A better understanding of Chlamydia trachomatis infection (chlamydia)-related sequelae can provide a framework for effective chlamydia control strategies. The objective of this study was to estimate risks and risk factors of pelvic inflammatory disease (PID), ectopic pregnancy and tubal factor infertility (TFI) with a follow-up time of up until 8 years in women previously tested for chlamydia in the Chlamydia Screening Implementation study (CSI) and participating in the Netherlands Chlamydia Cohort Study (NECCST).

Women who participated in the CSI 2008-2011 (n=13 498) were invited in 2015-2016 for NECCST. Chlamydia positive was defined as a positive CSI-PCR test, positive chlamydia serology and/or self-reported infection (time dependent). Data on PID, ectopic pregnancy and TFI were collected by self-completed questionnaires. Incidence rates and HRs were compared between chlamydia-positive and chlamydia-negative women corrected for confounders.Of 5704 women included, 29.5% (95% CI 28.3 to 30.7) were chlamydia positive. The incidence rate of PID was 1.8 per 1000 person-years (py) (1.6 to 2.2) overall, 4.4 per 1000 py (3.3 to 5.7) among chlamydia positives compared with 1.4 per 1000 py (1.1 to 1.7) for chlamydia negatives. For TFI, this was 0.4 per 1000 py (0.3 to 0.5) overall, 1.3 per 1000 py (0.8 to 2.1) and 0.2 per 1000 py (0.1 to 0.4) among chlamydia positives and negatives, respectively. And for ectopic pregnancy, this was 0.6 per 1000 py (0.5 to 0.8) overall, 0.8 per 1000 py (0.4 to 1.5) and 0.6 per 1000 py (0.4 to 0.8) for chlamydia negatives. Among chlamydia-positive women, the strongest risk factor for PID was symptomatic versus asymptomatic infection (adjusted HR 2.88, 1.4 to 4.5) and for TFI age <20 versus >24 years at first infection (HR 4.35, 1.1 to 16.8).We found a considerably higher risk for PID and TFI in chlamydia-positive women, but the incidence for ectopic pregnancy was comparable between chlamydia-positive and chlamydia-negative women. Overall, the incidence rates of sequelae remained low.NTR-5597.

OBJECTIVE

The purpose of this study was to evaluate patients after arthroscopic repair of meniscal horizontal tears with a marrow-stimulating technique through clinical signs and second-look arthroscopy.

METHODS

We retrospectively reviewed a consecutive series of 32 meniscal repairs with horizontal cleavage tears and evaluated them through clinical assessment and second-look arthroscopic examinations. Arthroscopic meniscal repair and a marrow-stimulating technique were performed. Functional outcomes were evaluated using the visual analog scale (VAS) pain score, Lysholm knee scoring scale, and Tegner activity scale. Assessment of meniscal healing was evaluated clinically by the presence of meniscal signs; second-look arthroscopy was performed in 11 patients. Correlation between chronicity of a meniscal lesion (time from initial symptom [TFIS]) and meniscal healing was evaluated.

RESULTS

The mean follow-up period was 45.6 ± 13.9 months. Improvements in mean VAS scores from 6.7 to 1.9 (P < .001) were observed. The Lysholm score increased from 48.0 ± 14.4 to 92.0 ± 6.3 (P < .001). The Tegner activity score increased from 3.3 ± 1.1 to 6.8 ± 0.8 (P < .001). At the last follow-up, 29 of 32 patients (91%) were evaluated as healing in the clinical assessment. Of the 11 patients who underwent second-look arthroscopy, 8 (73%) showed complete healing, 2 (18%) had incomplete healing, and 1 (9%) failed to heal. Correlation between TFIS and meniscal healing was clinically significant (P = .001) but arthroscopically insignificant (P = .085) on second-look arthroscopy.

CONCLUSIONS

The meniscal repair procedure for horizontal cleavage tears in the present study suggests an alternative treatment option to approach the treatment of meniscal tears extending into the avascular zone and degenerative tissue. The marrow-stimulating technique using a cannulated reamer can be considered as an alternative method for the augmentation of meniscal healing.

METHODS

Level IV, therapeutic case series.

OBJECTIVE

Data for the assessment of frailty in acutely ill hospitalized older adults remains limited. Using the Frailty Index (FI) as "gold standard," we compared (1) the diagnostic performance of 3 frailty measures (FRAIL, Clinical Frailty Scale [CFS], and Tilburg Frailty Indicator [TFI]) in identifying frailty, and (2) their ability to predict negative outcomes at 12 months after enrollment.

METHODS

Prospective cohort study.

METHODS

We recruited 210 patients (mean age 89.4 ± 4.6 years, 69.5% female), admitted to the Department of Geriatric Medicine in a 1300-bed tertiary hospital.

METHODS

Premorbid frailty status was determined. Data on comorbidities, severity of illness, functional status, and cognitive status were gathered. We compared area under receiver operator characteristic curves (AUC) for each frailty measure against the reference FI. Multiple logistic regression was used to examine the independent association between frailty and the outcomes of interest.

RESULTS

Frailty prevalence estimates were 87.1% (FI), 81.0% (CFS), 80.0% (TFI), and 50.0% (FRAIL). AUC against FI ranged from 0.81 (95% confidence interval [CI] 0.72-0.90: FRAIL) to 0.91 (95% CI 0.87-0.95: CFS). Only FRAIL was associated with higher in-hospital mortality (6.7% vs 1.0%, P = .031). FRAIL and CFS were significantly associated with increased length of hospitalization (10 [6.0-17.5] vs 8 [5.0-14.0] days, P = .043 and 9 [5.0-17.0] vs 7 [4.25-11.75] days, P = .036, respectively). CFS and FI were highly associated with mortality at 12-month (CFS, frail vs nonfrail: 32.9% vs 2.5%, P < .001, and FI, frail vs nonfrail: 30.6% vs 3.7%, P < .001). CFS also conferred the greatest risk of 12-month mortality (odds ratio [OR] 5.78, 95% CI 3.19-10.48, P < .001) and composite outcomes of institutionalization and/or mortality (OR 3.69, 95% CI 2.31-5.88, P < .001), adjusted for age, sex, and severity of illness.

CONCLUSIONS

Our study affirms the utility of frailty assessment tools among older persons in acute care. FRAIL conferred highest risk of in-hospital mortality. However, CFS had greatest risk of mortality and institutionalization within 12 months.

The purpose of this study was to investigate the effect of dental fluorosis on shear bond strength of a composite material to dentine. Forty human premolar teeth were classified according to the severity of fluorosis using the Thylstrup and Fejerskov index and were divided into four groups (TFI scores of 0, 3, 4 and 5) of 10 teeth. Non-fluorosed teeth (TFI score of 0) served as the control group. A self-etching light-cured bonding system, Clearfil SE Bond, and a micro-hybrid light-cured composite, Clearfil AP-X were selected for the study. Buccal surfaces of mounted teeth were ground flat to expose the dentine. Composite cylinders, 4 mm diameter and 4 mm length, were bonded to the treated dentine surfaces. Shear bond strength was measured with an universal testing machine at a cross-head speed of 0.5 mm min-1. After failure, the fracture surfaces were examined under a stereo microscope. The mean bond strength was 24.37 +/- 3.54 MPa for non-fluorosed teeth and varied between 22.72 +/- 3.52 and 27.02 +/- 5.91 MPa for fluorosed teeth. The difference between the mean values for bond strength was not statistically significant (P>> 0.05). Adhesive mode of failure was most prevalent in non-fluorosed teeth. It can be concluded that fluorosis does not affect the shear bond strength of composite material to human dentine.

Melatonin activates membrane-bound G-protein-coupled receptors mt1 and MT2, but may also bind a family of orphan nuclear receptors, including RORalpha and RZRbeta, representing another potential molecular mechanism of melatonin action. Recently, we demonstrated that melatonin downregulates gonadotropin-releasing hormone (GnRH) gene expression in the GT1-7 cell line, specifically at the level of the neuron-specific GnRH gene enhancer. In this study, we have examined the region located at -1736/-1728 of the GnRH enhancer shown to be involved in the repression of GnRH by melatonin. This region includes hexameric consensus binding sites for orphan nuclear receptors, including ROR/RZR and COUP-TFI, as well as other defined consensus binding sites for AP-1 and C/EBP. Using electrophoretic mobility shift analysis (EMSA), we have demonstrated that GT1-7 nuclear proteins bind specifically to this region of the GnRH enhancer to form 4 complexes. EMSA antibody supershift analysis indicates that the transcription factors COUP-TFI and C/EBP beta bind two specific complexes, but RORalpha, Oct-1, Pbx-1, c-fos, or c-jun antibodies failed to produce any detectable supershifts. These results provide the first evidence that melatonin may mediate its direct neuroendocrine control of GnRH gene expression through transcription factor binding at specific regions of the GnRH enhancer.

We have cloned the 5'-region of the murine N-methyl-d-aspartate (NMDA) receptor channel subunit NR2C (GluRepsilon3) gene and characterized the cis- and trans-activating regulatory elements responsible for its tissue specific activity. By using a native epsilon3-promoter/lacZ-construct & various 5'-deletion constructs, we compared beta-galactosidase expression in non-neuronal NIH3T3 cells and in neuronal epsilon3-gene-expressing HT-4 cells and show that large parts of the epsilon3 promoter are responsible for the repression of the epsilon3 gene in non-neuronal cells. Deletion of exon 1 sequences led to an enhancement of epsilon3 transcription, suggesting a role of the 5'-untranslated region in epsilon3 gene regulation. Sequence analysis of the promoter region revealed potential binding sites for the transcription factor Sp1, the murine fushi tarazu factor1 (FTZ-F1) homologues, embryonic LTR binding proteins (ELP1,2,3) and steroidogenic factor (SF-1), as well as for the chicken ovalbumin upstream promoter transcription-factor (COUP-TF). Electrophoretic mobility shift assays confirmed specific binding of Sp1, SF-1 and COUP-TFI. Whereas point mutation studies indicate that, in neuronal HT-4 cells, Sp1 is apparently not critically involved in basal epsilon3 gene transcription, SF1 is a positive regulator. This was evident from a selective enhancement of epsilon3-promoter-driven reporter gene expression upon cotransfection of an SF1-expression vector, which was reverted by deletion and point mutation of the SF1 binding site.

Measurement of hemodynamic parameters by noninvasive techniques is gaining more and more popularity in the face of severe complications associated with invasive methods. Thoracic electrical bioimpedance is a noninvasive means of estimating cardiac output (CO) and pulmonary edema formation. The validity of this method, however, has been controversial. In the present study a new bioimpedance monitoring system (NCCOM 3) was used in 10 intensive care patients undergoing mechanical hemofiltration (group I) and in 20 cardiac surgery patients undergoing either aortic valve replacement (AVR, group IIa, n = 10) or aorto-coronary bypass grafting (CABG, group IIb, n = 10). In cardiac surgery patients the measurements were performed before as well as after extracorporeal circulation (ECC). CO measured by the impedance monitor was compared to the standard thermodilution method; pulmonary fluids were estimated by a thermo-dye technique and by measurement of total electrical impedance (base impedance), expressed as the thoracic fluid index (TFI). The principal finding of the study was that CO as measured by the two techniques differed significantly in all groups with regard to absolute values. The relative changes in CO, however, were comparable in both intensive care patients and CABG patients. In patients with special thoracic blood flow conditions (regurgitation in aortic insufficiency patients), no corresponding course of CO could be found.(ABSTRACT TRUNCATED AT 250 WORDS)

Chicken ovalbumin upstream promoter-transcription factor I (COUP-TFI, or NR2F1) is an orphan nuclear receptor that plays a major role in the development of the nervous system. We show here that three ETS response elements in the COUP-TFI promoter mediate its transcription. A reporter gene containing these ETS binding sites is activated by Ets-1, while the same reporter with point mutations on all three ETS response elements is not. We also show that Ets-1 binds to these response elements and that other ETS factors also transactivate the COUP-TFI promoter. In addition, COUP-TFI is coexpressed with some ETS factors in the mouse embryo. These results indicate that members of the ETS family can activate COUP-TFI gene expression.

Down-regulation of the MHC class I enhancer in tumorigenic Ad12 cells is associated with strong binding of COUP-TF and negligible binding of activator NF-kappaB. By comparison, in nontumorigenic Ad5 cells, class I expression is high due to negligible binding of COUP-TF and strong binding of NF-kappaB. Here, we show that COUP-TFII, but not COUP-TFI, is expressed in Ad12-transformed cells. The dramatically stronger DNA binding of COUP-TFII to the class I enhancer in Ad12- compared to Ad5-transformed cells correlates with higher COUP-TFII promoter activity and higher levels of COUP-TFII mRNA and protein. Significantly, NF-kappaB p50/p52 double-knockout cells enabled us to demonstrate directly that COUP-TFII can completely repress both nonactivated and NF-kappaB-activated MHC class I transcription.

Apoptosis of nucleated cells is regulated by caspases, a group of cysteine proteases, and is characterized by phosphatidylserine expression on the outer leaflet of the plasma membrane. Reports indicate that platelets contain caspases. However, the role of caspases in platelet function is not well understood. When platelets become activated, they express phosphatidylserine (PS) on the outer leaflet of the plasma membrane. In addition, platelets aggregate when activated. The aims of this study were to determine if caspase inhibition (using the pan-caspase inhibitor zVAD-fmk): (1) decreased PS expression and (2) decreased platelet aggregation following activation. Flow cytometry was used to determine PS expression and a platelet aggregometer was used to assess aggregation. We found that platelets treated with zVAD-fmk significantly decreased both A23187-induced PS exposure (total fluorescence index, TFI: A23187=791.42+/-174; zVAD+A23187=92.97+/-57, p<==0.05) and ADP-induced PS exposure (TFI: ADP=669.24+/-145, zVAD+ADP=174.6+/-151, p<==0.05). Further, treatment with zVAD-fmk significantly decreased ADP-induced platelet aggregation (%: untreated=80+/-1.5, zVAD treated=69+/-3.0, p<==0.05). These results indicate that caspases play a role in platelet activation, suggesting a unique physiologic role for these proteases.

Previous studies have shown that retreatment of relapsed/refractory multiple myeloma (MM) with a second course of bortezomib therapy could be effective in heavily pre-treated patients. In this study, the results of a multicentre, retrospective survey were reported involving patients in Switzerland with MM who responded to initial bortezomib therapy; 43 patients were enrolled and 42 were evaluated for response. The overall response rate (complete response [CR] + near CR [nCR] + partial response [PR]) to bortezomib retreatment was 64.3%, and the clinical benefit rate (CR + nCR + PR + stable disease) for retreatment was 83%. The response rate to bortezomib retreatment in the subgroup with a first treatment-free interval (TFI) >6 months was higher than that in the subgroup with first TFI ≤6 months (74.1% vs. 46.7%) and lower in patients who received concomitant dexamethasone with bortezomib retreatment (57.1% vs. 78.6%). The median overall survival (OS) from first diagnosis of MM was 9.3 years, and after retreatment with bortezomib the median OS was 1.7 years. In total, 85.7% of patients who achieved CR or nCR with initial bortezomib treatment achieved CR or nCR with retreatment. Bortezomib as retreatment was well tolerated, and the safety profile was consistent with previous studies of bortezomib in relapsed MM. The most common adverse drug reaction attributed to bortezomib was peripheral neuropathy in 5 patients. In conclusion, bortezomib retreatment was a well-tolerated, effective therapeutic option for relapsed MM patients in the Swiss clinical setting who have previously responded to bortezomib, particularly for those who experienced an initial TFI of >6 months.

An artificial gravity and ergometric exercise loading device for human use was manufactured. It has the capacity of a max 2 G-load at the heart level, and a max 150 W of work-load. Eight subjects (six completed) were subjected to four repeated trials with or without 20 W ergometric exercise. Anti-G score, defined as the G-load x running time to the endpoint, was significantly higher in the exercise trials than standing trials. Heart rate (HR), mean arterial pressure (MAP), thoracic fluid index (TFI) were significantly superior during the exercise trials. Artificial gravity by centrifuge at 1.2 or 1.4 G with 40 or 60 W of ergometric workload may be an excellent countermeasure against cardiovascular deconditioning after long exposure to microgravity.

Different retinoic acid receptor-beta (RAR-beta) isoforms seem to have contrasting biological effects in human carcinogenesis. Both in vitro and in vivo data indicate that RAR-beta2 expression is frequently lost or reduced (and transfecting RAR-beta2 suppresses growth and promotes apoptosis) in various cancer cells and tissues, whereas RAR-beta4 expression is increased in several cancer cell lines. To clarify the effects of different RAR-beta isoforms in esophageal carcinogenesis, we used real-time quantitative reverse transcription-PCR to assess in vivo RAR-beta mRNA levels in specimens of normal and malignant human esophageal tissue, comparing these levels with each other and the expressions of other genes. RAR-beta2 mRNA expression was significantly reduced (i.e., lower in cancer than normal tissue) in 67% (18 of 27, P = 0.001) and RAR-beta(4) mRNA was increased in 52% (14 of 27, P = 0.054) of our esophageal cancer cases. The expressions of RAR-beta1, chicken ovalbumin upstream promoter-transcription factor-I (COUP-TFI), COUP-TFII, and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) mRNA were reduced, whereas epidermal growth factor receptor and cyclin D1 expressions were increased in tumor compared with in normal tissues. Reduced RAR-beta2 expression correlated with increased RAR-beta4 expression (P = 0.002) and with the suppression of COUP-TFI and COUP-TFII (P = 0.050 and 0.023, respectively) in tumor samples. These are the first in vivo expression patterns of RAR-beta2 and RAR-beta4 reported in humans or animals and support the in vitro data on these isoforms and their contrasting biological effects in human carcinogenesis.

Several anti-apoptotic proteins are induced in CA1 neurons after transient forebrain ischemia (TFI), but fail to protect the majority of these cells from demise. Correlating cell death morphologies (apoptosis-like and necrosis-like death) with immunohistochemistry (IHC), we investigated whether anti-apoptosis contributes to survival, compromises apoptosis effector functions and/or delays death in CA1 neurons 1-7 days after TFI. As surrogate markers for bioenergetic failure, the IHC of respiratory chain complex (RCC) subunits was investigated. Dentate granule cell (DGC) apoptosis following colchicine injection severed as a reference for classical apoptosis. Heat shock protein 70 (Hsp70), neuronal apoptosis inhibitory protein (NAIP) and manganese superoxide dismutase (MnSOD) were upregulated in the majority of intact CA1 neurons paralleling the occurrence of CA1 neuronal death (days 3-7) as well as in a proportion of apoptosis-(<50%) and necrosis-like (<30%) CA1 neurons. Colchicine did not provoke an anti-apoptotic response in DGC at all. In addition, more than 70% of apoptosis- and necrosis-like CA1 neurons had completely lost their RCC subunits suggesting bioenergetic failure; by contrast, following colchicine injection, 88% of all apoptotic DGC presented RCC subunits. Thus, anti-apoptotic proteins may, in a subset of ischemic CA1 neurons, prevent cell death, while in others, affected by pronounced energy failure, they may cause secondary necrosis.

BACKGROUND

Acoustic microstreaming (AMS) may be useful to the clinician when using the ultrasonic scaler to remove particulate matter from the teeth. The aim of this study was to detect and measure the effects of AMS produced by ultrasonic scalers.

METHODS

For the study, an ultrasonic generator was selected with 4 differently shaped scaling tip inserts (TFI-3, TFI-9, TFI-1, and P-12). A plaque substitute (0.2 mm thick soft cream cheese) was coated onto a microscope slide and immersed in water. The ultrasonic scaler tip was placed in the water and orientated either perpendicular or parallel to the slide. The instrument was operated both contacting the slide under a load of 0.3 N and non-contacting at various distances from the slide surface. This was repeated with the tip parallel to the slide. The area of medium removed was quantified by digital image analysis.

RESULTS

It was found that AMS removed the plaque substitute from around the tip. The TFI-9 insert significantly removed more material with increasing displacement amplitude (P <0.05). Significantly larger areas of plaque substitute were removed when the tips of the TFI-3, TFI-9, and P-12 inserts were orientated perpendicularly to the slide compared to the parallel orientation (P <0.05). Of the 4 inserts used, the TFI-9 insert removed the most material while the straight tip produced no apparent removal. Removal by AMS required the presence of a water medium and such forces were found to decrease with distance from the scaling tip. No plaque substitute removal was seen at a distance of 7 mm for the TFI-9 insert at 37.5 microm displacement with the tip orientation parallel to the slide.

CONCLUSIONS

It is concluded that AMS occurs around ultrasonic scalers and this depends on the displacement amplitude, tip orientation, and presence of a water medium. AMS may play a role in disruption of subgingival biofilms associated with periodontal disease.

Estrogen replacement therapy (ERT) elicits a deleterious, instead of protective, effect on neuropathology in diabetic ovariectomized (OVX) rats subjected to cerebral ischemia. This transformation may be linked to an estrogen-associated increase in function of the receptor for advanced glycation end-products (RAGE). Moreover, under diabetic conditions, advanced glycation end-products (AGEs) are excessively generated through the aldose reductase (AR)-polyol pathway. As such, in diabetic rats given ERT, a RAGE-related exacerbation of post-ischemic brain injury can occur. Thus, in the present study, we evaluated the contribution of AR in estrogen's detrimental effect on diabetic animals subjected to transient forebrain ischemia (TFI). Streptozotocin- and 17-beta estradiol-treated OVX female rats were divided into two groups, where AR activity was blocked using epalrestat; or AGEs production was restricted, via administrating the protein glycation crosslink breaker, ALT-711. In all animals, ERT was initiated approximately 10days before TFI. Pial venular leukocyte adhesion was evaluated over 10h post-TFI using a cranial window/intravital microscopy technique. In vehicle-treated control groups, a significant increase in leukocyte adhesion was observed post-TFI. Leukocyte extravasation, starting at approximately 6h post-TFI, was detected in most of the control animals. Chronic administration of either epalrestat or ALT-711 was associated with a marked decrease in post-TFI leukocyte adhesion, and the complete prevention of leukocyte extravasation. Animals receiving either epalrestat or ALT-711 exhibited a significant improvement in neurologic function, at 72h post-ischemia, compared to vehicle-treated controls. Post-ischemic (72h) histopathology was significantly reduced by epalrestat. Compared to the non-diabetic (ND) controls, diabetic OVX rats in the absence or presence of ERT showed a significant 2-fold or 3-fold increase in cortical AR mRNA levels, respectively. In contrast, only a modest increase in AR protein expression, relative to ND control, was detected in the two diabetic groups. The present findings suggest that AR participates in estrogen's deleterious action on post-ischemic neuropathology in diabetics by promoting inflammation. Targeting the AR-controlled polyol pathway may be a clinically promising strategy to restore the neuroprotection of ERT in diabetic females.

OBJECTIVE

To explore the association between fluoride in drinking water and the prevalence and severity of fluorosis and dental caries in children living in communities receiving fluoridated salt.

METHODS

Participants were schoolchildren (n = 457) living in two rural areas of the State of Morelos, Mexico, where the water fluoride concentration was 0.70 or 1.50 ppm. Dental caries status was assessed using Pitts' criteria. Lesions that were classified as D3 (decayed) were identified to determine the decayed, missing, and filled teeth index (D3MFT). Fluorosis was assessed using the Thylstrup-Fejerskov Index (TFI). Information regarding drinking water source and oral hygiene practices (tooth brushing frequency, dentifrice use, and oral hygiene index) was obtained.

RESULTS

The prevalence of fluorosis (TFI ≥1) in communities with 0.70 and 1.50 ppm water fluoride was 39.4 and 60.5% (p = 0.014), respectively, while the prevalence of more severe forms (TFI ≥4) was 7.9 and 25.5% (p < 0.001), respectively. The mean D3MFT was 0.49 (±1.01) in the 0.70 ppm community and 0.61 (±1.47) in the 1.50 ppm community (p = 0.349). A logistic regression model for caries (D3 >1) showed that higher fluorosis categories (TFI 5-6 OR = 6.81, p = 0.001) were associated with higher caries experience, adjusted by age, number of teeth present, tooth brushing frequency, bottled water use, and natural water fluoride concentration.

CONCLUSIONS

The prevalence of fluorosis was associated with the water fluoride concentration. Fluorosis at moderate and severe levels was associated with a higher prevalence of dental caries, compared with lesser degrees of fluorosis. The impact of dental fluorosis should be considered in dental public health programs.

BACKGROUND

Tumor of the follicular infundibulum (TFI) is a rare benign adnexal tumor that has characteristic histopathologic features.

OBJECTIVE

Our purpose was to describe the clinical and pathologic features of 12 patients with TFI.

METHODS

Of 121,500 cutaneous biopsy specimens recorded between 1981 and 1993, all TFIs were identified and examined by conventional microscopy. The clinical and histologic findings were compared with those of previously published cases.

RESULTS

Of the 12 patients, seven had a solitary tumor, two had eruptive TFI involving the face, and three TFIs were incidentally discovered in association with nevus sebaceus or fibroma. TFI-like changes were also observed in the wall of a hybrid cyst. The most discriminating features of TFI were the horizontal platelike organization of the tumor and the dense elastic network beneath the tumor. Of the different forms of TFI, only eruptive tumors can be clinically identified because they are small hypopigmented macules.

CONCLUSIONS

We classify TFIs as (1) solitary tumors, (2) eruptive tumors, (3) TFI associated with other lesions of Cowden's disease, (4) TFI associated with a single tumor such as nevus sebaceus, and (5) TFI-like epidermal changes.

BACKGROUND

We evaluated the patterns of care and clinical outcomes of metastatic breast cancer patients treated with first-line trastuzumab-based therapy after previous (neo)adjuvant trastuzumab.

METHODS

A total of 416 consecutive, HER2-positive metastatic breast cancer patients who had received first-line trastuzumab-based therapy were identified at 14 Italian centers. A total of 113 patients had presented with de novo stage IV disease and were analyzed separately. Dichotomous clinical outcomes were analyzed using logistic regression and time-to-event outcomes using Cox proportional hazards models.

RESULTS

In the 202 trastuzumab-naïve patients and 101 patients with previous trastuzumab exposure, we observed the following outcomes, respectively: overall response rate, 69.9% versus 61.3% (adjusted odds ratio [OR], 0.62; p = .131), clinical benefit rate, 79.1% versus 72.5% (adjusted OR, 0.73; p = .370), median progression-free survival (PFS), 16.1 months versus 12.0 months (adjusted hazards ratio [HR], 1.33; p = .045), and median overall survival (OS), 52.2 months versus 48.2 months (adjusted HR, 1.18; p = .404). Patients with a trastuzumab-free interval (TFI) <6 months, visceral involvement, and hormone receptor-negative disease showed a worse OS compared with patients with a TFI of ≥6 months (29.5 vs. 48.3 months; p = .331), nonvisceral involvement (48.0 vs. 60.3 months; p = .270), and hormone receptor-positive disease (39.8 vs. 58.6 months; p = .003), respectively.

CONCLUSIONS

Despite the inferior median PFS, trastuzumab-based therapy was an effective first-line treatment for patients relapsing after (neo)adjuvant trastuzumab. Previous trastuzumab exposure and the respective TFI, type of first site of disease relapse, and hormone receptor status should be considered in the choice of the best first-line treatment option for HER2-positive metastatic breast cancer patients.

BACKGROUND

Besides Chlamydiae trachomatis and Mycoplasma genitalium, Mycoplasma hominis may also cause infertility due to damage of the Fallopian tubes. Therefore serum samples from infertile women were analyzed for antibodies to M. hominis.

METHODS

Sera from 304 infertile women were investigated for seropositivity to M. hominis by immunoblotting and a developed ELISA. Women were classified into groups based on the type of infertility: infertile due to lack of passage in Fallopian tubes (TFI, tubal factor infertility), an infertile male partner (MFI, male factor infertility) and unexplained infertility (UFI, unexplained factor infertility). Three M. hominis isolates were used in the immunoblotting analysis and clear differences in patient immunoprofiles were observed between two isolates. For the ELISA we used a mixture of Triton X-114 extracted membrane proteins from those two M. hominis isolates as antigen.

RESULTS

Ninety-seven sera (32%) were seropositive to M. hominis when tested by the ELISA. There was a significant correlation between TFI and seropositivity to M. hominis (P = 0.0015, OR = 2.21, CI = 1.35-3.61). We compared the seropositivity of 304 patients to M. hominis with the presence of antibodies against two other bacteria Chlamydiae trachomatis and Mycoplasma genitalium and there was no statistical correlation between those bacteria and M. hominis.

CONCLUSIONS

Our results indicate that M. hominis may be an independent predictor of TFI.

In this article, we integrate medical anthropological and analytical epidemiological methods, forms of data analysis, and interpretive insights to examine the culture-specific behavioral factors that place poor, urban Egyptian women at risk of tubal-factor infertility (TFI). Such risk factors include biomedically and ethnomedically produced iatrogenesis, including the consequences of the practice of female circumcision, and male sexual behavior leading to sterilizing sexually transmitted diseases (STDs) in their female sexual partners. We examine the socio-cultural and political-economic context in which infertility-producing behavioral risk factors are maintained, and we explore the ways in which these risk factors are perceived by biomedically trained Egyptian gynecologists.

Chlamydia trachomatis infection is associated with pelvic inflammatory disease (PID) and tubal factor infertility (TFI). We investigated the role of C. trachomatis as a target antigen of endometrial and salpingeal tissue lymphocytes derived from PID and TFI patients. Antigen specificity of the tissue originated T lymphocyte lines (TLL) was tested against C. trachomatis elementary bodies and chlamydial heat shock protein 60 (CHSP60). C. trachomatis antigen stimulated proliferation in two out of eight endometrial TLL derived from PID patients and three out of four TLL derived from TFI patients. All (n = 4) TLL derived from the salpingeal specimens responded to CHSP60 compared with only one out of 12 TLL derived from the endometrial specimens. In-vivo expression of interferon-gamma (IFN-gamma) mRNA revealed that it was present in nine of 13 specimens obtained from PID patients. The dominant activity of type-1 T lymphocytes was confirmed by the in-vitro production of IFN-gamma (median 1007 pg/ml) from all (n = 5) C. trachomatis specific TLL while IL-5 secretion was lower (median 779 pg/ml). In conclusion, C. trachomatis reactive TLL were established from in-vivo activated lymphocytes from the upper genital tract tissue of PID and TFI patients. The reactivity of the salpingeal TLL to CHSP60 provided further evidence that immunoreactivity to CHSP60 is a predominant response in patients with tubal damage.

OBJECTIVE

Objective of our laboratory study was to determine the impact of dental fluorosis severity on the formation of caries in the human enamel and dentine.

METHODS

Thirty-three human molars were grouped according to modified Thylstrup-Fejerskov index (TFI) into normal (N, TFI 0), mild fluorosis (ML, TFI 1-3) and moderate fluorosis (MD, TFI 4-6). Three mesio-distal sections were made in corono-apical axis of the tooth, giving enamel and dentine samples. They were embedded in an epoxy resin, and polished. Half of the polished surface was covered with an acid resistant varnish and immersed in standard acidified buffer solution (pH 4.5) for 48 h to create artificial caries lesions. They were treated with 5% NaOCl for 45 min and sectioned longitudinally along the center into two halves. Cut surfaces were polished and observed under a confocal laser scanning microscope for depth of demineralization. Morphology of the demineralized zones was observed under a field emission scanning electron microscope (FE-SEM). Data were analyzed using one-way ANOVA and Sheffe test (p=0.05).

RESULTS

Statistically significant difference in depth of demineralization was found between N and MD groups (p=0.046) in the enamel, and between N and ML (p=0.002), N and MD (p<0.001), ML and MD (p=0.029) in dentine. FE-SEM observation of the normal enamel showed direct dissolution with large fissures. Spongy appearance of intertubular dentine gradually disappeared from N to MD.

CONCLUSIONS

Moderately fluorosed enamel showed a significant caries resistance. In contrast, mild and moderately fluorosed dentine was significantly caries susceptible in vitro.

OBJECTIVE

To determine the effect of grinding on the bonding effectiveness of a self-etch and an etch-and-rinse adhesive to fluorosed enamel.

METHODS

The teeth were classified using the Thylstrup and Fejerskov index (TFI). Fluorosed teeth (TFI=5) obtained from Isparta (Turkey) and control teeth (TFI=0) obtained from Leuven (Belgium) were used. Using a depth-marking diamond bur, 0.3mm of enamel was removed from mid-buccal and mid-palatal/lingual surfaces of the teeth, whereas the area adjacent to the ground area was left unprepared. A two-step self-etch (Clearfil Protect Bond, Kuraray) and a three-step etch-and-rinse adhesive (Optibond FL, Kerr) were used to bond the resin composite to the ground and unground enamel. Rectangular micro-specimens were prepared using the slow-speed diamond saw and tested in tensile to determine the micro-tensile bond strength (microTBS).

RESULTS

The microTBS to unground fluorosed enamel was significantly lower than to ground fluorosed enamel for Clearfil Protect Bond (15.8+/-15.2 and 45.0+/-12.4MPa, p<0.0001) and for Optibond FL (35.5+/-21.4 and 50.5+/-12.3MPa, p<0.05), respectively. In control teeth, Clearfil Protect Bond bonded better to ground enamel (p<0.01), whereas OptiBond FL exhibited a similar bonding effectiveness to ground and unground enamel (p=0.0634).

CONCLUSIONS

Preparation of enamel improved the resin-enamel bond strength in fluorosed teeth. The bonding effectiveness to unground enamel was lower in fluorosed teeth than in control teeth for the self-etch adhesive tested.