Serum parathyroid hormone and active vitamin D in chronic periodontitis.

OBJECTIVES: To study the association between periodontitis and serum parathyroid hormone (PTH) and the response of PTH to periodontal therapy in type 1 diabetic patients (T1DM). We also investigated the PTH-1,25(OH)2 D axis in the T1DM group. METHODS: Periodontal health status was recorded in 54 periodontitis patients and 30 periodontally healthy controls (case-control data). Data were also collected from patients with type 1 diabetes mellitus at the baseline (n = 76) and after periodontal therapy (intervention data) (n = 53). RESULTS: Periodontitis was not associated with serum PTH in the case-control data or at the baseline of the intervention data. A post-therapy increase in serum PTH was found in 61% of the T1DM patients; in patients with moderate or severe periodontitis (n = 26) the average increase was 0.6 pmol/l (p = 0.016) and in patients with no or mild periodontitis (n = 27) 0.2 pmol/l (p = 0.250). In 47% of the T1DM patients, an increase in PTH was associated with an increase in serum 1,25(OH)2 D. CONCLUSION: An association between serum PTH and periodontal infection was found only after periodontal therapy in T1DM patients. This post-treatment response in serum PTH may partly explain the previously reported increase in serum 1,25(OH)2 D.

Interleukin 6 gene polymorphism -174 is associated with the diffuse type gastric carcinoma.

The aim of this study was to assess the significance of the interleukin 6 gene polymorphism -174 in gastric cancer risk. The interleukin 6 -174 G/C (rs1800795) gene polymorphisms was analyzed in gastric cancer, peptic ulcer, and nonulcer dyspepsia patients and in healthy control subjects and the data were correlated with the histopathological features of the patients' biopsies. The interleukin 6 -174 GG and GC genotypes have been previously associated with high interleukin 6 serum levels. We discovered that the interleukin 6 -174 GG and GC genotypes are associated with an increased risk of the diffuse histologic subtype of gastric carcinomas (OR: 6.809, P = 0.034), but absent in the intestinal type carcinomas (OR: 1.109, P = 0.908). No significant associations with peptic ulcer, gastric atrophy, or intestinal metaplasia were seen. Our results demonstrate that the interleukin 6 -174 GG and GC genotypes increase the risk of the diffuse type gastric carcinoma, but not the intestinal type gastric carcinoma or its precursor conditions, including atrophy or intestinal metaplasia. Thus, interleukin 6 seems to be an important carcinogenetic factor in the diffuse type gastric adenocarcinoma and its carcinogenetic effect could be noninflammatory.

Serum osteoprotegerin and periodontal destruction in subjects with type 1 diabetes mellitus.

AIM: Besides their role in bone metabolism, receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) are also known to be associated with inflammation. We explored associations between the extent/severity of periodontitis and circulating levels of sRANKL and OPG and their ratio using a cross-sectional study design. SUBJECTS & METHODS: The extent of periodontal inflammation and tissue destruction and the serum levels of sRANKL (pg/ml) and OPG (pg/ml) were determined in 80 subjects with type 1 diabetes mellitus (T1DM). Plaque-, age-, gender-, smoking-, HbA1c- and body mass index-adjusted associations between periodontal parameters and serum sRANKL, OPG and their ratio were studied using multiple linear regression analysis. RESULTS: Adjusted regression analyses of all the subjects indicated a significant positive association between AL ≥ 4 mm and severity of periodontitis and the level of serum OPG. A major drop in the strength and statistical significance of the above association was observed when the analyses included only non-smokers. Serum sRANKL level and sRANKL/OPG ratio were not associated with periodontitis. CONCLUSION: Our observations suggest that serum OPG may be an indicator of periodontal tissue destruction in T1DM.

Serum and tissue CD23, IL-15, and FasL in cow's-milk protein-sensitive enteropathy and in coeliac disease.

OBJECTIVES: The aim of the study was to explore pathogenesis and find new serum markers for cow's-milk-sensitive enteropathy (CMSE) and coeliac disease (CD). We assessed the intestinal expression and serum concentration of CD23, IL-15, and FasL. We hypothesised that the serum levels of CD23, a protein expressed in the lymphoid follicles, would be associated with lymphonodular hyperplasia (LNH), a feature characteristic of CMSE. We also presumed that interleukin (IL)-15 and FasL, functionally connected with proliferation and apoptosis of the intraepithelial lymphocytes (IELs), would relate with the increased numbers of IELs present in both CMSE and CD. METHODS: Twenty-three children with CMSE, 20 with untreated CD, and 14 controls were studied for CD3, α/ß- and γ/δ-expressing IELs, and for duodenal and ileal expression of CD23, FasL, and IL-15 by immunohistochemistry, and for serum concentration of sCD23, sFasL, and sIL-15 by enzyme-linked immunosorbent assay. RESULTS: There was a trend for increase in sCD23 serum levels in untreated CMSE and in CD (P = 0.074; P = 0.077). CD23 was expressed in the mucosal germinal centres, but sCD23 was not related to presence of LNH. In CMSE, there was a trend for increase in serum sFasL (P = 0.07) and high levels associated with LNH (P = 0.025) and correlated with the IEL numbers (P < 0.05). Mucosal high endothelial venules adjacent to lymphoid follicles showed an intensive FasL expression. CONCLUSIONS: Serum sCD23 shows a trend of increment in CMSE and CD, and in the latter, sCD23 level may provide information about the severity of villous atrophy. In CMSE, high serum sFasL indicates both LNH and an increase of IELs, suggesting importance of FasL-mediated mechanisms in the pathogenesis of these features characteristic of CMSE. Further studies are necessary to evaluate whether intensive FasL expression in mucosal high endothelial venules presents a regulatory element in mucosal immunity.

Histopathology of gastric erosions. Association with etiological factors and chronicity.

BACKGROUND: The histopathologic characteristics of the antral erosions, and a comparison with samples systematically collected from the background antral mucosa, have not been studied previously. Similarly, unknown is the association of these features with suspected etiological factors and chronicity of erosion. MATERIAL AND METHODS: We studied 117 patients with gastric erosions in the absence of peptic ulcer disease. With 28 patients available for a follow-up 19 years later, sites of erosions and background mucosa were biopsied and histopathology of both independently assessed at both visits. Helicobacter pylori status was examined from the biopsies taken in the initial and follow-up gastroscopies. Only subjects originally displaying antral erosions were included. The presence of Herpes simplex virus (HSV) antibodies was analyzed and use of nonsteroidal anti-inflammatory drug (NSAID) was inquired. RESULTS: Initially, the inflammation was more active in the region of erosions than elsewhere in antral mucosa. More active inflammation in the erosion was associated with HSV seropositivity, Helicobacter pylori infection, and the recent use of NSAIDs. In the follow-up visit, antral erosions were present in 38% (3/8) of Helicobacter pylori negatives and in 35% (7/20) of positives (p = ns). The Helicobacter pylori positive subjects with chronic or recurrent erosions had initially higher scores of neutrophils compared to subjects with nonrecurrent or nonchronic erosions (2.7 ± 0.5 vs 1.2 ± 1.0; p = .002). CONCLUSIONS: Focally enhanced inflammation is characteristic for gastric erosions. This focal inflammation was associated with HSV seropositivity or NSAID use suggesting that such inflammation may be important in the pathogenesis of gastric antral erosions. Highly active inflammation in the erosions associates with their chronicity.

Serum high-density lipoprotein cholesterol level associated with the extent of periodontal inflammation in type 1 diabetic subjects.

AIM: High-density lipoprotein (HDL) cholesterol is known for its anti-inflammatory and antioxidant activities in protection against cardiovascular diseases. We investigated whether a protective association also exists between serum HDL and periodontal inflammation in type 1 diabetic subjects (T1DM). METHODS: Plaque and periodontal inflammation (bleeding and PD ≥ 4 mm) were examined in 80 subjects with T1DM. The serum levels of glycosylated haemoglobin (HbA1c, %) and HDL (mmol/l) were determined. Adjusted associations between inflammation and serum HDL were analysed using linear regression analysis. To study the linearity of the association, the subjects were categorized into HDL tertiles (I-III). RESULTS: A statistically significant negative association was observed between serum HDL level and the extent of bleeding and PD ≥ 4 mm. Subjects in HDL tertiles II and III (high HDL) presented significantly fewer inflamed sites when compared with the subjects in tertile I (low HDL), whereas no significant difference in the number of inflamed sites was observed between tertiles II and III. CONCLUSIONS: Based on the finding of a negative association between serum HDL and periodontal inflammation, HDL may be considered a marker of susceptibility to periodontal inflammation. A longitudinal study is needed to verify possible causal relationship between serum HDL and inflammation.

Serum interleukin-6 may modulate periodontal inflammation in type 1 diabetic subjects.

AIMS: To evaluate the associations between serum inflammatory biomarkers and periodontal inflammation in subjects with type 1 diabetes mellitus (T1DM). Our hypothesis was that local host responses may be modulated by the serum inflammatory mediators. MATERIAL AND METHODS: Plaque, bleeding on probing and probing pocket depth (PD) were examined in 80 T1DM subjects at the baseline and in 58 subjects 8 weeks after periodontal therapy. The levels of glycosylated haemoglobin, serum interleukin (IL)-6, ultrasensitive C-reactive protein and the lipid profile were measured at the baseline and after therapy. Stratification of the sample separately by smoking and body mass index (BMI) was performed. Adjusted associations between the levels of systemic biomarkers and periodontal parameters were studied using multiple regression models. RESULTS: The level of serum IL-6 was associated with the extent of bleeding and PD≥4 mm at the baseline in non-smokers and in subjects with BMI≤26 kg/m(2). These associations were also evident after periodontal therapy. Subjects with a high after-therapy IL-6 level presented poorer periodontal healing than those with a low level. CONCLUSIONS: The observed associations may be considered to be suggestive of a modulatory effect of IL-6 on host responses in T1DM subjects.

Serum levels of interleukin-10 and tumour necrosis factor-α in chronic periodontitis.

AIMS: To investigate, using a cross-sectional study design, whether the extent of periodontal inflammation associates with the serum levels of cytokine interleukin (IL)-10 and tumour necrosis factor (TNF)-α and their ratio. MATERIAL AND METHODS: The study group consisted of 61 subjects with chronic periodontitis and 30 control subjects with minimally inflamed periodontal tissues. Probing pocket depth (PD), bleeding on probing (BOP) and periodontal attachment level (AL) were measured. The serum IL-10 (pg/ml) and TNF-α (U/l) levels were analysed using enzyme-linked immunosorbent assays. After categorization of the subjects, associations between serum IL-10 and TNF-α levels and the extent of periodontal inflammation were studied using linear regression models adjusted for age, gender, body mass index and smoking. RESULTS: A negative, partly dose-dependent association existed between the extent of BOP, PD ≥ 4 mm and AL ≥ 4 mm and serum IL-10 level. The subjects in the periodontitis group presented significantly higher serum TNF-α levels and their TNF-α/IL-10 ratio was approximately threefold when compared with the ratio in the control group. CONCLUSIONS: The significantly higher serum TNF-α/IL-10 ratio in the subjects with chronic periodontitis when compared with the ratio in the controls is indicative of a stronger systemic pro-inflammatory state in chronic periodontitis.

IL-6(-174) genotype associated with the extent of periodontal disease in type 1 diabetic subjects.

AIM: The aim of this study was to investigate whether genetic polymorphism in certain cytokine and receptor molecule genes and diabetic status associate with the extent of periodontal disease in type 1 diabetes mellitus (DM). MATERIAL AND METHODS: Eighty patients with type 1 DM participated. Visible plaque, bleeding on probing (BOP), probing pocket depth (PD) and attachment level (AL) were examined clinically and glycosylated haemoglobin (HbA1c) levels were used to assess the glycemic control of DM. CD-14, IL-6, TNF-alpha, IL-10, IL-1alpha, IL-1beta and TLR-4 gene polymorphisms were studied using the polymerase chain reaction (PCR). RESULTS: The 3-year HbA1c was good (<7.5%) in 16%, acceptable (7.5-8.5%) in 36% and poor (>8.5%) in 48% of the subjects. IL-6(-174) genotype and 3-year GHbA1c associated significantly with BOP and PD>or=4 mm, subjects with the GG genotype of the IL-6(-174) exhibiting more severe periodontal disease than those with the GC/CC genotype. After stratification by IL-6 genotype, associations between the extent of periodontal disease and 3-year HbA1c levels remained significant in subjects carrying the GC/CC but not the GG genotype. CONCLUSIONS: In addition to the HbA1c level, the IL-6(-174) genotype is a significant susceptibility factor for periodontal disease among type 1 diabetics.

Xylitol-supplemented nutrition enhances bacterial killing and prolongs survival of rats in experimental pneumococcal sepsis.

BACKGROUND: Xylitol has antiadhesive effects on Streptococcus pneumoniae and inhibits its growth, and has also been found to be effective in preventing acute otitis media and has been used in intensive care as a valuable source of energy. RESULTS: We evaluated the oxidative burst of neutrophils in rats fed with and without xylitol. The mean increase in the percentage of activated neutrophils from the baseline was higher in the xylitol-exposed group than in the control group (58.1% vs 51.4%, P = 0.03 for the difference) and the mean induced increase in the median strength of the burst per neutrophil was similarly higher in the xylitol group (159.6 vs 140.3, P = 0.04). In two pneumococcal sepsis experiments rats were fed either a basal powder diet (control group) or the same diet supplemented with 10% or 20% xylitol and infected with an intraperitoneal inoculation of S. pneumoniae after two weeks. The mean survival time was 48 hours in the xylitol groups and 34 hours in the control groups (P < 0.001 in log rank test). CONCLUSION: Xylitol has beneficial effects on both the oxidative killing of bacteria in neutrophilic leucocytes and on the survival of rats with experimental pneumococcal sepsis.

Cost analysis and health-related quality of life of home and self-care satellite haemodialysis.

BACKGROUND: Home haemodialysis (HHD) and self-care satellite dialyses (SHD) have been suggested to offer significant benefits over conventional in-centre haemodialysis. However, little is known about differences between these two modalities. The purpose of the study was to analyse costs and health-related quality of life (HRQoL) of HHD and SHD. METHODS: On 15 October 2004, a total of 65 patients attended self-care haemodialysis in the area. Of those patients, 33 were on HHD and 32 on SHD. Cost data were collected from those study patients who were on dialysis the whole calendar year 2004 (23/33 HHD and 28/32 SHD patients). HRQoL was measured by the generic 15D instrument. The questionnaire was administered to all the study patients. A total of 23/33 of HHD and 24/32 of SHD patients returned the questionnaire. RESULTS: Direct medical costs of dialysis and hospital treatment were higher in HHD (31 834 +/- 6046 EUR/year, mean +/- SD) than in SHD (27 528 +/- 4325), P < 0.005. By contrast, travel costs were lower in HHD (426 +/- 743 EUR/year) than in SHD (5228 +/- 4236), P < 0.001. Costs of pharmaceuticals did not differ significantly. There was no significant difference in the total costs between HHD and SHD (38 477 +/- 7685 and 39 781 +/- 10 226 EUR/year), P = not significant. There were no significant differences in the total 15D score or in the 15 dimensions of the 15D instrument between home and satellite patients. CONCLUSIONS: HHD and SHD are, from the patient's perspective, equally effective in providing health. Although there were significant differences in the distribution of costs (which needs to be taken into account when evaluating different treatment strategies), total costs were similar. However, in the HHD setting, patients had on average more and longer sessions. Patient preference should be the main decisive factor when choosing between home or satellite haemodialysis.

Human leucocyte antigen and TNFalpha polymorphism association in microscopic colitis.

OBJECTIVES: Coeliac disease (CD) is common in patients with microscopic colitis (MC). The human leucocyte antigen (HLA)-DR3-DQ2 haplotype is strongly associated with CD, and there is evidence for an association with MC. We analysed the genetic background of MC by assessing the haplotypes of HLA-DR3-DQ2 and HLA-DR4-DQ8. In addition, TNFalpha gene polymorphism (-308) associated with susceptibility to several autoimmune diseases was studied. METHODS: Eighty patients with MC including 29 with collagenous colitis (CC) and 51 with lymphocytic colitis (LC) were typed for HLA-DR3-DQ2, and HLA-DR4-DQ8 molecule encoding genes using either an allele-specific PCR, or hybridization with sequence-specific oligonucleotides. Duodenal biopsies (N=78) confirmed the diagnosis of CD in 15 (18.8%) patients. TNFalpha(308) alleles were analyzed in 78 patients with MC (27 with CC and 51 with LC). A control group of 3627 patients was used in the HLA study and 178 patients in the TNFalpha study. RESULTS: HLA-DR3-DQ2 haplotype was more frequent in patients with MC (43.8%) including both subgroups (LC, 44.8%; CC, 43.1%; P<0.001), and MC with CD (86.7%; P<0.001) and without CD (33.3%; P=0.003), compared with the controls (18.1%). Similarly, the TNF2 carrier rate was higher in MC (46.2%; P<0.001) including both CC (44.4%; P=0.031) and LC (47.1%; P=0.001), and both MC patients with CD (66.7%; P=0.001) and without CD (39.3%; P=0.019), compared with the controls (23%). CONCLUSION: Both CC and LC are associated with the HLA-DR3-DQ2 haplotype and with TNF2 allele carriage. These associations are present also in MC patients without CD. The shared predisposing HLA-DR3-DQ2 haplotype and the high prevalence of CD in patients with MC suggest an epidemiological overlap, and probably some similarities in the pathogenesis of CD and MC.

Elispot Igra With Purified Protein Derivative Stimulation For Diagnosing Nontuberculous Mycobacterial Cervical Lympadenitis.

Childhood cervical lymphadenitis caused by nontuberculous mycobacteria is a diagnostic challenge for the clinician. We present a new promising diagnostic method for childhood nontuberculous mycobacterial lymphadenitis. The modified T-SPOT.TB test with purified protein derivative as an additional antigen is noninvasive with estimated sensitivity and specificity of 1.00 and 0.81, respectively.

Combined Expression of IFN-γ, IL-17, and IL-4 mRNA by Recall PBMCs Moderately Discriminates Active Tuberculosis from Latent Mycobacterium tuberculosis Infection in Patients with Miscellaneous Inflammatory Underlying Conditions.

New biomarkers are needed for discriminating active tuberculosis (TB) from latent TB infection (LTBI), especially in vulnerable groups representing the major diagnostic challenge. This pilot study was carried out to explore the diagnostic potential of selected genes, IFN-γ, IL-17, IL-4, and FoxP3, associated with TB immunity and immunopathology. IFN-γ, IL-17, IL-4, and FoxP3 mRNA expression levels were measured by quantitative reverse transcription PCR (RT-qPCR) from antigen-stimulated peripheral blood mononuclear cells of patients with active TB (n = 25); patients with miscellaneous inflammatory disorders and concomitant LTBI (n = 20), rheumatoid arthritis (RA) being the most predominant in the group (n = 11); and in healthy Bacillus Calmette-Guérin (BCG) vaccinees (n = 8). While the levels of FoxP3 mRNA did not differ between the tested groups, the cumulative expression levels of purified protein derivative-stimulated IFN-γ, IL-17, and IL-4 mRNAs were found to distinguish active TB from the whole group of LTBI with 48% sensitivity and 85% specificity. When restricting the LTBI group to RA cases only, the sensitivity was 56% and specificity 100%. When interpreting the result as positive in at least one of the mRNAs IFN-γ, IL-17, or IL-4, sensitivity of 64% and specificities of 75% (heterogeneous group of LTBI) or 100% (LTBI with RA) were achieved. Moderate discrimination of active TB from LTBI with miscellaneous inflammatory underlying conditions by using combined quantitative expression of IFN-γ, IL-17, and IL-4 mRNA seems not to be of high diagnostic potential.

Role of Helicobacter pylori and interleukin 6 -174 gene polymorphism in dyslipidemia: a case-control study.

OBJECTIVE: To assess the role of Helicobacter pylori infection and interleukin 6 polymorphism -174 (rs1800795) in dyslipidemia. DESIGN: Case-control study comparing serum lipids between H. pylori positive and negative patients and controlling for IL-6 -174 polymorphism, age, sex and smoking. SETTING: 3 hospitals performing outpatient endoscopies in the city of Oulu, Finland. PARTICIPANTS: 199 adult patients with dyspepsia symptoms fulfilling Rome criteria originating from ethnically Finnish population. Patients with an immunosuppressive disorder or malignant disease, treated H. pylori infection, immunosuppressive or anticoagulant medication, previous gastric surgery or ongoing antibiotic treatment were excluded. PRIMARY OUTCOME MEASURES: Association of H. pylori infection and serum lipid concentrations in the whole group or in genotype-based subgroups. The associations between peptic ulcer, gastric mucosal inflammation and serum lipid concentrations were assessed as secondary outcomes. RESULTS: The median high-density lipoprotein (HDL) serum concentration was significantly lower in the H. pylori positive group (0.81 mmol/L) than in the negative group (0.95 mmol/L; p<0.001). In the genotype subgroup analyses, a similar association between H. pylori infection and HDL serum levels was seen within the IL-6 -174 CC genotype group (HDL 0.72 vs 1.06 mmol/L, respectively; p<0.001), but no significant associations were seen in the GC or GG genotype groups. Additionally, patients with peptic ulcer demonstrated lower HDL levels (0.75 mmol/L) than H. pylori positive patients without ulcer (0.86 mmol/L; p=0.010). CONCLUSIONS: H. pylori infection associated significantly with low serum levels of HDL in the IL-6 -174 CC genotype patients but not in the other genotypes. This suggests that the association between H. pylori infection and serum HDL could be transmitted through IL-6. We suggest that the role of IL-6 genotype should also be studied in relation to other associations between gastrointestinal microbiome and cardiovascular risk factors.

Genetic variations in IL6 associate with intervertebral disc disease characterized by sciatica.

Intervertebral disc disease (IDD) characterized by sciatica is a common disorder affecting about 5% of individuals. Environmental factors can predispose to this disease, but IDD has a strong genetic background. Recent evidence suggests that inflammation is one of the key factors in the etiology of IDD. Here, a possible role of the inflammatory mediator genes was studied in 155 patients with IDD-related sciatica and 179 controls. Forty-eight patients were analyzed for mutations in the IL1A, IL1B, IL6 and TNFA genes, and 16 polymorphisms in 10 candidate cytokine genes (IL1A, IL1B, IL1RN, TNFA, IL2, IL4, IL4R, IL6, IL10, IFNG) were genotyped from all subjects. No disease-causing mutations were identified in IL1A, IL1B, IL6 or TNFA. Allele frequencies were, however, significantly different between the two groups for IL6 SNP, T15A in exon 5 (P=0.007). Furthermore, the genotypes AA and AT of the exon 5 SNP were more common in the patients (P=0.011; OR=4.4, 95% CI=1.2-15.7; AR=7.5%, 1.6-13.1%). Haplotypes were then generated for four IL6 SNPs, G-597A, G-572C, G-174C, and T15A in exon 5. Haplotype GGGA was more common in the patients (P=0.011; OR=4.8, 95% CI=1.6-14.5). To evaluate attributable risk, haplotype pairs were assigned for the individuals. The presence of GGGA/GGGA or GGGA/other genotypes had an OR of 5.4 (95% CI=1.5-19.2). Association of GGGA with disease was highly significant (P=0.0033), and the associated AR was 6.8% (1.9-11.5%). These findings support the role of IL-6 genetic variations in discogenic pain.

Toll-Like Receptor 4 Wild Type Homozygozity of Polymorphisms +896 and +1196 Is Associated with High Gastrin Serum Levels and Peptic Ulcer Risk.

Toll-like receptor 4 is a part of the innate immune system and recognizes Helicobacter pylori lipopolysaccharide. The goal of this study was to analyze the role of Toll-like receptor 4 polymorphisms +896 (rs4986790) and +1196 (rs4986791) in the pathogenesis of Helicobacter pylori related gastroduodenal diseases in relation to gastric secretion and inflammation. Toll-like receptor 4 polymorphisms, serum gastrin-17 and pepsinogen I and II concentrations were determined, and gastroscopies with histopathological analyses were performed to 216 dyspeptic patients. As genotype controls, 179 controls and 61 gastric cancer patients were studied. In our study, the Toll-like receptor 4 +896 and +1196 polymorphisms were in total linkage disequilibrium. The homozygous wild types displayed higher gastrin-17 serum concentrations than the mutants (p = 0.001) and this effect was independent of Helicobacter pylori. The homozygous wild types also displayed an increased risk for peptic ulcers (OR: 4.390). Toll-like receptor 4 genotypes did not show any association with Helicobacter pylori positivity or the features of gastric inflammation. Toll-like receptor 4 expression was seen in gastrin and somatostatin expressing cells of antral mucosa by immunohistochemistry. Our results suggest a role for Toll-like receptor 4 in gastric acid regulation and that the Toll-like receptor 4 +896 and +1196 wild type homozygozity increases peptic ulcer risk via gastrin secretion.

Chlamydial heat shock protein 60--specific T cells in inflamed salpingeal tissue.

OBJECTIVE: To evaluate the role of chlamydial heat shock protein 60 (CHSP60)-specific T-lymphocytes in tubal factor infertility. DESIGN: Case series of patients with tubal factor infertility. SETTING: Infertility Clinic, Department of Obstetrics and Gynecology, Helsinki University Central Hospital and Laboratory of Cell-Mediated Immunity, National Public Health Institute, Oulu, Finland. PATIENT(S): Five patients with tubal factor infertility who underwent elective salpingectomy because of hydrosalpinges. INTERVENTION: Collection of salpingeal tissue specimens for in vitro culture of T-lymphocytes. MAIN OUTCOME MEASURE(S): Cloning of Chlamydia trachomatis and CHSP60-specific T-lymphocyte lines derived from inflamed salpingeal tissue. Cytokine production analysis of the established T-lymphocyte clones. RESULT(S): Seventy-seven (34%) of the 229 T-lymphocyte clones recognized C. trachomatis and C. pneumoniae elementary bodies as target antigens. One-third of these Chlamydia genus-specific T-lymphocyte clones further recognized CHSP60 as the target antigen. Most of the CHSP60-specific T-lymphocyte clones produced predominantly IL-10. CONCLUSION(S): CHSP60 may be an important T-lymphocyte antigen involved in the immunopathogenesis of tubal damage associated with chronic C. trachomatis infection.

Almost anyone can have home therapy but can we overcome the barriers?

BACKGROUND: Home dialysis, including both peritoneal and haemodialysis, has been shown to improve patient wellbeing as well as being an economically beneficial alternative to hospital-based therapies. OBJECTIVES: This paper discusses the major barriers to home therapies, particularly in relation to home haemodialysis (HHD) and systems that can be used to overcome them. RESULTS: The use of HHD varies considerably between and within countries. The major limitation is lack of experience and education. A well-planned pre-dialysis education programme seems to be one essential key to the growth of home therapies. CONCLUSIONS: Key points in providing a successful home therapy programme are a highly motivated multidisciplinary team including a dedicated nephrologist and high-level nursing expertise. In addition, an effective pre-dialysis education programme for identifying suitable patients is required.

Head-to-head comparison of humoral immune responses to Vi capsular polysaccharide and Salmonella Typhi Ty21a typhoid vaccines--a randomized trial.

BACKGROUND: The two typhoid vaccines, the parenteral Vi capsular polysaccharide and the oral live whole-cell Salmonella Typhi Ty21a vaccine, provide similar levels of protection in field trials. Sharing no antigens, they are thought to confer protection by different mechanisms. This is the first head-to-head study to compare the humoral immune responses to these two vaccines. METHODS: 50 age- and gender-matched volunteers were immunized, 25 with the Vi and 25 with the Ty21a vaccine. Circulating plasmablasts reactive with whole-cell Salmonella Typhi or one of the typhoidal antigenic structures, Vi, O-9,12, and H-d antigens, were identified as antibody-secreting cells (ASC) with ELISPOT. Homing receptor (HR) expressions were determined. These results were compared with ASC in four patients with typhoid fever. Antibodies to S. Typhi lipopolysaccharides were assessed in cultures of ALS (antibodies in lymphocyte supernatants) and in serum with ELISA. RESULTS: In 49 out of 50 vaccinees, no typhoid-specific plasmablasts were seen before vaccination. On day 7, response to Vi antigen was mounted in 24/25 volunteers in the Vi, and none in the Ty21a group; response to S. Typhi and O-9,12 was mounted in 49/50 vaccinees; and to H-d in 3/50. The numbers of typhoid-specific plasmablasts (total of ASC to Vi, O-9,12 and H-d antigens) proved equal in the vaccination groups. The HR expressions indicated a mainly systemic homing in the Vi and intestinal in the Ty21a group, the latter resembling that in natural infection. Plasmablasts proved more sensitive than serum and ALS in assessing the immune response. CONCLUSIONS: The typhoid-specific humoral responses to Vi and Ty21a vaccines are similar in magnitude, but differ in expected localization and antigen-specificity. The unforeseen O antigen-specific response in the Vi group is probably due to lipopolysaccharide contaminating the vaccine preparation. Only the response to Ty21a vaccine was found to imitate that in natural infection. TRIAL REGISTRATION: Current Controlled Trials Ltd. c/o BioMed Central ISRCTN68125331.