Subpopulation difference scanning: a strategy for exclusion mapping of susceptibility genes.

BACKGROUND: Association mapping is a common strategy for finding disease-related genes in complex disorders. Different association study designs exist, such as case-control studies or admixture mapping. METHODS: We propose a strategy, subpopulation difference scanning (SDS), to exclude large fractions of the genome as locations of genes for complex disorders. This strategy is applicable to genes explaining disease incidence differences within founder populations, for example, in cardiovascular diseases in Finland. RESULTS: The strategy consists of genotyping a set of markers from unrelated individuals sampled from subpopulations with differing disease incidence but otherwise as similar as possible. When comparing allele or haplotype frequencies between the subpopulations, the genomic areas with little difference can be excluded as possible locations for genes causing the difference in incidence, and other areas therefore targeted with case-control studies. As tests of this strategy, we use real and simulated data to show that under realistic assumptions of population history and disease risk parameters, the strategy saves efforts of sampling and genotyping and most efficiently detects genes of low risk--that is, those most difficult to find with other strategies. CONCLUSION: In contrast to admixture mapping that uses the mixing of two different populations, the SDS strategy takes advantage of drift within highly related subpopulations.

L1CAM, INP10, P-cadherin, tPA and ITGB4 over-expression in malignant pleural mesotheliomas revealed by combined use of cDNA and tissue microarray.

Malignant pleural mesothelioma (MM) is a rare tumour with high mortality, which can exhibit various morphologies classified as epithelioid, biphasic and sarcomatoid subtypes. To investigate the molecular changes in these tumours, we studied gene expression patterns by combined use of cDNA arrays and tumour tissue microarrays (TMA). Deregulation of the expression of 588 cancer-related genes was screened in 16 MM comprising all three subtypes and compared with references, i.e. normal mesothelial cell lines and pleural mesothelium. Array data were analysed using three statistical methods; principal component analysis (PCA), permutation test and receiver operating characteristic (ROC) curves. Eleven genes were verified by real-time RT-PCR. Genes encoding two adhesion molecules [COL1A2 and integrin beta4 (ITGB4)] and a chemokine (INP10) were up-regulated in MM compared with both the cell lines and pleural mesothelium. There was a type-specific up-regulation of semaphorin E, ITGB4 and P-cadherin in epithelioid MM, matrix metalloproteinase 9 (MMP9) and tissue-type plasminogen activator (tPA) in sarcomatoid MM and neural cell adhesion molecule L1 (L1CAM) and INP10 in biphasic MM. Immunohistochemistry on TMA containing 47 MM (26 epithelioid, 15 sarcomatoid and six biphasic) was performed for five proteins, ITGB4, P-cadherin, tPA, INP10 and L1CAM. INP10 expression was increased in MM in general compared with normal mesothelium, while increased expression of P-cadherin, L1CAM and ITGB4 was more specific in MMs exhibiting an epithelioid growth pattern. The over-expression of tPA was more frequent in epithelioid MM despite higher mRNA levels in sarcomatoid and biphasic MM. We conclude that several proteins, associated with cell adhesion either directly (ITGB4, L1CAM, P-cadherin) or as a regulatory factor (INP10), are differentially expressed in MM. In particular, INP10, ITGB4 and COL1A2 were up-regulated in MM compared with both reference sample types, suggesting a relationship with development of these tumours.

Serum tartrate-resistant acid phosphatase 5b in monitoring bisphosphonate treatment with clodronate: a comparison with urinary N-terminal telopeptide of type I collagen and serum type I procollagen amino-terminal propeptide.

Osteoclastic tartrate-resistant acid phosphatase activity in serum (S-TRACP 5b) was measured in postmenopausal women ( n =59, mean age 56.1 years) with vertebral osteopenia before and during 2-year treatment with an 800-mg daily dose of clodronate, with a non-amino bisphosphonate. Changes in TRACP 5b were compared with those in urinary excretion of type I collagen amino-terminal telopeptide (U-NTX), corrected for creatinine excretion, a well-established marker of bone resorption, and to serum type I procollagen amino-terminal propeptide (S-PINP), a marker of bone formation. Marker changes 1 year after start of treatment were correlated with changes in bone mineral density (BMD). The least significant change (LSC) for each marker and BMD was calculated from values for subjects receiving placebo. Responders to treatment were those exhibiting a change larger than LSC. In response to clodronate treatment S-TRACP 5b (mean change up to -18%) decreased less than did U-NTX (up to -51%) or S-PINP (up to -46%). Marker changes correlated with changes in lumbar spine and trochanter BMD. The most efficient marker for finding responders to treatment was S-PINP, which changed more than the LSC (32%) in 72% of the subjects at the 1-year time point and in 79% at the 2-year time point. S-TRACP 5b change exceeded the LSC (27%) in 40% and 34% of the subjects at each time point, while U-NTX change exceeded the LSC (55%) in 55% and 40%, respectively. We conclude that, in terms of the proportion of subjects exhibiting any change exceeding the LSC, S-TRACP 5b did not appear to be superior to U-NTX and S-PINP in the follow-up of clodronate treatment. The reason may lie in the mechanism of action of clodronate, which rather than reducing the number of TRACP 5b-secreting osteoclasts, reduces the activity of bone proteolytic enzymes and thus the rate of bone organic matrix degradation. This is seen in decreased amounts of type I collagen breakdown products (U-NTX), and through coupling of bone resorption with bone formation, in a decrease in circulating levels of the marker that reflects new collagen formation (S-PINP).

Prevention of bone loss by clodronate in early postmenopausal women with vertebral osteopenia: a dose-finding study.

This double-masked, placebo-controlled study was undertaken to determine the efficacy and safety of oral clodronate in the prevention of bone loss in early postmenopausal women with vertebral osteopenia. Altogether 610 women with a mean age of 53 years were recruited for the study. They were 1-5 years postmenopausal and their lumbar spine bone mineral density (BMD) was at least 1 standard deviation below the mean of premenopausal women ( T-score < or =-1). The subjects were randomized into five study groups to receive either placebo, clodronate 65 mg, 400 mg or 800 mg daily, or intermittent clodronate in 3 month cycles with 400 mg daily for 15 days followed with no treatment for 75 days for 3 years. One hundred and eighty-seven of 509 women who completed the primary study continued in the extension study of 2 years in which previous placebo users were switched to clodronate 800 mg daily, while previous users of 400 mg or 800 mg of clodronate used either placebo or 800 mg of clodronate daily. In the primary study clodronate was administered in the evening, and in the extension 1 h before breakfast on an empty stomach. In the primary study mean changes in lumbar spine BMD were -3.4% in the placebo group and +0.4% in 800 mg clodronate group [difference between groups at 3 years 3.8% (95% CI 2.7% to 4.9%, p<0.0001)], and in the trochanter area BMD -1.1% in the placebo group, and + 0.4% in the 800 mg clodronate group [difference between groups at 3 years 1.5% (95% CI 0.05% to 2.9%)]. During the extension study mean changes in lumbar spine BMD were +1.5% in the clodronate group and -0.2 % in the placebo group [difference between groups 1.7% (CI 0.4% to 3.0%, p = 0.010)] and in trochanter BMD were +2.5% in the clodronate group and no change in the placebo group [difference between groups 2.1% (CI 0.3% to 3.9%, p = 0.007)]. No statistically significant differences between the placebo and 800 mg clodronate groups were found in the femoral neck BMD. In the primary study the urinary excretion of type I collagen aminoterminal telopeptide (NTX) decreased by 44% ( p<0.0001 compared with placebo) and that of deoxypyridinoline by 18% ( p<0.0001) in the clodronate 800 mg group. In the extension study urinary NTX decreased by 51% ( p<0.0001) in those who were switched to 800 mg of clodronate and increased by 67% ( p<0.0001) in those who stopped using that dose. There was no difference in the frequency of gastrointestinal complaints between clodronate- and placebo-treated patients in the primary study, but they were more common among women who received clodronate in the extension phase. Clodronate in daily doses of 400-800 mg caused a slight elevation of aminotransferase levels, usually within the reference range. In bone biopsies no defect in mineralization was found. In conclusion, clodronate in a daily dose of 800 mg prevents early postmenopausal bone loss at the sites of the skeleton in which cancellous bone predominates. It effectively reduces bone resorption and bone turnover rate. Antifracture efficacy of clodronate remains to be established by prospective, placebo-controlled trials.

Expression of myeloid-specific genes in childhood acute lymphoblastic leukemia - a cDNA array study.

Several specific cytogenetic changes are known to be associated with childhood acute lymphoblastic leukemia (ALL), and many of them are important prognostic factors for the disease. Little is known, however, about the changes in gene expression in ALL. Recently, the development of cDNA array technology has enabled the study of expression of hundreds to thousands of genes in a single experiment. We used the cDNA array method to study the gene expression profiles of 17 children with precursor-B ALL. Normal B cells from adenoids were used as reference material. We discuss the 25 genes that were most over-expressed compared to the reference. These included four genes that are normally expressed only in the myeloid lineages of the hematopoietic cells: RNASE2, GCSFR, PRTN3 and CLC. We also detected over-expression of S100A12, expressed in nerve cells but also in myeloid cells. In addition to the myeloid-specific genes, other over-expressed genes included AML1, LCP2 and FGF6. In conclusion, our study revealed novel information about gene expression in childhood ALL. The data obtained may contribute to further studies of the pathogenesis and prognosis of childhood ALL.

Positive fitness consequences of interspecific interaction with a potential competitor.

The coexistence of species sharing mutual resources is usually thought to be limited by negative processes such as interspecific competition. This is because an overlap in resource use leads to negative fitness consequences, and traits favouring avoidance of potential competitors, for example in habitat selection, are therefore selected for. However, species interactions are acknowledged to vary from negative (competition) to mutualism, although empirical evidence for positive interspecific interactions from natural communities of other than plants and sessile animals is scarce. Here, we experimentally examined the habitat selection and its fitness consequences of a migrant bird, the pied flycatcher (Ficedula hypoleuca), in relation to the presence of competitively superior birds, resident titmice (Parus spp.). Experiments were conducted on two spatial scales: landscape and nest-site scale. We demonstrate that pied flycatchers were attracted to and accrued fitness benefits from the presence of titmice. Flycatchers breeding in tight association with titmice initiated breeding earlier, had larger broods and heavier young than solitarily breeding flycatchers. This paradoxical result indicates that species interactions may switch from negative to positive and that the coexistence of species is not always restricted by negative costs caused by other species.

FGF-8b increases angiogenic capacity and tumor growth of androgen-regulated S115 breast cancer cells.

Fibroblast growth factor 8 (FGF-8) is a secreted heparin-binding protein, which has transforming potential. Alternative splicing of the mouse Fgf-8 gene potentially codes for eight protein isoforms (a-h) which differ in their transforming capacity in transfected cells. S115 mouse mammary tumor cells express a transformed phenotype and secrete FGF-8 in an androgen-dependent manner. In order to study the role of FGF-8 isoforms in the induction of transformed phenotype of breast cancer cells, we over-expressed FGF-8 isoforms a, b and e in S115 cells. Over-expression of FGF-8b, but not FGF-8a or FGF-8e, induced androgen and anchorage independent growth of S115 cells. FGF-8b-transfected S115 cells formed rapidly growing tumors with increased vascularization when injected s.c. into nude mice. FGF-8a also slightly increased tumor growth and probably tumor vascularization but FGF-8e was not found to have any effects. The angiogenic activity of FGF-8b and heparin-binding growth factor fraction (HBGF) of S115 cell conditioned media was tested in in vitro and in vivo models for angiogenesis using immortomouse brain capillary endothelial cells (IBEC) and chorion allantoic membrane (CAM) assays. Recombinant FGF-8b protein was able to stimulate proliferation, migration, and vessel-like tube formation of IBECs. In addition, stimulatory effect of S115-HBGF on IBE cell proliferation was evident. A positive angiogenic response to FGF-8b was also seen in CAM assay. The results demonstrate that the expression of Fgf-8b is able to promote vessel formation. Angiogenic capacity probably markedly contributes to the ability of FGF-8b to increase tumor growth of androgen-regulated S115 mouse breast cancer cells.

Enhanced invasion and tumor growth of fibroblast growth factor 8b-overexpressing MCF-7 human breast cancer cells.

Fibroblast growth factor 8 (FGF-8) is a secreted heparin-binding protein, which has mitogenic and transforming activity. Increased expression of FGF-8 has been found in human breast cancer, and it has a potential autocrine role in its progression. Human FGF-8 is alternatively spliced to generate four protein isoforms (a, b, e, and f). Isoform b has been shown to be the most transforming. In this work, we studied the role of FGF-8b in the growth (in vitro and in vivo) of MCF-7 human breast cancer cells, which proliferate in an estrogen-dependent manner. Constitutive overexpression of FGF-8b in MCF-7 cells down-regulated FGF-8b-binding receptors FGF receptor (FGFR) 1IIIc, FGFR2IIIc, and FGFR4 found to be expressed in these cells. FGF-8b overexpression led to an increase in the anchorage-independent proliferation rate in suspension culture and colony formation in soft agar, when MCF-7 cells were cultured with or without estradiol. FGF-8b also provided an additional growth advantage for cells stimulated with estradiol. In addition, FGF-8b-transfected cells invaded more actively through Matrigel than did control cells. This was possibly due to the increased secretion of matrix metalloproteinase 9. In vivo, FGF-8b-transfected MCF-7 cells formed faster growing tumors than vector-only-transfected cells when xenografted into nude mice. The tumors formed by FGF-8b-transfected cells were more vascular than the tumors formed by vector-only-transfected cells. In conclusion, FGF-8b expression confers a growth advantage to MCF-7 breast carcinoma cells, both in vitro and in vivo. In addition to stimulation of proliferation, this growth advantage probably arises from increased invasion and tumor vascularization induced by FGF-8b. The results suggest that FGF-8b signaling may be an important factor in the regulation of tumorigenesis and progression of human breast cancer.

Expression of fibroblast growth factor (FGF)-8 isoforms and FGF receptors in human ovarian tumors.

FGF-8 is a mitogenic growth factor, which is widely expressed during embryonic development but only at a very low level in adult tissues. Alternative splicing of the human FGF-8 gene potentially allows coding for 4 protein isoforms (a, b, e, f), which differ in their transforming capacity. The FGF-8 isoforms preferentially activate the receptors FGFR1IIIc, FGFR2IIIc, FGFR3IIIc and FGFR4. FGF-8 is over-expressed in human breast and prostate cancers. Expression has also been found in RT-PCR studies of human ovarian and testicular cancers. The present study was undertaken to examine which FGF-8 isoforms are expressed in ovarian cancer and whether FGF-8 receptors are also expressed. Specimens from 5 normal human ovaries and 51 ovarian tumors (1 benign tumor, 8 borderline malignancies, 42 malignant tumors of different histopathological types) were studied by RT-PCR and immunohistochemistry. FGF-8 isoform b was expressed in all ovarian tumors and in all 7 ovarian-cancer cell lines studied. Isoform a was co-expressed in 9 malignant ovarian tumors. FGF-8 mRNA was not detected by RT-PCR of 3 normal ovary samples. Immunohistochemical staining localized FGF-8 protein to cancer cells. In general, the increased intensity of FGF-8 staining was associated with loss of differentiation within the tumors (Bowker's test, p = 0.37). FGF-8 staining of surface epithelium observed on 2 normal ovaries was very faint. RT-PCR showed that FGFR1IIIc, FGFR2IIIc and FGFR4 were the FGF-8 receptors expressed in normal ovaries and in ovarian tumors. FGF-8 receptor immunoreactivity was preferentially found in normal ovary surface epithelium and tumor cells but also in some stromal cells. Collectively, our results show that ovarian cancers of a wide variety of histological types expressing receptors for FGF-8 have acquired the capacity of expressing FGF-8. This suggests that FGF-8 has an important role in ovarian tumorigenesis.

Clonality of Vibrio anguillarum strains isolated from fish from the Scandinavian countries, Sweden, Finland and Denmark.

In order to investigate whether outbreaks of vibriosis in the Baltic region were caused by the spread of certain pathogenic clones, 291 Vibrio anguillarum isolates from Finland (n = 156), Sweden (n = 88) and Denmark (n = 47) were studied with respect to serogroup, ribotype, plasmid content, and biochemical phenotypes as expressed with the PhenePlate (PhP) typing system. For comparison, 54 V. anguillarum serogroup O1 from other countries worldwide were included. Most isolates from Finland, Sweden and Denmark belonged to serogroup O1 (255), followed by O2 (30). Four Finnish isolates cross-reacted strongly with antisera against two new serogroups VaNT2 and VaNT4, whereas two strains were non-typeable. The serogroup O1 isolates displayed ten different ribotype patterns, whereas the other strains were considerably more diverse with respect to ribotypes. Most of the O1 isolates carried the 67 kb virulence plasmid and a group of Finnish isolates, in addition, carried an 86 kb plasmid. Additional plasmids with molecular weights of 63, 76, 135 or 260-290 kb were found in single O1 isolates. With few exceptions, strains of serogroup O2 either had no plasmids or carried one or two small plasmids. PhenePlate typing revealed considerable diversity within the species, serogroup O1 being the most homogeneous. A few PhP types were dominant, whereas other types were observed only in one to four isolates. The prevalence of the different types changed significantly from one year to another but in Finland, one clonal lineage became increasingly important from 1992 (20% of isolates) to 1996 (80%). Remaining clones were mostly restricted to specific geographic areas. By cluster analysis, it was demonstrated that most of the isolates from Finland, Sweden and Denmark belonged to two clusters, and most of the strains from Southern Europe fell into two other, distinct clusters. Most isolates from the UK, North America, Chile and Tasmania grouped together in a distinct cluster. For the typing of V. anguillarum, O-serotyping should be the primary method. For isolates belonging to serogroups other than O1, plasmid profiling in combination with ribotyping gives a very good discrimination between strains, whereas for serogroup O1, another method is required. It is concluded that PhP typing is a tool that provides a good discrimination between O1 isolates.

Growth and weight gain in children with vesicoureteral reflux receiving medical versus surgical treatment: 10-year results of a prospective, randomized study. International Reflux Study in Children (European Branch).

In children with vesicoureteral reflux (VUR) and urinary tract infection, retardation of growth and weight gain at the time of diagnosis and catch-up growth during follow-up, mostly after operating for VUR, have been reported. A controlled trial comparing the effect on growth of surgical treatment and long-term prophylactic antibiotic treatment has not been reported previously. Between 1980 and 1985, 306 children younger than 11 y with non-obstructive grade III or IV VUR, with a history of symptomatic urinary tract infection, were randomly allocated to surgical or medical treatment. Of these, 236 were followed for 10 y, 118 randomized to surgical treatment (mean age at entry 3.5 +/- 2.3 y) and 118 to medical treatment (mean age at entry 3.8 +/- 2.5 y). All children had renal function and blood pressure in the normal range. Body height, measured at start and after 1, 5 and 10 y, was transformed to standard deviation score of height for chronological age (SDSH-CA) and body weight to percentage of ideal body weight for height (%IBW). The evolution of SDSH-CA and %IBW was similar in both treatment groups (SDSH-CA: surgical: start, 0.23 +/- 1.4; 10 y, 0.40 +/- 1.0; medical: start, 0.14 +/- 1.2; 10 y, 0.44 +/- 1.2; %IBW: surgical: start, 99 +/- 9%; 10 y, 107 +/- 14%; medical: start, 98 +/- 10%; 10 y, 105 +/- 16%). While children starting the study below the age of 3 y (SDSH-CA 0.55 +/- 1.34) started significantly taller than those older than 3 y (SDSH-CA -0.1 +/- 1.39), the young ones demonstrated a significant drop in SDSH-CA during the 1st year (SDSH-CA 0.19 +/- 1.23), which was regained up to the 10th year (SDSH-CA 0.6 +/- 1.13), and the older ones steadily gained height up to an SDSH-CA of 0.28 +/- 1.05 at 10 y. During all of the study period, treatment protocol, grade of VUR, renal parenchymal scars at entrance and urinary tract infections did not influence growth and weight gain. Age at entry and gender were the only significant correlates with growth and weight gain.

Microcatheter embolization of hemorrhages.

PURPOSE: To evaluate the efficacy of embolotherapy using microcatheters in patients with hemorrhage from various locations. METHODS: Among 29 patients there were 13 with severe epistaxis, 7 with gastrointestinal bleeding, 4 with hemorrhage in the kidney, 4 with bleeding in pelvic organs and 1 with bleeding in the shoulder region. In all cases, a Tracker-18 or Tracker-10 microcatheter was advanced coaxially through a 4.1 Fr guiding catheter in order to reach the bleeding site as distally as possible. Polyvinyl alcohol microparticles and/or platinum microcoils were used as embolic material. RESULTS: The bleeding was stopped in 90% (26 of 29) of cases. In 66% of cases the treatment was curative, in 7% preoperative, and in 17% palliative. There were 3 clinical failures. CONCLUSION: Microcatheter embolization is an effective and safe means of managing different kinds of hemorrhage of various causes from a variety of sites.

Antibodies against 12 serotypes of Actinobacillus pleuropneumoniae in finnish slaughter sows.

To determine the prevalence of A. pleuropneumoniae serotypes in Finnish pig populations, 692 blood samples of sows were randomly collected from Finnish slaughterhouses. These were assayed with a direct ELISA for 12 Actinobacillus pleuropneumoniae serotypes. The specificity of the ELISA was tested using rabbit antisera against these serotypes. Cross-reactions were detected between serotypes 6 and 8 and between serotypes 1, 9 and 11, and serotype 5 antiserum reacted with serotype 6 antigen, but the other serotypes did not cross-react. When assaying the blood samples serotype 3 and 2 antibodies were found in 51% and 26% of samples, respectively. Other serotypes were found only in smaller numbers. Most of the samples, 61%, had antibodies towards some serotype of A. pleuropneumoniae. Antibodies towards serotypes 2 and 3 were found in pigs throughout Finland.

Detection of toxigenic Pasteurella multocida infections in swine herds by assaying antibodies in sow colostrum.

Toxigenic Pasteurella multocida is the causative agent of progressive atrophic rhinitis (PAR), a serious respiratory infection of swine. Diagnosis of the disease has hitherto been based on clinical signs, pathologic findings, and subsequent isolation of the agent. The best Finnish pig breeding herds participating in the Finnish Pig Health Scheme have been surveyed for PAR since 1963, and the disease has been eradicated from these herds. In this study, a total of 5,650 colostrum samples from 188 Finnish Pig Health Scheme herds were analyzed with a new serologic screening method: an enzyme-linked immunosorbent assay (ELISA) able to detect antibodies to the toxin of P. multocida (PMT). Although the herds had been continuously controlled for PAR, 1 herd with PMT antibodies was found. The positive reactions in the ELISA were confirmed by isolating the causative organism. The origin of the infection also appeared to be obvious. The serologic ELISA is a suitable method for the detection and screening of toxigenic P. multocida-infected pig herds.

Effect of concomitant administration of clodronate and estramustine phosphate on their bioavailability in patients with metastasized prostate cancer.

Estramustine phosphate is generally used as a second-line treatment in patients with advanced prostate cancer. The bone metastases due to the cancer are often treated simultaneously with clodronate in order to relieve the bone pain. Therefore, the interaction of clodronate (800 mg orally four times daily) and estramustine phosphate (280 mg orally twice daily) on their bioavailability was studied in twelve patients with prostate carcinoma and bone metastases. The drugs were first given separately, each to six patients, for five days, and then concomitantly for the same period. The bioavailabilities of the drugs were calculated on the last day of each treatment period. When clodronate was given alone, its concentrations in serum and AUC for one dose interval (6 hr) did not differ from those obtained with the drug given concomitantly with estramustine phosphate, nor did the combination of estramustine phosphate change the excretion of clodronate in urine. The serum concentrations of estramustine phosphate were elevated by about 80% when the drug was given together with clodronate. The AUC for one dose interval (12 hr) was also significantly higher for estramustine phosphate with clodronate than without clodronate. The urinary excretion of estrone, a major metabolite of estramustine phosphate, was also significantly higher after the admission with clodronate. The results suggest that clodronate increases the oral bioavailability of estramustine phosphate.

Malignant fibrous histiocytoma of the prostate. Case report.

A prostatic tumour removed suprapubically in a 57-year old man was found to be a malignant fibrous histiocytoma. Postoperative radiation therapy was given and 3 1/2 years later chemotherapy, epirubicin was initiated due to a local recurrence and lung metastases. Now 6 years later the health condition is good, lung metastases have not proceeded. Adjuvant radiation and chemotherapy after surgery may have a favourable effect on the outcome of MFH of the prostate.

Actinobacillus pleuropneumoniae serotype-2 antibodies in sow colostrum in Finnish pig-health-scheme herds.

A direct ELISA with phenol-extracted antigen for Actinobacillus pleuropneumoniae serotype 2 was developed. The test was specific when tested with rabbit antisera prepared against different A. pleuropneumoniae serotypes. It had better-than-moderate repeatability and it made a clear distinction between positive and negative samples. A total of 5477 colostrum samples from breeding sows from herds participating in the Finnish Pig-health Scheme were tested using the ELISA test. A total of 1307 positive samples were found in 129 out of 154 herds, thus indicating that most of the disease-control herds in Finland are infected with A. pleuropneumoniae serotype 2. These infections were almost entirely subclinical.

The effect of combined intravenous and oral clodronate treatment on bone pain in patients with metastatic prostate cancer.

Although osteosclerotic metastases are characteristic of prostate cancer, bone resorption is also accelerated. Clodronate is a specific inhibitor of osteoclastic bone resorption and relieves bone pain of osteolytic lesions in myelomatosis and breast cancer. The present open study included 16 prostate cancer patients who had painful bone metastases and who had failed hormonal therapy. Clodronate was given intravenously for six days (300 mg/day) followed by oral treatment for 21 days (3200 mg/day). A clear pain relief was found in nine of the 16 (56%) patients after intravenous administration. During the next three weeks with oral administration there was still pain reduction in five patients, while in three patients the pain increased. The treatment had no effect on conventional tumour markers but urinary hydroxyproline excretion decreased, indicating reduced bone resorption. Clodronate offers an alternative for treating patients with painful metastases from prostate cancer.

Aetiology, diagnosis and treatment of patients with renal trauma. A survey on patients in the Tampere area during two decades.

A material of 185 renal traumas treated during 1972-1991 was analyzed. A typical patient was a young man; the mean age was 30 years. The most common aetiology was traffic accident (45%). Penetrating traumas were rare (2%). The most common and significant finding was macroscopic haematuria, but the absence of haematuria did not exclude renal trauma. Unexpected findings were seen in 7% of cases. The most common renal injuries were contusion (69%) and laceration (20%) which were mostly treated conservatively (85%) with good results. Only 15% of patients were operated. Renal complications were few both in the conservatively and in the surgically treated patients. No mortality was seen.

Surgical results in the International Reflux Study in Children (Europe).

In the European part of the International Reflux Study in Children (7 participating centers) 151 infants and children were randomly allocated to surgical treatment of primary grades III and IV vesicoureteral reflux. Reimplantation was performed unilaterally in 65 patients and bilaterally in 86, for a total of 237 ureters reimplanted. The patients were followed at regular intervals for 5 years. Reflux was absent in 231 of the reimplanted ureters (97.5%) at the end of 5 years. No patient underwent reoperation for reflux. In 10 ureters (4.2%, 10 patients) obstruction developed postoperatively and 7 needed reoperation. All reoperations were performed on the left side. Of the obstructed kidneys new scars developed in 6 during the 5-year followup. Including these cases, the number of new renal scars was equal in the surgical and medical groups (20 each). The number of pyelonephritic episodes during followup was significantly less in the surgical group (without chemoprophylaxis) than in the medical group (on chemoprophylaxis). No kidneys were lost and no child became hypertensive. If voiding cystourethrography and excretory urography were normal 6 months postoperatively, the reflux had been permanently eradicated and postoperative obstruction could be ruled out. In this study the patients who underwent reimplantation had a 74% (112 of 151) chance of an uncomplicated postoperative course (no persisting reflux, obstruction, pyelonephritis or severe renal damage).