Primary familial brain calcification linked to deletion of 5' noncoding region of SLC20A2.

OBJECTIVES: Primary familial brain calcification (PFBC) is a rare neurological disease often inherited as a dominant trait. Mutations in four genes (SLC20A2, PDGFB, PDGFRB, and XPR1) have been reported in patients with PFBC. Of these, point mutations or small deletions in SLC20A2 are most common. Thus far, only one large deletion covering entire SLC20A2 and several smaller, exonic deletions of SLC20A2 have been reported. The aim of this study was to identify the causative gene defect in a Finnish PFBC family with three affected patients. MATERIALS AND METHODS: A Finnish family with three PFBC patients and five unaffected subjects was studied. Sanger sequencing was used to exclude mutations in the coding and splice site regions of SLC20A2, PDGFRB, and PDGFB. Whole-exome (WES) and whole-genome sequencing (WGS) were performed to identify the causative mutation. A SNP array was used in segregation analysis. RESULTS: Copy number analysis of the WGS data revealed a heterozygous deletion of ~578 kb on chromosome 8. The deletion removes the 5' UTR region, the noncoding exon 1 and the putative promoter region of SLC20A2 as well as the coding regions of six other genes. CONCLUSIONS: Our results support haploinsufficiency of SLC20A2 as a pathogenetic mechanism in PFBC. Analysis of copy number variations (CNVs) is emerging as a crucial step in the molecular genetic diagnostics of PFBC, and it should not be limited to coding regions, as causative variants may reside in the noncoding parts of known disease-associated genes.

Intrafamilial clinical variability in individuals carrying the CHCHD10 mutation Gly66Val.

OBJECTIVES: Mutations in the CHCHD10 gene, which encodes a mitochondrially targeted protein, have emerged as an important cause of motor neuron disease and frontotemporal lobar degeneration. The aim of this study was to assess the clinical variability in a large family carrying the p.Gly66Val mutation of the CHCHD10 gene. This mutation has recently been reported to cause late-onset spinal muscular atrophy (SMAJ) or sensorimotor axonal Charcot-Marie-Tooth neuropathy (CMT2) in the Finnish population. MATERIALS AND METHODS: Nine affected members of an extended Finnish pedigree were included in the study. Detailed clinical and neurophysiological examinations were performed. The CHCHD10 p.Gly66Val mutation was examined by Sanger sequencing. RESULTS: The heterozygous p.Gly66Val mutation was present in all affected individuals from whom a DNA sample was available. The clinical phenotype varied from proximal sensorimotor neuropathy to spinal muscular atrophy and in one case resembled motor neuron disease ALS at its early stages. The age of onset varied from 30 to 73 years. CONCLUSIONS: Our data demonstrate that even within the same family, the p.Gly66Val variant can cause variable phenotypes ranging from CMT2-type axonal neuropathy to spinal muscular atrophy, which may also present as an ALS-like disease. The spectrum of CHCHD10-related neuromuscular disease has widened rapidly, and we recommend keeping the threshold for genetic testing low particularly when dominant inheritance or mitochondrial pathology is present.

Susceptibility of green and conventional building materials to microbial growth.

Green building materials are becoming more popular. However, little is known about their ability to support or limit microbial growth. The growth of fungi was evaluated on five building materials. Two green, two conventional building materials and wood as a positive control were selected. The materials were inoculated with Aspergillus versicolor, Cladosporium cladosporioides and Penicillium brevicompactum, in the absence and presence of house dust. Microbial growth was assessed at four different time points by cultivation and determining fungal biomass using the N-acetylhexosaminidase (NAHA) enzyme assay. No clear differences were seen between green and conventional building materials in their susceptibility to support microbial growth. The presence of dust, an external source of nutrients, promoted growth of all the fungal species similarly on green and conventional materials. The results also showed a correlation coefficient ranging from 0.81 to 0.88 between NAHA activity and culturable counts. The results suggest that the growth of microbes on a material surface depends on the availability of organic matter rather than the classification of the material as green or conventional. NAHA activity and culturability correlated well indicating that the two methods used in the experiments gave similar trends for the growth of fungi on material surfaces.

Effects of fungal species, cultivation time, growth substrate, and air exposure velocity on the fluorescence properties of airborne fungal spores.

UNLABELLED: Real-time bioaerosol monitoring is possible with fluorescence based instruments. This study provides information on major factors that can affect the fluorescence properties of airborne fungal spores. Two fluorescence-based bioaerosol detectors, BioScout, and ultraviolet aerodynamic particle sizer (UVAPS), were used to study fluorescent particle fractions (FPFs) of released spores of three fungal species (Aspergillus versicolor, Cladosporium cladosporioides, and Penicillium brevicompactum). Two culture media (agar and gypsum board), three ages of the culture (one week, one month, and four months), and three aerosolization air velocities (5, 15, and 27 m/s) were tested. The results showed that the FPF values for spores released from gypsum were typically lower than for those released from agar indicating that poor nutrient substrate produces spores with lower amounts of fluorescent compounds. The results also showed higher FPF values with lower air velocities in aerosolization. This indicates that easily released fully developed spores have more fluorescent compounds compared to forcibly extracted non-matured spores. The FPFs typically were lower with older samples. The FPF results between the two instruments were similar, except with four-month-old samples. The results can be utilized in field measurements of fungal spores to estimate actual concentrations and compare different instruments with fluorescence-based devices as well as in instrument calibration and testing in laboratory conditions. PRACTICAL IMPLICATIONS: Fluorescence-based instruments are the only choice for real-time detection of fungal spores at the moment. In general, all fluorescence-based bioaerosol instruments are tested against known bacterial and fungal spores in laboratory conditions. This study showed that fungal species, growth substrate, age of culture, and air current exposure rate have an effect on detection efficiency of fungal spores in the fluorescence-based instruments. Therefore, these factors should be considered in the instrument calibration process. The results are also important when interpreting results of fluorescence-based field measurements of fungal spores.

Indoor aerosols: from personal exposure to risk assessment.

Motivated by growing considerations of the scale, severity, and risks associated with human exposure to indoor particulate matter, this work reviewed existing literature to: (i) identify state-of-the-art experimental techniques used for personal exposure assessment; (ii) compare exposure levels reported for domestic/school settings in different countries (excluding exposure to environmental tobacco smoke and particulate matter from biomass cooking in developing countries); (iii) assess the contribution of outdoor background vs indoor sources to personal exposure; and (iv) examine scientific understanding of the risks posed by personal exposure to indoor aerosols. Limited studies assessing integrated daily residential exposure to just one particle size fraction, ultrafine particles, show that the contribution of indoor sources ranged from 19% to 76%. This indicates a strong dependence on resident activities, source events and site specificity, and highlights the importance of indoor sources for total personal exposure. Further, it was assessed that 10-30% of the total burden of disease from particulate matter exposure was due to indoor-generated particles, signifying that indoor environments are likely to be a dominant environmental factor affecting human health. However, due to challenges associated with conducting epidemiological assessments, the role of indoor-generated particles has not been fully acknowledged, and improved exposure/risk assessment methods are still needed, together with a serious focus on exposure control.

Airborne enteric micro-organisms and ammonia levels in diaper-changing rooms in kindergartens.

AIMS: We evaluated risks associated with diaper changing in Finnish kindergartens where children were using either modern disposable paper or reusable cloth diapers. METHODS AND RESULTS: We determined enteric micro-organisms and ammonia in diaper-changing rooms in four kindergartens in autumn and winter in the ambient air. No coliphages were detected in the air. The numbers of faecal coliforms and enterococci in air were typically low regardless of whether the children used either paper or cloth diapers. Ammonia concentrations increased over the background level because of diaper changing. CONCLUSIONS: The numbers of bacteria or coliphages are not expected to pose any high air hygiene risks, and increased ammonia air concentrations are unlikely to impair the health of staff or children when diapers are changed in modern kindergartens. However, increased ammonia gas concentrations indicate that some other diaper-related gas-phase emissions should be studied to understand better diaper-related health risks. SIGNIFICANCE AND IMPACT OF THE STUDY: Modern reusable cloth baby diapers and the modern paper baby diapers used in this study are equally safe with respect to risks from airborne virus, bacteria or ammonia.

Volatile organic compounds and formaldehyde as explaining factors for sensory irritation in office environments.

This study's database comprised results of volatile organic compound (VOC) measurements from 176 office buildings. In 23 of the 176 buildings, formaldehyde measurements were also conducted. It was suspected that the buildings had indoor air problems, but a walk-through inspection did not reveal any clear, abnormal contaminant sources. The 50 most abundant VOCs and their concentrations in 520 air samples were analyzed. The irritation potency was estimated for 33 out of the 50 common VOCs and their mixtures, as well as for formaldehyde. This information was used to calculate the recommended indoor air levels (RILs) for the VOCs. The RILs were considerably higher than the measured mean indoor air concentrations in the buildings. However, the RIL for formaldehyde was exceeded in most of the 23 buildings studied. According to the evaluation of irritation potency, formaldehyde was a more likely cause of sensory irritation than the mixture of common nonreactive VOCs at the concentrations that occurred in the buildings without abnormal indoor sources. Furthermore, environmental symptoms of office workers were characterized in 20 office buildings (including the database of 176 office buildings) with the aid of an indoor air questionnaire. The most frequent symptoms related to the indoor environment were involved the upper respiratory tract. However, no relationship could be shown between the reported symptoms and the occurrence of VOC and formaldehyde concentrations in these buildings. Generally, the study results indicated that formaldehyde was the more likely agent causing sensory irritation than the mixture of the common nonreactive VOCs at the concentrations occurring in the buildings without abnormal indoor sources.

Retention of fungal enzyme activity in environmental liquid and filter samples.

Fungal biomass can be determined by measuring the beta-N-acetylhexos-aminidase (NAHA) enzyme activity. NAHA, an enzyme present in fungal mycelium and spores, has been detected in inactive, dormant and non-viable cells. Very little information is available on the enzyme activity of different species or retention of the activity under various storage conditions. This study used fluorometry to evaluate the enzyme activity of liquid and filter samples containing spores of four fungal species from genera Penicillium, Cladosporium, Aspergillus, and Acremonium. When fungal spores were stored on a filter, enzyme activity was more stable than when the spores were maintained in suspension for one year. The enzyme activity in suspension samples increased with most of the differences detected between the values at the baseline and 12 months being statistically significant. The results indicate that enzyme activity varies between species. Cladosporium spores had highest NAHA content per spore, whereas Acremonium did not exhibit any detectable enzyme activity even when viability was detected. The results indicated that samples should be stored as dry filter samples.

Oxidized LDL and thickness of carotid intima-media are associated with coronary atherosclerosis in middle-aged men: lower levels of oxidized LDL with statin therapy.

We investigated the relation between serum lipids including oxidized LDL and the severity of coronary atherosclerosis. Serum lipids and oxidized LDL was measured in 62 men (33-66 years), who underwent diagnostic coronary angiography and sonography to measure the carotid intima-media thickness. LDL oxidation was found in chemical analyses to be due to conjugated fatty acids in cholesteryl esters and triglycerides. Regression analysis indicated that the carotid intima-media thickness and the ratio of LDL diene conjugation to LDL cholesterol (the ox-LDL:LDL ratio) were the only factors associated independently with the severity of coronary atherosclerosis. The patients with multi-vessel disease who did not use lipid lowering therapy had a 50% thicker carotid intima media (P = 0.030) and a 41% higher ox-LDL:LDL ratio (P = 0.020) than patients with normal vessels. Further, patients with multi-vessel disease on statin therapy had a 24% lower ox-LDL:LDL ratio than the subjects with multi-vessel disease who did not use lipid lowering drugs (P = 0.027), although the concentration of LDL cholesterol did not differ between the groups. This study supports the hypothesis that lipid oxidation plays a role in the development of atherosclerosis.

Ergosterol content in various fungal species and biocontaminated building materials

This paper reports the ergosterol content for microbial cultures of six filamentous fungi, three yeast species, and one actinomycete and the ergosterol levels in 40 samples of building materials (wood chip, gypsum board, and glass wool) contaminated by microorganisms. The samples were hydrolyzed in alkaline methanol, and sterols were silylated and analyzed by gas chromatography-mass spectrometry. The average ergosterol content varied widely among the fungal species over the range of 2.6 to 42 &mgr;g/ml of dry mass or 0.00011 to 17 pg/spore or cell. Ergosterol could not be detected in the actinomycete culture. The results for both the fungal cultures and building material samples supported the idea that the ergosterol content reflects the concentration of filamentous fungi but it underestimates the occurrence of yeast cells. The ergosterol content in building material samples ranged from 0.017 to 68 &mgr;g/g of dry mass of material. A good agreement between the ergosterol concentration and viable fungal concentrations was detected in the wood chip (r > 0.66, P 0.48, P 0.63, P < 0.0001). In conclusion, the ergosterol concentration could be a suitable marker for estimation of fungal concentrations in contaminated building materials with certain reservations, including the underestimation of yeast concentrations.

Tumour-associated trypsin inhibitor in the diagnosis of pancreatic carcinoma.

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.

Nuclear magnetic resonance spectroscopy of plasma to distinguish between malignant and benign diseases causing jaundice and cholestasis.

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.

Vitamin D and prostate cancer.

Our recent epidemiological study (Ahonen et al., Cancer Causes Control 11(2000) (847-852)) suggests that vitamin D deficiency may increase the risk of initiation and progression of prostate cancer. The nested case-control study was based on a 13-year follow-up of about 19000 middle-aged men free of clinically verified prostate cancer. More than one-half of the serum samples had 25OH-vitamin D (25-VD) levels below 50 nmol/l, suggesting VD deficiency. Prostate cancer risk was highest among the group of younger men (40-51 years) with low serum 25-VD, whereas low serum 25-VD appeared not to increase the risk of prostate cancer in older men (>51 years). This suggests that VD has a protective role against prostate cancer only before the andropause, when serum androgen concentrations are higher. The lowest 25-VD concentrations in the younger men were associated with more aggressive prostate cancer. Furthermore, the high 25-VD levels delayed the appearance of clinically verified prostate cancer by 1.8 years. Since these results suggest that vitamin D has a protective role against prostate cancer, we tried to determine whether full spectrum lighting (FSL) during working hours could increase serum 25-VD concentrations. After 1-month exposure, there was no significant increase in the serum 25-VD level, although there was a bias towards slightly increasing values in the test group as opposed to decreasing values in controls. There was no significant change in the skin urocanic acid production. The possibility to use FSL in cancer prevention is discussed. In order to clarify the mechanism of VD action on cell proliferation and differentiation, we performed studies with the rat and human prostates as well prostate cancer cell lines. It is possible that 25-VD may have a direct role in the host anticancer defence activity, but the metabolism of vitamin D in the prostate may also play an important role in its action. We raised antibodies against human 1alpha-hydroxylase and 24-hydroxylase. Our preliminary results suggest that vitamin D is actively metabolised in the prostate. Vitamin D appears to upregulate androgen receptor expression, whereas androgens seem to upregulate vitamin D receptor (VDR). This may at least partially explain the androgen dependence of VD action. VD alone or administered with androgen causes a suppression of epithelial cell proliferation. VD can activate mitogen-activated kinases, erk-1 and erk-2, within minutes and p38 within hours. Also, auto/paracrine regulation might be involved, since keratinocyte growth factor (mRNA and protein) was clearly induced by VD. Based on these studies, a putative model for VD action on cell proliferation and differentiation is presented.

Stereospecific modulation of GABA(A) receptor function by urocanic acid isomers.

A deamination product of histidine, urocanic acid, accumulates in the skin of mammals as trans-urocanic acid. Ultraviolet (UV) irradition converts it to the cis-isomer that is an important mediator in UV-induced immunosuppression. We have recently shown that urocanic acid interferes with the agonist binding to GABA(A) receptors. We now report that the effects of urocanic acid on binding of a convulsant ligand (t-butylbicyclo[35S]phosphorothionate) to GABA(A) receptors in brain membrane homogenates are dependent on pH of the incubation medium, the agonistic actions being enhanced at the normal pH of the skin (5.5). Using Xenopus laevis oocytes expressing recombinant rat alpha1beta1gamma2S GABA(A) receptors, the low pH potentiated the direct agonistic action of trans-urocanic acid under two-electrode voltage-clamp, whereas cis-urocanic acid retained its low efficacy both at pH 5.5 and 7.4. The results thus indicate clear differences between urocanic acid isomers in functional activity at one putative receptor site of immunosuppression, the GABA(A) receptor, the presence of which in the skin remains to be demonstrated.

Urocanic acid concentration and photoisomerization in Caucasian skin phototypes.

To investigate the relationship between erythemal sensitivity of the skin to UV radiation and epidermal urocanic acid (UCA) concentration, 45 healthy volunteers of anamnestic skin phototypes (ASP) 1-IV were studied. In 16 of the subjects, we analyzed UCA photoisomerization after graded UVB exposures. The median and mean total UCA concentration in unirradiated skin was 22.4 and 35.3 nmol/cm2, and no statistically significant difference in total UCA concentrations was detectable either between ASP I through II and III through IV or between the phototested skin type (PSP) groups 1 through 2 and 3 through 4. The relative amount of the cis-isomer varied between 3 and 35%, with median and mean values of 7 and 12%, respectively. No statistically significant difference in absolute or relative cis-UCA concentrations was detectable between ASP I through II and III through IV, but a significantly lower absolute (P < 0.009) and relative (P < 0.002) cis-UCA concentration in unirradiated skin was recorded in PSP groups 1 through 2, compared to types 3 through 4. In all tested subjects, an erythemally weighted dose of 1 mJ/cm2 sufficed to cause trans- to cis-UCA isomerization. When comparing photosensitive (skin phototype I) and phototolerant (phototypes III and IV) individuals, who were irradiated with a reference 5 mJ/cm2 UV dose or with fractions of 0.1-1.0 of their individual minimal erythema dose values, no skin phototype-dependent difference in ability to photoisomerize was discernible.

Clinical evaluation of tissue polypeptide antigen (TPA) in the diagnosis of pancreatic carcinoma.

The serum values of tissue polypeptide antigen (TPA) were measured in a prospective series of 100 patients with jaundice, 54 patients with suspicion of chronic pancreatitis or a pancreatic tumour, and 19 patients with unjaundiced cholestasis to assess its value in diagnosing pancreatic cancer. There were altogether 25 patients with a cancer of the pancreas including 2 patients with a cancer of the papilla of Vater. The highest serum TPA values were noticed in patients with pancreatic cancer, but raised values were also seen in patients with malignant or benign liver diseases, and with cholangiocarcinoma. The sensitivity of TPA was 52% with a specificity of 85% and an efficiency of 80%. In comparison to CEA, CA 50 and CA 242, TPA showed lower sensitivity but higher specificity. When TPA was combined with the other markers, the specificity and efficiency improved clearly in all combinations, being highest in that of TPA and CA 242 (specificity 94.5%, efficiency 87.2%). The results suggest that the TPA test has a useful complementary role in the clinical use of the current serum tumour markers in the diagnosis of pancreatic cancer.

A prospective study of the value of imaging, serum markers and their combination in the diagnosis of pancreatic carcinoma in symptomatic patients.

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 value of combined use of serum tumour markers and nuclear magnetic spectroscopy of plasma in the detection of pancreatic cancer among patients with jaundice or cholestasis: results from a prospective study.

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.

Clinical value of serum tumour markers CEA, CA 50 and CA 242 in the distinction between malignant versus benign diseases causing jaundice and cholestasis; results from a prospective study.

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.

Small intestinal mucin antigen (SIMA); a novel tumour marker in colorectal cancer?

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.