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PubMed2006

Quantitative analysis of brain asymmetry by using the divergence measure: normal-pathological brain discrimination.

RATIONALE AND OBJECTIVES: The human brain demonstrates approximate bilateral symmetry of anatomy, function, neurochemical activity, and electrophysiology. This symmetry reflected in radiological images may be affected by pathology. Hence quantitative analysis of brain symmetry may enable the normal and pathological brain discrimination. We propose a method based on the Jeffreys divergence measure (J-divergence), which attempts to quantify "approximate symmetry" and also aids to classify the brain as bilaterally symmetrical/asymmetrical (normal/abnormal). MATERIALS AND METHODS: The dataset included studies of 101 patients (59 without detectable pathologies and 42 with different abnormalities). First, the midsagittal plane is computed for the volume data that divides the head into two hemispheres. The J-divergence is calculated from the density functions of intensities of both the hemispheres. Statistical analysis was conducted to find the best distribution for normal/abnormal datasets. RESULTS: Statistical tests showed that the lognormal distribution best characterizes the values of the J-divergence for both normal and abnormal cases, and the threshold value for the Jeffreys divergence measure to classify the brains with and without detectable pathologies is T = 0.007. The threshold value had a sensitivity of 88.1% and specificity of 90.9%. CONCLUSION: The proposed method is fast and simple to compute. The high sensitivity and specificity indicate the results are encouraging. This method can be used for the initial analysis of data, detection of pathology, classification of dataset as presumably normal/abnormal, and localization of abnormality.

Algorithms↗
PubMed2004

Accuracy of the Speed's and Yergason's tests in detecting biceps pathology and SLAP lesions: comparison with arthroscopic findings.

PURPOSE: The purpose of this study was to explore and describe reasons for variation in diagnostic accuracy of clinical tests using Yergason's and Speed's tests in predicting biceps tendon pathology and SLAP lesions. Shoulder arthroscopy was used as the gold standard. TYPE OF STUDY: Prospective blinded study of consecutive patients with a wide spectrum of shoulder conditions. METHODS: One hundred fifty-two subjects (65 women and 87 men) with complaints of shoulder pain were examined. Fifty subjects (16 women and 34 men) ranging in age from 24 to 79 years (mean age, 50 years; SD = 14.36) met the criteria for surgery. The validity of the Yergason's and Speed's tests was evaluated against findings at surgery. RESULTS: The surgical findings related to biceps pathology and SLAP lesions were as follows: 2 bicipital tendonitis, both associated with significant rotator cuff pathology; 10 biceps partial tears; and 2 complete ruptures. Fifteen patients had SLAP lesion type I, 12 type II, and 1 type IV. The sensitivity, specificity, and positive and negative predictive values were 43%, 79%, 60%, and 65% for Yergason's test and 32%, 75%, 50%, and 58% for Speed's test, respectively. The likelihood ratios were 1.28 and 0.91 for Speed's test and 2.05 and 0.72 for Yergason's test. These ratios were provided to assist clinicians in calculating the probability of biceps pathology and SLAP lesions for a single patient with a different history-specific prevalence of having the pathology. CONCLUSIONS: Although Speed's and Yergason's tests are moderately specific, they do not generate a large change in the post-test probability and are unlikely to make a significant change in the pretest diagnosis. Clinicians should understand that clinical examination tests do not perform consistently and have variable predictive values in different patient populations and settings. LEVEL OF EVIDENCE: Level I diagnostic study: testing of previously developed criteria in a series of consecutive patients (using surgery as gold standard).

Adult↗
PubMed2006

Gender differences in quality of life and extent of rotator cuff pathology.

PURPOSE: The purpose of this study was to investigate the effect of age and gender on functional and emotional status and extent of rotator cuff and associated pathology in patients undergoing arthroscopic surgery. TYPE OF STUDY: Historical cohort study. METHODS: This study involved 279 patients who underwent rotator cuff decompression or rotator cuff repair and for whom scores for the 5 domains of a preoperative rotator cuff outcome measure were available. Arthroscopic examination was used to identify the extent of pathology in the rotator cuff, biceps tendon, and superior labrum. RESULTS: Over a period of 3 years, 108 women and 171 men underwent surgery. There was a statistically significant difference in the domain of emotions (P = .024) for men and women. The levels of symptoms (P = .020), difficulty with performing sports and recreational activities (P = .043), and emotions (P = .001) were significantly different between individuals under 55 years of age and those 55 and older, with older patients reporting less difficulty. In terms of extent of pathology, the chi-square analysis showed a statistically significant difference in the incidence of full-thickness tears (P < .0001) between different age groups and SLAP lesions types II to IV (P = .009) between men and women. CONCLUSIONS: Female candidates for rotator cuff-related surgeries report more emotional difficulties. Older age group appear to have less functional and emotional disability despite an increase in the prevalence of major rotator cuff pathology. Gender and age have important roles on quality of life and extent of shoulder pathology. LEVEL OF EVIDENCE: Level II, investigating the outcome of disease.

Age Factors↗
PubMed2005

Transgenic AD model mice, effects of potential anti-AD treatments on inflammation and pathology.

The extracellular deposition of amyloid (A) peptides in plaques, and neurofibrillary tangles are the two characteristic pathological features of Alzheimer's disease (AD). Plaques are surrounded by activated astrocytes and microglia, to study the relation between amyloid neuropathology and inflammation, we examined the changes in amyloid pathology in the hippocampus following three different treatments aimed at reducing the amyloid burden. (1) To investigate the effects of long-term cholinergic deafferentation, we lesioned the fimbria-fornix pathway in our AD-model mice at 7 months of age, and 11 months post-lesion the mice were sacrificed for histopathological analysis. The fimbria-fornix transection resulted in a substantial depletion of cholinergic markers in the hippocampus, but the lesion did not result in an alteration in hippocampal A deposition and inflammation (i.e., numbers or staining density of astrocytes and microglia). (2) To investigate the effects of estrogen, we ovariectomized mice and treated them with estrogen (sham-lesion, zero dose, low dose, and high dose) and studied the pathology at different postsurgery intervals. Estrogen depletion (i.e., ovariectomy) or estrogen replacement did not affect A deposition or inflammation at any time point. (3) In the final studies, we treated mice with flurbiprofen and an NO-donating derivative of flurbiprofen (HCT 1026) for several months (from 6 till 14 months of age), and studied the A pathology and inflammation in the brain. Sham treatment, flurbiprofen, and the low-dose HCT 1026 did not affect pathology; however, a higher dose of HCT 1026 reduced both A load and amount of microglial activation surrounding plaques.

Acetylcholinesterase↗
PubMed2006

In utero magnetic resonance of non-isolated ventriculomegaly: Does ventricular size or morphology reflect pathology?

AIM: To confirm whether ventricular size or morphology reflects the underlying pathology in foetuses referred with a diagnosis of possible ventriculomegaly (Vm) and central nervous system (CNS) pathology. METHODS: Retrospective analysis of 40 in utero magnetic resonance (MR) examinations was undertaken. Ventricular size was measured on axial sections by two observers, and morphology was agreed by consensus. Results were analysed according to gestational age at referral, degree of Vm (mild 10-15 mm, moderate/severe >15 mm) and morphology. RESULTS: Nine cases had no Vm (mean gestational age 23.6 weeks, range 19-33), 17 had mild Vm (mean age 23.9 weeks, range 20-31), and 14 had moderate/severe Vm (mean age 25.9 weeks, range 20-35). All groups had a mix of morphology and pathology. Eighteen suspected cases of spina bifida were referred and 17 confirmed (mean age 22.6 weeks, range 19-30) using MR. The morphology was mixed, five cases (27.8%) had an angular appearance (this morphology was only seen in cases with spina bifida). Fourteen cases (77.8%) had Vm (eight mild, six severe). Of the thirteen cases of agenesis of the corpus callosum (ACC) suspected on ultrasound, seven were confirmed using MR (mean age 26.5 weeks, range 20-35). Of those seven cases with ACC confirmed on MR, and three additional cases only detected by in utero MR, five had colpocephaly, seven had Vm (four mild, three severe). CONCLUSION: Severity of Vm did not reflect the type, or presence, of underlying pathology. Morphology appears an indicator of pathology. Angular ventricles should initiate a search for spinal defects. Colpocephaly may indicate ACC.

Brain Diseases↗
PubMed2003

Effects of endocrine disrupting compounds on the pathology and oestrogen receptor alpha and beta distribution in the uterus and cervix of ewe lambs.

A number of chemicals have been classed as endocrine disrupting compounds due to their ability to mimic the actions of endogenous hormones in vivo and in vitro. The objective of this experiment was to determine the pathological changes and oestrogen receptor (ER) distribution in the cervix and uterus of prepubertal ovariectomised ewe lambs following exposure to a range of compounds with a predominantly oestrogenic effect. Lambs were exposed to diethylstilbestrol (0.175 mg/kg biweekly), bisphenol-A (3.5mg/kg biweekly) or octylphenol (3.5mg/kg biweekly) for 6 weeks. Following sacrifice, uterine and cervical tissue pathology was assessed. The endometrial and myometrial areas were quantified and the distribution of ERalpha and ERbeta assessed by immunohistochemistry. No differences were observed between control and octylphenol-exposed lambs in uterine gross pathology and histopathology. Uteri from bisphenol-A- and diethylstilbestrol-exposed lambs were heavier than both control and octylphenol-exposed lambs. In the bisphenol-A-exposed lambs, endometrial oedema accounted for a significant increase in the endometrial cross-sectional area over the other groups. Uteri from animals exposed to diethylstilbestrol showed variable pathology including oedema and cellular proliferation. Keratinisation of the cervical epithelium was observed in both bisphenol-A- and diethylstilbestrol-exposed lambs. Exposure to diethylstilbestrol and bisphenol-A was associated with a diffuse intracellular distribution of ERalpha and ERbeta in the uterine endometrium. This was in addition to the strong cytoplasmic staining of uterine epithelial cells and nuclear staining of specific sub-epithelial cells observed in all groups. We conclude that a 6-week exposure of lambs to bisphenol-A and diethylstilbestrol altered the uterocervical environment and has the potential to disrupt subsequent reproductive function. Pathological changes could not be detected in the uterus or cervix of lambs exposed to octylphenol.

Animals↗
PubMed2004

Pathology review for paediatric non-Hodgkin's lymphoma patients in Japan; a report from the Japan association of childhood leukaemia study (JACLS).

A central pathology review system with an immunophenotyping laboratory was established in Japan to support the clinical trial, the Japan Association of Childhood Leukaemia Study (JACLS) NHL-98, for patients with paediatric non-Hodgkin's lymphoma (NHL). Pathology samples from 155 clinically-suspected NHL cases were evaluated centrally initially using the Revised European-American Lymphoma (REAL) classification in a rapid review (within 2 weeks after surgery/biopsy) and then later at the consensus review (once a year). The samples were subsequently re-classified according to the new World Health Organisation (WHO) classification. After the pathology review, 96 (62%) patients were eligible for the study, and 58 of them (60%) had extra-nodal primaries. These NHL cases included B-cell lymphomas (precursor B-cell, 11; Burkitt, 18; diffuse large B-cell, 18; not otherwise specified, 3) and T/Natural Killer (NK)-cell lymphomas (precursor T-cell, 23; anaplastic large cell, 20; others, 3). There was excellent concordance in making the diagnoses (95/96, 99%) and typing (93/96, 97%) of NHL between the rapid and consensus reviews. Five cases, initially diagnosed as diffuse large B-cell lymphoma by the review, were re-classified as Burkitt lymphoma according to the immunocytochemical criteria by the WHO classification. A total of 59 (38%) cases were excluded from the study: they were Hodgkin lymphoma (7), leukaemias (11), reactive lymphoid hyperplasia (20), necrotizing lymphadenitis (7), no consensus diagnosis (1), insufficient materials (2), and others (11). This is the first report of the central pathology review from the paediatric NHL group study in Japan. Because various diseases, either neoplastic or reactive, mimicked NHL, clinically and histopathologically, the central pathology review system was critical and essential for patient enrollment and protocol assignment in our clinical trial. Through the two-step review system, highly reliable data were generated to support this study.

Adolescent↗
PubMed2006

When requests become orders--a formative investigation into the impact of a computerized physician order entry system on a pathology laboratory service.

PURPOSE: The purpose of this study was to identify the key implications of the implementation of a computerized physician order entry (CPOE) system on pathology laboratory services. METHODS: An in-depth qualitative study using observation, focus groups and interviews with pathology staff, managers, clinicians and information systems staff during implementation of a CPOE system in 2004 at a major Australian teaching hospital. RESULTS: Pathology laboratories experienced a shift in their work roles resulting in altered work practices, responsibilities and procedures. These changes were marked by terminological and procedural changes in the test order process from when clinicians issued a request for a test, to the new system that established clinical orders at the point of care. This change was accompanied by some organizational dysfunctions including the emergence of a new category of "frustrated" orders without specimens; problems with the procedure of adding tests to previously existing specimens; the appearance of discrepancies in the recorded time of specimen collection. In response to these changes, hospital and pathology staff adopted a variety of means to cope with their changed circumstances. These ranged from efforts to increase clinical awareness to compensatory laboratory workarounds and enforced rule changes. CONCLUSIONS: CPOE systems can have a major impact on the nature of the work of pathology laboratories. Understanding how and why these changes occur can be enhanced through considering the organizational and social contexts involved. The effectiveness of CPOE systems will rely on how administrators and staff approach and deal with these challenges.

Clinical Laboratory Information Systems↗
PubMed2005

Improved biochemical outcome with adjuvant radiotherapy after radical prostatectomy for prostate cancer with poor pathologic features.

PURPOSE: The indications for adjuvant external beam radiotherapy (EBRT) after radical prostatectomy (RP) are poorly defined. We performed a retrospective comparison of our institution's experience treating prostate cancer with RP vs. RP followed by adjuvant EBRT. METHODS AND MATERIALS: Between 1987 and 1998, 617 patients with clinical Stage T1-T2N0M0 prostate cancer underwent RP. Patients who underwent preoperative androgen deprivation and those with positive lymph nodes were excluded. Of the 617 patients, 34 (5.5%) with an undetectable postoperative prostate-specific antigen (PSA) level underwent adjuvant prostatic fossa RT at a median of 0.25 year (range, 0.1-0.6) postoperatively because of poor pathologic features. The median total dose was 59.4 Gy (range, 50.4-66.6 Gy) in 1.8-2.0-Gy fractions. These 34 RP+RT patients were compared with the remaining 583 RP patients. Biochemical failure was defined as any postoperative PSA level > or =0.1 ng/mL and any postoperative PSA level > or =0.3 ng/mL (at least 30 days after surgery). Administration of androgen deprivation was also scored as biochemical failure when applying either definition. The median clinical follow-up was 8.2 years (range, 0.1-11.2 years) for RP and 8.4 years (range, 0.3-13.8 years) for RP+RT. RESULTS: Radical prostatectomy + radiation therapy patients had a greater pathologic Gleason score (mean, 7.3 vs. 6.5; p < 0.01) and pathologic T stage (median, T3a vs. T2c; p < 0.01). Age (median, 65.7 years) and pretreatment PSA level (median, 7.9 ng/mL) were similar between the treatment groups. Extracapsular extension was present in 72% of RP+RT patients vs. 27% of RP patients (p < 0.01). The RP+RT patients were more likely to have seminal vesicle invasion (29% vs. 9%, p < 0.01) and positive margins (73% vs. 36%, p < 0.01). Despite these poor pathologic features, the 5-year biochemical control (BC) rate (PSA <0.1 ng/mL) was 57% for RP+RT and 47% for RP (p = 0.28). For patients with extracapsular extension, the 5-year BC rate was 52% for RP+RT vs. 30% for RP (p < 0.01). The 5-year BC rate for patients with seminal vesicle invasion was 60% for RP+RT vs. 18% for RP (p < 0.01). For those with positive margins, the 5-year BC rate was 64% for RP+RT vs. 27% for RP (p < 0.01). The use of adjuvant RT remained statistically significant on multivariate analysis when applying either biochemical failure definition. Adjuvant RT also remained statistically significant when including the postoperative PSA level (>30 days after surgery) in the multivariate analyses. In addition, 99 (17%) of the 583 RP patients required salvage prostatic fossa RT (median dose, 59.4 Gy) at a median interval of 1.3 years after surgery (range, 0.1-8.4) for a palpable recurrence (n = 10) or a detectable/rising postoperative PSA level (n = 89). The median PSA level before salvage RT was 0.8 ng/mL (mean, 3.2 ng/mL). The 5-year and 8-year BC rate, using the PSA <0.1 ng/mL definition, from the date of salvage RT was 41% and 35%, respectively. The 5-year and 8-year BC rate, using the PSA <0.3 ng/mL definition, was 46% and 36%, respectively. The 8-year local recurrence rate after salvage RT was 4%. CONCLUSION: Adjuvant RT demonstrated improved efficacy against prostate cancer. For patients with poor pathologic features (extracapsular extension, seminal vesicle invasion, positive margins), adjuvant RT improved the biochemical outcome independent of other prognostic factors.

Aged↗
PubMed2005

FDG-PET in the prediction of pathologic response after neoadjuvant chemoradiotherapy in locally advanced, resectable esophageal cancer.

PURPOSE: To assess the efficacy of 18Fluorodeoxyglucose-positron emission tomography (FDG-PET) for predicting a pathologic response in locally advanced esophageal cancer after neoadjuvant chemoradiotherapy. METHODS AND MATERIALS: All enrolled patients were treated with neoadjuvant chemoradiotherapy followed by esophagectomy and underwent two FDG-PET scans, before and after neoadjuvant chemoradiotherapy. We compared the results of the preoperative FDG-PET scans with the pathologic results. RESULTS: From July 2001 to July 2004, 32 patients (29 men and 3 women) were enrolled in this study. Pathologic complete response (pCR) in the esophagus was achieved in 21 of 32 patients (66%). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) in the primary tumors of the preoperative FDG-PET were 27%, 95%, 75%, and 71%, respectively. In regional lymph nodes, these values were 16%, 98%, 36%, and 93%, respectively. The mean standardized uptake value (SUV) of primary tumors was initially 5.6 +/- 3.6 and changed to 1.5 +/- 1.3 after neoadjuvant chemoradiotherapy (p < 0.05). If analysis of metabolic response (SUV decrease, DeltaSUV) was limited to initially highly metabolic primary tumors (SUV > or =4.0), pathologic response was correlated with metabolic response (p = 0.006). CONCLUSIONS: This study suggested that the pathologic response of an initially highly metabolic tumor after neoadjuvant chemoradiotherapy could be correlated with the metabolic response, and FDG-PET can provide additional information on tumor response to chemoradiotherapy.

Aged↗
PubMed2005

Cure of innate intestinal immune pathology by CD4+CD25+ regulatory T cells.

CD4+CD25+ regulatory T (T(R)) cells are a naturally occurring population of T cells that suppress the development of a variety of pathological immune responses. However, as human inflammatory diseases are usually not diagnosed until after the onset of clinical symptoms, it is of great interest to determine whether CD4+CD25+ T(R) cells can reverse established pathology. To examine this question we have utilized a murine model of human inflammatory bowel disease (IBD), where pathology is triggered by infection of immune deficient RAG-/- mice with the pathogenic bacterium Helicobacter hepaticus. Here we demonstrate that adoptively transferred CD4+CD25+ T(R) cells can cure established intestinal inflammation that is mediated by innate immune activation in H. hepaticus-infected RAG-/- mice. CD4+CD25+ T(R) cell-mediated amelioration of innate intestinal pathology was accompanied by a reversal in systemic innate immune activation, but did not involve any detectable anti-bacterial effects, as bacterial colonization levels were unchanged. Cure of established pathology was not achieved using subpopulations of CD4+CD25- T cells, further emphasizing the enhanced regulatory activity of CD4+CD25+ T(R) cells.

Animals↗
PubMed2005

Modern treatment of pathological fractures in children.

Pathological fractures in children occur from a variety of causes. The clinician has to develop an individual strategy that weighs up the pros and cons of treatment, considering the bone biology and the biomechanics at the fracture site. Determining the lesional pathology is paramount, whether it is in the form of a neoplastic or non-neoplastic entity, so that bone healing can be maximized. Time-efficient protection and reconstruction of the child's musculoskeletal system is the aim of the surgeon's intervention. The whole strategy must be individualized to every situation. Combinations of diseases, fracture sites, and children are many, whereas treatment options are fewer. Options include non-operative management with observation, and intralesional resection with or without bone grafting, and with or without internal fixation. A thoughtful, disciplined, and systematic approach will be successful most often. The goals of treating a child's pathological fracture are all based on establishing a diagnosis. Only after establishing the diagnosis with certainty can a proper treatment strategy be formulated. Fracture management is then based on five points: (a) pain relief and comfort of the child; (b) achieve Local control or containment of the pathological lesion; (c) skeletal stabilization, preservation of growth, and maintain anatomical alignment; (d) fracture union; and (e) restoration of function. Maintaining perspective will facilitate optimal patient care and minimize the confounding variables that seem to plague the treatment of pathological fractures.

Adolescent↗
PubMed2006

CT imaging of wet specimens from a pathology museum: How to build a "virtual museum" for radiopathological correlation teaching.

X-rays and CT have been used to examine specimens such as human remains, mummies and formalin-fixed specimens. However, CT has not been used to study formalin-fixed wet specimens within their containers. The purpose of our study is firstly to demonstrate the role of CT as a non-destructive imaging method for the study of wet pathological specimens and secondly to use the CT data as a method for teaching pathological and radiological correlation. CT scanning of 31 musculoskeletal specimens from a pathology museum was carried out. Images were reconstructed using both soft-tissue and bone algorithms. Further processing of the data produced coronal and sagittal reformats of each specimen. The container and storage solution were manually removed using Volume Viewer Voxtool software to produce a 3D reconstruction of each specimen. Photographs of each specimen (container and close-up) were displayed alongside selected coronal, sagittal, 3D reconstructions and cine sequences in a specially designed computer program. CT is a non-destructive imaging modality for building didactic materials from wet specimens in a Pathology Museum, for teaching radiological and pathological correlation.

Algorithms↗
PubMed2007

Third molar periodontal pathology and caries in senior adults.

PURPOSE: This study was designed to assess the prevalence at enrollment and incidence over 36 months of periodontal pathology and caries affecting third molars in a community-based study of people over the age of 65 years in North Carolina. SUBJECTS AND METHODS: A sub-sample of 818 subjects with dental examinations taken from the Piedmont 65+ Study was available for analysis. All visible teeth were examined. Periodontal probing (PD) measures were taken at 2 sites, mesiobuccal and buccal/facial. Clinical data on caries experience were collected by visual-tactile examination. At enrollment, 342 subjects had at least 1 visible third molar that could be examined. PD measures were available for 276 of these same subjects. The significance of comparisons between third molars and nonthird molars were determined by chi(2) tests and the statistical significance was set at .05. RESULTS: Most of the 342 subjects with at least 1 visible third molar were female (57%) or African American (63%). Mean age was 73 years (SD 5.5 years). Of the 197 subjects with caries experience, third molars were affected in 49% of subjects, less than the 87% in nonthird molars. Third molar caries experience was associated with caries experience on nonthird molar teeth (P < .01). Clinical attachment level (CAL) greater than 3 mm was detected at enrollment in third molars in 68% of subjects, and in nonthird molars in 96%. With one exception, CAL greater than 3 mm in third molars was associated with CAL greater than 3 mm elsewhere in the mouth. Few subjects (17%) had clinical evidence of both caries and periodontal pathology affecting third molars. In this older population of individuals with third molars, 21% were free of periodontal pathology or caries experience. CONCLUSIONS: Data on the prevalence of third molar periodontal pathology and third molar caries experience in an elderly population should be useful to both clinicians and their younger patients when considering the merits of retaining or removing third molars with no evidence of pathology.

Black or African American↗
PubMed2006

An adjunctive preventive treatment for heart disease and a set of diagnostic tests to detect it: insulin-like growth factor-1 deficiency and cell membrane pathology are an inevitable cause of heart disease.

Coronary heart disease (CHD) is a preventable disease with high morbidity and mortality. Largely omitted from the efforts at detection and treatment are the contributions of the lungs, the skeletal muscles and the arteries to heart disease pathology. Also omitted are the effects of the age-related decline in insulin-like growth factor-1 (IGF-1) and the age-related increase in cell membrane pathology. The hypothesis on which this model is based postulates that growing older, over time, necessarily results in pathological changes in the heart, the lungs, the skeletal muscles and the arteries. Additionally, the age-related decline in (IGF-1) that occurs in the otherwise healthy aged population also causes similar pathological changes. The drug portion of the proposed treatment includes the use of the drug acetyl-l-carnitine (ALC) to increase the age-related decreased IGF-1 levels. The drug centrophenoxine (CPH) is used to reverse the age-related pathological changes that inevitably occur in the heart, the lungs, the skeletal muscles and the arteries. A testing procedure is included to improve the detection of heart disease and to monitor the results. It consists of five tests: the monitoring of plasma IGF-1 levels; the monitoring of blood pressure, and in particular elevated systolic blood pressure; the monitoring of blood pressure variability over time; a heart rate recovery time test and a heart rate reserve test. Heart rate reserve is defined as the difference between maximal heart rate and resting heart rate, after treadmill exercise. The changes in test results noted during treatment are an indicator of progress or deterioration in the prevention of heart disease, whatever the case may be.

Blood Pressure↗
PubMedDate not supplied

Glial activation and pathological pain.

Pain is a sensation we have all experienced. For most of us, the pain has been temporary. However, for patients with pathological pain, the pain experience is unending, with little hope for therapeutic relief. Pathological pain is characterized by an amplified response to normally innocuous stimuli, and an amplified response to acute pain. Pathological pain has long been described as the result of dysfunctional neuronal activity. While neuronal functioning is indeed altered, there is significant evidence showing that exaggerated pain is regulated by the activation of astrocytes and microglia. In exaggerated pain, astrocytes, and microglia are activated by neuronal signals including substance P, glutamate, and fractalkine. Activation of glia by these substances leads to the release of mediators that then act on other glia and neurons. These include a family of proteins called "proinflammatory cytokines" released from microglia and astrocytes. These cytokines have been shown to be critical mediators of exaggerated pain. Some patients with pathological pain also report "extra-territorial" and/or "mirror" image pain. That is, exaggerated pain is experienced not only in the area of trauma. In extra-territorial pain, pain is also perceived as arising from neighboring healthy tissues outside of the site of trauma. In the rare cases of mirror-image pain, such pain is perceived as arising from the healthy, corresponding body part on the opposite side of the body. New data suggest that activation of astrocyte communication via gap junctions may mediate such spread of pain. While traditional therapies for pathological pain have focused on neuronal targets, the following review describes glia as newly recognized mediators of exaggerated pain, and as new therapeutic targets. Moreover, the glial-neuronal interactions discussed here are likely not exclusive to pain, but rather are likely to play significant roles in other behavioral phenomena.

Animals↗
PubMed2005

The amyloid pathology progresses in a neurotransmitter-specific manner.

Past studies using transgenic models of early-staged amyloid pathology, have suggested that the amyloid pathology progresses in a neurotransmitter-specific manner where cholinergic terminals appear most vulnerable, followed by glutamatergic terminals and finally by somewhat more resistant GABAergic terminals. To determine whether this neurotransmitter-specific progression persists at later pathological stages, presynaptic bouton densities, and the areas of occupation and localization of plaque adjacent dystrophic neurites were quantified in 18-month-old APP(K670N, M671L)+PS1(M146L) doubly transgenic mice. Quantification revealed that transgenic animals had significantly lower cholinergic, glutamatergic and GABAergic presynaptic bouton densities. Cholinergic and glutamatergic dystrophic neurites appear to be heavily influenced by fibrillar Abeta as both types displayed a decreasing area of occupation with respect to increasing plaque size. Furthermore, cholinergic dystrophic neurites reside in closer proximity to plaques than glutamatergic dystrophic neurites, while GABAergic dystrophic neurites were minimal regardless of plaque size. To investigate whether similarities exist in the human AD pathology, a monoclonal antibody (McKA1) against the human vesicular glutamate transporter 1 (VGluT1) was developed. Subsequent staining in AD brain tissue revealed the novel presence of glutamatergic dystrophic neurites, to our knowledge the first evidence of a structural glutamatergic deficit in the AD pathology.

Acetylcholine↗
PubMed2003

MRI correlates of pathology in parkinsonism: segmented inversion recovery ratio imaging (SIRRIM).

The two commonest, clinically well-defined, forms of parkinsonism are idiopathic Parkinson's disease (PD) and progressive supranuclear palsy (PSP). Both involve, inter alia, pathological changes in the substantia nigra pars compacta (SN(C)). In PD there is neuronal loss with associated Lewy body pathology and microglial activation. Three morphological features have been identified [Brain 114 (1991), 2283; Greenfield's Neuropathology 2 (1997), 289]. First, there is a gradient of pathological change such that the lateral segments are more affected than the medial. Second, there is thinning of the pigmented tissue, and third, there is a broadening of the overall structure in a dorsal-ventral direction, possibly caused by the migration of melanin-laden macrophages [Greenfield's Neuropathology 2 (1997), 289]. In contrast, PSP is characterized pathologically by intraneuronal neurofibrillary tangles. There are two morphological features in the SN(C) [Brain 114 (1991), 2283]. First, the gradient of pathological change is in the opposite direction to that of PD (i.e., the medial segments are more affected than the lateral). Second, there is atrophy. Any technique sensitive to neuropathology should be capable of detecting these features. We have previously reported on a new approach to detecting signal change in the substantia nigra in PD. This makes use of a ratio of images acquired by two distinct inversion recovery sequences [J. Neurol, Neurosurg. Psychiatry 67 (1999), 815; Am. J. Neuroradiol. 21 (2000) 697]. The prior work suggests that the technique is sensitive to, but not necessarily specific for, PD. We present here a preliminary report on an extension of the work. This is a semiautomated segmentation analysis that enables the substantia nigra to be displayed as an isolated structure. The technique is now given the acronym SIRRIM (segmented inversion recovery ratio imaging). In contrast to our earlier work, it allows for a more accurate assessment of the gross abnormalities. We report typical SIRRIM images of the SN(C). Images are shown for three subjects: a normal control, a patient with PD, and a "disease control" (a patient with PSP). In these examples all three morphological features of PD, as well as both morphological features of PSP, have radiological correlates. These preliminary findings suggest that SIRRIM may be specific for both diseases.

Aged↗