BACKGROUND

In the emergent setting of ST-elevation myocardial infarction (STEMI), transradial intervention (TRI) is less frequently employed than transfemoral intervention (TFI). Because of the greater technical complexity of TRI, a potential compromise in door-to-balloon (DTB) time remains a major concern of centers adopting TRI for STEMI.

METHODS

We performed a propensity-matched analysis, with 1:1 matching of TRI and TFI patients comparing DTB time, 30-day major adverse cardiac event (MACE), and bleeding outcomes of 1052 consecutive STEMI patients managed at our center during a 2-year transition program from routine TFI to TRI access for STEMI.

RESULTS

From January 2008 to April 2010, 359 (34.1%) STEMI patients underwent TRI and the remaining 693 (65.9%) STEMI patients underwent TFI. In 283 propensity score matched pairs of TRI and TFI patients, TRI was associated with shorter DTB time (63.6min vs 69.4min, p=0.027) and more patients having DTB time<90min (88.3% vs 82.3%, p=0.043). Thirty-day MACE occurred in 1.0% in the TRI group and 3.0% in the TFI group (p=0.129). There was no significant difference in major (p=0.313) or minor bleeding (p=0.714) between the TRI and TFI groups. There was a twofold greater use of glycoprotein (GP) IIb/IIIa inhibitor in the TRI group (68.5%) compared with the TFI group (36.4%) (p<0.001).

CONCLUSIONS

Compared with TFI, TRI was not associated with longer DTB time during our center's transition from routine TFI to TRI in STEMI. Our experience suggests that the transition to TRI in STEMI can be safely achieved with DTB times that are comparable and possibly better than propensity-matched TFI cases.

Tumor necrosis factor receptor (TNF) and internleukin-1 (IL-1) are the most potent proinflammatory cytokines involving in autoimmune and inflammatory human diseases. Many anti-inflammatory agents have been exploited for anti-inflammation treatments by targeting cytokines including TNF and IL-1. Theoretically, simultaneously neutralizing or blocking two important inflammatory mediators may achieve a synergistic therapeutic effect. We have developed a recombinant fusion protein, TNFR2-Fc-IL-1ra (TFI), which consists of a TNF-neutralizing domain that specifically binds to TNF-α, an IL-1 receptor antagonist domain, and a dimerization Fc portion of human IgG1, for bifunctional inflammatory inhibitor. Recombinant DNA expressing the sequence of this fusion protein was expressed in CHO-S cells. The protein product was purified using a two-step purification protocol and the identity of the protein was confirmed by western blot analysis. The purified recombinant protein had a purity of about 98 % as determined by HPLC, and a molecular mass of 164.6 kDa as determined by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. The results of cell binding inhibition indicate that TFI was able to strongly neutralize TNF activity and antagonize IL-1r activity, suggesting that TFI may be used as a bifunctional ligand with enhanced anti-inflammatory effect. The result obtained in this study may provide a platform for extending bifunctional anti-inflammatory drug development.

OBJECTIVE

To determine the androgen status of men with mild ankylosing spondylitis (AS) and to evaluate the relationship of sex hormones with bone mineral density (BMD) and vertebral fractures.

METHODS

Fifty-six male patients with mild AS were studied. All patients had BMD measured by dual x-ray absorptiometry (DXA) of the lumbar spine and hip, and had radiographs of the thoracic and lumbar spines. Radiographs were evaluated morphometrically, and vertebral fractures were defined using established criteria. Serum total testosterone, sex hormone binding globulin (SHBG), follicle stimulating hormone (FSH), and luteininzing hormone (LH) were measured in the patients with AS and 52 age matched controls. Testosterone free index (TFI) was calculated.

RESULTS

There was a small, not significant reduction in serum total testosterone in patients with AS compared to controls [16.02 (5.0) vs 21.0 (6.2) nmol/l]. Serum SHBG was significantly lower in patients with AS [27.29 (10.6) vs 35.0 (13.0) nmol/l; p < 0.001] compared to controls. There was no significant difference in the mean TFI between patients and controls [58.7 (21.2) vs 60 (22.2) nmol/l; p>> 0.05] or in the levels of LH and FSH. No significant correlation was found between sex hormones, BMD, and vertebral fractures in patients with AS.

CONCLUSIONS

Sex hormones are not altered significantly in patients with mild AS and do not appear to be related to BMD or vertebral fractures. Osteopenia in men with mild AS is therefore unlikely to be secondary to hypogonadism.

Transient forebrain ischemia (TFI) leads to hippocampal CA1 pyramidal cell death which is aggravated by glucocorticoids (GC). It is unknown how GC affect apoptosis and necrosis in cerebral ischemia. We therefore investigated the co-localization of activated caspase-3 (casp-3) with apoptosis- and necrosis-like cell death morphologies in CA1 of rats treated with dexamethasone prior to TFI (DPTI). In addition, apoptosis- (casp-9, casp-3, casp-3-cleaved PARP and cleaved α-spectrin 145/150 and 120kDa) and necrosis-related (calpain-specific casp-9 cleavage, μ-calpain upregulation and cleaved α-spectrin 145/150kDa) cell death mechanisms were investigated by Western blot analysis. DPTI expedited CA1 neuronal death from day 4 to day 1 and increased the magnitude of CA1 neuronal death from 66.2% to 91.3% at day 7. Furthermore, DPTI decreased the overall (days 1-7) percentage of dying neurons displaying apoptosis-like morphology from 4.7% to 0.3% and, conversely, increased the percentage of neurons with necrosis-like morphology from 95.3% to 99.7%. In animals subjected to TFI without dexamethasone (ischemia-only), 7.4% of all dying CA1 neurons were casp-3-immunoreactive (IR), of which 3.1% co-localized with apoptosis-like and 4.3% with necrosis-like changes. By contrast, DPTI decreased the percentage of dying neurons with casp-3 IR to 1.4%, of which 0.3% co-localized with apoptosis-like changes and 1.1% with necrosis-like changes. Western blot analysis from DPTI animals showed a significant elevation of μ-calpain, a calpain-produced necrosis-related casp-9 fragment (25kDa) and cleavage of α-spectrin into 145/150kDa fragments at day 4, whereas in ischemia-only animals a significant increase of casp-3-cleaved PARP, cleavage of α-spectrin into 145/150 and 120kDa fragments was detected at day 7. We conclude that DPTI, in addition to augmenting and expediting CA1 neuronal death, causes a shift from apoptosis-like cell death to necrosis involving μ-calpain activation.

Fabry disease, caused by a deficiency of lysosomal enzyme alpha-galactosidase A (alpha-gal A), is one of the inherited disorders potentially treatable by gene transfer to hematopoietic stem cells. In this study, a high-titer amphotropic retroviral producer cell line, MFG-alpha-gal A, was established. CD34+ cells from normal umbilical cord blood were transduced by centrifugal enhancement. The alpha-gal A activity in transduced cells increased 3.6-fold above the activity in nontransduced cells. Transduction efficiency measured by PCR for the integrated alpha-gal A cDNA in CFU-GM colonies was in the range of 42-88% (average, 63%). The expression of functional enzyme in TFI erythroleukemia was sustained for as long as cells remained in culture (84 days) and for 28 days in LTC-IC cultures of CD34+ cells. The ability of the transduced CD34+ cells to secrete the enzyme and to correct enzyme-deficient Fabry fibroblasts was assessed by cocultivation of these cells. The enzyme was secreted into the medium from transduced CD34+ cells and taken up by Fabry fibroblasts through mannose 6-phosphate receptors. These findings suggest that genetically corrected hematopoietic stem/progenitor cells can be an enzymatic source for neighboring enzyme-deficient cells, and can potentially be useful for gene therapy of Fabry disease.

BACKGROUND

Despite several attempts to reach a single definition of frailty, no consensus has been reached. The definitions previously published have tried to prove its utility in predicting negative health outcomes. The objective of the present study is to compare the predictive value of 3 different frailty instruments, for selected outcomes.

METHODS

The study sample includes 1278 participants of the Three-City study, a French prospective population-based study, assessed for frailty using Fried's phenotype criteria, Rockwood's Frailty Index and Tilburg Frailty Indicator. To assess the risk of mortality, incident disability, falls, institutionalization and hospitalization for a follow up period of 12 years, Cox proportional hazard models with delayed entry have been used. The area under the time-dependent ROC curve has been used to estimate and compare the ability of the three instruments of frailty to predict the previous adverse outcomes at 12 years.

RESULTS

Five hundred ninety four participants were identified as non-robust with Fried's criteria; 169 with Rockwood's FI and 303 with TFI. The three scales consistently identified 91 participants as non-robust and 574 as robust. Rockwood's FI was a statistically significant predictor of mortality, incident disability and falls, and a strong predictor of hospitalization.

CONCLUSIONS

In the absence of a "gold standard" definition of frailty, a debate on what measures and how to include them is open. A clue may be that one should select the appropriate definition according to the to-be predicted outcome, the setting and the underlying etiology of frailty.

Plasmids found in six strains of Thiobacillus ferrooxidans were mapped and compared in an effort to detect the origin of replication. Four strains yielded an identical 9.8-kb plasmid, p<em>TFI</em>91. Restriction mapping and Southern blot hybridization analysis were used to confirm this finding. Dissimilar plasmids found in two other strains contained a conserved 2.2-kb SacI region common to p<em>TFI</em>91. DNA sequence analysis of this region showed structural features common to bacterial plasmid replicons. A comparison of the p<em>TFI</em>91 origin with those of T. ferrooxidans pTF-FC2 and other broad host range vectors did not show significant homologous DNA sequences. To verify the replication function, a chloramphenicol acetyl transferase marker gene was ligated at the unique sites of p<em>TFI</em>91, and the plasmid was transformed into Escherichia coli DH5 alpha cells but no transformants were identified. To test the replication of p<em>TFI</em>91 independent of DNA polymerase I in E. coli, different restriction fragments of p<em>TFI</em>91 were cloned into pHSG398 (Cmr, ColEI origin) and transformed into the polA1 mutant SF800, but chloramphenicol-resistant transformants were not detected. Electrotransformation of T. ferrooxidans <em>TFI</em>-70 and Pseudomonas putida ATCC 19151 also failed to yield transformants. The results suggested that the p<em>TFI</em>91 plasmid replicon does not function either in E. coli or in P. putida. Since p<em>TFI</em>91 contains the same origin of replication as other plasmids in several other T. ferrooxidans strains, this replicon may be commonly distributed in T. ferrooxidans.

Nuclear orphan receptors are known to be important mediators of neurogenesis, but the target genes of these transcription factors in the vertebrate nervous system remain largely undefined. We have previously shown that a 500-base pair fragment in the first intron of the GRIK5 gene, which encodes the kainate-preferring glutamate receptor subunit KA2, down-regulates gene expression. In our present studies, mutation of an 11-base pair element within this fragment resulted in a loss of nuclear protein binding and reverses negative regulation by the intron. Using yeast one-hybrid screening, we have identified intron-binding proteins from rat brain as COUP-TFI, EAR2, and NURR1. Gel shift studies with postnatal day 2 rat brain extract indicate the presence of COUP-TFs, EAR2, and NURR1 in the DNA-protein complex. Competition assays with GRIK5-binding site mutations show that the recombinant clones exhibit differential binding characteristics and suggest that the DNA-protein complex from postnatal day 2 rat brain may consist primarily of EAR2. The DNA binding activity was also observed to be enriched in rat neural tissue and developmentally regulated. Co-transfection assays showed that recombinant nuclear orphan receptors function as transcriptional repressors in both CV1 cells and rat CG4 oligodendrocyte cells. Direct interaction of the orphan receptors with and relief of repression by TFIIB indicate likely role(s) in active and/or transrepression. Our findings are thus consistent with the notion that multiple nuclear orphan receptors can regulate the transcription of a widely expressed neurotransmitter receptor gene by binding a common element in an intron and directly modulating the activity of the transcription machinery.

BACKGROUND

Peripheral nerve injuries are encountered frequently in clinical practice. In nerve repair, an end-to-end suture is the preferable choice of treatment. However, where primary closure is not possible, the defect is to be repaired with a nerve graft.

METHODS

A total of 21 female Wistar rats weighing 230 to 290 g were used in the study. They were classified into the following 3 groups: (I) nerve graft, (II) vein graft, and (III) minced nerve graft. In group I, after exposure of the tibial nerve, a 1-cm-long nerve gap was created on the tibial nerve, and the defect was repaired epineurally by using the autogenous nerve. In group II, the 1-cm tibial nerve defect was repaired by using an autogenous vein graft. In group III, a 1-cm nerve graft was divided to 3 equal parts, with one of the nerve parts being minced with microscissors and placed in the vein graft lumen. Thereafter, a 1-cm tibial nerve defect was repaired by the vein graft filled with minced nerve tissue. The tibial function indices (TFIs) were calculated for functional assessment using the Bain-Mackinnon-Hunter formula. Light and electron microscopic evaluations were performed for morphometric assessment. In addition, the myelinated fibers were counted in all groups.

RESULTS

The TFIs of group II were found to be the lowest among all the groups after the sixth week, whereas the TFI of group I was found to be better than the other groups after the sixth week. There was no difference in TFIs between group I and group III. On the basis of the number of myelinated fibers, there was no statistically significant difference between group I and group III, whereas the difference was significant (P<0.05) between groups I/III and group II. Presence of peripheral nerves in light microscopic evaluation revealed normal characteristics of myelinated fibers in all groups. The myelinated axon profile was near normal in the nerve graft group in electron microscopic evaluation. However, there were more degenerated axons with disturbed contours and vacuolizations in the vein graft group compared to the minced nerve graft group.

CONCLUSIONS

We can conclude that using minced nerve tissue in vein grafts as a conduit increases the regeneration of nerves (almost like the nerve graft group) and it may not be caused by donor-site morbidity. It can be used in the repair of nerve defects instead of autogenous nerve grafts after further experimental evidence and clinical trials.

OBJECTIVE

To determine changes in the prevalence of dental fluorosis, and in perceptions of aesthetic concerns due to dental fluorosis after water fluoridation ceased.

METHODS

Schoolchildren in second and third grades were examined in 1993-94, 1996-97 and 2002-03 to determine changes in the prevalence of dental fluorosis following fluoridation cessation of the public water supplies in 1992. The Thylstrup-Fejerskov Index (TFI) was used to quantify dental fluorosis. Perceptions of aesthetics were assessed by questionnaires which were sent home to parents. Residence and dental histories were confirmed on all children to determine the extent of exposure to all types of fluorides. Comparisons between the three surveys were used to establish the influence of fluoridated water and other fluoride sources on the occurrence and severity of dental fluorosis. Aesthetic ratings from parents were used to assess the aesthetic conditions of maxillary anterior teeth across the three surveys.

RESULTS

When fluoride was removed from the water supply in 1992, the prevalence and severity of TFI scores decreased significantly from the 1993-94 survey cycle when compared with the 1996-97 and 2002-03 survey cycles. The use of fluoride supplements and fluoride dentifrice also decreased during this study period. Analyses were unable to determine the influence of these different fluoride exposures on the changes in TFI scores over time. Comparisons of aesthetic ratings from parents between survey cycles failed to show any significant differences.

Recently, it has been shown that CYP17 gene transcription is activated by SF-1 (Steroidogenic Factor-1) binding to a cyclic AMP-responsive sequence within the promoter region of the gene, whereas it is inhibited by COUP-TF (Chicken Ovalbumin Upstream Promoter-Transcription Factor) binding to the sequence. We have shown that transcriptional repression by COUP-TFI is mediated by corepressors, N-CoR (nuclear receptor corepressor) and SMRT (silencing mediator for retinoid and thyroid hormone-receptor). Therefore, we compared the expression of COUP-TFI, N-CoR and SMRT in non-hyperfunctioning adrenocortical adenomas and normal adrenal glands. We found significantly higher expression of COUP-TFI mRNA in non-hyperfunctioning adenomas (n=5, 227+/-18%) than in normal adrenals (n=5, 96+/-4%). Interestingly, the pattern of N-CoR and SMRT expression was different compared with COUP-TFI expression. These data suggest that COUP-TFI, N-CoR, and SMRT may play a differential role in steroid biosynthesis of non-hyperfunctioning adenomas.

OBJECTIVE

To validate and improve an established prognostic index in patients with recurrent ovarian cancer.

METHODS

A Canadian three-covariate prognostic index (tumour grade at diagnosis, initial performance status, and time to relapse/primary progression (TRP)) was validated in a well-defined cohort of comparable Danish patients. Potential parameters to be included in an improved prognostic index were revealed by univariate and multivariate analyses in the Danish validation group.

RESULTS

The Canadian index validated in the Danish patient population (n=189) found a statistical significant difference in survival between the prognostic groups good and intermediate (P<0.0001), whereas there was no significant difference in survival between the prognostic groups intermediate and poor (P=0.51). In order to improve the accuracy of the index, the candidate parameters, treatment free interval (TFI), CA125 level and performance status, at time of relapse/primary progression, were added, whereas the parameters, tumour grade, and initial performance status, from the Canadian index were excluded. As the correlation coefficient between TRP and TFI was very high (r=0.91), TRP was substituted with TFI in the improved prognostic model. The final model was: 0.8 (performance status)+0.33 log (CA125)-1.31 log (TFI). The improved model was a good predictor of one-year survival (AUC 0.85; logistic regression; P<0.0001). The median survival (with 95% CI) of the four prognostic groups (A-D) was 50.6 (34.0-not available), 25.0 (22.1-33.6), 11.3 (8.5-12.9), and 5.2 (3.5-6.3) months, respectively.

CONCLUSIONS

A novel prognostic model (the Copenhagen index) for patients with recurrent ovarian cancer is presented.

To evaluate the impact of treatment modality, tumor size, time from therapy, and demographic features on tinnitus distress, as measured by the Tinnitus Functional Index (TFI) in patients treated for sporadic acoustic neuroma.

Cross-sectional observation study.

A Web-based 44-question online survey was made available on the Acoustic Neuroma Association Web site for 3 months. Of 154 unique surveys that were completed in entirety, further screening netted 143 study participants. Questions included the TFI, treatment modality, tumor size, time from therapy, demographic features, and hearing status of both ears.

Tinnitus distress following treatment for acoustic neuroma is independent of treatment type, tumor size, tumor laterality, time after treatment, age, and gender. Tinnitus Functional Index scores closely mirror severity profile of the study population as reported in the pivotal TFI instrument validation study by Meikle et al.(17) Tinnitus is "not a problem" in 20% of respondents, a "small problem" in 20%, a "moderate problem" in 11%, a "big problem" in 22%, and a "very big problem" in 27%. Subscale analysis suggests that acoustic tumor patients struggle most with tinnitus intrusiveness and loss of control.

Whereas tinnitus is a common symptom in acoustic neuroma patients in both the pre- and posttreatment settings, clinicians can provide counsel that choice of treatment modality, tumor size, age, and gender have little to no bearing on severity of posttreatment tinnitus distress. Tinnitus severity does not differ among the treatment choices of open microsurgery, stereotactic radiosurgery, external beam radiation, and observation.

NA Laryngoscope, 126:1639-1643, 2016.

BACKGROUND

Tinnitus occurs in a large part of the general population with prevalences ranging from 10% to 15% in an adult population. One subtype is cervicogenic somatic tinnitus, arising from cervical spine dysfunctions, justifying cervical spine assessment and treatment. This study aims to investigate the effect of a standardized physical therapy treatment, directed to the cervical spine, on tinnitus. Additionally, a second aim is to identify a subgroup within the tinnitus population that benefits from physical therapy treatment.

METHODS

This study is designed as a randomized controlled trial with delayed treatment design. Patients with severe subjective tinnitus (Tinnitus Functional Index (TFI) between 25 and 90 points), in combination with neck complaints (Neck Bournemouth Questionnaire (NBQ) >14 points) will be recruited from the University Hospital of Antwerp. Patients suffering from tinnitus with clear otological etiologies, severe depression, traumatic cervical spine injury, tumors, cervical spine surgery, or conditions in which physical therapy is contra-indicated, will be excluded.After screening for eligibility, baseline data such as TFI, NBQ, and a set of cervical biomechanical and sensorimotor tests will be collected. Patients are randomized in an immediate therapy group and in a group with a delayed start of therapy by 6 weeks. Patients will receive physical therapy with a maximum of 12 sessions of 30 min for a 6-week program. Data from the TFI and NBQ will be collected at baseline (week 0), at the start of therapy (weeks 0 or 6), at the end of therapy (weeks 6 or 12), 6 weeks after therapy (weeks 12 or 18), and 3 months after therapy (weeks 18 or 24). Secondary outcome measures will be collected at baseline and 6 weeks after the therapy (weeks 12 or 18), as the maximal therapy effect on the cervical spine dysfunctions is expected at that moment.

CONCLUSIONS

This study is the first to investigate the effect of a standardized physical therapy treatment protocol on somatic tinnitus with a prospective comparative delayed design and with blinded evaluator for baseline, end of therapy, and 6 and 12 weeks after therapy.

BACKGROUND

12 September 2013, ClinicalTrials.gov: NCT02016313.

Herein, we describe a 63-year-old male with multiple tumors arising within a nevus sebaceus on the posterior scalp. On histopathologic examination, four distinct tumors were identified: trichoblastoma, syringocystadenoma papilliferum, desmoplastic trichilemmoma and tumor of the follicular infundibulum (TFI). Within the TFI component of the nevus sebaceus, there was intracytoplasmic accumulation of eosinophilic keratin, as shown on pancytokeratin-stained sections, imparting a signet-ring appearance to the cells. To our knowledge, this is the first report of signet-ring cells arising within a TFI occurring in a nevus sebaceus. We discuss this case as well as review the literature on multiple tumors arising within nevus sebaceus and signet-ring cell changes in primary cutaneous tumors.

Soluble tumor necrosis factor (TNF) receptor-2 (TNFR2) and interleukin-1 receptor antagonist (IL-1ra) were fused to the Fc portion of IgG1 using recombinant DNA technology. The resulting dual-domain cytokine ligand, TNFR2-Fc-IL-1ra, specifically binds to TNF and to the type I IL-1 receptor (IL-1RI). This study was designed to characterize the kinetic profile of (99m)Tc-labeled TNFR2-Fc-IL-1ra (TFI) for imaging inflammatory response in an ischemic-reperfused (IR) rat heart model.

METHODS

The IR model was created by ligating the left coronary artery for 45 min, followed by 2-h reperfusion. Cardiac SPECT images of TFI in the IR model (n = 6) were dynamically acquired for 3 h. Correlative data of myocardial TFI distribution versus microsphere-determined tissue blood flow were acquired in 3 extra IR hearts. Inflammation targeting affinity of TFI was compared with 2 individual cytokine radioligands, (99m)Tc-IL-1ra-Fc (IF) and (99m)Tc-TNFR2-Fc (TF) (n = 6 each group). Myocardial cytokine expression was evaluated by immunochemical assay.

RESULTS

Increased TFI uptake was found in the ischemic area and correlated with the severity of ischemia. At 3 h after injection, the ratio of hot-spot accumulation in the ischemic area to a remote viable zone was 5.39 ± 1.11 for TFI, which was greater than that for IF (3.28 ± 0.81) and TF (3.29 ± 0.75) (P < 0.05). The in vivo uptake profiles of TFI, TF, and IF were consistent with ex vivo radioactive measurements and correlated with upregulated IL-1 and TNF expression.

CONCLUSIONS

The dual-domain TFI is promising for noninvasive detection of inflammatory reactions in IR myocardium because of its more potent affinity to the inflammatory sites compared with TF and IF.

A 67-year-old man is reported with multiple tumors of follicular infundibulum containing ducts. Approximately 30 hypopigmented, scaling macules and minimally elevated papules were present on the face. Skin biopsy specimens from 5 representative lesions revealed similar findings. There was a proliferation of ramifying strands of pale-staining keratinocytes in the upper dermis showing connections with follicular infundibula of vellus follicles and epidermis. There was evidence of hair follicle differentiation with small follicular bulbs, papillary mesenchymal bodies, keratocysts, and occasional hair shafts in the tumor. These findings are characteristic of prior reports of TFI. Ducts were also present within the epithelial cords. Carcinoembryonic antigen, gross cystic disease fluid protein-15, epithelial membrane antigen, and S-100 protein were identified within the tumor. We theorize that the ductal elements within these TFI reflect the multipotential differentiating capacity of portions of infundibular epithelium.

OBJECTIVE

To study the levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in tubal fluids of tubal factor infertile (TFI) women due to chlamydia trachomatis (CT) infection and its implication.

METHODS

Twenty-two TFI women with CT infection (group A), twenty-three TFI women without CT infection (group B) and nineteen fertile women with normal tubes (group control) were enrolled for study. Levels of TNF-alpha and IL-6 in tubal fluids were measured by enzyme-linked immunosorbent assay.

RESULTS

Group A had significantly higher TNF-alpha levels than those of group control (178 ng/L versus 124 ng/L, P < 0.01). Moreover, women with tubal blocks had significantly higher TNF-alpha those of tubal adhesions (199 ng/L versus 142 ng/L, P < 0.01). IL-6 levels of group A were significantly higher than those of group B and group control (681 ng/L versus 264 ng/L and 229 ng/L, both P < 0.01), but there is no difference between group B and group control.

CONCLUSIONS

Local TNF-alpha and IL-6 levels increased in silent tubal infection of CT. TNF-alpha had a positive relevance with the degree of tubal damage.

The aim of the present study was to assess the objectivity and accuracy of a new system to evaluate pregnancy prognosis in tubal factor infertility (TFI) patients. Retrospective study in 469 TFI patients were pre- and postoperatively scored using the new system as mild, moderate or severe TFI, based on tubal adhesions, patency, morphology and structure. Follow-up was assessed to determine pregnancy outcomes. Laparoscopic salpingoplasty and hydrotubation, hysteroscopic-laparoscopic salpingoplasty and hydrotubation, and laparoscopic hydrotubation all decreased TFI scores to a similar extent. The pre- and postoperative TFI classification was significantly associated with intrauterine pregnancy (mild: 43.6% vs. moderate: 34.0% vs. severe: 19.4%, P < 0.0001) and live births (mild: 35.9% and moderate: 31.5% vs. severe: 16.8%, P = 0.0002) rates. Multivariate analysis showed that the preoperative disease course (P = 0.02), preoperative TFI score (P < 0.0001), and postoperative TFI score (P = 0.0007) were independently associated with the rate of intrauterine pregnancy rate. Multivariate analysis also showed that the postoperative TFI score (P = 0.001), pelvic inflammatory disease (P = 0.03) and age (P = 0.03) were independently associated with the rate of live births.

CONCLUSIONS

We devised a new classification system for TFI prognosis. Salpingoplasty improved these scores. Both pre- and postoperative TFI assessments using this new system are associated with pregnancy prognosis in TFI patients.

BACKGROUND

Interleukin-12 (IL-12) and related cytokines induce activation and differentiation of T cells. Our aim was to investigate the associations between genetic differences in IL-12-family cytokines and the pathogenesis of chlamydial disease.

METHODS

The final study population consisted of 100 women with Chlamydia trachomatis-induced tubal factor infertility (TFI) and 125 pregnant women as controls. Three single nucleotide polymorphisms (SNPs) of IL12A and seven SNPs of IL12B genes were determined from isolated DNA using the Sequenom system with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry.

RESULTS

We found that the IL12B SNP rs3212227 was associated with both susceptibility and severity of TFI. The minor allele C was rare and only one CC homozygote was found among the controls. AC heterozygotes were more common among TFI cases than among controls (P = 0.009) and were associated with increased risk of TFI [odds ratios (OR) = 2.44, 95% confidence intervals (CI) = 1.23-4.87]. Carrying the minor allele C was also associated with disease severity (P for trend = 0.008) and moderate (OR = 2.51, 95% CI = 1.06-5.95) and severe tubal damage (OR = 2.73, 95% CI = 1.15-6.52).

CONCLUSIONS

The results suggest that variation in the IL12B gene partly explains inter-individual differences in disease susceptibility and severity.

Intracellular pattern-recognition receptors NOD1 and NOD2 are capable of sensing common structural units of bacterial walls. Recognition triggers specific immune signalling pathways and leads to pro-inflammatory cytokine upregulation and adequate immune response. We investigated whether two functional polymorphisms in NOD1 and NOD2 exert an effect on susceptibility to (STD patients) and severity of (female patients visiting the fertility clinic) Chlamydia trachomatis infection in 807 Dutch Caucasian women. A significant association of the NOD1 +32656 GG insertion variant with protection against infection with C. trachomatis has been detected [p: 0.0057; OR: 0.52]. When comparing C. trachomatis-positive women without symptoms to C. trachomatis-positive women with symptoms, and to C. trachomatis-positive women with TFI, we observed an increasing trend in carriage of the GG allele [Ptrend: 0.0003]. NOD2 1007fs failed to reveal an association. We hypothesize that the underlying mechanism might be a functional effect of the GG insertion on IFN-beta-dependent regulation of immune response in the genital tract. The research is part of an ongoing effort of identifying key polymorphisms that determine the risk of TFI and effectively translating them into the clinical setting for the purpose of optimizing diagnostic management of women at risk for developing TFI.

Tinnitus can be related to many different aetiologies such as hearing loss or a noise trauma, but it can also be related to the somatosensory system of the cervical spine, called cervicogenic somatic tinnitus(CST). Recently, a positive effect of multi-modal cervical physical therapy on tinnitus severity in patients with CST was demonstrated. To date however, the outcome of the intervention cannot be predicted.

To identify prognostic indicators for decrease in tinnitus severity after cervical physical therapy in patients with CST.

Patients with moderate to severe subjective tinnitus (Tinnitus Functional Index(TFI):25-90points) and neck complaints (Neck Bournemouth Questionnaire(NBQ)>> 14points).

All patients received multimodal cervical physical therapy for 6 weeks (12 sessions). This physical therapy contained a combination of manual mobilizations and exercises of the cervical spine.

TFI and NBQ-scores were documented at baseline, after treatment and after a 6-weeks follow-up period. Impairments in cervical spine mobility and muscle function were identified at baseline and after 6-weeks follow-up.

Patients with co-varying (increasing or decreasing simultaneously) tinnitus and neck complaints had significantly lower TFI-scores after treatment (p = 0.001) and follow-up (p = 0.03). The presence of this co-variation and a combination of low pitched tinnitus and increasing tinnitus during inadequate cervical spine postures are prognostic indicators for a decrease in TFI-scores after cervical physical therapy (adjusted R2 = 0.357).

Patients who experience a decrease in tinnitus annoyance from cervical physical therapy are those with co-varying tinnitus and neck complaints and those with a combination of low-pitched tinnitus and increasing tinnitus during inadequate cervical spine postures.

BACKGROUND

Tinnitus can be related to many different aetiologies such as hearing loss or a noise trauma, but it can also be related to the somatosensory system of the cervical spine, called cervicogenic somatic tinnitus (CST). Case studies suggest a positive effect of cervical spine treatment on tinnitus complaints in patients with CST, but no experimental studies are available.

OBJECTIVE

To investigate the effect of a multimodal cervical physical therapy treatment on tinnitus complaints in patients with CST.

METHODS

Randomized controlled trial.

METHODS

Patients with a combination of severe subjective tinnitus (Tinnitus Functional Index (TFI): 25-90 points) and neck complaints (Neck Bournemouth Questionnaire (NBQ)>> 14 points).

METHODS

All patients received cervical physical therapy for 6 weeks (12 sessions). Patients were randomized in an immediate-start therapy group (n = 19) and a 6-week delayed-start therapy group (n = 19).

METHODS

TFI and NBQ-scores were documented at baseline, after the wait-and-see period in the delayed-start group, after treatment and after 6 weeks follow-up. The Global Perceived Effect (GPE) was documented at all measuring moments, except at baseline.

RESULTS

In all patients (n = 38) TFI and NBQ-scores decreased significantly after treatment (p = 0.04 and p < 0.001). NBQ-scores remained significantly lower after follow-up (p = 0.001). Immediately after treatment, 53% (n = 38) experienced substantial improvement of tinnitus. This effect was maintained in 24% of patients after follow-up at six weeks.

CONCLUSIONS

Cervical physical therapy can have a positive effect on subjective tinnitus complaints in patients with a combination of tinnitus and neck complaints. Larger studies, using more responsive outcome measures, are however necessary to prove this effect.

BACKGROUND

NCT02016313.