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Biomedical subjects

M Haarala

Publications and source records attributed to M Haarala.

11 recordsLinked to original sources

Differences in connective tissue gene expression between normally functioning, polycystic and post-menopausal ovaries.

Arrested follicular maturation is a characteristic feature of polycystic ovary syndrome (PCOS). Follicles mature in ovarian stroma composed of extracellular matrix (ECM). However, little is known of the expression of ECM genes in polycystic ovaries. The present study compares the expression levels of genes coding for collagens, matrix metalloproteinases (MMP), their inhibitors (TIMP) and cathepsins in polycystic ovaries using fertile and post-menopausal ovaries as controls. In northern analyses, the gene expression profiles of type I and III collagen of PCOS samples resembled those observed in normal follicular phase ovaries, while mRNA levels of proalpha1(IV) collagen and TIMP-3 mRNA were significantly lower in polycystic than control ovaries. During the normal menstrual cycle, an increase was observed in MMP-9 gene expression during the luteal phase. In post-menopausal ovaries, mRNA levels for type I, III and IV collagens and osteonectin were reduced, while the MMP, TIMP (excluding TIMP-3) and cathepsins did not reflect this metabolic down-regulation. Immunohistochemical staining for MMP-9 and TIMP-4 suggested differences between polycystic and normally functioning ovaries. These data demonstrate that normal ovarian functions are associated with changes in production and degradation of ECM. The alterations observed in the production and/or distribution of type IV collagen, TIMP-3 and TIMP-4 suggest involvement of basement membranes in the pathogenesis of PCOS.

Connective Tissue↗

Mutations of TP53 do not correlate with the sensitivity to paclitaxel--a study using 27 gynaecological cancer cell lines.

The correlation between inactivation of the TP53 gene through mutation or the presence of high-risk human papillomavirus (HPV) DNA and intrinsic paclitaxel sensitivity was studied in 27 gynaecological cancer cell lines. IC(50) values, as a measure of drug sensitivity, were determined using a 96-well clonogenic assay. TP53 mutations were investigated with polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct DNA sequencing. HPV status was studied with PCR using HPV consensus primers. TP53 mutations were found in 7/11 vulvar SCC cell lines. Only 2/9 endometrial and 1/7 ovarian cancer cell lines carried TP53 mutations. One vulvar and one endometrial cancer cell line were HPV-positive; both carrying HPV type-16 DNA. Thus, TP53 was functionally normal in 3/11 vulvar, 6/9 endometrial and 6/7 ovarian cancer cell lines. The IC(50) values for paclitaxel were 0.60-2.9, 0.49-2.3 and 0.40-3.4 nM in the vulvar, endometrial and ovarian cancer cell lines, respectively. No correlation could be demonstrated between inactivation of the TP53 gene and paclitaxel sensitivity in vitro; the cell lines were evaluated as one group or according to their anatomical origin or histology. Previous reports have given inconclusive results, partly due to the cell types used, i.e. normal, cancerous or transformed cells. Our results support the view that paclitaxel sensitivity of tumour-derived cancer cell lines is not related to the TP53 status.

Antineoplastic Agents, Phytogenic↗

Lower urinary tract symptoms in patients with Sjögren's syndrome and systemic lupus erythematosus.

Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) are autoimmune diseases which have many similarities with interstitial cystitis (IC), a urinary bladder disease with unknown etiology. This survey on the occurrence, severity and nature of lower urinary tract symptoms among patients suffering from SS or SLE showed that these patients have significantly more urinary complaints, especially irritative bladder symptoms, than age- and sex-matched controls. We studied 36 patients with SS, 85 patients with SLE and 121 controls. In these groups, 25%, 29% and 66%, respectively, were free of urinary symptoms. The prevalences of mild symptoms were 61%, 62% and 27%, and severe symptoms 14%, 9% and 7% in the respective groups. SS and SLE patients with urinary complaints reported mostly urinary frequency (27% and 62%) and suprapubic pain (36% and 34%). The most common symptom in the control group was stress urinary incontinence. The frequency of lower urinary tract problems in patients with SS and SLE supports the concept that autoimmune disorders also have bladder affections.

Adult↗

The role of Borrelia burgdorferi in interstitial cystitis.

BACKGROUND/AIMS: Borrelia burgdorferi spirochete has been found both in bladder biopsies and the urine of patients with Lyme disease (LD) as well as in experimental animals. The urological symptoms in borreliosis resemble those of interstitial cystitis (IC): frequency, urgency and nocturia. The aim of this studies is to find the role of B. burgdorferi in interstitial cystitis. METHODS: We studied antibodies against B. burgdorferi from serum samples of 50 IC patients with two separate EIA tests. Patients with positive serology in both tests underwent cystoscopy and a bladder biopsy was taken. The presence of borrelia DNA was studied with borrelia-specific polymerase chain reaction (PCR), and with universal bacterial PCR. RESULTS: IgM class antibodies to B. burgdorferi were not found, but IgG antibodies were found in four samples (8%). This was higher than in the control material (2%). One patient's sample was strongly positive, whereas three samples were weakly positive. Bladder biopsies taken from the 4 patients were negative for borrelia DNA in both PCR tests. None of the seropositive patients had any symptoms consistent with LD. CONCLUSION: These results indicate that persistent infection of B. burgdorferi has no role in the etiology of IC. On the other hand a connection with a past borrelia infection and IC is not excluded.

Adult↗

Urinary bacterial flora of women with urethral syndrome and interstitial cystitis.

The aerobic and anaerobic bacterial flora in the first voided and in the midstream urine of healthy females (n = 5) and female patients with either urethral syndrome (US) (n = 5) or interstitial cystitis (IC) (n = 14) were studied. Bacteria were grown on media enabling isolation of fastidious and aerobic as well as obligatory anaerobic species. In healthy females only gram-positive rods were found whereas US patients also harbored streptococci. Patients with IC presented also with Enterobacteriae and anaerobic bacteria. Five IC patients with severe symptoms were treated with metronidazole; 2 out of 3 patients with anaerobic bacteria in the pretreatment specimens had no anaerobes after metronidazole therapy and in 1 patient streptococci disappeared after the therapy. One patient with severe symptoms and Bacteroides fragilis in the midstream urine became symptom-free after 2 weeks of metronidazole treatment. Although there is uncertainty whether the US and IC are not related to an infectious etiology, the bacterial flora in urethral and in midstream urine in these conditions differs considerably from that of healthy females.

Adolescent↗

Comparison of a 10-mg controlled release oxybutynin tablet with a 5-mg oxybutynin tablet in urge incontinent patients.

Oxybutynin has long been used for the treatment of patients with detrusor overactivity and urinary urge incontinence. The short half-life of oxybutynin administered as a conventional tablet formulation or syrup requires 2-3 times daily dosage to be effective. A new controlled release (CR) tablet for once-daily administration has been developed. The efficacy and tolerability of this new controlled release tablet was compared to that of a 5-mg conventional oxybutynin tablet administered twice daily. Seventeen female incontinent patients were studied in a double-dummy crossover trial. Efficacy and tolerability were assessed by using a voiding diary, pad-weighing test, visual-analogue scale (VAS), and questionnaire. Adverse events were recorded spontaneously on a questionnaire by the patients themselves throughout the study. Serum concentrations of oxybutynin and its active metabolite N-desethyloxybutynin were studied after both a single dose and multiple dosage. There was no difference in efficacy between the two formulations. Depending on the parameters tested, the change from baseline values in a positive direction ranged from 15 to 53%. The incidence of adverse events was similar with both formulations. Oxybutynin or its metabolite showed no cumulation during the multiple dosage with a 10-mg CR tablet. The controlled release tablet formulation is as effective and as well-tolerated as the conventional one, but has the advantage of only once-a-day dosage, enhancing treatment compliance.

Adult↗

Endoscopic colposuspension with simplified extraperitoneal approach.

The retropubic colposuspension (Burch procedure) has been proven an effective treatment for female genuine stress urinary incontinence. During this decade, laparoscopic approach has gained access in continence surgery also. Endoscopic colposuspension can be performed either extraperitoneally or transperitoneally. If there is no need for intra-abdominal procedures the extraperitoneal approach for colposuspension is feasible. Generally a balloon dissection is used to develop the extraperitoneal space, but here we present a modified technique where no balloon is needed. This modification is easy to perform, quicker and decreases the costs of the procedure compared to transperitoneal approach. We also summarize the results of our first 46 patients, 24 of which were operated extraperitoneally and 22 by transperitoneal approach with concomitant pelvic surgery.

Adult↗

Viruses and interstitial cystitis: adenovirus genomes cannot be demonstrated in urinary bladder biopsies.

Microbes may be involved in the pathogenesis of interstitial cystitis (IC). Adenoviruses and BK virus (BKV) can infect epithelial cells in urinary bladder and they are causative agents for hemorrhagic cystitis. We therefore studied the presence of adenovirus and BKV genomes in urinary bladder tissue specimens of patients with IC using polymerase chain reaction (PCR) and in situ hybridization (ISH). Controls were specimens from cases with transitional cell carcinoma of the bladder. Nucleic acids were extracted from paraffin sections of the bladder tissue for PCR. Primers detecting all adenovirus types were used. In situ hybridization was carried out for the paraffin sections using digoxigenin-labeled DNA probes for adenovirus and BKV. The adenovirus DNA PCR was able to detect one to two infected cells/specimen. All the seven IC cases studied and six controls were negative for adenovirus DNA by PCR and ISH. The ISH test for BKV genomes was also considered negative in IC cases and controls. The specimens which were negative in PCR tests yielded a signal with beta-globin primers, thus being amplifiable. We conclude that adenovirus and BKV do not play a major pathogenetic role in interstitial cystitis.

Adenoviridae↗

Absence of bacterial DNA in the bladder of patients with interstitial cystitis.

PURPOSE: Although bacterial infection has been long considered a possible cause of interstitial cystitis (IC), no definitive proof for or against this hypothesis has been presented so far. We have used 16S rDNA bacterial polymerase chain reaction to study bladder biopsies and sterile urine samples from patients suffering from IC. This method is sensitive and detects all known eubacteria. MATERIALS AND METHODS: Bladder biopsies and sterile urine samples obtained by transabdominal puncture were studied from 11 patients with IC. As controls we studied 4 patients with other urological problems leading to partly similar symptoms and 5 healthy individuals. RESULTS: All samples from the IC patients were negative. One positive sample was obtained from a woman with a history of urinary tract infections who suffered from nonIC ulcerative cystitis. Her sterile urine sample yielded Lactobacillus acidophilus. CONCLUSION: These results indicate that an ongoing bacterial infection is not the cause of interstitial cystitis.

Cystitis, Interstitial↗

Sutureless endoscopic colposuspension with fibrin sealant.

Endoscopic colposuspension by using fibrin sealant as a substitute for sutures was performed in 17 women suffering from urodynamically verified type I-II stress urinary incontinence. Two-puncture technique was used with a 10-mm trocar for optics and a 5-mm trocar for instrumentation. The two-component fibrin sealant, Tisseel (1 ml) by using special applicator device, Duploject was applied with tube on both sides of the urethrovesical area. After that the urethrovesical junction was pressed for 5 min against the retropubic periost by the surgeon's index and middle fingers placed in the vagina. The average duration of the procedure was 20 min, excluding learning curve for the first two cases. The indwelling catheter and vaginal packing were removed and all patients discharged on the first postoperative day. All but two patients experienced excellent immediate response. Of the 12 patients followed > 6 months, 10 patients were completely dry and two were markedly improved. In our experience, laparoscopic colposuspension with fibrin sealant appears to be a promising new approach in correcting stress incontinence in women.

Adult↗

Urinary tract fistulas following abdominal hysterectomy.

Sixteen patients with urinary tract fistulas (14 vesicovaginal and two ureterovaginal) following simple abdominal hysterectomy were treated over a period of 17 years. Most vesicovaginal fistulas were treated by a transvesical technique, which proved to be a comfortable and successful method in our hands. Closure of the fistula followed usually more than four weeks after diagnosis. Earlier repair, which has been forwarded as an alternative therapy, might give equally good results and would save the patient from the severe hygienic problem of continuous urinary leakage. Conservative treatment with an indwelling urinary catheter led to spontaneous closure of the fistula in one patient. Two ureterovaginal fistulas were corrected by an anti-reflux ureteroneocystostomy.

Catheters, Indwelling↗