Symptomatic Research Articles

Expression levels of the receptor activator of NF-κB ligand and osteoprotegerin and the number of gram-negative bacteria in symptomatic and asymptomatic periapical lesions

ObjectiveThe study aimed to verify the potential correlation between the detected amount of gram-negative bacteria and the radiographic sizes of the lesions in patients with symptomatic and asymptomatic apical periodontitis. Furthermore, to evaluate whether the expression of receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) and the RANKL/OPG ratio are differentially regulated in both groups. DesignTwenty patients with periapical lesions were divided into two groups: symptomatic (SYM) n=10 and asymptomatic (ASYM) n=10. After periapical surgery, the lesions were collected and processed for histological examination, and immunohistochemistry. The percentage of RANKL- and OPG-immunopositive areas relative to the total area of the microscopic field was calculated. For gram staining, the number of gram-negative cells per microscopic field was assessed. The radiographs of each patient were processed and measured. The Student’s t-test and the Pearson correlation coefficient were performed. ResultsThe SYM group showed a significantly higher number of gram-negative cells (p=0.007) when compared to the ASYM group. A higher number of gram-negative bacteria occurred more frequently in larger periapical lesions and the SYM group (p=0.03). The expression for RANKL and OPG and the RANKL/OPG ratio were not significantly different between the groups. There was a significant positive correlation between the number of bacteria and OPG levels in the SYM group (p=0.01). ConclusionThe number of bacteria seems to influence the symptoms and the radiographic size of a periapical lesion. Gram-negative bacteria may play an important role in OPG activity in the SYM group.

Musculoskeletal loading in the symptomatic and asymptomatic knees of middle-aged osteoarthritis patients.

This study quantified the contributions by muscles, gravity, and inertia to the tibiofemoral compartment forces in the symptomatic (SYM) and asymptomatic (ASYM) limbs of varus mal-aligned medial knee osteoarthritis (OA) patients, and compared the results with healthy controls (CON). Muscle forces and tibiofemoral compartment loads were calculated using gait data from 39 OA patients and 15 controls aged 49 ± 7 years. Patients exhibited lower knee flexion angle, higher hip abduction, and knee adduction angles, lower internal knee flexion torque but higher external knee adduction moment. Muscle forces were highest in CON except hamstrings, which was highest in SYM. ASYM muscle forces were lowest for biceps femoris short head and gastrocnemius but otherwise intermediate between SYM and CON. In all subjects, vasti, hamstrings, gastrocnemius, soleus, gluteus medius, gluteus maximus, and gravity were the largest contributors to medial compartment force (MCF). Inertial contributions were negligible. Highest MCF was found in SYM throughout stance. Small increases in contributions from hamstrings, gluteus maximus, gastrocnemius, and gravity at the first peak; soleus and rectus femoris at the second peak; and soleus, gluteus maximus, gluteus medius, and gravity during mid-stance summed to produce significantly higher total MCF. Compared to CON, the ASYM limb exhibited similar peak MCF but higher mid-stance MCF. In patients, diminished non-knee-spanning muscle forces did not produce correspondingly diminished MCF contributions due to the influence of mal-alignment. Our findings emphasize consideration of muscle function, lower-limb alignment, and mid-stance loads in developing interventions for OA, and inclusion of the asymptomatic limb in clinical assessments. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:321-330, 2017.

White Matter Abnormalities Track Disease Progression in PSEN1 Autosomal Dominant Alzheimer's Disease.

PSEN1 mutations are the most frequent cause of autosomal dominant Alzheimer's disease (ADAD), and show nearly full penetrance. There is presently increasing interest in the study of biomarkers that track disease progression in order to test therapeutic interventions in ADAD. We used white mater (WM) volumetric characteristics and diffusion tensor imaging (DTI) metrics to investigate correlations with the normalized time to expected symptoms onset (relative age ratio) and group differences in a cohort of 36 subjects from PSEN1 ADAD families: 22 mutation carriers, 10 symptomatic (SMC) and 12 asymptomatic (AMC), and 14 non-carriers (NC). Subjects underwent a 3T MRI. WM morphometric data and DTI metrics were analyzed. We found that PSEN1 MC showed significant negative correlation between fractional anisotropy (FA) and the relative age ratio in the genus and body of corpus callosum and corona radiate (p < 0.05 Family-wise error correction (FWE) at cluster level) and positive correlation with mean diffusivity (MD), axial diffusivity (AxD), and radial diffusivity (RD) in the splenium of corpus callosum. SMC presented WM volume loss, reduced FA and increased MD, AxD, and RD in the anterior and posterior corona radiate, corpus callosum (p < 0.05 FWE) compared with NC. No significant differences were observed between AMC and NC in WM volume or DTI measures. These findings suggest that the integrity of the WM deteriorates linearly in PSEN1 ADAD from the early phases of the disease; thus DTI metrics might be useful to monitor the disease progression. However, the lack of significant alterations at the preclinical stages suggests that these indexes might not be good candidates for early markers of the disease.

PWE-024 The colorectal cancer mdt: how many errors occur, do they matter and can they be averted?

Introduction The colorectal cancer multidisciplinary team (CRC MDT) provides a common pathway for patients from Bowel Cancer Screening (BCS), symptomatic (SYM), 2-week wait (2WW) and tertiary (TER) pathways. These pathways are complex and variable and hence error prone. Improved endoscopic techniques have transformed CRC management but little is known about improvements required for the MDT. Enhancing MDT quality by addressing errors can raise quality assurance at the bridge between diagnostic and therapeutic pathways. Objectives: To prospectively record Patient Safety Incidents (PSIs) identified at CRC MDT across different patient pathways. Method Two independent clinical observers prospectively evaluated CRC MDTs in real time. Patients were subcategorised by clinical pathway: BCS, 2WW, SYM and TER. PSIs were noted qualitatively for each patient and subsequently categorised. PSIs were defined as near misses, adverse events and sub-optimal clinical processes negatively impacting the patient’s cancer care. Results 412 MDT patient discussions (SYM n = 165, 2WW n = 97, TER n = 97 BCS n = 53) over 27 meetings were prospectively analysed. Medical notes were unavailable for 73 (21%) patients. 146 PSIs were identified: SYM n = 62 (42%), 2WW n = 37 (25%), TER n = 31 (21%), BCS n = 16 (11%). There was a trend towards more errors in the SYM group and fewer in BCS, although there was no significant difference between groups (p = 0.39). [Table 1][1]illustrates examples of severe PSIs. Many PSIs related to miscommunication, incomplete clinical data and poor non-technical skills such as leadership and inclusive team discussion. Although many PSIs did not have direct patient consequences they represent areas for improvement to avoid future significant errors. ![Abstract PWE-024 Table 1][2] Abstract PWE-024 Table 1 Conclusion Multiple errors were observed across the CRC MDT irrespective of patient subgroups. We propose a minimum patient data set and MDT team training in non-technical skills. Further work is underway to categorise PSIs by expert consensus, identify strategies to prevent avoidable error and ensure accountability for correcting errors. Examining PSIs arising outside the MDT provides a valuable opportunity to correct errors in other parts of the cancer pathway that may otherwise go un-noticed. Disclosure of interest None Declared. [1]: #F1 [2]: pending:yes

Herpes simplex virus type 1 glycoprotein B-specific effector memory CD8+ T cells are associated with asymptomatic ocular herpes disease in both humans and "humanized" HLA transgenic mice (HUM6P.245)

Abstract We have dissected the phenotype and the function of HSV-1 glycoprotein B- (gB-) specific CD8+ T cells from HLA-A*02:01 positive, HSV-1 seropositive asymptomatic (ASYMP) individuals (who have never had clinical herpes disease) and symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent ocular herpes disease). We found that: (i) healthy ASYMP individuals maintained a significantly higher proportion of differentiated HSV-1 gB-specific effector memory CD8+ T cells (TEM, CD45RAlowCCR7lowCD44highCD62Llow). In contrast, SYMP patients had frequent less-differentiated central memory CD8+ T cells (TCM, CD45RAlowCCR7highCD44lowCD62Lhigh); (ii) ASYMP individuals had significantly higher proportions of multi-functional effector CD8+ T cells, which responded mainly to gB342-350 and gB561-569 “ASYMP” epitopes, and simultaneously produced IFN-g, CD107a/b, granzyme B and perforin. In contrast, effector CD8+ T cells from SYMP individuals were mostly mono-functional and were directed mainly against non-overlapping gB17-25 and gB183-191 “SYMP” epitopes; (iii) immunization of HLA-A*02:01 transgenic mouse model of ocular herpes with “ASYMP” CD8+ TEM cell epitopes, but not with “SYMP” CD8+ TCM cell epitopes, induced a strong CD8+ T cell-dependent protective immunity against ocular herpes infection and disease. Our findings provide insights into the role of CD8+ TEM cells in protection against herpes and should be considered in the development of an effective vaccine.

Herpes simplex virus tegument protein VP11/12-derived epitopes preferentially recall polyfunctional effector memory CD8+ T cells from seropositive asymptomatic individuals and protect “humanized” HLA-A*02:01 transgenic mice against ocular herpes (VIR6P.1172)

Abstract In this study, we used multiple prediction computer-assisted algorithms to identify 10 potential HLA-A*02:01-restricted CD8+ T cell epitopes from the 716 amino acids sequence of Herpes Simplex Virus type 1 virion tegument phosphoprotein 11/12 (HSV-1 VP11/12). Three out of ten epitopes exhibited high to moderate binding affinity to HLA-A*02:01 molecules. In ten sequentially studied HLA-A*02:01 positive, HSV seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease), the most frequent, robust and polyfunctional effector CD8+ T-cell responses, as assessed by a combination of tetramer frequency, granzyme B, granzyme K, perforin, CD107a/b cytotoxic degranulation, IFN-g and multiplex cytokines assays, were predominantly directed against three epitopes: VP11/1266-74, VP11/12220-228 and VP11/12702-710. Interestingly, ASYMP individuals had significantly higher proportion of CD45RAlowCCR7lowCD44highCD62LlowCD27lowCD28lowCD8+ effector memory T cells (TEM) specific to the three epitopes, compared to symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent ocular herpetic disease). Moreover, immunization of HLA-A*02:01 transgenic mice with the three ASYMP CD8+ TEM cell epitopes induced a strong protective immunity against ocular herpes infection and disease. Our findings outline the features of protective HSV-specific CD8+ T cells that should guide the development of an effective T-cell-based herpes vaccine.

Phenotypic and functional characterization of herpes simplex virus glycoprotein B epitope-specific effector and memory CD8+ T cells from symptomatic and asymptomatic individuals with ocular herpes.

Herpes simplex virus 1 (HSV-1) glycoprotein B (gB)-specific CD8(+) T cells protect mice from herpes infection and disease. However, whether and which HSV-1 gB-specific CD8(+) T cells play a key role in the "natural" protection seen in HSV-1-seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease) remain to be determined. In this study, we have dissected the phenotypes and the functions of HSV-1 gB-specific CD8(+) T cells from HLA-A*02:01 positive, HSV-1 seropositive ASYMP and symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent ocular herpes disease). We found the following. (i) Healthy ASYMP individuals maintained a significantly higher proportion of differentiated HSV-1 gB-specific effector memory CD8(+) T cells (TEM cells) (CD45RA(low) CCR7(low) CD44(high) CD62L(low)). In contrast, SYMP patients had frequent less-differentiated central memory CD8(+) T cells (TCM cells) (CD45RA(low) CCR7(high) CD44(low) CD62L(high)). (ii) ASYMP individuals had significantly higher proportions of multifunctional effector CD8(+) T cells which responded mainly to gB342-350 and gB561-569 "ASYMP" epitopes, and simultaneously produced IFN-γ, CD107(a/b), granzyme B, and perforin. In contrast, effector CD8(+) T cells from SYMP individuals were mostly monofunctional and were directed mainly against nonoverlapping gB17-25 and gB183-191 "SYMP" epitopes. (iii) Immunization of an HLA-A*02:01 transgenic mouse model of ocular herpes with "ASYMP" CD8(+) TEM cell epitopes, but not with "SYMP" CD8(+) TCM cell epitopes, induced a strong CD8(+) T cell-dependent protective immunity against ocular herpes infection and disease. Our findings provide insights into the role of HSV-specific CD8(+) TEM cells in protection against herpes and should be considered in the development of an effective vaccine. A significantly higher proportion of differentiated and multifunctional HSV-1 gB-specific effector memory CD8(+) T cells (TEM cells) (CD45RA(low) CCR7(low) CD44(high) CD62L(low)) were found in healthy ASYMP individuals who are seropositive for HSV-1 but never had any recurrent herpetic disease, while there were frequent less-differentiated and monofunctional central memory CD8(+) T cells (TCM cells) (CD45RA(low) CCR7(high) CD44(low) CD62L(high)) in SYMP patients. Immunization with "ASYMP" CD8(+) TEM cell epitopes, but not with "SYMP" CD8(+) TCM cell epitopes, induced a strong protective HSV-specific CD8(+) T cell response in HLA-A*02:01 transgenic mice. These findings are important for the development of a safe and effective T cell-based herpes vaccine.

Filtering approach based on empirical mode decomposition improves the assessment of short scale complexity in long QT syndrome type 1 population.

This study assesses the complexity of heart period (HP) and QT variability series through sample entropy (SampEn) in long QT syndrome type 1 individuals. In order to improve signal-to-noise ratio SampEn was evaluated over the original series (SampEn0) and over the residual computed by subtracting the first oscillatory mode identified by empirical mode decomposition (SampEn(EMD1R)). HP and QT interval were continuously extracted during daytime (2:00-6:00 PM) from 24 hour Holter recordings in 14 non mutation carriers (NMCs) and 34 mutation carriers (MCs) subdivided in 11 asymptomatic (ASYMP) and 23 symptomatic (SYMP). Both NMCs and MCs belonged to the same family line. While SampEn0 did not show differences among the three groups, Samp(EnEMD1R) assessed over the QT series significantly decreased in ASYMP subjects. SampEn(EMD1R) identified a possible factor (i.e. the lower short scale QT complexity) that might contribute to the different risk profile of the ASYMP group.

Exogenous protein HSP70 blocks neurodegeneration in the rat model of the clinical stage of Parkinson's disease.

According to modern views, impairment of protein folding is a serious danger for cell survival and a molecular basis for neurodegeneration (1, 2). A decrease in the activity of the ubiquitin proteasome system, which is responsible for disposal of misfolded proteins, may cause accumulation of toxic oligomers of α synuclein and degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars com� pacta (SNpc) and their axons in the striatum. This mechanism plays the key role in the pathogenesis of Parkinson's disease (PD) (3-6). This disease still has no cure due to commonly late diagnosis and symp� tomatic treatment, which cannot stop neuron death (7, 8). In recent years, the use of chaperones, particu� larly heat shock proteins of the 70�kDa family (HSP70), which are able to recover misfolded pro� teins, is considered as a promising therapeutic strategy, including treatment of PD (9-13). Neurons of SNpc during a moderate decrease in proteasome function survive mainly when they have increased content of inducible chaperone Hsp70i (14). The protective effects of exogenous Hsp70i in PD have not been stud� ied. The aim of this study was to investigate if intrana� sal administration of recombinant Hsp70i could atten� uate neurodegeneration and reduce motor impair� ment in the model of the clinical stage of PD. The rat model of a prolonged clinical stage of PD (up to 21 days) was created using the modern views on the molecular mechanisms of neurodegeneration by diminishing the proteasome activity in the nigrostri� atal system. The protective effects of exogenous Hsp70 were evaluated in this model. We discovered for the first time that intranasal administration of recombi� nant Hsp70 in the dynamics of clinical stage reduced the loss of DAergic neurons in SNpc by a factor of two and recovered motor functions. Our results can be used for further clinical study of chaperones drugs and their inductors elevating the Hsp70 level in the brain to develop methods of preventive treatment and to search new ways of blocking neurodegeneration at the clinical stage of PD. These results can be considered to be a priority. The study was carried out on male Wistar rats

Evolving Brain Functional Abnormalities in PSEN1 Mutation Carriers: A Resting and Visual Encoding fMRI Study

PSEN1 mutations are the most frequent cause of familial Alzheimer's disease and show nearly full penetrance. Here we studied alterations in brain function in a cohort of 19 PSEN1 mutation carriers: 8 symptomatic (SMC) and 11 asymptomatic (AMC). Asymptomatic carriers were, on average, 12 years younger than the predicted age of disease onset. Thirteen healthy subjects were used as a control group (CTR). Subjects underwent a 10-min resting-state functional magnetic resonance imaging (fMRI) scan and also performed a visual encoding task. The analysis of resting-state fMRI data revealed alterations in the default mode network, with increased frontal connectivity and reduced posterior connectivity in AMC and decreased frontal and increased posterior connectivity in SMC. During task-related fMRI, SMC showed reduced activity in regions of the left occipital and left prefrontal cortices, while both AMC and SMC showed increased activity in a region within the precuneus/posterior cingulate, all as compared to CTR. Our findings suggest that fMRI can detect evolving changes in brain mechanisms in PSEN1 mutation carriers and support the use of this technique as a biomarker in Alzheimer's disease, even before the appearance of clinical symptoms.

Periodontopathogen and Epstein-Barr Virus-Associated Periapical Periodontitis May Be the Source of Retrograde Infectious Peri-Implantitis

Herpesviral-bacterial synergism may play a role in periodontitis and peri-implantitis etiopathogenesis. Periapical periodontitis (PP) lesions can predict future apical peri-implantitis complications. This pilot study aimed to substantiate herpesviral-bacterial coinfection in symptomatic (SP) and asymptomatic (AP) PP and assess associations with periodontopathogen salivary contamination in patients receiving implants. Polymerase chain reaction (PCR)-based identification was performed on PP granulation tissue (GT) from 33 SP and AP patients and compared with unstimulated whole saliva. Quantitative PCR evaluated Epstein-Barr virus (EBV) and cytomegalovirus copy counts. SP GT had higher proportions of periodontopathogens. Symptomatic patients were 3.7 times more likely to be infected with EBV than AP (p = .07; 95% CI: 0.8-16.2). SP were 2.9, 2.1, 3.6, and 1.6 times more likely to be infected with Treponema denticola, Prevotella intermedia, Aggregatibacter actinomycetemcomitans, and Porphyromonas gingivalis, respectively. The odds ratio of EBV infecting PP lesions was two times higher in those positive for the virus in saliva. Saliva Tannerella forsythia-positive patients were 15 times more likely to present this pathogen in PP lesions (p = .038). Saliva EBV-positive individuals were 7 and 3.5 times more likely to yield GT contamination with T. forsythia and T. denticola, respectively. EBV copy counts were significantly higher in SP (p < .01). A causal association between EBV, specific bacterial anaerobic infection, and symptomatic PP is likely. EBV high prevalence underscores the viral etiological importance. Salivary EBV contamination is likely to be associated with viral and bacterial GT infection. Saliva PCR analysis can be a good predictor of GT specific infection and help establish antimicrobial therapy. If confirmed by prospective longitudinal clinical trials, antiviral therapy could possibly benefit SP and nonresponsive to treatment individuals and help prevent potential peri-implant infectious complications.

Neopterin: A potential marker in chronic peripheral arterial disease

Neopterin is a marker of macrophage activation that has exhibited high plasma levels in atherosclerotic diseases including coronary heart disease and critical limb ischemia. The role of neopterin in chronic peripheral arterial disease (PAD) has yet to be elucidated. In the present study, neopterin (Ν) serum concentrations were analyzed in asymptomatic (AsP) and symptomatic (SyP) patients with PAD as well as controls (C). In total 120 subjects, 40 AsP [ankle brachial index (ABI) ≤0.90], 40 SyP (ABI ≤0.90 plus pain in legs) and 40 controls (ABI >0.9) were enrolled. The results of the present study showed that neopterin plasma levels were statistically different among the groups. These findings demonstrated that activation of N‑mediated monocyte‑macrophage, was also observed in chronic PAD.

Expression Levels of Matrix Metalloproteinase-9 and Gram-negative Bacteria in Symptomatic and Asymptomatic Periapical Lesions

IntroductionThe aim of this study was to test the hypothesis that the expression of matrix metalloproteinase (MMP)-9 is significantly elevated in patients with symptomatic apical periodontitis and to correlate this with the detected amount of gram-negative bacteria. MethodsTwenty-six patients with periapical lesions involving at least 2 teeth were included in this study. The patients were divided into 2 groups: the symptomatic (SYM) group included 13 patients expressing pain with periapical lesions, and the asymptomatic (ASYM) group included 13 patients expressing no pain. Root canal treatment was performed followed by endodontic surgery and periapical lesion collection. Periapical lesions were serially cut into 4-μ sections. Some sections were processed for histologic examination using hematoxylin-eosin stain. Other sections were processed for immunohistochemical examination. For MMP-9, the area fraction of the positive cells was measured, and the percentage of the MMP-9–immunopositive area to the total area of the microscopic field was calculated. For gram-negative stain cells, the number of cells showing the pink-red color was counted per microscopic field. The Student's t test was used to compare the SYM and ASYM groups. The Pearson correlation coefficient was used to determine a significant correlation between the number of cells and the MMP-9 level. The significance level was set at P ≤ .05. ResultsThe SYM group showed a statistically significantly higher mean number of gram-negative cells (P = .001) and MMP-9 area percent (P < .001) than the ASYM group. There was a statistically significant positive (r = .927) correlation between the number of gram-negative cells and the MMP-9 area percent (P < .001). ConclusionsThere is good evidence to suspect a significant role of gram-negative bacteria and MMP-9 in symptomatic periapical lesions.

Vulnerable Vulvas: Female Genital Integrity in Health and Dis-ease

Vulnerable Vulvas: Female Genital Integrity in Health and Dis-ease ChristineLabuski There's only so much it can give before it either splits oryou just cry "Uncle!" You know the vulva isn't an easy place to look. You are like 100 percent of women who walk in the door. The vulva gets... I don't want to say, forgotten. —Dr. Robichaud, vulva clinic physician I started thinking about the vulva in earnest in the early 1990s. To be clear, it wasn't a big leap; I was already a gynecological nurse practitioner. But having come of professional age in reproductive health clinics, I was accustomed to directing my attention toward the practices that undermined the sexual health of my patients, rather than toward the more material aspects of their bodies. "Why aren't you using condoms with your new partner?" and "How can I help you to avoid another unwanted pregnancy?" were the typical—and behaviorally laden — circuits through which I assessed my patients' well-being. A current of genital hesitation was palpable during these encounters, most of which were literally framed by gynecological stirrups: a drape sheet pulled tightly over the knees, being "grossed out" by explicit references to female anatomy, or a flat refusal of the mirror I routinely offered for mutual genital inspection. During these years, I occasionally speculated about whether this hesitation affected FeministStudies39, no. 1. © 2013 by Feminist Studies, Inc. 248 Christine Labuski 249 the sexual choices that my patients made. But ultimately their vulvas, like their vaginas and internal pelvic cavities, were more like bodily vehicles through which I worked my women's health magic; canvases upon which I could inscribe the (feminist) rules and regulations for a sexually "healthy" lifestyle. This changed on the day I saw the before and after photographs of a woman who had undergone a cancer-related radical vulvectomy. I was at a women's health conference, attending a session about gyne cological cancers. I didn't specialize in oncology, but the presenter had moonlighted several years earlier at the abortion clinic where I worked. Dr. Nichols was compassionate, bright, and informative, and I was fully expecting to learn something from him;11 was not, how ever, prepared for the larger-than-life images that loomed before me that afternoon. Labia that had once protruded outward from the vaginal opening, touching themselves in their fleshy symmetry, had been replaced by a sheet of shiny white skin; hairless and with out a fold in sight, this stretch of skin was interrupted by two open ings whose more functional aspects were now very hard to miss. Even Nichols's engaging style could not mitigate the intensity of seeing a woman whose vulva had been cut away so drastically. Nor could it diminish the dismay I felt after hearing that she had been symp tomatic for quite some time. Nichols underscored that this case was far from unique and that, although malignancies were often subtle, female genitalia were too often lost because neither women nor their providers adequately understood what constituted a normal vulva. These days I think about vulvas almost constantly, only now I do so as a cultural anthropologist. Instead of asking questions about the individual behaviors of a particular woman, I examine collec tive practices, specifically those that structure the hesitation toward female genitalia that I am now certain conditions the reality of vulvar cancer. Recently my research led me to this recommendation, from a 2004 overview of gynecological cancers: Because there is evidence of diagnostic delays, that is, women seek medical care in advanced stages of the disease, some authors recom mend that women perform self-examination monthly and also that physicians be made aware of the features of [vulvar] disease.2 250 Christine Labuski Like Nichols, these authors (Duarte-Franco and Franco) ask clini cians to be more proactive in their vulvar surveillance: to promote more self-exams and to learn more about the diagnostic features of malignant abnormalities. Missing from their unfortunately brief discussion, however, are recommendations toward achieving either of these goals. A primary goal of this essay is to initiate a discussion about the challenges involved in promoting vulvar self-examinations in the...

Treatment options for lumbar spinal stenosis in the elderly - an evidence based approach to a staged stepwise surgical treatment

Spinal stenosis is found frequently in the elderly, especially after the age of 55. The condition has become increasingly symp tomatic of longer life expectancy and a more active life style in the senior age group. Symptoms can range from an occasional, spontaneously reversible backache and claudication to full blown severe walking difficulties. More severe presentations of this condi- tion frequently lead to a more rapid advancement of other existing co-morbidities such as Diabetes Mellitus and Ischemic Heart Diseases, which require the ability to regularly exercise in order to maintain good control over the condition.

Relationship between neuropathology and disease progression in the SOD1 G93A ALS mouse

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons. However, recent reports suggest an active role of non-neuronal cells in the pathogenesis of the disease. Here, we examined quantitatively the temporal development of neuropathologic features in the brain and spinal cord of a mouse model of ALS (SOD1 G93A). Four phases of the disease were studied in both male and female SOD1 G93A mice: presymptomatic (PRE-SYM), symptomatic (SYM), endstage (ES) and moribund (MB). Compared to their control littermates, SOD1 G93A mice showed an increase in astrogliosis in the motor cortex, spinal cord and motor trigeminal nucleus in the SYM phase that worsened progressively in ES and MB animals. Associated with this increase in astrogliosis was a concomitant increase in motor neuron cell death in the spinal cord and motor trigeminal nucleus in both ES and MB mice, as well as in the ventrolateral thalamus in MB animals. In contrast, microglial activation was significantly increased in all the same regions but only when the mice were in the MB phase. These results suggest that astrogliosis preceded or occurred concurrently with neuronal degeneration whereas prominent microgliosis was evident later (MB stage), after significant motor neuron degeneration had occurred. Hence, our findings support a role for astrocytes in modulating the progression of non-cell autonomous degeneration of motor neurons, with microglia playing a role in clearing degenerating neurons.

Recommendations for standardization and phenotype definitions in genetic studies of osteoarthritis: the TREAT-OA consortium

To address the need for standardization of osteoarthritis (OA) phenotypes by examining the effect of heterogeneity among symptomatic (SOA) and radiographic osteoarthritis (ROA) phenotypes. Descriptions of OA phenotypes of the 28 studies involved in the TREAT-OA consortium were collected. We investigated whether different OA definitions result in different association results by creating various hip OA definitions in one large population based cohort (the Rotterdam Study I (RSI)) and testing those for association with gender, age and body mass index using one-way ANOVA. For ROA, we standardized the hip-, knee- and hand ROA definitions and calculated prevalence's of ROA before and after standardization in nine cohort studies. This procedure could only be performed in cohort studies and standardization of SOA definitions was not feasible at this moment. In this consortium, all studies with SOA phenotypes (knee, hip and hand) used a different definition and/or assessment of OA status. For knee-, hip- and hand ROA five, four and seven different definitions were used, respectively. Different hip ROA definitions do lead to different association results. For example, we showed in the RSI that hip OA defined as "at least definite joint space narrowing (JSN) and one definite osteophyte" was not associated with gender (P =0.22), but defined as "at least one definite osteophyte" was significantly associated with gender (P=3×10(-9)). Therefore, a standardization process was undertaken for ROA definitions. Before standardization a wide range of ROA prevalence's was observed in the nine cohorts studied. After standardization the range in prevalence of knee- and hip ROA was small. Phenotype definitions influence the prevalence of OA and association with clinical variables. ROA phenotypes within the TREAT-OA consortium were standardized to reduce heterogeneity and improve power in future genetics studies.

A 56‐Year‐Old Woman with Rash, Paralytic Ileus, and Massive Gastrointestinal Bleeding

Diagnosis: Strongyloides stercoralis hyperinfection syndrome in a patient with human T lymphotropic virus type 1 (HTLV 1) infection. The duodenal sample obtained through a nasogastric tube showed multiple filariform larvae of Strongyloides stercoralis (figure 1; figure 2). Enzyme-linked immunosorbent assay (ELISA) test for toxins of Clostridium difficile had negative results, and stool cultures for bacteria showed no growth. Cultures of blood samples obtained during the abdominal catastrophe were positive for Escherichia coli. Strongyloidiasis is a parasitic disease that is caused by the soil-transmitted nematode 5. stercoralis, which is estimated to affect almost 300 million people worldwide. Once infected, humans may harbor the parasite for decades. Most of the in fections due to S. stercoralis are asymptomatic or mildly symp tomatic. However, in the presence of immunosuppressive con ditions (such as high-dose steroid use, use of cytotoxic drugs, malignancies, human immunodeficiency virus infection, mal nutrition, and more recently, HTLV-1 infection), an autoin fective cycle may ensue that amplifies the infection and leads to the hyperinfection syndrome [1], Multiple erosions in the colonic mucosa result from the migration of the filariform lar va across the intestinal wall and may induce massive bleed ing, which is associated with significant mortality [2]. The family history of T cell leukemia lymphoma in this patient raised the suspicion of HTLV-1 infection, which was confirmed by means of an ELISA and Western blot tests. The patient recalled that her sister had also been infected with HTLV-1. Further evaluation of her relatives revealed that 2 of

Palatal tremor in childhood: clinical and therapeutic considerations

Palatal tremor (PT) is a rhythmic movement of the soft palate that often causes an ear click. PT can be symptomatic (SPT) or essential (EPT). The symptomatic form usually occurs in adults and the essential form mainly occurs in children. Several different treatments for EPT in children appear in the literature with variable reported efficacy. This report details four paediatric patients with EPT (three males, one female; mean age 6y 4mo [SD 6mo]; age at onset 6–7y) treated with piracetam (2‐oxo‐1‐pyrrolidine acetamide). Piracetam was used to treat EPT because of its antimyoclonic properties. All children showed a good response to doses of 100 to 300mg/kg/day. EPT relapsed on withdrawal of piracetam and remitted on reintroduction. Piracetam's effect on EPT was sustained. It is concluded that piracetam is an effective drug for the treatment of EPT in children.

Palatal tremor in childhood: clinical and therapeutic considerations

Palatal tremor (PT) is a rhythmic movement of the soft palate that often causes an ear click. PT can be symptomatic (SPT) or essential (EPT). The symptomatic form usually occurs in adults and the essential form mainly occurs in children. Several different treatments for EPT in children appear in the literature with variable reported efficacy. This report details four paediatric patients with EPT (three males, one female; mean age 6y 4mo [SD 6mo]; age at onset 6-7y) treated with piracetam (2-oxo-1-pyrrolidine acetamide). Piracetam was used to treat EPT because of its antimyoclonic properties. All children showed a good response to doses of 100 to 300mg/kg/day. EPT relapsed on withdrawal of piracetam and remitted on reintroduction. Piracetam's effect on EPT was sustained. It is concluded that piracetam is an effective drug for the treatment of EPT in children.