| 1. |
- Dlugosz, Aldona, et al.
(författare)
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Chlamydia trachomatis antigens in enteroendocrine cells and macrophages of the small bowel in patients with severe irritable bowel syndrome
- 2010
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Ingår i: BMC Gastroenterology. - 1471-230X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Inflammation and immune activation have repeatedly been suggested as pathogentic factors in irritable bowel syndrome (IBS). The driving force for immune activation in IBS remains unknown. The aim of our study was to find out if the obligate intracellular pathogen Chlamydia could be involved in the pathogenesis of IBS. Methods: We studied 65 patients (61 females) with IBS and 42 (29 females) healthy controls in which IBS had been excluded. Full thickness biopsies from the jejunum and mucosa biopsies from the duodenum and the jejunum were stained with a monoclonal antibody to Chlamydia lipopolysaccharide (LPS) and species-specific monoclonal antibodies to C. trachomatis and C. pneumoniae. We used polyclonal antibodies to chromogranin A, CD68, CD11c, and CD117 to identify enteroendocrine cells, macrophages, dendritic, and mast cells, respectively. Results: Chlamydia LPS was present in 89% of patients with IBS, but in only 14% of healthy controls (p < 0.001) and 79% of LPS-positive biopsies were also positive for C. trachomatis major outer membrane protein (MOMP). Staining for C. pneumoniae was negative in both patients and controls. Chlamydia LPS was detected in enteroendocrine cells of the mucosa in 90% of positive biopsies and in subepithelial macrophages in 69% of biopsies. Biopsies taken at different time points in 19 patients revealed persistence of Chlamydia LPS up to 11 years. The odds ratio for the association of Chlamydia LPS with presence of IBS (43.1; 95% CI: 13.2-140.7) is much higher than any previously described pathogenetic marker in IBS. Conclusions: We found C. trachomatis antigens in enteroendocrine cells and macrophages in the small bowel mucosa of patients with IBS. Further studies are required to clarify if the presence of such antigens has a role in the pathogenesis of IBS.
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| 2. |
- Tornblom, M, et al.
(författare)
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Diagnostic value of percent free prostate-specific antigen: retrospective analysis of a population-based screening study with emphasis on men with PSA levels less than 3.0 ng/mL
- 1999
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Ingår i: Urology. - 1527-9995 .- 0090-4295. ; 53:5, s. 945-950
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To retrospectively investigate the use of percent free prostate-specific antigen (PSA) compared with total PSA in serum as predictor of prostate cancer in men selected randomly from the general population who underwent biopsy on the basis of abnormal findings on digital rectal examination (DRE) or transrectal ultrasound (TRUS) and/or serum PSA levels greater than 10 ng/mL. METHODS: A single intervention, population-based screening study was undertaken in 1988 and 1989. Of the 2400 men aged 55 to 70 years invited to participate, 1782 men responded and were examined with DRE, TRUS, and PSA testing (Tandem-Hybritech). In 1995, frozen serum samples from 1748 men were analyzed for percent free PSA (Prostatus, Wallac OY). Five-year follow-up data on new cancers in the screened population were obtained from the Swedish Cancer Registry (SCR). RESULTS: Of the 1748 men, 367 underwent TRUS-guided biopsies because of abnormal findings on either DRE or TRUS or serum PSA levels of greater than 10 ng/mL. This resulted in the diagnosis of 64 cases of prostate cancer (3.7%). PSA levels of 3.0 ng/mL or greater were found in 55 (86%) of 64 cancer cases and in 399 (24%) of the 1684 benign cases. Among the 1294 men with PSA less than 3.0 ng/mL, 9 prostate cancers were diagnosed (14% of all prostate cancers). All 9 patients with cancer and with PSA less than 3.0 ng/mL had a percent free PSA of 18% or less. In the group of 1109 patients with PSA less than 3.0 ng/mL and a percent free PSA greater than 18%, 159 biopsies were performed because of abnormal DRE or TRUS. However, no prostate cancer was diagnosed in this category of patients. Five years after the screening intervention, 7 more cases of prostate cancer were clinically diagnosed in the screened population according to the SCR. CONCLUSIONS: The combination of PSA levels less than 3.0 ng/mL and percent free PSA greater than 18% defines a large part of the population at a very low risk of cancer of the prostate both at the time of screening and during the following 5 years. Men in this group may be spared DRE, and longer screening intervals may be considered. However, the risk of having prostate cancer is not negligible in men with PSA less than 3.0 ng/mL and percent free PSA of 18% or less. The results of this study indicate that biopsy should be recommended to men fulfilling these criteria, although these results should be confirmed in larger prospective studies because of the limited number of patients with prostate cancer in the present series.
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| 3. |
- Tornblom, M, et al.
(författare)
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Lead time associated with screening for prostate cancer
- 2004
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 108:1, s. 122-129
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Tidskriftsartikel (refereegranskat)abstract
- Screening serum levels of prostate-specific antigen (PSA) is now a major strategy for early detection of prostate cancer (PC). Quantification of the lead time thus obtained is important both for understanding the development of PC and for evaluating the advantages and disadvantages of widespread screening. In our study, 1,233 randomly selected men living in Stockholm in 1988 were invited to participate in an early detection (ED) program, in which suspicious findings provided by digital rectal examination (DRE), transrectal ultrasonography (TRUS) and/or a PSA value greater than or equal to10.0 ng/mL were followed up by biopsy. The cumulative incidence (Kaplan-Meier) of PC in the 946 participants (ED) during 12 years of follow-up was compared to that of an age-matched, randomly selected reference population (RP) of 657 men for whom PSA values (from frozen serum samples) could also be obtained. The PC incidence in men in the RP with PSA values >3.0 ng/mL reached the corresponding level for the ED group after 10.6 years (the "catch-up" point). After 12 years of follow-up, the estimated median lead time for men with PSA values in this interval was 4.5 years in the ED population, compared to 7.8 years in the RP. With 20 years of follow-up, the estimated median lead time of the RP was enhanced to 10.7 years. The lead time in connection with PC was influenced by the initial PSA level (although with large variations), length of follow-up and sensitivity of the ED procedure employed. The ED program described here was not associated with major overdetection.
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| 4. |
- Tornblom, M, et al.
(författare)
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Variation in percentage-free prostate-specific antigen (PSA) with prostate volume, age and total PSA level
- 2001
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Ingår i: BJU International. - : Wiley. - 1464-4096. ; 87:7, s. 638-642
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To examine the correlation between prostate volume, patient age and total prostate-specific antigen (tPSA) with the percentage-free PSA (f/tPSA) in a population-based cohort of men with no prostate cancer and with a tPSA of < 10.0 ng/mL. SUBJECTS AND METHODS: Men who in 1988-1989, after randomized selection in the general population, participated in a population-based screening study for prostate cancer, were investigated. In all, 1622 of the men (aged 55-70 years) were considered free from prostate cancer and had a tPSA level of < 10.0 ng/mL. The f/tPSA and tPSA were determined in frozen sera from each individual, and related to prostate volume and age measured at the time of the study. The entire population was investigated, as were four subpopulations based on tPSA levels (< 2.0, 2.0-3.9, 4.0-6.9 and 7.0-9.9 ng/mL). Statistical calculations included multiple regression and correlation analysis. RESULTS: The f/tPSA level varied with prostate volume and age, but the decisive factor for this variation was the tPSA level. The closest correlation was in the tPSA interval 7.0-9.9 ng/mL, where volume and age together explained 47% of the variation in f/tPSA. Also, for men with tPSA levels in each of the intervals 2.0-3.9, 4.0-6.9 and 7.0-9.9 ng/mL, the f/tPSA increased with higher prostate volumes and age. In men with tPSA levels of < 2.0 ng/mL the f/tPSA was not affected by variations in prostate volume or age. CONCLUSION: The variation in f/tPSA with prostate volume, age and tPSA is highly dependent on the tPSA level. Volume and age in the tPSA interval 7.0-9.9 ng/mL can explain almost half the variation in f/tPSA, whereas this influence is insignificant in men with a tPSA of < 2.0 ng/mL.
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| 5. |
- Tornblom-Paulander, Sara, et al.
(författare)
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Novel topical formulation of lidocaine provides significant pain relief for intrauterine device insertion: pharmacokinetic evaluation and randomized placebo-controlled trial
- 2015
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Ingår i: Fertility and Sterility. - : Elsevier. - 0015-0282 .- 1556-5653. ; 103:2, s. 422-427
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the pharmacokinetics, safety, and analgesic efficacy of a novel topical formulation of lidocaine at insertion of an intrauterine device (IUD). Design: Randomized controlled trial; phase-I and phase-II studies. Setting: University and public hospitals. Patient(s): Women aged greater than= 18 years who wanted to receive an IUD. Four women were parous in phase I; all in phase II were nulliparous. Intervention(s): A single, 8.5-mL dose of lidocaine formulation (SHACT) was administered (to the portio, cervix, and uterus) with a specially designed applicator. Main Outcome Measure(s): The phase-I study (single-arm) was designed for pharmacokinetic assessment; the phase-II study (randomized) was intended for investigation of efficacy and safety. Result(s): From the phase-I study (15 participants), mean pharmacokinetic values were: maximum plasma concentration: 351 +/- 205 ng/mL; time taken to reach maximum concentration: 68 +/- 41 minutes; and area under the concentration-time curve from 0 to 180 minutes: 717 +/- 421 ng*h/mL. Pain relief was observed with lidocaine vs. placebo in the phase-II study (218 women, randomized). Mean visual analog scale score for maximum pain during the first 10 minutes after IUD insertion was 36% lower with lidocaine than with placebo (28.3 +/- 24.6 vs. 44.2 +/- 26.0). Pain intensity was also significantly lower in the lidocaine group at 30 minutes. On average, 3 of 4 patients will have less pain with lidocaine than with placebo. Adverse events were similar in the placebo and lidocaine groups. No serious adverse events were reported. Conclusion(s): Lidocaine provides pain relief lasting for 30-60 minutes for women undergoing IUD insertion, without any safety concerns. Further studies of this lidocaine formulation, for IUD insertion and other clinical applications, are planned. (C) 2015 by American Society for Reproductive Medicine.
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| 6. |
- Veress, Bela, et al.
(författare)
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Intestinal lymphocytic epithelioganglionitis: a unique combination of inflammation in bowel dysmotility: a histopathological and immunohistochemical analysis of 28 cases
- 2009
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Ingår i: Histopathology. - : Wiley. - 0309-0167 .- 1365-2559. ; 54:5, s. 539-549
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal lymphocytic epithelioganglionitis: a unique combination of inflammation in bowel dysmotility: a histopathological and immunohistochemical analysis of 28 cases Visceral inflammatory neuropathies are enteric disorders underlying various forms of bowel dysmotility. The aim was to analyse the microscopic characteristics of a unique combination of intraepithelial lymphocytosis and myenteric ganglioneuritis. Paraffin sections of full-thickness proximal jejunal biopsy specimens from 28 patients, with proven disorders of gastrointestinal motility, were analysed following conventional and immunohistochemical staining. Serial transversal and tangential sectioning visualized large myenteric plexus areas. Between 1993 and 2005, 28 patients with inflammatory neuropathy (25 female and three male) showed this combination of lymphocytic infiltration. Two of the patients also had coeliac disease. The mean number of intraepithelial CD3+ lymphocytes was 36 per 100 epithelial cells (range 27-68; upper normal limit 25 lymphocytes). There was myenteric ganglionitis of variable severity (mean 4.6 myenteric lymphocytes per ganglion; upper normal limit two lymphocytes) with cytotoxic T-cell predominance. Myenteric neurons showed signs of degeneration and an abnormal immunohistological pattern. Hyperplasia and hypertrophy of Cajal cells were observed. The longitudinal muscle layer was thickened in many cases. A subset of patients with gastrointestinal motility disorders exhibit the combination of intraepithelial lymphocytosis and myenteric ganglionitis in full thickness biopsy specimens of the small bowel. We suggest calling this entity 'intestinal lymphocytic epithelioganglionitis'.
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