PubMed Health⌕ Search

Biomedical subjects

J Seppänen

Publications and source records attributed to J Seppänen.

At least 19 recordsLinked to original sources
PubMed2004

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).

Acid Phosphatase↗
PubMed2002

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.

Absorptiometry, Photon↗
PubMed2000

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.

Adult↗
PubMed1999

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.

Animals↗
PubMed1999

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.

Body Height↗
PubMed1996

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.

Actinobacillus Infections↗
PubMed1996

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.

Administration, Oral↗
PubMed1996

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.

Animals↗
PubMed1994

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.

Actinobacillus Infections↗
PubMed1994

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.

Administration, Oral↗
PubMed1993

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.

Accidental Falls↗
PubMed1992

Effect of oral clodronate on bone pain. A controlled study in patients with metastic prostatic cancer.

Although osteosclerotic metastases are characteristic of prostatic carcinoma, bone resorption is also accelerated. Since clodronate inhibits bone resorption and relieves bone pain, we have given it to patients with painful bone disease from prostatic cancer after failure of hormonal therapy. All patients received estramustine phosphate orally. Simultaneously they were randomly allocated to clodronate (36) and placebo (39) groups. Clodronate was given by mouth. The dose was 3.2 g for the first month, thereafter 1.6 g. Pain relief was more distinct in the clodronate group where one third of patients were totally free of bone pain. The use of analgesics stopped in 38% of patients on clodronate and in 18% on placebo which effect probably belongs to estramustine phosphate. Serum calcium concentration decreased more markedly in the clodronate group. Clodronate dose of 3.2 g seemed to be more potent than that of 1.6 g. Side effects were uncommon and occurred equally in both groups. No significant differences were seen in median survival or survival rates between the groups.

Administration, Oral↗
PubMed1992

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).

Child↗
PubMed1992

Imipenem-cilastatin vs. tobramycin and metronidazole for appendicitis-related infections.

The efficacy of imipenem-cilastatin was compared with that of tobramycin and metronidazole for the treatment of appendicitis-associated abdominal infections in children in an open, randomized trial. Two hundred eighteen patients between 2.5 and 16.8 years of age hospitalized for appendectomy because of suspected acute appendicitis were allocated to 5 treatment groups. The appendix was perforated in 54 (33.8%) of the 160 cases with appendicitis. All patients responded favorably to treatment. Infection in the wound occurred in 15 of 125 (12.0%) of those without preoperative antibiotic therapy and in 5 of 83 (6.0%) of those given imipenem preoperatively (P = 0.12; 95% confidence interval, -2.2 to 14.2%). C-reactive protein decreased significantly faster in those with perforated appendix treated with imipenem than in those treated with tobramycin and metronidazole (58.2 mg/liter vs. 89.4 mg/liter, P less than 0.05 on the third postoperative day). Imipenem-cilastatin was at least as effective and economically comparable as tobramycin and metronidazole for the treatment of appendicitis-associated infections in children.

Adolescent↗
PubMed1991

Aetiological and precipitating factors for childhood enuresis.

Aetiological factors for enuresis in 68 nightwetting (NW) and 73 day and mixed day and nightwetting (DW/MW) children were examined against a random sample of 142 control children drawn from a population of 3,375 seven-year-old children. Twenty-six variables concerning age, sex, social background, life changes, familial and perinatal history, development, growth, neurological damage, psychic structure and urinary tract disorders were included in the logistic regression analysis. The familial influence on enuresis was clearly seen in both nightwetters and daywetters. The NW children were further discriminated from the controls by items connected with delayed development, such as slower growth and poorer visuomotor and spatial perception. Marital separation or birth of a sibling were also found to be precipitating factors especially for nightwetters. The DW/MW children were discriminated from the controls by perinatal risk factors, signs of neurological dysfunction and smaller voided volume, and especially secondary daywetters by urinary tract infections. These models showed that there are similarities between nocturnal and diurnal enuresis, although there are still many differences and every individual case requires consideration of all these disposing factors.

Child↗
PubMed1990

Screening of urinary tract abnormalities among day and nightwetting children.

In order to detect possible urinary tract abnormalities among wetters, assessments of previous history completed by ultrasonography of the urinary tract and uroflowmetry were obtained for 145 wetting children and a random sample of 156 sex-matched non-wetting children drawn from a population of 3,375 seven-year-olds. Ultrasonography revealed abnormalities, including both morphological ones and cases with incomplete bladder emptying, in 5 out of 73 nightwetters (6.8%, 95% confidence limit, CL, 1.1-12.6), 10 out of 72 day and day and nightwetters (hereafter daywetters) (13.9%, CL 5.9-21.9) and 4 controls (2.6%, CL 0.1-5.0), the figure for the daywetters differing significantly from that for the controls (p less than 0.01). A fractioned voiding curve was recognized in 1 nightwetter (1.4%, CL -1.3-4.0), 7 daywetters (9.7%, CL 2.9-16.6) and 7 controls (4.5%, CL 1.2-7.7) the difference between the nightwetters and daywetters being significant (p less than 0.05). Depending on the previous history and abnormal findings in ultrasonography or uroflowmetry, examinations were continued with intravenous pyelography, voiding cystography, cystoscopy and/or by cystometry. Finally, marked structural or functional disorders of the urinary tract were detected in 11 out of 72 daywetters (15.3%, CL 7.0-23.6), 1 out of 73 pure nightwetters and 1 out of 156 control children. It is concluded that imaging of the urinary tract is not necessary for pure nightwetters, while ultrasonography or uroflowmetry and more sophisticated radiological or urological methods should be focused on those children with daytime wetting and clinical symptoms of voiding disturbances.

Child↗
PubMed1988

Cinoxacin vs trimethoprim--safety and efficacy in the prophylaxis of uncomplicated urinary tract infections.

This study reports the results of long-term (24 weeks) low-dose prophylaxis in 26 young female patients suffering from recurrent uncomplicated urinary tract infection (UTI). The patients were randomized in a double-blind manner to treatment with 100 mg trimethoprim (TMP, 12 patients) or 500 mg cinoxacin (CNO, 14 patients) at bedtime. The duration of prophylaxis in the TMP group was 2016 and in the CNO group 2352 days. Blood chemistry, haematological and urinary parameters were closely monitored during treatment and the latter were followed for a further 4-6 weeks. The prophylactic efficacy of the drugs was equal and significant (p less than 0.05). In the TMP group one recurrence and in the CNO group two recurrences occurred during treatment, two recurrences being observed in each group during the follow-up period of 4-6 weeks. Trimethoprim is well documented and widely used; cinoxacin provides a new alternative for long-term prophylaxis.

Adolescent↗