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PubMed2001

Shifts in relative prevalence of laryngeal pathology in a treatment-seeking population.

The prevalence of laryngeal pathology in a treatment-seeking population of southwestern Ohio underwent a 15-year reexamination. Relationships between pathology and demographic variables of age, gender, and occupation were investigated. Data were collected from 1,158 new patients seen by participating otolaryngologists between 1996 and 1998. The most frequent pathologies were reflux laryngitis, functional (including diagnoses of laryngeal myasthenia and hoarseness), vocal fold paralysis, nodules, and laryngitis. Pathologies were found to occur more often in females, with some pathologies more common to one gender. Pathologies occurred more often in the older age categories. The most common occupations found in the sample were retired persons, executives/managers, and homemakers. Comparisons were made to an earlier investigation of laryngeal pathology in the same otolaryngology practices. Differences from the previous study were noted in the prevalence of pathology and the distribution of demographic variables. Relationships between pathology and demographic variables reported by the two studies were examined for consistency.

Adult↗
PubMed2006

Sex differences in subclinical and DSM-IV pathological gambling: results from the National Epidemiologic Survey on Alcohol and Related Conditions.

BACKGROUND: To examine sex differences in DSM-IV subclinical and pathological gambling in nationally representative data of the US population. METHOD: Data come from a large (n = 43093) representative sample of the adult US population. RESULTS: The lifetime prevalence rate of DSM-IV pathological gambling was 0.64% (95% CI 0.50-0.78) for men and 0.23% (95% CI 0.17-0.29) for women, whereas the lifetime prevalence of subclinical pathological gambling was 6.79% (95% CI 6.32-7.26) for men and 3.26% (95% CI 2.93-3.59) for women. For subclinical pathological gambling, men were significantly (p < 0.01) more likely than women to have smoked more than two packs of cigarettes a day, to be classified as heavy drinkers and to have lifetime diagnoses of alcohol and drug use disorders. Women with subclinical and pathological gambling were significantly more likely than men to have lifetime mood and anxiety disorders. With respect to pathological gambling, women had later ages of onset of the disorder, and were significantly more likely than men to report gambling to relieve depressed mood and to prefer casino gambling. Rates of treatment-seeking for DSM-IV pathological gambling were low for both men and women. CONCLUSIONS: There are important sex differences in the prevalence, symptom pattern, sociodemographic and clinical correlates and course of DSM-IV subclinical and pathological gambling. Results underscore the need to investigate sex differences in the social determinants, neurobiology and treatment response of DSM-IV subclinical and pathological gambling.

Adolescent↗
PubMed2006

Serotonin dysfunction in pathological gamblers: increased prolactin response to oral m-CPP versus placebo.

OBJECTIVE: Acute administration of the partial serotonin (5-HT) agonist meta-chlorophenylpiperazine (m-CPP), that is used also as a street drug, has been reported to induce a "high" and craving response in various impulsive and substance addiction disorders. INTRODUCTION: To clarify altered 5-HT metabolism in pathological gamblers and to explore the specific role of serotonergic system in non-substance addictions, we assessed behavioral ("high" and "craving") and neuroendocrine (prolactin and cortisol) responses to an oral single dose of m-CPP and placebo in pathological gamblers and matched controls. Moreover, the relationship between neuroendocrine outcome and clinical severity has been assessed. METHOD: Twenty-six pathological gamblers and 26 healthy control subjects enter a double-blind, placebo-controlled-crossed administration of orally dose m-CPP 0.5 mg/kg. Outcome measures included prolactin and cortisol levels, gambling severity, mood, craving and "high" scales. RESULTS: Pathological gamblers had significantly increased prolactin response compared to controls at 180 minutes and at 210 minutes post-administration. Greater pathological gamblers severity correlated with increased neuroendocrine responsiveness to m-CCP, suggesting greater 5-HT dysregulation. Pathological gambling patients had a significantly increased "high" sensation after m-CPP administration compared with control. CONCLUSION: These results provide additional evidence for 5-HT disturbance in pathological gamblers and they support the hypotheses that the role of the 5-HT dysfunction related to the experience of "high" might represent the pathway that leads to dyscontrolled behavior in pathological gamblers. Furthermore, the "high" feeling induced by m-CPP in pathological subjects may represent a marker of vulnerability to both behavioral and substance addictions.

Adult↗
PubMed2006

Health correlates of pathological gambling in a methadone maintenance clinic.

This study compared methadone maintenance patients with and without pathological gambling (n = 167). Participants completed a self-report survey assessing lifetime pathological gambling and past-2-month gambling behavior, and they completed the SF-12v2 Health Survey, a measure of current mental and physical health. In the sample, 52.7% were classified as lifetime pathological gamblers, and the majority of pathological gamblers were actively gambling within the past 2 months. Multivariate analysis of covariance revealed that methadone maintenance patients with pathological gambling had significantly poorer mental and physical health than methadone maintenance patients without pathological gambling. These results suggest that pathological gamblers receiving methadone maintenance may benefit from additional psychosocial services. In fact, most pathological gamblers in the sample expressed interest in gambling-related services. These results extend previous research in other populations that has found that pathological gamblers report poorer mental and physical health than nonpathological gamblers.

Behavior, Addictive↗
PubMed2003

Mucosal IgG and IgA responses to human papillomavirus type 16 capsid proteins in HPV16-infected women without visible pathology.

Human papillomavirus type 16 (HPV16) may infect the cervical epithelium without producing pathological changes for a long time. To investigate if mucosal antibodies are induced in HPV16-infected women without visible pathology, cervical mucus from HPV16-infected patients with and without evident pathology, along with mucus from uninfected women were analyzed for the presence of mucosal IgG and secretory IgA (sIgA) antibodies to HPV16 capsid proteins by ELISA. sIgA and IgG antibodies were found in a significantly higher proportion of infected patients compared with uninfected women (p < 0.0001). sIgA antibodies were present in 13.1% of infected patients without visible pathology, the proportion of positivity increased to 27.0% in patients with visible pathology (p = 0.001). Mucosal IgG response was observed in 6.5% of patients without and 27.5% of patients with visible pathology (p = 0.00005). The antibody mean signal strength was significantly higher in patients with than in patients without pathological evidence (p < 0.005). In conclusion, both sIgA and IgG are found in patients without pathological signs of infection, however, the response increases significantly in patients with pathological evidence, suggesting that the appearance of these changes might be associated with a more vigorous antibody-mediated mucosal reaction.

Adult↗
PubMed2004

Predictive value of [18F]FDG PET for pathological response of breast cancer to neo-adjuvant chemotherapy.

BACKGROUND: The aim of this prospective study was to evaluate the predictive value of [18F]fluorodeoxyglucose positron emission tomography (FDG PET) for the pathological response of breast cancer after completion of neo-adjuvant chemotherapy. METHODS: Fifty patients with newly diagnosed, non-inflammatory, large or locally advanced breast cancer undergoing neo-adjuvant chemotherapy were eligible for this study. Clinical assessment was accomplished by comparing initial tumor size with preoperative tumor size. Pathological responses were classified into three groups: pathological non-response (pNR), pathological partial response (pPR) and pathological complete response (pCR). To determine the effect of reduction rate (RR) of peak standardized uptake values for tumor responses, logistic regression analyses were performed. To identify an optimal threshold value of RR for the prediction of pathological response, receiver operating characteristic analysis was performed. RESULTS: Eight per cent (four of 50) of the patients had pCR and 46% had pPR. Ten per cent of patients had clinical CR and 52% had clinical PR. In clinical response, the RRs (+/- SD) of CR (-83.4 +/- 12), PR (-81.8 +/- 22.7) and NR (-79.7 +/- 31.9) showed no statistical differences (P > 0.05). However, for pathological responses, the RR of CR (-96.5 +/- 3.4) had a lower value than those of PR (-87.9 +/- 15.1) and NR (-56.2 +/- 29.6) (P = 0.0006; CR versus PR, P < 0.05; CR versus NR, P < 0.05; PR versus NR, P < 0.01). When -88% of RR was used as threshold value for differentiation between pCR and pPR, the area under the curve (AUC) was 0.788 [standard error (SE) 0.106; 95% confidence interval (CI) 0.589-0.920]. The sensitivity and specificity were 100% and 56.5%, respectively. When -79% of RR was used as threshold value for differentiation between pathological responders and non-responders, the AUC was 0.838 (SE 0.059; 95% CI 0.707-0.927). The sensitivity and specificity were 85.2% and 82.6%, respectively. CONCLUSIONS: Despite some limitations, this study suggests a possible predictive value of FDG PET for the assessment of the pathological response of primary breast cancer after neo-adjuvant chemotherapy. However, these findings deserve further investigation on a larger number of patients, and more frequent and earlier PET scans in each patient need to be performed to allow a better validation of the differentiation between the responder and non-responder groups.

Adult↗
PubMed2003

Interleukin-1B (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) gene polymorphisms are not associated with tubal pathology and Chlamydia trachomatis-related tubal factor subfertility.

BACKGROUND: Chlamydia trachomatis infections have been associated with tubal pathology. However, not all C.trachomatis-infected women actually develop tubal pathology. Recently, host genetic factors such as the interleukin-1 gene cluster have been linked to inflammatory and infectious diseases. METHODS: Dutch Caucasian women were investigated for (i) the role of interleukin-1B (IL-1B) and interleukin-1 receptor antagonist (IL-1RN) gene polymorphisms in tubal pathology (group 1); and (ii) the presence of these gene polymorphisms in C.trachomatis IgG-positive women with and without tubal pathology (group 2). Group 1 consisted of women with (n = 40) or without (n = 95) tubal pathology, respectively, and group 2 of C.trachomatis IgG-positive women of whom 28 had tubal pathology at laparoscopy and 47 did not. IL-1B-511 and IL-1B+3954 gene polymorphisms were assessed by PCR-restriction fragment length polymorphism (RFLP), and the variable number of tandem repeats (VNTR) of the IL-1RN gene were assessed by a PCR-based assay. RESULTS: Neither IL-1B-511, IL-1B+3954 nor IL-1RN genotypes, allele or carrier frequencies showed significant association with tubal pathology or C.trachomatis post-infection-based tubal pathology. CONCLUSIONS: The data obtained suggest that specific IL-1 gene polymorphisms are not associated with the tubal pathology risk or to the development of C.trachomatis-based post-infectious severe sequelae.

Adult↗
PubMed2000

The role and impact of pathology review on stage and grade assessment of stages Ta and T1 bladder tumors: a combined analysis of 5 European Organization for Research and Treatment of Cancer Trials.

PURPOSE: Pathological interpretations are largely subject to interpathologist and intrapathologist variation. Differences in tumor stage and grade exist in local and review pathological findings in patients with stage Ta-T1 bladder tumors who are entered in randomized trials of adjuvant treatment after transurethral resection. Because they are diagnosed and treated based on local pathological results, it is important to determine the reliability of local pathological evaluations and the extent to which pathology review may change the treatment decision process. MATERIALS AND METHODS: We assessed local and review pathology results in 1,400 patients treated in 5 European Organization for Research and Treatment of Cancer randomized phase III trials comparing various adjuvant prophylactic treatment strategies for primary or recurrent stage Ta-T1 transitional cell bladder cancer. RESULTS: We noted large variations in T category and grade. Pathology review down staged T category to stage Ta in 53% of cases originally classified as stage T1. There was agreement in only 57% and 50% of stage Ta grade 1 and stage T1 grade 3 cases, of which 10% were reclassified as muscle invasive disease greater than stage T1. While T category and grade have prognostic importance, differences in the prognosis based on local and review pathological studies were slight. CONCLUSIONS: Pathology review is not mandatory in low and intermediate risk cases since it has little impact on the prognosis and treatment decision making. In high risk cases of stage T1 grade 3 disease stage or grade is often changed, so that review remains essential in this subgroup.

Carcinoma, Transitional Cell↗
PubMed2005

Antisocial personality disorder is associated with increased severity of gambling, medical, drug and psychiatric problems among treatment-seeking pathological gamblers.

AIMS: To evaluate systematically whether pathological gamblers with antisocial personality disorder (ASPD) experience increased severity of gambling, medical, psychiatric, substance use and psychosocial problems compared to pathological gamblers without ASPD. PARTICIPANTS, DESIGN AND MEASUREMENTS: Pathological gamblers (n = 237) entering an out-patient treatment study for pathological gambling completed the ASPD section of the Structured Clinical Interview for Diagnostic and Statistical Manual version IV (DSM-IV) Personality Disorders, California Psychological Inventory-Socialization Scale, Addiction Severity Index (ASI), Brief Symptom Inventory (BSI) and gambling questionnaires. SETTING: Pathological gambling research clinic. FINDINGS: Thirty-nine (16.5%) pathological gamblers met DSM-IV diagnostic criteria for ASPD. Compared to pathological gamblers without ASPD, pathological gamblers with ASPD were younger, more likely to be male and divorced/separated, and had fewer years of education. They also began gambling earlier in life, reported increased severity of gambling, medical and drug problems, and scored higher on the paranoid ideation, somatization and phobic anxiety subscales of the BSI. Further, logistic regression identified male gender, history of illicit drug use and severity of gambling and medical problems as independent predictors of ASPD. CONCLUSIONS: These results underscore the importance of assessing a wide range of behaviors and personality indices, including ASPD, among treatment-seeking pathological gamblers.

Adult↗
PubMed2005

Clinical and pathological responses of progestin therapy for non-atypical endometrial hyperplasia: a prospective study.

AIMS: To evaluate the clinical and pathological responses and factors predicting non-responders to various progestins currently prescribed for the treatment of non-atypical endometrial hyperplasia. METHODS: A prospective observational study was conducted in the Gynecologic Endocrinology Unit, Faculty of Medicine, Siriraj Hospital, Thailand, from 1998 to 2003. A 6-month course of progestin therapy was offered to all patients. The clinical response was evaluated from the vaginal bleeding pattern during the first 4 months of treatment. The pathological response was evaluated from the histopathology of the endometrium after completion of the 6-month therapy. RESULTS: Of 250 registered patients, the number of cases qualified for the evaluation of the clinical and pathological response were 198 and 134 cases, respectively, revealing the overall clinical and pathological response rates of 93.4% and 92.5%, respectively. Among 13 clinical non-responders, 84.6% might have associated pelvic pathology. Among 10 pathological non-responders, three had surgical treatment, and progressive disease was found in one case. Significant factors predicting clinical non-responders included a history of prior bleeding (odds ratio [OR] = 8.79, 95% confidence interval [CI] = 1.63, 47.53), the presence of associated pelvic pathology (OR = 25.52, 95% CI = 3.21, 203.01), and treatment using progestins other than medroxyprogesterone acetate. Factors predicting pathological non-responders were not statistically significant. CONCLUSIONS: The current regimens of progestin therapy for non-atypical endometrial hyperplasia have high response rates. Patients who fail to have a clinical response should be evaluated for associated pelvic pathology. Follow-up endometrial biopsy should be offered to the patients, because 7.5% have persistent or progressive lesions, necessitating aggressive treatment.

Adult↗
PubMed1994

The influence of review pathology on study outcome of a randomized multicentre superficial bladder cancer trial. Members of the Dutch South East Cooperative Urological Group.

OBJECTIVE: To determine whether differences between local and review pathology in a multicentre study influence the results of treatment and results from prognostic factor analysis. PATIENTS AND METHODS: A randomized multicentre study in superficial bladder cancer is reported, in which the influence of local and review pathology on the study outcome was investigated. RESULTS: The conformity between local and review pathology of the pT category was 79.3%, of the grade 70.2%, and the combination of both 59.7%. In local pathology, undergrading was more frequent than overgrading and overstaging more frequent than understaging. However, the risks of recurrent disease in the separate stage and grade groups remained the same after correcting the pathology result. A prognostic factor analysis with regard to the risk of recurrent disease was carried out. The Cox hazard ratios of tumour localization, multiplicity, patient age (significant factors), tumour grade, size, history and gender (not significant) remained almost the same after correction for review pathology. Only the prognostic relevance of tumour stage increased after pathology correction. CONCLUSION: We conclude that, although review pathology caused considerable changes in the pathology results, this did not change the results of treatment, and hardly altered the results of a prognostic factor analysis in this randomized study.

Carcinoma, Transitional Cell↗
PubMed2005

Can Alzheimer's type pathology influence the clinical phenotype of Parkinson's disease?

OBJECTIVES: Patients with clinical and pathological diagnosis of Parkinson's disease (PD) may, at death, also be found to have the pathological changes of Alzheimer's disease (AD). With this study we aim to determine the influence of AD pathology on the clinical phenotype of PD. METHODS: We studied 64 patients who donated their brains to the University of Miami Brain Endowment Bank(TM) and fulfilled the clinical and pathological criteria for PD. For the evaluation of AD pathology we used the CERAD criteria. Dementia was diagnosed, in life, also using standard criteria. Case histories were abstracted and reviewed by one investigator (SP) who then made comparisons between patients. RESULTS: Patients with AD pathology (PD-AD) were older both at the time of diagnosis and death. The presence of AD pathology did not seem to influence disease duration in our cohort of PD patients. As expected there was a clear relation between AD pathology and dementia but not all PD-AD patients were demented. Psychosis and depression were also found to be more prevalent in the PD-AD patients. In the comparison between demented and non-demented PD-AD patients dementia was more likely to appear in patients with PD and definite criteria for AD. CONCLUSION: Apart from dementia AD pathology seems to be associated with a number of other clinical characteristics of PD.

Age of Onset↗
PubMed2001

Pathology and neuroimaging in pediatric temporal lobectomy for intractable epilepsy.

OBJECTIVES: Firstly, to study the pathology at surgery in children undergoing temporal lobectomy for intractable partial epilepsy. Secondly, to compare neuroimaging techniques (CT, MRI) in the preoperative detection of pathology. Lastly, to examine the surgical outcome in children. METHODS: Forty-two pediatric patients undergoing temporal lobectomy for intractable epilepsy at the Comprehensive Epilepsy Program at the University of Alberta Hospital between the years 1988-1998 were studied. Patients had extensive preoperative investigations including CT and MRI. The pathology at surgery was reviewed and compared to preoperative neuroimaging. Charts were reviewed to determine surgical outcome. RESULTS: Brain tumors were the most common pathology, found in 13/42 patients. Mesial temporal sclerosis (MTS) was found in 8 patients and dual pathology in an additional 5. Focal cortical dysplasia (FCD) was seen in 4 patients, 1 patient had a porencephalic cyst and 4 patients had tubers of tuberous sclerosis. Seven patients had no specific pathology detected. MRI was clearly more sensitive than CT in the detection of pathology. MRI was abnormal in 27/42 cases (64%), while CT scan was found to be abnormal in only 12/39 (31%). Surgical outcome was excellent, with 34/42 patients (80%) having an Engel class I outcome. One patient had significant improvement with an Engel class II outcome, 3 (7%) had little improvement (Engel class III) and 4 (10%) were unchanged (Engel class IV). Three patients (7%) had surgical complications. CONCLUSIONS: A wide variety of developmental pathology is seen following temporal lobectomy for intractable epilepsy of childhood. Brain tumors, FCD and MTS are common. MRI is superior to CT in the detection of pathology, which may be subtle in children. Surgical outcome is excellent, with most children being seizure free and few complications being seen.

Adolescent↗
PubMed1993

Pathological laughing and crying following stroke: validation of a measurement scale and a double-blind treatment study.

OBJECTIVE: This study was undertaken to test the reliability and validity of the Pathological Laughter and Crying Scale and the effectiveness of nortriptyline treatment for patients with emotional lability following stroke. METHOD: Eighty-two patients with ischemic brain injury-54 who had been hospitalized with acute stroke and 28 others who requested treatment for pathological laughing and crying--were given standardized psychiatric and neurological assessments and then administered the Pathological Laughter and Crying Scale. The 54 acute stroke patients were used to evaluate the Pathological Laughter and Crying Scale, and the 28 patients with pathological emotional display were randomly assigned to nortriptyline treatment or placebo in a 6-week double-blind trial to assess the efficacy of a tricyclic antidepressant in treatment of this disorder. RESULTS: The interrater reliability on the Pathological Laughter and Crying Scale for a subgroup of 15 patients was 0.93, and the test-retest reliability of the scale was excellent. After 4 and 6 weeks of treatment, scores on the Pathological Laughter and Crying Scale showed significantly greater improvement in the 14 patients given nortriptyline than in the 14 given placebo. Although almost one-half of these patients also had major depression, the improvement in emotional lability was independent of depression status. In addition, response to treatment was not significantly affected by lesion location or time since stroke. CONCLUSIONS: The severity of symptoms in pathological emotional display can be reliably quantified with the Pathological Laughter and Crying Scale, and treatment with nortriptyline can effectively ameliorate this emotional disorder.

Affective Symptoms↗
PubMed2002

Neoadjuvant hormonal therapy prior to radical prostatectomy: evaluation of pathological downstaging and biochemical relapse.

OBJECTIVES: The effect of neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy (RP) on pathological downstaging of prostate cancer and biochemical relapse of serum prostate specific antigen (PSA) level was evaluated. MATERIALS AND METHODS: Twenty selected patients with prostate cancer, who were treated with hormonal therapy and demonstrated biochemical downstaging by reduction of PSA prior to RP and bilateral pelvic node dissection at the Tohsei National Hospital between January 1997 and August 2001, are reported on. The complete RP specimens of these 20 men were used for accurate evaluation of the pathological stage. All 20 patients received NHT; ten patients were treated with leuprolide plus flutamide and 10 received leuprolide plus chlormadinone acetate (CMA). RESULTS: Decreases in serum PSA values were demonstrated from a pre-hormonal average of 49.7 ng/ml to an average of 0.52 ng/ml after NHT. Of the three clinical stages, A2-C, for cancer patients, two of the 20 patients had stage A2, two had stage B1, nine had stage B2, and seven had stage C. Of the 20 patients with biochemical downstaging, two had pathological stage B1, seven had pathological stage B2, eight had pathological stage C, and three had positive pelvic lymph nodes. Ten (50%) of the 20 patients were reported to have positive surgical margins. Seminal vesical extension was observed in two cases, and penetration was not observed. Positive nodes were identified in three (15%) patients. Among the seven clinical stage C patients, one had pathological stage B1 disease and two had pathological stage B2. Four of nine patients with clinical stage B2 prostatic cancer had pathological stage C disease. The actuarial incidence of a rising PSA at 3 years for the leuprolide plus CMA group was 28.9% compared with 37.5%for the group receiving leuprolide plus flutamide. The cases of biochemical relapse did not necessarily indicate a high stage and had no tendency to be high for baseline PSA level, positive margin rates or Gleason scores. CONCLUSIONS: A significant decrease in the rate of penetration could be observed after NHT, though it was not so effective for pathological downstaging, and changes in the preoperative PSA level did not predict those patients who might have a favorable result.

Adenocarcinoma↗
PubMed2005

Transgenic mouse model of tau pathology in astrocytes leading to nervous system degeneration.

Filamentous tau inclusions in neurons and glia are neuropathological hallmarks of sporadic and familial tauopathies. Because tau gene mutations are pathogenic for the autosomal dominant tauopathy "frontotemporal dementia and parkinsonism linked to chromosome 17," tau abnormalities are implicated directly in the onset and/or progression of disease. Although filamentous tau aggregates are acknowledged to play roles in degenerative mechanisms resulting in neuron loss, the contributions of glial tau pathology to neurodegeneration remain essentially unexplored. To begin to elucidate the role of glial pathology in tauopathies, we generated a transgenic (Tg) mouse model of astrocytic tau pathology by expressing the human tau protein driven by the glial fibrillary acidic protein (GFAP) promoter. Whereas endogenous tau was not detected in astrocytes of control mice, in GFAP/tau Tg mice there was robust astrocytic tau expression that was associated with a redistribution of the GFAP network. Subsequently, there was an age-dependent accumulation of tau pathology in astrocytes that was Gallyas and variably thioflavine S positive as observed in many tauopathies. The tau pathology in these Tg mice was abnormally phosphorylated, ubiquitinated, and filamentous, and the emergence of this pathology coincided with accumulation of insoluble tau protein. Furthermore, in regions with robust astrocytic tau pathology, there was mild blood- brain barrier disruption, induction of low-molecular-weight heat shock proteins, and focal neuron degeneration. Thus, these Tg mice recapitulate key features of astrocytic pathology observed in human tauopathies and demonstrate functional consequences of this pathology including neuron degeneration in the absence of neuronal tau inclusions.

Age Factors↗
PubMed2006

Impaired glutamate transport in a mouse model of tau pathology in astrocytes.

Filamentous tau inclusions in neurons and glia are neuropathological hallmarks of tauopathies. The discovery of microtubule-associated protein tau gene mutations that are pathogenic for a heterogenous group of neurodegenerative disorders, called frontotemporal dementia and parkinsonism linked to chromosome-17 (FTDP-17), directly implicate tau abnormalities in the onset/progression of disease. Although the role of tau pathology in neurons in disease pathogenesis is well accepted, the contribution of glial pathology is essentially unknown. We recently generated a transgenic (Tg) mouse model of tau pathology in astrocytes by expressing the human tau protein under the control of the glial fibrillary acidic protein (GFAP) promoter. Both wild-type and FTDP-17 mutant GFAP/tau Tg animals manifest an age-dependent accumulation of tau inclusions in astrocytes that resembles the pathology observed in human tauopathies. We further demonstrate that both strains of Tg mice manifest compromised motor function that correlates with altered expression of the glial glutamate-aspartate transporter and occurs before the development of tau pathology. Subsequently, the Tg mice manifest additional deficits in neuromuscular strength that correlates with reduced expression of glutamate transporter-1 (GLT-1) and occurs concurrent with tau inclusion pathology. Reduced GLT-1 expression was associated with a progressive decrease in sodium-dependent glutamate transport capacity. Reductions in GLT-1 expression were also observed in corticobasal degeneration, a tauopathy with prominent pathology in astrocytes. Less robust changes were observed in Alzheimer's disease in which neuronal tau pathology predominates. Thus, these Tg mice recapitulate features of astrocytic pathology observed in tauopathies and implicate a role for altered astrocyte function in the pathogenesis of these disorders.

Amino Acid Substitution↗
PubMed1997

Pathologic migration of anterior teeth in patients with moderate to severe periodontitis.

The purpose of this study was to determine the prevalence of pathologic migration of anterior teeth in patients with moderate to severe periodontitis. The correlation between pathologic migration of anterior teeth and attachment loss (AL) was investigated, and an attempt was made to identify the most common early form of pathologic migration. Prevalence of tooth migration was studied in a group of 343 patients with moderate to severe periodontitis before treatment. The presence of pathologic migration was determined from the chief complaint and patient awareness o tooth movement in the last 5 years. Forty-four patients (age range 18 to 69; mean = 48.75) with 75 pairs of migrated and non-migrated teeth were studied further to determine if there is a correlation between severity of periodontal AL and pathologic migration. Migrated teeth were compared to control contralateral teeth that did not have migration. In addition, tooth mobility of the anterior teeth on 36 of the 44 patients was measured using the mobility meter. It was anticipated that tooth mobility would follow the same pattern as AL in relation to pathologic migration. The type and severity of displacement was recorded for each tooth affected by migration. The types of pathologic migration recorded were diastema, extrusion, rotation, facial flaring, and drifting into edentulous spaces. Pathologic migration prevalence was 30.03% +/- 2.5 (103/343 subjects). The mean AL of migrated teeth (4.79 +/- 0.28 mm) was significantly greater (P < 0.0001) than control teeth (3.21 +/- 0.18 mm). The numeric values (called PTV) of migrated teeth (17.6 +/- 1.5) were significantly greater (P < 0.0001) than control teeth (9.4 +/- 1.1). It was difficult to identify a primary form of displacement, as most patients demonstrated a combination of movements. The percentage of the 44 patients who presented with a specific type of movement was: facial flaring (90.9 +/- 4.4%), diastema (88.6 +/- 4.8%), rotation (72.7 +/- 6.8%), extrusion (68.2 +/- 7.1%), and tipping (13.6 +/- 5.2%). The results of this study confirms clinical impressions that periodontal disease destruction of the attachment apparatus plays a major role in the etiology of pathologic migration.

Adolescent↗