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PubMed2004

Factors associated with HPV persistence after treatment for high-grade cervical intra-epithelial neoplasia with large loop excision of the transformation zone (LLETZ).

BACKGROUND AND OBJECTIVE: Human Papillomavirus (HPV) persistence after high-grade cervical intra-epithelial neoplasia (CIN) removal may be associated with residual lesions or risk of disease recurrence. Knowledge regarding the factors associated with HPV persistence following CIN treatment is still limited. The main purpose of this longitudinal study was to assess the association between characteristics of the patients and their cervical lesions with high-risk HPV-type persistence, detected by commercially available Hybrid Capture II (HC II), after CIN 2 and 3 treatment with large loop excision of the transformation zone (LLETZ). STUDY DESIGN: For this cohort study, a total of 94 women submitted to LLETZ between March 2001 and September 2002 were included. Only women with at least one follow-up visit at 6 or 12 months and confirmed CIN 2 or 3 in the cone specimen were considered. In each visit women answered to a questionnaire and undertook Pap smear and HC II specimens collection. McNemar's, chi-square and Fisher tests were used for univariate analysis. Generalized Estimating Equations (GEE) were used for multivariate analysis. All calculations were performed within 95% confidence intervals (95% CI). RESULTS: Histological evaluation showed 12 (13%) women with CIN, 2 and 82 (87%) with CIN 3 and conization margins were compromised in 27 (29%) cases. Eighty-seven (92%) women showed positive HC II tests prior to LLETZ. Of women initially HPV negative, none had a positive HC II during follow-up. The proportion of positive HPV tests was reduced from 92% to 20%(P < 0.01) at the first visit and to 22% (P < 0.01) at the second visit after LLETZ. Multivariate analysis showed that smoking and age above 35 years (irrespective of margin status) were strongly associated with positive HPV during follow-up. CONCLUSION: HPV persistence following LLETZ was associated with smoking and with the interaction between age and conization margins.

Adolescent↗
PubMed2006

Not polymorphism but methylation of class II transactivator gene promoter IV associated with persistent HBV infection.

BACKGROUND: Class II transactivator (CIITA) is the major rate-limiting regulator for expression of class II major histocompability complex (MHC-II). Human CIITA gene expression is controlled by four distinct promoters (pIto pIV). OBJECTIVE: To evaluate the relationship among polymorphism and methylation status of CIITA gene promoters and persistent hepatitis B virus (HBV) infection. METHODS: We recruited 21 patients with hepatocellular carcinoma (HCC), 45 liver cirrhosis (LC), 65 chronic hepatitis B (CHB), 26 acute hepatitis B (AHB) and 95 healthy blood donors. Polymorphism of CIITA gene promoters was assayed by PCR-SSCP-sequencing. Bioinformatics analysis was employed to predict the existence of CpG islands. Methylation-specific PCR (MSP) was used to detect the methylation status of CIITA gene pIV. RESULTS: No sequence differences were observed at CIITA genes pI, III and IV among HCC, LC, CHB, AHB patients and healthy controls. No CpG islands were found in the pI, pII and pIII sequences, but there was a CpG island in pIV. The frequency of methylated POV was not significantly different within persistent HBV infection groups (patients with HCC, LC or CHB). Significance was found between the persistent infection group and acute HBV infection or healthy controls. CONCLUSIONS: CIITA gene promoter sequences are conserved. PIV is highly methylated and associated with host susceptibility to HBV persistent infection.

DNA Methylation↗
PubMed2006

Estrogen treatment success in recurrent and persistent labial agglutination.

STUDY OBJECTIVE: To estimate the success rate of conservative medical management and indications for surgery in cases of recurrent and/or persistent labial agglutination. DESIGN: A retrospective chart review was performed of girls treated for labial agglutination between 1996 and 2004. Records were reviewed for age, length of time of symptoms, previous treatments, results of topical estrogen therapy, and indications for surgery. SETTING: The study was performed in a tertiary care teaching university hospital. PARTICIPANTS: Charts of 67 girls with labial agglutination who were treated at the pediatric and adolescent gynecology clinic between 1996 and 2004 were reviewed. The average age was 4.1 years (range 0.6-14 years). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Improvement of persistent or recurrent agglutination labial agglutination with estrogen. RESULTS: Out of the 67 charts reviewed, 48 had recurrent or persistent disease. Within those 48 girls, initial treatments included: topical estrogen in 40 (83%), oral and topical estrogen in 1 (2%), topical estrogen in addition to manual separation in 5 (10%), and treated with manual separation alone in 2 (4%). Five girls were immediately treated surgically due to urinary problems or parents declining further topical treatment. Forty-three were treated with topical estrogen therapy with the following results: 15 opened either partially or completely, 9 required surgery, and 19 did not follow up. In the subset of girls with prior manual separation, 2 had resolution of adhesions with estrogen, 3 required surgery, and 2 had no follow-up. CONCLUSION: This study suggests that re-treatment of persistent or recurrent labial agglutination with topical estrogen therapy following detailed application instruction leads to avoidance of surgical intervention in at least 35% of cases. Even in cases which previously required manual separation, an attempt at conservative medical management may be considered.

Administration, Topical↗
PubMed2004

Psychological aspects of persistent pain: current state of the science.

UNLABELLED: This article provides an overview of current research on psychological aspects of persistent pain. It is divided into 3 sections. In section 1, recent studies are reviewed that provide evidence that psychological factors are related to adjustment to persistent pain. This section addresses research on factors associated with increased pain and poorer adjustment to pain (ie, pain catastrophizing, pain-related anxiety and fear of pain, and helplessness) and factors associated with decreased pain and improved adjustment to pain (ie, self-efficacy, pain coping strategies, readiness to change, and acceptance). In section 2, we review recent research on behavioral and psychosocial interventions for patients with persistent pain. Topics addressed include early intervention, tailoring treatment, telephone/Internet-based treatment, caregiver-assisted treatment, and exposure-based protocols. In section 3, we conclude with a general discussion that highlights steps needed to advance this area of research including developing more comprehensive and integrative conceptual models, increasing attention to the social context of pain, examining the link of psychological factors to pain-related brain activation patterns, and investigating the mechanisms underlying the efficacy of psychological treatments for pain. PERSPECTIVE: This is one of several invited commentaries to appear in The Journal of Pain in recognition of The Decade of Pain Research. This article provides an overview of current research on psychological aspects of persistent pain, and highlights steps needed to advance this area of research.

Adaptation, Psychological↗
PubMed2005

Persistence conditions of symmetric social hybridogenesis in haplo-diploid hymenoptera.

In eusocial Hymenoptera species, females variably develop into either alate females (queens) or workers, and in most cases, caste differentiation is determined environmentally. Recently, however, female castes in two harvester ant species, Pogonomyrmex rugosus and P. barbatus, were found to be determined genetically in hybrid zones of these two species. In the hybrid populations, homozygous females (e.g. AA or BB) and heterozygous females (AB) develop into alate females and workers, respectively. This genetic caste determination system is called symmetric social hybridogenesis (SSH). It is clear that populations with SSH can persist only if all four genotypes (AA and BB females, and A and B males) coexist simultaneously. However, it is not obvious that these populations are always persistent when the four genotypes simultaneously exist. Here, we examined the stability and persistence of an SSH population using a simple mathematical model. According to the analysis of the model, the SSH population persists only when some conditions are satisfied: (1) each female mates with more than two males, and (2) male production increases less steeply than linearly with increasing numbers of workers in a colony, and alate female production increases more steeply than linearly with increasing numbers of workers, or (2') male production increases more steeply than linearly with increasing numbers of workers in a colony, and alate female production increases much more steeply than male production. Therefore, it is not obvious that SSH populations are maintained and are stable for long periods. We discuss whether these conditions are satisfied in real SSH populations.

Animals↗
PubMed2004

Late incidence and predictors of persistent or recurrent heart failure in patients with mitral prosthetic valves.

OBJECTIVE: The study's objective was to examine factors associated with persistent or recurrent congestive heart failure after mitral valve replacement. METHODS: Patients who underwent mitral valve replacement with contemporary prostheses (N = 708) were followed with annual clinical assessment and echocardiography. Cox proportional hazard models were developed to evaluate the impact of demographic, comorbid, and valve-related variables on the occurrence of congestive heart failure after mitral valve replacement, defined as the composite outcome of New York Heart Association class III or IV symptoms or death caused by congestive heart failure postoperatively. Factors associated with all-cause mortality were also examined. Models were bootstrapped 1000 times. RESULTS: The total follow-up was 3376 patient-years (mean 4.8 +/- 3.7 years, range 60 days to 17.1 years). Freedom from New York Heart Association III or IV symptoms or death caused by congestive heart failure was 96.1% +/- 0.8%, 82.7% +/- 1.7%, 66.4% +/- 3.0%, and 38.8% +/- 6.9% at 1, 5, 10, and 15 years, respectively. Preoperative New York Heart Association class, left ventricular grade, atrial fibrillation, coronary artery disease, smoking, persistent tricuspid regurgitation, and redo status predicted congestive heart failure postoperatively (all P <.05). Patients who underwent mitral valve replacement for pure mitral stenosis had less congestive heart failure events after surgery than those with regurgitation or mixed disease. Prosthesis size and elevated transprosthesis gradients were not predictive of freedom from congestive heart failure after mitral valve replacement. Atrial fibrillation, persistent tricuspid regurgitation, and surgical referral for mitral valve replacement at an advanced functional stage were also risk factors for all-cause mortality. CONCLUSIONS: This study identifies the incidence of and risk factors for congestive heart failure and death late after mitral valve replacement. Although prosthesis size has no effect, other potentially modifiable factors such as atrial fibrillation, persistent tricuspid regurgitation, and late surgical referral have a negative impact on freedom from congestive heart failure and overall survival after mitral valve replacement.

Female↗
PubMed2006

Endoscopic treatment of vesicovasal and vesicoureteral reflux in infants with persisting mesonephric duct.

PURPOSE: We present a minimally invasive endoscopic approach for the treatment of persisting mesonephric duct in male infants. MATERIALS AND METHODS: Five male infants 2 to 8 months old were referred with a history of recurrent sepsis, epididymo-orchitis and anorectal malformation that was treated elsewhere with initial colostomy. All infants had edematous unilateral testes, fever and poor feeding. Urine and blood cultures yielded the same microorganisms. All infections occurred while the infants were on regimens of prophylactic antibiotics. Comprehensive urological evaluations confirmed ipsilateral renal agenesis, sacral hypoplasia (3 patients), high anorectal malformation, and vesicovasal and vesicoureteral reflux. RESULTS: All 5 infants underwent urethrocystoscopy under general anesthesia. The ectopic persisting mesonephric duct entered the bladder neck and proximal prostatic urethra. Injection of 0.4 to 0.7 ml Urocol, used as a bulking agent, was administered submucosally at the opening of the persisting mesonephric duct. In 1 patient the orifice of the anomalous duct was not found during urethrocystoscopy, and ipsilateral vas ligation by titanium clips was performed. The results in the remaining 4 patients were excellent, and no further episodes of epididymitis were observed during a mean followup of 30 months. CONCLUSIONS: The diagnosis of persisting mesonephric duct should be considered in a male child with anorectal anomalies and recurrent epididymo-orchitis, and can be confirmed by radiological studies and cystoscopy. Endoscopic treatment of this anomaly should be considered first line therapy in these patients. However, surgical intervention is mandatory for children not responding to the procedure.

Cystoscopy↗
PubMed2007

Subureteral injection of dextranomer/hyaluronic acid copolymer for persistent vesicoureteral reflux following ureteroneocystostomy.

PURPOSE: We sought to evaluate the use of subureteral dextranomer/hyaluronic acid copolymer injection for persistent vesicoureteral reflux following ureteroneocystostomy. MATERIALS AND METHODS: We performed a retrospective review of patients who had undergone dextranomer/hyaluronic acid injection between 2002 and 2005 for persistent vesicoureteral reflux following ureteroneocystostomy. Analysis included evaluation of patient demographics, reflux grades, voiding dysfunction, reflux resolution rates and operative complications. Success was defined as no reflux on voiding cystourethrogram at 1 to 6 months postoperatively. RESULTS: A total of 12 cases with 14 refluxing ureters were reviewed. Of the 12 patients treated 9 (10 ureters) had adequate followup. Mean followup was 10 months. Seven of 10 ureters (70%) demonstrated resolution of reflux after the initial injection. A second dextranomer/hyaluronic acid injection resulted in complete resolution in 2 of the 3 failed ureters (67%). Resolution in the remaining failed ureter could not be assessed due to insufficient patient followup. In children with adequate followup success was ultimately achieved in 9 of 9 ureters (100%) using up to 2 injections. A comparison of clinical factors between patients with success after the initial injection and those requiring 2 injections showed that the presence of persistent voiding dysfunction was the only parameter that was statistically significant. All patients tolerated the procedure without complications. CONCLUSIONS: Considering the difficulties inherent in repeat surgery and the high success rate of dextranomer/hyaluronic acid injection in this series, this treatment is an appealing and reasonable option for patients with persistent vesicoureteral reflux following open ureteroneocystostomy.

Child↗
PubMed2006

Effects of tick population dynamics and host densities on the persistence of tick-borne infections.

The transmission and the persistence of tick-borne infections are strongly influenced by the densities and the structure of host populations. By extending previous models and analysis, in this paper we analyse how the persistence of ticks and pathogens, is affected by the dynamics of tick populations, and by their host densities. The effect of host densities on infection persistence is explored through the analysis and simulation of a series of models that include different assumptions on tick-host dynamics and consider different routes of infection transmission. Ticks are assumed to feed on two types of host species which vary in their reservoir competence. Too low densities of competent hosts (i.e., hosts where transmission can occur) do not sustain the infection cycle, while too high densities of incompetent hosts may dilute the competent hosts so much to make infection persistence impossible. A dilution effect may occur also for competent hosts as a consequence of reduced tick to host ratio; this is possible only if the regulation of tick populations is such that tick density does not increase linearly with host densities.

Algorithms↗
PubMed2005

Genetic variability of measles virus in acute and persistent infections.

RNA viruses have high nucleotide substitution rates, and therefore the potential to mutate rapidly. In the case of vaccine preventable RNA viruses, this may potentially lead to emergence of vaccine escape mutants. The WHO has targeted measles virus (MV) for elimination in many regions, and its genetic variability is monitored to estimate appearance of such mutants. Phylogenetic analysis of partial N or H genes of 230 MV strains circulating in the UK over a 10-year period was performed. Substitution rates in three outbreaks were determined to be 3.9 x 10(-3) to 6.7 x 10(-3) per nucleotide per annum. This is an order of magnitude higher than previously reported for circulating MV. Analysis of virus detected sporadically in the UK between 1992 and 2000 lead to a slightly higher substitution rate of 7.8 x 10(-3) per site per year. Additionally, genetic variability of persistent MV, isolated from subacute sclerosing panencephalitis (SSPE) patients, was investigated and appeared more stable than circulating viruses. Profiles of nucleotide changes in acute and persistent virus were compared. In acute virus, 33% of all mutation events occurred from A-to-G, which contrasts the predominant U-to-C mutations found in persistent infections. Mutations do not seem to be driven by positive selection and no association with known biological functions could be found. We conclude that substitution rates in circulating virus may be higher than in persistent, hypermutated virus and that the high substitution rate of MV may allow evolution of escape. Diversity of circulating strains should be closely monitored in the future.

Acute Disease↗
PubMed2005

Differential expression of chlamydial signal transduction genes in normal and interferon gamma-induced persistent Chlamydophila pneumoniae infections.

Characteristic features of the persistent chlamydial developmental cycle, associated with chronic infections in both humans and animals, include the generation of non-replicative, morphologically aberrant bodies which are distinct from normal propagating reticulate bodies. Previous studies have correlated these morphological and metabolic changes with differential expression of diverse functional subsets of chlamydial genes. To further investigate these correlations, we compared mRNA expression of predicted chlamydial signal transduction genes between normal Chlamydophila pneumoniae A-03 infections in HEp-2 cells and those treated with gamma interferon (IFN-gamma) by using real-time RT-PCR. Inspection of the Cp. pneumoniae genome revealed at least 39 candidate signal transduction genes, of which 30 were differentially expressed in Cp. pneumoniae mediated persistence. Functional sub-groups of differentially expressed signal transduction genes include chlamydial GTPases (hflX, ychF, yhbZ and yphC), linked to bacterial cellular processes such as cell cycle control and ribosome assembly and stability. Other up-regulated signal transduction genes sharing similarity to bacterial stress response genes (htrA, surE, lytB and hrcA) were also detected. The transcriptional changes observed for the majority of signal transduction genes appear to be unique for Cp. pneumoniae, as similar changes were not observed in recent whole genomic analysis of C. trachomatis IFN-gamma mediated persistence. These results suggest that chlamydial signal transduction genes play potentially important roles in the establishment and maintenance of Cp. pneumoniae persistence, likely as part of the IFN-gamma response stimulon as described for C. trachomatis, but with considerable differences in the transcriptional profile.

Cell Line↗
PubMed2005

Impact of inhibition of Qo site of mitochondrial complex III with myxothiazol on persistent sodium currents via superoxide and protein kinase C in rat hippocampal CA1 cells.

Inhibition of Qo site of mitochondrial complex III under hypoxia has received attention, but its downstream pathways remain unclear. We used Qo site inhibitor myxothiazol to mimic the inhibition of the Qo site of complex III and studied the effects of the inhibition of this site on persistent and transient sodium currents and neuron excitability in rat hippocampal CA1 cells. The results showed myxothiazol apparently increased persistent sodium currents but with a weak effect on transient sodium currents; the effect of myxothiazol on persistent sodium currents was blocked by protein kinase C inhibitor and superoxide scavengers, but not by hydrogen peroxide scavenger and hydroxyl radical formation inhibitor; myxothiazol could increase the activity of protein kinase C and neuron excitability. These results suggest that the inhibition of Qo site of mitochondrial complex III increases persistent sodium currents via superoxide production and protein kinase C activation.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed2005

Psychobiology of persistent antisocial behavior: stress, early vulnerabilities and the attenuation hypothesis.

Stress experienced during the sensitive prenatal, postnatal and early childhood periods of brain development can have damaging consequences for developing biological systems. Stressors imposed by early physical vulnerabilities and an adverse care giving environment is proposed to set in motion early precursors of later persistent antisocial behavior. The purpose of this report is to present an integrated theoretical perspective of potential mechanisms involved in the development of persistent antisocial behavior with an emphasis on early stressors and the neuroendocrinology of stress. The attenuation of endocrine physiology of the stress system is considered a key mechanism involved in persistent antisocial behavior. The amygdala is considered a structure/process linking subjective experiences, emotional learning, brain development and stress physiology. Attenuated cortisol level subsequent to early vulnerabilities is considered a risk marker for persistent antisocial behavior.

Animals↗
PubMed2007

Persistence of long-term memory storage requires a late protein synthesis- and BDNF- dependent phase in the hippocampus.

Persistence is the most characteristic attribute of long-term memory (LTM). To understand LTM, we must understand how memory traces persist over time despite the short-lived nature and rapid turnover of their molecular substrates. It is widely accepted that LTM formation is dependent upon hippocampal de novo protein synthesis and Brain-Derived Neurotrophic Factor (BDNF) signaling during or early after acquisition. Here we show that 12 hr after acquisition of a one-trial associative learning task, there is a novel protein synthesis and BDNF-dependent phase in the rat hippocampus that is critical for the persistence of LTM storage. Our findings indicate that a delayed stabilization phase is specifically required for maintenance, but not formation, of the memory trace. We propose that memory formation and memory persistence share some of the same molecular mechanisms and that recurrent rounds of consolidation-like events take place in the hippocampus for maintenance of the memory trace.

Animals↗
PubMed2004

Heterosynaptic co-activation of glutamatergic and dopaminergic afferents is required to induce persistent long-term potentiation.

The persistence of protein synthesis-dependent long-term potentiation (late-LTP) is thought to require heterosynaptic activation of both glutamate and neuromodulatory receptors in the hippocampus. The present series of experiments contrasts two alternative accounts of heterosynaptic activation. The original version of the synaptic-tag hypothesis of the variable persistence of LTP implied that neuromodulatory and glutamatergic activation could occur independently, albeit within a critical time-window; an alternative view is that there needs to be simultaneous co-activation of both receptors to trigger the up-regulation of relevant protein synthesis (Neuron 34 (2002) 235). Our findings include a replication, over 6 h post-LTP-induction, of earlier findings showing heterosynaptic influences on LTP persistence. Specifically, 'strong' tetanisation with multiple trains of stimulation of one input pathway in a conventional hippocampal slice preparation induces a D1/D5 receptor-dependent form of late-LTP that enables 'weak' tetanic stimulation to induce late-LTP on an independent pathway. However, we also observed that when the first pathway was tetanised in the presence of AP5, not only was no LTP observed on that pathway, but there was also no rescue of late-LTP on the second pathway. Thus, it appears that DA receptors must be co-activated with NMDA receptors in a common pool of neurons to enable LTP persistence, although late-LTP can still be induced by selective activation of glutamatergic synapses if this occurs at time periods shortly before or shortly after this essential coactivation.

Animals↗
PubMed2005

Computational and in vitro studies of persistent activity: edging towards cellular and synaptic mechanisms of working memory.

Persistent neural activity selective to features of an extinct stimulus has been identified as the neural correlate of working memory processes. The precise nature of the physiological substrate for this self-sustained activity is still unknown. In the last few years, this problem has gathered experimental together with computational neuroscientists in a quest to identify the cellular and network mechanisms involved. I introduce here the attractor theory framework within which current persistent activity computational models are built, and I then review the main physiological mechanisms that have been linked thereby to persistent activity and working memory. Open computational and physiological issues with these models are discussed, together with their potential experimental validation in current in vitro models of persistent activity.

Action Potentials↗
PubMedDate not supplied

Correlates of mothers' persistent depressive symptoms: a national study.

PURPOSE: The purpose of this study was to examine the prevalence, persistence, and correlates of mothers' depressive symptoms over a 5-year period in a nationally representative sample of the United States population. METHOD: Data from 2235 mothers in the National Survey of Families and Households, Wave I, 1987-1988, and Wave II, 1992-1994, were analyzed. Outcome measures were scores on the Center for Epidemiological Studies Depression Scale (CES-D, 12-item version) and a validated three-item depression screen. RESULTS: One fifth of study mothers had positive CES-D scores and almost half (48%) had negative CES-D scores in both waves. Wave I risk factors for persistent "positive" CES-D scores were maternal age less than 30 years (24%), African-American (33%), never married (26%) or divorced (32%), education less than high school (35%), and indigent (32%). Adjusted odds ratios (AOR) and 95% confidence intervals for persistent "positive" versus persistent "negative" CES-D scores were: age less than 30 years (Wave I), AOR = 1.64, (1.22-2.21); unmarried (Wave II), AOR = 2.60, (1.89-3.56); education less than high school (Wave II), AOR = 2.18, (1.41-3.38); and indigent (Wave II), AOR = 2.09 (1.36-3.21). DISCUSSION: About one fifth of the study sample reported high depressive symptoms twice over a 5-year period. Depression in women, especially mothers, is an urgent public health problem.

Adult↗
PubMed2004

What incites new daily persistent headache in children?

This study asked what incites the development of a new daily persistent headache in children. A total of 175 children with chronic daily headache were prospectively identified and observed by the author. Of these patients, 40 (23%) with a new daily persistent headache were identified. These patients had no significant prior headache history. Seventeen patients (43%) had the onset of their symptoms during an infection. Of these patients, over half had positive Epstein-Barr virus serology at the onset of symptoms. Nine patients (23%) manifested minor head injuries at the onset of their symptoms, yet had a normal examination and neuroimaging. Symptom onset was also associated with surgery (four patients) and high-altitude camping (one patient). In five patients, no specific etiologic factor could be identified. Four patients were initially identified as having idiopathic intracranial hypertension, yet their chronic headache persisted despite the normalization of their intracranial pressure. Similar findings were observed in episodic migraine patients who abruptly developed the onset of chronic migraine. In conclusion, the onset of new daily persistent headache in childhood is typically associated with a physiologic stress such as an infection, head trauma, or post-surgery.

Child↗