of participants, selected from the Kuopio Osteoporosis Study, which consisted primarily of all 14,220 women aged 47-56 years in Kuopio Province in 1989. After exclusion of 1521 women reporting past or present hormonal replacement therapy (HRT), 1605 women formed the final study population. Present HRT users had significantly higher lumbar BMD but not femoral BMD, than non-hormone users. Postmenopausal status, late menarche, and bilateral oophorectomy were risk factors for low BMD. Protective factors against low BMD were increased body weight, increased number of pregnancies, as well as hysterectomy without bilateral oophorectomy. The majority (43.8%) of these operations had been performed due to the presence of leiomyomas. No significant correlation was found between nulliparity, breast-feeding or amenorrhea before the age of 30 and BMD. In the multiple regression analysis, gynecological variables could account for only 18.4-26.8% of the variance in BMD, while time since last periods, age, age at menarche, weight and hysterectomy were the most significant variables. We conclude that reproductive history gives rise to some special risk groups, to whom BMD measurements and osteoporosis prevention efforts should be directed. However, it is impossible to predict BMD by gynecological characteristics.

1. Pilocarpine is a cholinomimetic natural alkaloid. Its interactions with testosterone hydroxylations, coumarin 7-hydroxylase (COH), dimethylnitrosamine N-demethylase (DMNA), pentoxyresorufin O-dealkylase (PROD) and 7-ethoxyresorufin O-deethylase (EROD), which are indicative of the activities of cytochrome P4502A5 (CYP2A5) or 6, 2E1, 2B, 1A, were examined in mouse and human liver microsomes. 2. In mouse liver microsomes the IC50 values of pilocarpine were 6 microM for COH and testosterone 15 alpha-hydroxylase (T15 alpha OH) activities, 4 microM for PROD, approximately 100 microM for DMNA and testosterone 6 beta-hydroxylase (T6 beta OH) activities and > 1 mM for EROD activity. 3. In human liver microsomes, the IC50 value for COH was 6 microM and for DMNA 10 microM; T15 alpha OH and PROD activities were not detectable but T6 beta OH and testosterone 16 beta/2 beta-hydroxylase activities were moderately inhibited (IC50 70 microM). 4. These results suggest that pilocarpine has (i) a high affinity towards phenobarbitone-inducible CYP2A4/5 and CYP2B activities in mouse liver, (ii) a high affinity towards CYP2A6 in human liver microsomes and (iii) a moderate affinity towards CYP3A enzyme(s) in both microsomal preparations. 5. The low IC50 concentrations in vitro indicate potential metabolic interactions between pilocarpine and several P450 enzymes.

We evaluated the long-term outcome of "negative appendix" (NA) by analysing the follow-up results of 76 patients identified from a group of 670 appendectomized patients. Randomly selected and histologically proven cases of true acute appendicitis (TA) matched for age and sex were identified to construct case control pairs. Special interest was focused on gender and age, by analysing the results separately in men and women in two age groups (15-39 years and > or = 40 years). The results showed that NA was most common in women aged 15-39 years (21% of appendectomized cases in this age group). At follow-up examination after a mean follow-up of 2.9 years two-thirds of patients were symptomfree. Women aged 15-39 years had significantly more complaints (P < 0.05) and findings (P < 0.05) than patients with TA. In women aged > or = 40 years no significant differences were detected, nor in either age groups in men. Lactose intolerance was the most common finding in symptomatic patients. In conclusion, patients with NA were mostly young women. At long-term follow-up the great majority of patients were symptomfree and appeared not to have developed any serious disease. Routine follow-up for patients with NA does not thus seem necessary.

Nineteen beagles (8.8 +/- 0.1 months, 8.5 +/- 0.2 kg, mean +/- SEM) were oophorectomized (OX) at the beginning of the study. The dogs were randomly allocated into three groups: control group (OX, n = 5), OX+clodronate 20 mg/kg orally group (OX + 20, n = 7) and OX+clodronate 40 mg/kg orally group (OX + 40, n = 7). Clodronate administration began the day following oophorectomy and was continued for eight months. Bone mineral density (BMD) was evaluated by dual energy X-ray absorptiometry (DEXA) at baseline and at four and eight months and by quantitative computed tomography (QCT) at baseline and at eight months. Bone biopsies were taken at the beginning and at the end of the study. The change in BMD (g/cm2) during eight months was +2.0% (NS) in OX, +2.3% (NS) in OX + 20 and +10.0% (P < 0.01) in OX + 40 group when measured by DEXA, QCT revealed the same results but in a lesser extent. There were no differences in static and dynamic histomorphometric parameters between the groups at the end of the study. In conclusion, clodronate at a dose 40 mg/kg/day orally increases BMD in young oophorectomized dogs.

We investigated the effect of clodronate on immobilization osteopenia (IO) induced by sciatic neurectomy in rats. 100 Wistar female rats were divided into 5 groups of 20 animals each: 1) sham-operated, control group, 2) IO+saline control group, 3) IO+clodronate 3 mg/kg/day, 4) IO+clodronate 10 mg/kg/day, and 5) IO+clodronate 30 mg/kg/day. Clodronate was administered subcutaneously beginning on the day after nerve sectioning. After 7 weeks, the animals were killed and both tibiae were removed. Bone mineral density, ash weight and calcium, phosphorus and magnesium contents of the ash of the tibiae were analyzed. The weight of the rats did not differ between the groups during the experiment. The ash weight of the tibiae decreased by 6.6 percent and the mineral density decreased by 5.1 percent after neurectomy. Clodronate reduced IO in a dose-dependent manner and the highest dose neutralized the effect of neurectomy. The calcium content of the ash decreased after neurectomy as compared to the sham-operated group, and clodronate increased it to the sham-operated level. The bone Ca/P ratio remained normal.

The effect of clodronate on healing of the fracture of osteopenic bone was studied in rats. A total of 165 female rats (14 +/- 1 weeks, 216 +/- 2 g) were divided into five fracture groups (n = 30), and a neurectomized group (n = 15). Osteopenia (op) was induced by right sciatic neurectomy 4 weeks before the fracture. Nonosteopenic (nop) rats were not operated. A closed prepinned diaphyseal fracture of the right femur was done by three-point bending method both to op and nop rats, and the left femur served as an unoperated control. All the fracture groups were divided into treatment (clodronate 10 mg/kg/day sc) and control (saline sc) groups, and the administration was continued throughout the study. The op rats were killed 2, 4, 8, and 12 weeks and nop rats 8 weeks after the fracture. Fracture healing was examined by x-ray and bone-bending strength. Neurectomy reduced bone strength (p < 0.01) at 4 weeks. Clodronate did not affect the bending strength of healing callus of op rats at 2, 4, 8, or 12 weeks after fracture, but reduced the strength of healing callus in nop rats (p < 0.05) at 8 weeks. Radiologic callus width increased in clodronate-treated groups both in op (8 and 12 weeks, p < 0.001) and nop rats (8 weeks, p < 0.05) when compared with saline-treated groups. Clodronate did not affect normal bone strength. In conclusion, clodronate did not affect the bending strength of op fracture nor the strength of the control bones. The remodeling of the fracture was delayed with clodronate.

Bone mineral density (BMD) of the spine and femoral neck was measured in a random stratified sample of 3222 perimenopausal women aged 47-59 years. A total of 969 women had used fluoridated drinking water (1.0-1.2 mg/l) for over 10 years. These women were compared with 2253 women with low levels of fluoride in drinking water (< 0.3 mg/l). BMD of the spine was significantly higher in the fluoride group than in the non-fluoride group (1.138 +/- 0.165 vs. 1.123 +/- 0.156 g/cm2, P = 0.026). Femoral neck BMDs did not differ between the groups. When the BMD values were adjusted for confounding factors (age, weight, menopausal status, calcium intake, physical activity level, deliveries, alcohol consumption and estrogen use), the differences between the groups increased (P < 0.001 for the spine and P = 0.004 for the femoral neck, respectively). There was no significant difference between the groups in the prevalence of self-reported fractures sustained during 1980-1989. We propose that the fluoridation of drinking water has a slight increasing effect on axial BMD in women in low fluoride areas.

The expression of proliferating cell nuclear antigen and p53 protein was analysed by immunocytochemical methods (PC10, CM1 antisera) in 139 patients with T1-2M0 prostatic adenocarcinomas followed-up for > 12 years. p53 protein was expressed in 21 (15%) tumours (15%), the fraction of positive nuclei being very low (mean SE, 1% +/- 0.7%). Accumulation of p53 protein in epithelial cells was independent of tumour stage and Gleason score, and had no effect on prognosis. In 4 cases, p53 protein was expressed only in stromal cells. The fraction of PCNA-positive nuclei (evaluable in 116 cases) was higher in T2 than in T1 tumours (p < 0.001); furthermore, high Gleason score was positively correlated with PCNA positivity (p < 0.001). A finding of over 5% of PCNA-positive nuclei predicted progression in T and M categories and were a sign of poor outcome. The fraction of PCNA-positive stromal-cell nuclei was related to T-category with a borderline significance (p = 0.06). In a multivariate analysis of the prognostic factors, independent predictors of survival included Gleason score (p < 0.001), fraction of PCNA-positive nuclei (p = 0.013), observation before therapy (p = 0.05), and T-category (p = 0.07) in that order of significance. The results suggest that overexpression of p53 protein is of marginal prognostic value in local prostatic adenocarcinomas, whereas direct measurement of cell proliferation by PCNA immunolabelling provides important prognostic information in T1-2M0 tumours, in addition to the Gleason score.

Population-based epidemiological studies on osteoporosis are few. Our study evaluated the effects of menopause and certain putative behavioural risk factors on bone mineral density (BMD). Spinal and femoral neck BMD were measured with dual X-ray absorptiometry (DXA) from 1600 perimenopausal women aged 48-59 years (mean 53.2 years) with no diseases or medications known to affect bone metabolism. These women were a selected sample of the Kuopio Osteoporosis Risk Factor and Prevention Study population (n = 14,220). There was a wide variation of BMD among perimenopausal women. Menopause had a major effect on BMD. Postmenopausal women had significantly lower BMD in both spine (-6.2%) and femoral neck (-3.9%) as compared with premenopausal women. Multiple regression analysis showed that weight, menopausal status, age, and grip strength were significant independent predictors of both spinal and femoral BMD. Additionally, physical activity was found to be a significant predictor of femoral BMD, and alcohol consumption was a significant predictor of spinal BMD. However, current anthropometric and lifestyle factors explained only 18.7-25.4% of the variability of BMD. Therefore, the estimation of the risk factor status at menopause is not an adequate substitute for bone densitometry. However, our results may in part help clinicians to identify the risk groups at which to direct bone density measurements.

Biogenic amines play an important role in regulating cell proliferation in the normal and neoplastic colon. Elevated histidine decarboxylase (HDC) activity has been measured in human colorectal tumors. H2 antagonists can suppress the growth of colorectal cancer and their inclusion in human therapy has been proposed. We studied the effects of histamine, cimetidine, mepyramine and alpha-fluoromethylhistidine (FMH) on the growth of colorectal tumors in ten patients in the 6-day mouse subrenal capsule assay (SRCA). The effect of the Hic antagonist DPPE was tested in two assays. In summary, a reduction of tumor size was achieved with histamine and DPPE. In addition, significant inhibition of tumor growth was seen in the FMH-treated animals. When pooled by their growth potential, as assessed by the growth of saline-treated controls, FMH and DPPE caused distinct tumor reduction in rapidly growing tumors. In the moderately growing tumors, histamine and mepyramine were the most effective.

The aim of the present prospective study was to evaluate the clinical value ol serum tumour markers CEA, CA 50 and CA 242 in patients with colorectal cancer (n = 138) and patients with benign gastrointestinal disease (n = 104). The cutoff levels (90% specificity) determined for each test were 2.5 ng/ml for CEA, 17 U/ml for CA 50 and 17 U/ml for CA 242. The diagnostic sensitivity of the CEA test was 0.63, that of the CA 50 test was 0.30 and 0.30 for the CA 242 test in detecting colorectal cancer. CEA, CA 50 and CA 242 tests were tested in a multivariate analysis to find the best combination of independent predictors of colorectal cancer. The most important predictor of colorectal cancer was CEA followed by CA 242. In order to calculate the contributions of tumour marker tests, a diagnostic score (DS) was developed. The sensitivity of the DS in detecting colorectal cancer was 0.47 with a specificity of 0.88 and an efficiency of 0.67. On the basis of this study, serum CEA and CA 242 seem to possess diagnostic value in preoperative evaluation of patients with colorectal cancer.

The aim of this study was to compare the effects of a bare laser fiber and a contact sapphire probe on normal Wistar rat liver in interstitial laser hyperthermia (ILH). We used two different powers (1W and 2W) and eight different exposure times (50s to 900s). The livers were examined after 3 days and in the long-term follow-up group after 2 months. The greatest necrotic lesions were achieved with 600-900J energy (2W, 300-450s) using a bare laser fiber. The diameter of the necrotic lesions plateaued with 2W power setting after 300J energy. Generally, necrotic lesions were greater using a bare fiber than a sapphire probe with equal energy levels. The lesions healed by granulation and fibrosis. No scars or necrotic lesions were found 2 months after treatment when a 1W power setting was used, whereas a power of 2W caused a clear scar in the rat liver. ILH treatment caused necrosis safely and the bare fiber produced a greater necrotic area than the sapphire probe.

The bone mineral density (BMD) of the lumbar vertebrae L2-4 and femoral neck was determined by dual-energy X-ray absorptiometry (DXA) in 3222 perimenopausal women-a random stratified sample of the population-based Kuopio Osteoporosis Study (OSTPRE). The mean age of the women was 53.4 years (range 47.9-59.6 years). Twenty-nine percent of the women were past users of oral contraceptives (OC) containing 50 micrograms or less of ethinyl estradiol and 7.4% (n = 250) of the women reported OC use for more than 6 years. There was a slight but statistically significant difference between OC users (n = 939) and non-users (n = 2283) in lumbar BMD (1.134 +/- 0.155 g/cm2 v 1.123 +/- 0.161 g/cm2, p = 0.014). A statistically significant difference was recorded also after adjustment for years since menopause, duration of hormonal replacement therapy (HRT) and present weight (p = 0.044). When the analysis was performed among women who had never used oestrogen replacement therapy (n = 1427) and among premenopausal women (n = 387), no differences in BMD were found between OC users and non-users. Similarly, femoral neck BMD did not differ between the groups. This population-based study demonstrated a slightly higher lumbar BMD among past OC users. However, OC users and non-users differed from each other in many behavioral characteristics. Thus, the differences in BMD may be accounted for more by other factors than by past OC use itself. The low-dosage estrogen OCs used today would not be expected to have any positive bone effects among future perimenopausal women.

The basement membrane (BM) structure and vascular density (VD) were analysed using collagen IV immunostaining in a series of 88 T1-2MO prostatic adenocarcinomas. The results were correlated with the established prognostic factors and patient survival based on a follow-up of > 11 years. Prostatic cancer cells retained their capacity to synthesize BM components, although defects in the BM structures were associated with T2 category and high Gleason score. Progression of the tumours was related to the defects in BM continuity, and defective BMs were also a sign of poor outcome. High grade tumours were occupied by dense vascular network and dense VD was a sign of a poor outcome. Gleason score was a significant predictor of progression and patient survival, as was the T-category. Multivariate analysis of the prognostic factors indicated that Gleason score included all the available independent prognostic information. The results show that all prostatic adenocarcinomas continue to synthesize BM components, although the structure and continuity is disturbed in poorly differentiated tumours. A rich vascular network is a sign of highly malignant phenotype in prostatic adenocarcinoma. However, an assessment of the BM and VD is of limited independent prognostic value.

The aim of this study was to assess the clinical value of five serum tumour markers, TPA, TPS, TAG 12, CA 15-3 and MCA, in the diagnosis of breast cancer. The serum values were measured in a prospective series of patients with breast cancer (n = 82) and benign breast disease (n = 25). The cut-off levels (90% specificity) determined for each test were 109.0 U/1 for TPA, 156.0 U/1 for TPS, 52.5 kU/1 cut-off level for TAG 12 and 24.9 kU/1 cut-off level for CA 15-3, and at the 12.0 kU/1 cut-off level for MCA. Using these cut-off levels the diagnostic sensitivity of the TPA test was 0.23, for the TPS test 0.15, 0.44 for the TAG 12 test, 0.13 for the CA 15-3 test and 0.10 for the MCA test in detecting breast cancer. When the cut-off levels were determined at 95th percentile level for each test, the cut-off level for TPA was 143.0 U/1, 279.0 U/1 cut-off level for TPS, 105.0 kU/1 cut-off level for TAG 12 and 36.7 kU/1 cut-off level for CA 15.3, and at the 15.3 kU/1 cut-off level for MCA. Using these cut-off levels the diagnostic sensitivity of the TPA test was 0.12, 0.01 for the TPS test, 0.06 for the TAG 12 test, 0.06 for the CA 15-3 test and 0.06 for the MCA test in detecting breast cancer. The correlation coefficients in breast cancer patients between TPA and TPS measurements was 0.82, between TPA and TAG 12 measurements it was 0.09, between TPA and CA 15-3 measurements it was 0.08, and 0.11 between TPA and MCA measurements. None of the serum markers studied were significant predictors in breast cancer diagnosis in a logistic regression analysis or in the discriminant analysis. Thus it seems that TPA, TPS, TAG 12, CA 15-3 and MCA have only limited value in breast cancer diagnosis, but their role in the follow-up and prediction of prognosis of breast cancer patients is a subject for further investigation.

The purpose of this study was to investigate the diagnostic accuracy of ultrasound (US), computed tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP) in the distinction between extrahepatic and intrahepatic causes of unjaundiced cholestasis. Moreover, attention was paid to the ability of these methods to distinguish between benign and malignant causes of obstruction. The inclusion criteria of laboratory values suggesting cholestasis were serum alkaline phosphatase 350 U/l and gammaglutamyl transpeptidase 100 U/l or liver-specific alkaline phosphatase elevated. The diagnostic value of the imaging methods was tested in 33 patients. The most common cause of unjaundiced obstruction was choledochal stone disease. The diagnostic sensitivities of US, CT and ERCP for the detection of extrahepatic cholestasis were 53%, 53% and 79%, respectively. In patients on whom all three imaging studies were done (n = 20), the difference between US and ERCP was statistically significant (p > 0.05). The specificities of US, CT and ERCP were 100%, 86% and 90%, respectively. CT was better than US in defining the benign nature of obstruction, but ERCP was superior in this respect. In malignant obstructions CT was comparable to ERCP. In conclusion, ERCP seems to be considerably sensitive for the detection of extrahepatic obstruction in cases of unjaundiced cholestasis, whereas US and CT are rather insensitive. The specificity of all these imaging methods is high. The results are in favour of CT as the best noninvasive investigation method, and also indicate the important role of ERCP. However, in many cases all three imaging methods are needed, and a flexible and complementary use of them is recommended.

Cocaine is eliminated and detoxified principally through the metabolism of nonspecific plasma and tissue esterases. Microsomal oxidative metabolism is of importance in cocaine N-demethylation, this being a principal pathway of cocaine bioactivation and hepatotoxicity. The contribution of different cytochrome P450 (CYP) enzymes to cocaine N-demethylase activity was studied in vitro with DBA/2 mouse and human liver microsomes, and cocaine hepatotoxicity was examined in vivo in DBA/2 male mice. Species dependent enzyme kinetics was observed. Cocaine N-demethylase displayed two Km values in murine liver (40-60 microM and 2-3 mM), whereas only one Km value was observed in human liver microsomes (2.3-2.7 mM). We suggest that CYP3A plays a prominent role in the N-demethylation of cocaine for the following reasons: (i) pregnenolone-16 alpha-carbonitrile, an inducer of CYP3As increases cocaine N-demethylase in parallel with testosterone 6 beta-hydroxylase activity and immunoreactive 3A protein in mouse liver; (ii) human and mouse cocaine N-demethylase and testosterone 6 beta-hydroxylase activities can be inhibited by triacetyloleandomycin, cannabidiol, or gestodene, all selective inhibitors of CYP3A P450s; (iii) antibodies directed against P450s within subfamilies 1A, 2A, 2B, 2C, or 2E inhibited cocaine N-demethylase activity only marginally, and finally, (iv) treatment of mice with triacetyloleandomycin or cannabidiol in vivo significantly attenuated the cocaine-elicited hepatotoxicity as assessed by the serum alanine aminotransferase activity and liver histology in parallel with decreased cocaine N-demethylase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

We evaluated the clinical utility of a new tumor marker tissue polypeptide specific antigen (TPS) in the diagnosis of pancreatic carcinoma. Serum concentrations were determined in 113 patients with jaundice, in 18 patients with laboratory values suggesting cholestasis and in 60 patients with suspicion of chronic pancreatitis or pancreatic tumor. Twenty-four of these 191 patients had pancreatic carcinoma and 2 patients had carcinoma of the papilla of Vater. The highest median serum TPS value was detected in patients with malignant liver disease, but high median values were also measured in patients with pancreatic cancer, bile duct cancer or benign liver disease. The sensitivity of TPS was 50.0%, with a specificity of 73% and an efficiency of 70%. In comparison with carcinoembryonic antigen (CEA), CA 50 and CA 242, the TPS test showed lower sensitivity, but the differences in specificity and negative predictive value were considerably smaller. The utility of TPS as a complementary test was also analyzed. When TPS was combined with other marker tests, their specificities clearly improved, being highest in the combination of TPS and CA 242 (92.5%). In this combination, efficiency and positive likelihood ratio were also clearly better (85% and 5.6) than those of the marker tests alone. In conclusion, TPS seems less accurate than CEA, CA 50 or CA 242 in the diagnosis of pancreatic cancer, but because of its different nature it may be considered to be used as a complementary test.

Periarticular osteoporosis is a common feature of rheumatoid arthritis. However, the cellular basis and the aetiology of periarticular bone loss have not been established. We studied periarticular bone samples obtained from metatarsal resections (n = 18) and total knee arthroplasties (n = 9) by histomorphometry. Autopsy material (n = 10) and patients with osteoarthrosis (n = 11) served as controls. Histomorphometrically, there was reduced trabecular bone volume and increased resorption surfaces in rheumatoid arthritis patients in most of the measured areas. The indices of bone turnover were most markedly increased in the vicinity of inflammatory cells and rheumatoid granulation tissue. Trabecular bone volume and the degree of inflammation as measured by the erythrocyte sedimentation rate (ESR) had a negative correlation. In addition, an elevated ESR was associated with increased osteoid parameters in periarticular bone. We conclude that periarticular bone loss in rheumatoid arthritis is due to increased bone resorption. Local inflammatory mediators might account for the increased bone turnover.

The serum values of tumour-associated trypsin inhibitor (TATI) were measured in a prospective series of 97 patients with jaundice, 36 patients with unjaundiced cholestasis and 21 patients with suspicion of chronic pancreatitis or a pancreatic tumour, to assess its value in diagnosing pancreatic cancer. There were altogether 15 patients with cancer of the pancreas and 2 patients with cancer of the papilla of Vater. The highest serum TATI values were noticed in patients with choledocholithiasis, and raised values were also seen in patients with malignant disease of the liver or bile ducts. In the patients with pancreatic cancer, chronic pancreatitis or benign liver disease, the serum TATI values showed lower levels. The sensitivity of TATI in diagnosing pancreatic cancer was 41.1% with a specificity of 63.5% and an efficiency of 61.0%. In comparison to carcinoembryonic antigen (CEA), carbohydrate antigens CA 50, CA 242, tissue polypeptide antigen and tissue polypeptide-specific antigen, TATI showed a lower diagnostic value. When TATI was analysed in combination with the other markers (two tests positive), the combination of CEA with TATI reached the highest specificity (95.6%), efficiency (89.6%) and positive likelihood ratio (9.3). The results suggest that the diagnostic value of TATI is inferior to that of the established markers, but because of its different nature, it may be of help when used in combination as a complementary serum tumour marker in the diagnosis of pancreatic cancer.

A case of phaeochromocytoma diagnosed and treated during pregnancy is presented. The diagnosis was made by the typical paroxysmal symptoms with high blood pressure and confirmed by elevated plasma and urine catecholamine levels and ultrasound. After a short-term blockade with alpha and beta adrenergic antagonists an almost 10 cm large tumour was successfully excised at caesarean section. The problems with treatment of phaeochromocytoma during pregnancy are also discussed.

The bone mineral density (BMD, g/cm2) of the lumbar spine (L2-L4) and femoral neck was measured twice with a 1-year interval by dual energy X-ray absorptiometry (DEXA) in 65 healthy children and adolescents aged 7-20 years. In addition, the BMD values were corrected for the size of bones to obtain the bone volumetric density (BMDvol, g/cm3) using a method developed previously. The annual increases of BMD and BMDvol in both spine and femoral neck were most marked in females at the time of menarche (during the age of 11-13 years), and in males between the ages of 13 and 17 years. The males showed significantly higher values in their mean annual increment rates of femoral bone mineral content (BMC) and femoral neck width, whereas no differences in spinal parameters were found. The acquisition of bone mass and bone density stopped or markedly diminished before the age of 20 years, supporting the theory that the major portion of the peak bone mass is attained in late adolescence. We could not find any significant relationship between the increment rate of bone density, and physical activity or calcium intake. This study emphasizes the significant effect of puberty and genetic factors on the development of bone mass and density.

Mineral density of the cortical bone of the mandible was determined by single-energy QCT (quantitative computed tomography) for 77 menopausal women. Bone mineral densities (BMD) were measured in the buccal and lingual layers of the cortex, distally from the foramen mentale, on both sides of the mandible. All the women were edentulous in that region, and the alveolar processes were far resorbed. These results were compared with the BMD values of the femoral neck, lumbar spine, and trabecular portion of the mandible between the detected layers of cortex. The BMD of the buccal cortex correlated remarkably well with all values, except those of the trabecular portion. Of the women tested, the correlations were lowest in the least osteoporotic group. The values for the lingual cortex did not correlate with other variables as well as did those for the buccal cortex, but in the most osteoporotic part of the sample the lingual cortex values correlated significantly with the BMD of the trabecular portion. The BMD values for the buccal cortex were significantly higher than those for the lingual cortex.

Mineral density of the trabecular bone of the mandible was determined by single-energy QCT (quantitative computed tomography) for 74 totally or nearly edentulous menopausal women. These results were compared with the bone mineral densities (BMD) of their lumbar area (L2-L4) and femoral collum, measured by dual-energy x-ray transmission, Lunar DPX. The remaining height of the residual ridge at the symphysis of the mandible was measured on computed tomography (CT) lateral projection view, and an index of the residual ridge status was introduced. To determine whether general osteoporosis status affects the remaining height of the residual ridges, we compared these values with all results for bone mineral density. The BMD of the lumbar area and that of the femoral collum correlated well with each other, but the BMD of the trabecular bone of the mandible did not correlate with either of the other two BMD measurements. Measurements of residual ridge height did not correlate with any BMD values. The effect of possible bone loss earlier in life is no longer apparent in mandibular height or trabecular BMD over 20 yr after tooth extractions.

We studied a combined utilization of serum tumour markers and proton nuclear magnetic resonance 1H NMR spectroscopy of plasma in the detection of pancreatic cancer. Serum concentrations of carcinoembryonic antigen (CEA), carboanhydrate antigens CA 50 and CA 242, and 1H NMR spectra of plasma were determined in a series of 51 patients, of whom 25 had malignant and 26 benign hepatopancreatobiliary disorder. The measurements in 1H NMR spectra were performed both manually and by computed technique, and both methylene (CH2) and methyl (CH3) peaks were evaluated. In the patients with pancreatic cancer (n = 17, including two cases of cancer of the papilla of Vater), the mean serum values of all tumour markers were significantly (p = 0.001) higher than in the patients with benign disease. The diagnostic sensitivity of the tumour markers alone reached 82-100% with a specificity of 35-82%. In the 1H NMR spectra of sera, the mean linewidth of the CH3-peak both in the manual and computed measurement was significantly narrower in the patients with pancreatic cancer than in the benign disease group. Using the cut-off level of 33 Hz, the sensitivity and specificity of 1H NMR alone was in the manual measurement 53% and 76%, respectively, while in the computed measurement the corresponding figures were 94% and 20%. When the serum tumour markers and 1H NMR spectroscopy were evaluated as combinations, both in the manual and computed measurements the specificities and positive likelihood ratios were clearly better than those of the tumour markers alone, but efficiencies improved only slightly. The results suggest that the combined use of tumour marker tests and 1H NMR of plasma gives only slightly improved accuracy in the diagnosis of pancreatic cancer.

The current multicenter study was conducted at five sites using 86 patients to evaluate the safety and efficacy of piperacillin/tazobactam (4 grams per 500 milligrams every eight hours) compared with imipenem/cilastatin (1 gram every eight hours) in the treatment of patients who were hospitalized with a clinically or bacteriologically confirmed diagnosis of intra-abdominal infection. Forty-seven patients received piperacillin/tazobactam and 39 received imipenem/cilastatin. The favorable response among patients who were clinically evaluable with a valid response in the group treated with piperacillin/tazobactam was 87 percent. In the group treated with imipenem/cilastatin it was 77 percent. Bacteriologic eradication rate among bacteriologically evaluable patients with a valid response in the group treated with piperacillin/tazobactam was 100 percent. In the group treated with imipenem/cilastatin it was 89 percent. The eradication rate of pathogens isolated from patients who were evaluable by biologic factors in the group treated with piperacillin/tazobactam was 100 percent and in the group treated with imipenem/cilastatin treatment, 96 percent. In the group treated with piperacillin/tazobactam the incidence and type of adverse reactions were similar to those seen with piperacillin alone. It is concluded that piperacillin/tazobactam is safe and efficacious in the treatment of patients hospitalized with intraabdominal infections and that tazobactam extends the spectrum of piperacillin.

The prognostic variables of 281 women with breast carcinoma (followed up for more than 8 years) were studied using Cox's analysis. Clinical and histologic features, nuclear morphometric variables, and mitotic indices were analyzed separately in progesterone receptor-negative (PR-) and -positive tumors (PR+). In PR- tumors, axillary lymph node status (p = 0.0025) and tumor size (p = 0.03) were predictors of survival in the univariate analysis. Tumor size (p < 0.0001), axillary lymph node status (p = 0.0006), the volume-corrected mitotic index (M/V index) (p = 0.0023), and the mitotic activity index (MAI) (p = 0.0067) were found to be related to survival according to univariate analysis of PR+ tumors. In PR- tumors, axillary lymph node status (p = 0.002), year of treatment (p = 0.017), and circumscription of the tumor margin (p = 0.02) had independent predictive value. In PR+ tumors, tumor size (p < 0.001), the MAI (p = 0.001), and axillary lymph node status (p = 0.04) predicted survival independently in Cox's analysis. In PR- tumors, histologic type (p = 0.008) was an independent predictor of recurrence-free survival, whereas in PR+ tumors, the M/V index (p < 0.001), tumor size (p = 0.007), and the standard deviation of the nuclear perimeter (p = 0.026) were independently related to recurrence-free survival. The results indicated that mitotic indices and nuclear morphometric variables are of limited value in predicting patient survival in breast carcinomas that are hormone receptor negative. Thus, a separate analysis is advocated for hormone receptor-positive and -negative tumors when the predictive value of quantitative measurements and histologic variables is tested in patients with breast cancer.

Excretion of polyamines first increases and then decreases in patients with multiple trauma receiving total parenteral nutrition (TPN). To separate the effects of trauma and TPN on polyamine excretion, we studied 12 patients with multiple trauma and 14 patients after surgery for colorectal malignancy. Patients were randomized to receive either TPN or hypocaloric glucose infusion. Urinary excretion of total and free polyamines, putrescine (PU), spermidine (SPD), and spermine (SP), and their metabolites, N1-acetylspermidine (N1-AcSPD) and N8-acetylspermidine (N8-AcSPD), and energy and nitrogen balance were measured. Polyamine excretion, excluding SP, markedly increased after trauma and surgery, exceeding the normal values by twofold to 10-fold. In patients receiving TPN, the excretion of total polyamines was 48% higher (P < .01), PU was 34% higher (P < .05), SPD was 35% higher (P < .05), and SP was 350% higher (P < .05) than in patients receiving hypocaloric glucose. Urinary excretion of SP was only 17% of the reference value during hypocaloric glucose (P < .05), but was normal during TPN. The difference in polyamine excretion between nutrition groups was more pronounced when normalized for nitrogen or energy balance. Patients receiving TPN were more hypermetabolic than patients receiving hypocaloric glucose (resting energy expenditure, 1.36 +/- 0.06 [SE] and 1.16 +/- 0.04 times predicted values, respectively; P < .025). Statistically, energy expenditure could explain the difference in polyamine excretion between nutrition groups.(ABSTRACT TRUNCATED AT 250 WORDS)

The sera of 51 patients with malignant (n = 25) and benign (n = 26) hepatopancreatobiliary disorders were analysed by 1H magnetic resonance spectroscopy (NMR) in order to distinguish between malignant and benign diseases causing jaundice and/or cholestasis. Macromolecular linewidths were determined both manually and automatically with a computed analysis, and both methylene (CH2) and methyl (CH3) resonances were evaluated. The mean linewidth of the CH3 peak was significantly narrower in the patients with malignant disease than in the patients with benign disease both in the manual and computed analyses, but no significant differences in the CH2 peak were detected. Diagnostic sensitivity and specificity of the CH3 peak determined in the computed analysis were 92% and 27% respectively. In the light of the current study, it seems obvious that because overlap between benign and malignant groups was too great, 1H NMR spectroscopy of plasma is not of practical value in distinguishing between benign and malignant causes of jaundice and/or cholestasis.

The number of silver stained nucleolar organiser regions (Ag-NORs) was enumerated in the biopsy specimens of 73 patients with human pancreatic adenocarcinoma. The number of Ag-NORs was related to histological features, S-phase fraction (SPF), DNA ploidy, morphometric nuclear features, clinical stage and survival. Grade I tumours had on average fewer Ag-NORs (mean +/- SD, 5.2 +/- 2.0) than grade II (mean +/- SD, 5.9 +/- 1.6) or grade III (mean +/- SD, 6.6 +/- 2.6) tumours. Patients with low SPF (0-7%) values had lower mean Ag-NORs counts (5.7 +/- 1.0) than patients with a high SPF (7%) (6.6 +/- 2.0) (p = 0.05) and the number of Ag-NORs was related almost significantly to mitotic index (p = 0.09). The Ag-NORs were not related significantly to DNA ploidy or to clinical stage. In survival analysis the number of Ag-NORs predicted prognosis significantly (p = 0.03). From the results we conclude that Ag-NORs are related to several malignant features in human pancreatic adenocarcinoma and that the number of Ag-NORs predicts survival.

Objective: To assess the accuracy of ultrasonography (US), computed tomography (CT), and endoscopic retrograde cholangiopancreatography (ERCP) in distinguishing between benign and malignant causes of jaundice and cholestasis without jaundice., Design: Prospective study., Setting: University Hospital in Finland., Subjects: A consecutive series of patients with jaundice (n = 187) or cholestasis without jaundice (n = 33)., Main Outcome Measures: Correlation between diagnosis on imaging and final diagnosis at follow up 6 months later. Final diagnoses made on histology (n = 79), cytology (n = 5), operative or endoscopic findings (n = 96), and clinical course or serology (n = 40)., Results: The most common benign disease was choledocholithiasis (n = 83) and the most common malignant disease was carcinoma of pancreas (n = 33). The benign nature of the extrahepatic obstruction was correctly defined by US, CT, and ERCP in 53%, 53%, and 90% of patients, respectively, and the corresponding figures for choledocholithiasis were 22%, 25%, and 79% (ERCP compared with each of the other techniques, p < 0.0001). Intrahepatic benign diseases were diagnosed by US and CT in a third of cases. Malignant extrahepatic obstruction was correctly diagnosed in 57%, 80%, and 83%, respectively and the corresponding figures for pancreatic cancer were 60%, 97%, and 89% (US compared with CT, p < 0.01, and with ERCP, p < 0.05). Intrahepatic malignant lesions were diagnosed by US, CT, and ERCP in 100%, 77%, and 60% of patients, respectively., Conclusions: When the obstruction was benign and extrahepatic ERCP was the most accurate, but when it was malignant CT was comparable. Intrahepatic disease was best diagnosed by US and CT. The results emphasise that the three methods of imaging are complementary.

The diagnostic accuracy of ultrasound (US), computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP), and tumour markers CEA, CA 50 and CA 242 in pancreatic cancer (n = 26) was studied in 113 patients with jaundice, in 20 patients with unjaundiced cholestasis, and in 60 patients with the suspicion of chronic pancreatitis or a pancreatic tumour. The sensitivities of US, CT and ERCP were 61.9%, 95.2% and 82.3%, the specificities 93.9%, 92.9% and 94.1%, and the efficiencies 91.6%, 96.6% and 92.1%, respectively. The sensitivities of CEA, CA 50 and CA 242 were 92.3%, 96.1% and 61.5%, the specificities 59.2%, 58.0% and 95.2%, and the efficiencies 63.7%, 63.2% and 90.6% respectively. The combined use of the imaging methods and tumour markers was also analysed. When either the imaging method or the serum marker test was required to be positive, the sensitivities of the combinations were clearly better than those of US and CA 242 alone, but only slightly better than those of CT, ERCP or the tumour markers CEA and CA 50 alone. When both the imaging test and the marker test were required to be positive, the specificities of the combinations were clearly better than those of CEA and CA 50 alone, but they did not exceed the specificity of the imaging methods or CA 242 alone. We conclude that CT, ERCP and CEA and CA 50 are highly sensitive in the diagnosis of pancreatic cancer in symptomatic patients, while the sensitivity of US and CA 242 is lower. The specificity of the imaging methods and CA 242 is high, but that of CEA and CA 50 is low. Imaging methods and serum tumour markers could be more used in clinical practice in a complementary manner. In patients with jaundice and/or cholestasis or with a suspicion of pancreatic tumour or chronic pancreatitis, the combined use may yield higher sensitivity than US alone and higher specificity than CEA or CA 50 alone.

The aim of the present study was to evaluate the clinical value of a new tumour marker TPS in sera from patients with breast cancer and patients with benign breast disease. The results for TPS were compared with those for TAG 12, CA 15-3 and MCA. The cutoff levels (90% specificity) determined for each test were 108.0 U/1 for TPS, 57.5 KU/1 for TAG 12, 24.8 KU/1 for CA 15-3 and 9.7 KU/1 for MCA. The diagnostic sensitivity of the TPS test was 0.21, for the TAG 12 test it was 0.2, 0.13 for the CA 15-3 test and 0.12 for the MCA test in detecting breast cancer. TPS, TAG 12, CA 15-3 and MCA tests were tested in a multivariate analysis to find the best combination of independent predictors of breast cancer. The most important predictor of breast cancer was TAG 12 followed by TPS. In order to calculate the contributions of tumour marker tests, a diagnostic score (DS) was developed. The diagnostic score (DS) was: DS = TPS x 0.0085 x TAG 12 x 0.0596 - CA 15-3 x 0.0866 - MCA x 0.2938 + 0.1738. The sensitivity of the DS in detecting breast cancer was 55% with a specificity of 90% and an efficiency of 64%. In conclusion, new tumour markers TPS and TAG 12 may have some value in breast cancer diagnosis. In particular, the results indicate the usefulness of computer assistance and a simple diagnostic score when tumour markers are used in breast cancer diagnosis.

A retrospective study including 55 cutaneous melanoma patients with 9.5 years follow-up was carried out to assess the significance of various prognostic factors. The histological samples were evaluated according to Clark's and Breslow's classifications and six nuclear features were measured by interactive morphometry. Mitotic activity was assessed by two different methods: mitotic activity index (MAI) and volume corrected mitotic index (M/V index). The overall disease-related five-year survival of patients was 76.4%. TNM stage (p = 0.0001), sex (p = 0.0024), M/V index (p = 0.003), standard deviation of nuclear form factor (p = 0.023), MAI (p = 0.02), shortest nuclear axis (p = 0.023) and Breslow's classification (p = 0.044) predicted survival in univariate analysis. A multivariate analysis including clinical, histological and morphometric features pointed the Clark's classification as the most important predictor of survival (p = 0.002), while the other variables included had no independent prognostic value. The prognostic importance of mitotic indices and morphometric features is clearly a subject for further studies in superficial melanomas.

The aim of the present study was to evaluate the clinical value of the preoperative serum tumour markers TAG 12, CA 15-3 and MCA in predicting a recurrence of breast cancer patients. The sensitivity of the TAG 12 test was 54%, that of the CA 15-3 test 15% and that of the MCA test 15% in predicting a recurrence of breast cancer. The most important predictor of breast cancer recurrence was TAG 12. In order to evaluate the contributions of different tumour marker serum test, a stepwise discriminant analysis was carried out. The discriminant function (DF) is DF = TAG 12 x 0.061 - CA 15-3 x 0.1336 - 0.396. The sensitivity of the DF in detecting recurrence of breast cancer was 63% with a specificity of 90% and an efficiency of 75%. In conclusion, the results indicate that a new tumour marker TAG 12 is superior to CA 15-3 and MCA in predicting breast cancer recurrence. In this study the discriminant function including TAG 12 and CA 15-3 was superior to single preoperative tumour marker tests. The results speak for the use of a decision support system to aid in predicting a recurrence of breast cancer.

A prospective study of 113 patients with jaundice and 20 patients with unjaundiced cholestasis was carried out to evaluate the value of serum tumour markers, carcinoembryonic antigen (CEA) and monoclonal antibodies CA 50 and CA 242, in the distinction between benign and malignant diseases causing jaundice and/or cholestasis. In the patients with malignant disease (n = 37) the serum values of all tumour markers were significantly higher than in the patients with benign disease (n = 96). The sensitivities of CEA, CA 50 and CA 242 in detecting malignancy were 70.2%, 94.5% and 56.7%, respectively, while the specificities were 57.2%, 33.3% and 77.0%, respectively. Serum alkaline phosphatase and bilirubin levels had a high positive correlation with CA 50, and CA 242 correlated positively with serum bilirubin levels. No correlation was seen between CEA and alkaline phosphatase or bilirubin levels. The CEA, CA 50 and CA 242 tests may be used as useful complements to other investigative methods in the distinction between benign and malignant causes of jaundice and/or cholestasis. In particular, the rather high specificity of the CA 242 test for malignant diseases seems promising.