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PubMed2004

Combined naevus: a benign lesion frequently misdiagnosed both clinically and pathologically as melanoma.

BACKGROUND: Combined naevi are characterised pathologically by the presence of two or more different types of melanocytic naevi in a single lesion. They are prone to clinical and pathological misdiagnosis as melanoma. Misdiagnosis may result in inappropriate treatment, patient anxiety and medicolegal consequences. AIMS: With the aim of reducing the incidence of misdiagnosis, this study documents the clinical and pathological features of a large series of combined naevi and describes how to distinguish them from melanoma. PATIENTS AND METHODS: The slides of skin lesions from 220 patients that were coded as combined naevus between 1990 and 2001 were retrieved from the archival files of the Department of Anatomical Pathology, Royal Prince Alfred Hospital, Sydney, Australia. The clinical notes, letters from referring pathologists (for consultation cases) and slides were reviewed and for each lesion clinical and pathological features were assessed. Thirty-eight cases were excluded either because they included only one naevus component or because there were atypical pathological features in the slides available for review. The remaining 182 cases formed the study population. RESULTS: The patients included 92 females and 87 males (1.1:1). In three cases the gender was not known. Mean and median patient ages were 29.6 and 28 years, respectively. The anatomical site of involvement was the trunk in 64 cases (35.2%), head and neck region in 43 cases (23.6%), upper extremity in 40 cases (22.0%), lower extremity in 18 cases (9.9%) and perineum and buttock region in eight cases (4.4%). In nine cases the site of involvement was not known. A pre-operative clinical diagnosis was recorded in 126 cases; of these, melanoma was suspected clinically in 33 cases (26.2%) while combined naevus was diagnosed clinically in only three cases (2.4%). Histologically, 180 cases included two different naevus components, and in two cases three different naevus components were present. The most common combination was a common acquired naevus of compound type associated with a blue naevus of deep penetrating naevus type; this occurred in 57 cases (31.3%). The referring pathologist recorded a preferred diagnosis in 88 of 122 consultation cases; of these, melanoma was suspected in 23 cases (26.1%) and in 23 cases combined naevus was favoured (26.1%). CONCLUSIONS: Combined naevus is an uncommon type of melanocytic naevus that is frequently misdiagnosed both clinically and pathologically. Knowledge and recognition of the pathological features of combined naevi and the important features that distinguish them from melanomas should reduce the frequency of misdiagnosis.

Adolescent↗
PubMed1997

Quantitative analysis of acute axonal pathology in experimental spinal cord contusion.

The major sensorimotor deficits that result from traumatic spinal cord injury (SCI) are due to loss of axons in ascending and descending pathways of the white matter (WM). Experimental treatments administered after a standardized SCI can reduce WM loss and long-term functional deficits. Thus, a significant proportion of WM loss occurs secondary to the mechanical injury and may be a target for therapeutic intervention. Presently, we know little of how and when secondary injury mechanisms operate in the WM after SCI. We therefore used a standardized rat model of clinically relevant contusion injury to examine axonal pathology over the first 24 h by light and electron microscopy. Based on qualitative evaluation of tissue at 15 min, 4 h, and 24 h after a "mild" SCI produced with a weight-drop device (10 g x 2.5 cm), we selected areas from the ventromedial WM at the lesion epicenter for quantitative analyses. We compared axon number and the proportion of axons with various axoplasmic and myelin abnormalities over time after SCI, as well as the effect of axon size on degree of pathology and loss. We found by 4 h postinjury (pi) axonal pathology was more severe than at 15 min and that a significant loss of large diameter axons had occurred; no significant additional loss of axons was seen by 24 h pi. When we compared axonal pathology after a more severe contusion (10 g x 17.5 cm), we found a greater loss of axons at 4 h. In addition, a higher proportion of the remaining axons demonstrated pathological alterations. We developed a semi-quantitative Axonal Injury Index (AII) as an overall measure of axonal pathology that was sensitive to the effects of injury severity at 4 h pi. The AII has greater statistical power than our individual measures of axonal pathology. Our results suggest that it may be possible to use the AII at 4 h pi to assess effects of potential therapeutic agents on acute axonal pathology after SCI.

Animals↗
PubMed1993

Normal and pathological saccadic dysmetria.

Initial saccades to visual targets are generally not precise in either normal subjects or patients with saccadic dysmetria. Quantitative criteria have to be applied to clearly distinguish between normal and pathological saccadic dysmetria, which is often found in patients with cerebellar lesions. To establish these criteria, the accuracy of visually guided horizontal saccades (10 degrees and 20 degrees target steps) was studied in a group of 24 patients with lesions affecting the cerebellum or its connections, and compared with data from 17 normal subjects. Eye movements were recorded with infrared oculography. Saccades of normal subjects had an average gain of 0.92-0.95 depending on the stimulus condition. Centripetal saccades were significantly larger than centrifugal saccades, for 20 degrees target steps. Most patients (n = 15) had significantly larger saccadic amplitudes than normal subjects (hypermetria), at least in one direction. Saccades in the opposite direction could be either hypometric, hypermetric or normal. Two patients had hypometric saccades in both directions. For one of the patients with hypermetria, in addition, the amplitude difference between centrifugal and centripetal saccades was significantly larger than in the normal subjects. Five patients had no significant pathology of the initial (primary) saccade, but a pathological pattern of corrective saccades. Two patients had normal saccades under all conditions. The quantitative comparison with normal subjects allows the detection even of mild pathology. According to our results, a pathology can be assumed when the average gain of saccades in at least one direction is 1.0 or more, or when more than two out of 20 saccades are followed by two corrective saccades of which the last is in the direction opposite to the initial saccade (pathological pattern of corrective saccades). Target steps of 20 degrees reveal a pathological condition more often than 10 degrees target steps. The application of quantitative criteria might be useful to establish a diagnosis of pathologic saccadic dysmetria even in instances in which it is clinically not obvious.

Adult↗
PubMed2001

Clinical and pathological findings in reexcision of incompletely excised basal cell carcinomas.

In common practice, patients with incompletely excised basal cell carcinomas (BCCs) are referred to elective reexcision. In previous reports, it was observed that tumor cells are found in only 50% of the reexcised specimens. The authors performed a retrospective analysis of a large series of patients to evaluate clinical and pathological findings in patients who underwent reexcision of incompletely excised BCCs. A total of 1,478 BCCs arising in 1,278 patients were excised by plastic surgeons in a plastic and reconstructive surgery department during a 4-year period. In 159 patients (10.8%), the excision was incomplete according to the pathological report. These tumors were defined as an incompletely excised BCCs. One hundred of the 159 patients with incompletely excised BCCs (62.9%) were reoperated. Residual tumor cells were found in 28 of 100 patients (28%) within the pathological specimen of the reexcised tissue (defined as positive reexcision, or +veRE). There was no correlation between +veRE and the age or sex of the patient. Location of the BCCs in the cheeks, eyelids, or ears was associated with a low percent of +veRE (10.0%, 13.3%, and 22.2% respectively). Pathological factors associated with a low percent of +veRE were dermal inflammatory infiltrate in the pathological specimen (p = 0.003) and sun damage pathological changes (p = 0.03), but there was no correlation with the pathological subtype distribution of the tumors. The authors conclude that lack of tumor cells at reexcision of incompletely excised BCCs is associated with location of the tumors in the cheeks, eyelids, and ears, and with pathological findings of dermal inflammatory infiltrates or sun damage changes. The roles of inflammatory and solar changes in the destruction of residual carcinoma cells should be investigated further.

Basal Cell Carcinoma↗
PubMed2006

Clinical and pathologic predictors of locoregional recurrence, distant metastasis, and overall survival in patients treated with chemoradiation and mesorectal excision for rectal cancer.

OBJECTIVES: To identify predictive factors for locoregional recurrence (LR), distant metastasis (DM), and overall survival (OS) in patients treated with chemoradiation and surgery for rectal cancer. METHODS: Between 1989 and 2001, 470 patients with rectal cancer were treated with preoperative (89%) or postoperative (11%) chemoradiation and mesorectal excision. Median radiation dose was 45 Gy; 97% received concurrent infusional 5-fluorouracil, and 65% received adjuvant chemotherapy. Median follow-up interval was 5.7 years. RESULTS: The 5-year rates of freedom from LR, freedom from DM, and OS were 90%, 79%, and 80%, respectively. On univariate analysis, significant predictors of LR were female sex, clinical T stage, pathologic T and N stages, and positive radial margin. Significant univariate predictors of DM were circumferential extent of tumor, tumor immobility, lymphovascular invasion, perineural involvement, and pathologic T and N stages. Significant univariate predictors of lower OS were age, circumferential extent of tumor, shorter distance from anal verge, tumor size, tumor immobility, anal canal involvement, lymphovascular invasion, perineural involvement, positive radial margin, and pathologic T and N stages. On Cox multivariate analysis, female sex and pathologic T and N stages independently predicted for LR; pathologic T and N stages independently predicted for DM; and age, circumferential extent of tumor, positive radial margin, and pathologic T and N stages independently predicted for lower OS. CONCLUSIONS: Pathologic T and N stages significantly predicted for all 3 end points (LR, DM and OS) on multivariate analysis. Investigations of more aggressive adjuvant chemotherapy appear warranted for pathologic stage T3/T4 or N1/2 rectal cancer.

Adult↗
PubMed2005

Clinical features of pathologic childhood aerophagia: early recognition and essential diagnostic criteria.

OBJECTIVE: This study investigated the early recognition and diagnosis of pathologic childhood aerophagia to avoid unnecessary diagnostic approaches and serious complications. METHODS: Between 1995 and 2003, data from 42 consecutive patients with pathologic childhood aerophagia, aged 2 to 16 years, were reviewed. An esophageal air sign was defined as an abnormal air shadow on the proximal esophagus adjacent to the trachea on a full-inflated chest radiograph. RESULTS: Of the 42 patients, the chief complaints were abdominal distention (52.4%), recurrent abdominal pain syndrome (21.4%), chronic diarrhea (11.9%), acute abdominal pain (7.1%) and others (7.2%). Mean symptom duration before diagnosis was 10.6 months (range, 1 to 60 months), and it exceeded 12 months for 16 (38.1%) patients. The clinical features common to all patients were abdominal distention that increased progressively during the day, increased flatus on sleep, increased bowel sound on auscultation and an air-distended stomach with increased gas in the small and large bowel by radiography. Visible or audible air swallowing (26.2%) and repetitive belching (9.5%) were also noted. Esophageal air sign was observed in 76.2% of the patients and in 9.7% of the controls (P=0.0001). The subgroups of pathologic childhood aerophagia divided by underlying associations were pathologic childhood aerophagia without severe mental retardation (76.2%), which consisted of psychological stresses and uncertain condition, and pathologic childhood aerophagia with severe mental retardation (23.8%). CONCLUSIONS: The common manifestations of pathologic childhood aerophagia may be its essential diagnostic criteria, and esophageal air sign may be useful for the early recognition of pathologic childhood aerophagia. Our observations show that the diagnostic clinical profiles suggested by Rome II criteria should be detailed and made clearer if they are to serve as diagnostic criteria for pathologic childhood aerophagia.

Abdominal Pain↗
PubMed2004

Ego-pathology and common symptom factors in schizophrenia.

The phenomenological construct of ego-pathology in schizophrenia has been widely referred to in psychopathological textbooks but was systematically assessed in very few empirical studies. This study investigated the association between ego-pathology (Ego-Pathology Inventory) and common symptom factors (Positive and Negative Symptom Scale) in paranoid schizophrenia patients within 3 days after admission and after 2 weeks of treatment. The predictive value of ego-pathology for short-term treatment outcome was also assessed. A factor analysis of all subscale scores revealed a four-factor solution: positive symptoms, negative symptoms, and two distinct ego-pathology factors, i.e., general and identity. Although the ego-pathology subscale "activity" loaded on the positive symptom factor, the other four subscales formed the two ego-pathology factors with no high loadings on other factors. High scores on ego-demarcation at admission predicted poor treatment outcome after 2 weeks. The findings suggest that ego-pathology might be used to capture additional and clinically meaningful symptom dimensions in schizophrenia.

Adult↗
PubMed2000

Descriptive features of Turkish pathological gamblers.

This study investigated the descriptive features of Turkish pathological gamblers. Participants were 31 male pathological gamblers and 42 "regular gamblers" who acted as controls. The subjects were diagnosed on the basis of DSM-IV pathological gambling criteria and completed the Turkish Version of South Oaks Gambling Screen (SOGS). The nonpathological group was quite comparable with the pathological gambling group with respect to types and frequency of gambling and socio-demographic features. The data on the variables that defined and discriminated pathological gamblers from regular gamblers were collected through administration of a 68-item questionnaire, prepared by the authors. Compared to the non pathological gamblers, the pathological gamblers gambled more to recover their losses, experienced craving for gambling more often, gambled more often to obtain relief from disturbing emotions, harboured more irrational and unrealistic cognitions to rationalize their gambling behavior and suffered more emotionally, financially and socially as a result of their involvement in gambling. The results of the study suggested that Turkish pathological gamblers are very much like their counterparts in Western countries.

Behavior, Addictive↗
PubMed2004

Comparison of clinical and pathological features in African-American and Caucasian patients with localized prostate cancer.

OBJECTIVE: To examine patient characteristics, prostate specific antigen (PSA) levels, and established preoperative and pathological prognostic factors to determine differences between Caucasian and African-American patients with localised prostate cancer, as it remains controversial whether African-American men present with more aggressive disease. PATIENTS AND METHODS: One hundred consecutive patients (aged 53-76 years) undergoing radical retropubic prostatectomy (RRP) at an equal-access tertiary-care centre were retrospectively reviewed. All patients had preoperative PSA levels, a physical examination (including clinical staging), and sextant biopsy. Insurance information was also collected. The same urological oncologist determined clinical staging and performed all the RRPs, and the same genitourinary pathologist determined the Gleason grade for biopsies and surgical specimens, pathological stage, percentage of tumour involvement, and specimen weight. African-American and Caucasian patients were compared for PSA, clinical stage, pathological stage, biopsy and pathological Gleason grade, organ confinement, margin status and specimen weight. Using preoperative and pathological data, both groups were also compared for over- and under-staging and -grading. The Wilcoxon rank test with P < 0.05 was used to determine statistically significant differences. RESULTS: African-American patients were more likely to be Medicaid or self-insured than Caucasian patients. Age, biopsy grade and clinical stage were not significantly different between the groups. African-American patients presented with a mean PSA level of 11.9 ng/mL and Caucasians with a mean of 8.5 ng/mL (P = 0.03). When clinical and biopsy data were compared with pathological data there were no differences between the groups in under/over-grading or under/over-staging. African-American patients had larger prostates per surgical specimen than their Caucasian counterparts (59.3 g vs 51.6 g, respectively; P = 0.04). CONCLUSIONS: In a referred, equal-access system, African-American patients presented with higher serum PSA levels and had larger prostates in the surgical specimen. However, African-American patients did not present at an earlier age or with higher Gleason grade or clinical stage, nor were pathological grade and stages higher. Other pathological features were no different. African-American patients were not under- or over-staged or under- or over-graded more than their Caucasian counterparts. This retrospective study does not suggest that African-American men present with more aggressive disease.

Aged↗
PubMed2005

WHO non-Hodgkin's lymphoma classification by criterion-based report review followed by targeted pathology review: an effective strategy for epidemiology studies.

In a previous criterion-based pathology report review of 717 cases of non-Hodgkin's lymphoma in an Australian population-based epidemiologic study, a WHO category could be assigned in 91% of cases, but confidence in this classification was high in only 57.5%. Given this lack of confidence, a pathology review was done in a subset of 315 cases, with the aims of assigning a WHO classification category and the corresponding International Classification of Diseases for Oncology, Third Edition code in all cases previously unclassified or classified with low confidence and testing the accuracy of report review in assigning a confident WHO classification. After pathology review, 10 cases were ineligible (not non-Hodgkin's lymphoma, 3.2%) and 99% (301 of 305) of the remainder were assigned a WHO classification, with high confidence in 87% (261 of 301). There was 78% overall agreement between the WHO classification assigned by report review and pathology review, with 92% agreement when there was high confidence in the report review classification and 69% agreement when there was low confidence. Eighteen percent of follicular lymphomas and 23% of diffuse large B-cell lymphomas were reclassified. The pathology review increased the accuracy of WHO classification by an estimated 12.5% in the 694 cases who were still eligible in the study. Although a potential error rate of 7.5% remained, reviewing more cases, or not reviewing any cases classified with high confidence, would have produced only a small change in accuracy. Criterion-based pathology report review of all cases followed by selective pathology review in cases classified with low confidence is recommended as a cost-saving and accurate strategy for pathology review in large epidemiologic studies.

Adult↗
PubMed1997

Severe pathological crying after left anterior choroidal artery infarct. Reversibility with paroxetine treatment.

BACKGROUND: There is increasing evidence that serotonergic neurotransmission may be damaged in poststroke pathological crying. A correlation between the clinical severity of pathological crying and the size of stroke-induced serotonergic pathway lesions is commonly accepted. We present a case of severe pathological crying after a limited left anterior choroidal artery territory infarction. CASE DESCRIPTION: A right-handed 55-year-old man who was a heavy smoker was admitted to the hospital after a right hemiplegia of sudden onset. Clinical examination revealed a right global hemiplegia including the face and a right hemihypoesthesia. Cerebral CT scan and MRI showed an infarct in the retrolenticular part of the posterior limb of the left internal capsule extending upward into the posterior paraventricular corona radiata region. Transesophageal echocardiography revealed an atrial septal aneurysm of 15-mm excursion without associated patent foramen ovale. From the first day of admission, the patient exhibited very frequent and intense fits of pathological crying. Their persistence led to initiation of treatment with the selective serotonin reuptake inhibitor paroxetine on day 30. Complete and immediate resolution of pathological crying occurred 24 hours after onset of therapy. Follow-up examination at day 90 confirmed the absence of relapse of pathological crying. CONCLUSIONS: We conclude that poststroke pathological crying in our patient may have been due to unilateral disruption of the capsular ascending projections of the serotonergic brain stem raphe nuclei. A small left-sided capsular lesion may have led to severe pathological crying. This disabling condition may be reversible with selective serotonin reuptake inhibitor therapy.

Cerebral Arteries↗
PubMed2000

Pathological gambling among cocaine-dependent outpatients.

OBJECTIVE: The authors investigated the occurrence of pathological gambling among cocaine-dependent outpatients, its influence on short-term outcome of treatment, and comparative characteristics of patients with and without pathological gambling. METHOD: The subjects were 313 cocaine-dependent (200 also opiate-dependent) outpatients in clinical trials of medication for cocaine dependence. Pathological gambling (DSM-III-R criteria) was assessed with the Diagnostic Interview Schedule, and sociodemographic and socioeconomic characteristics were determined with the Addiction Severity Index. Outcome was defined as time in treatment (proportion of maximum scheduled time) and proportion of cocaine-positive urine samples during treatment. RESULTS: Pathological gambling had a lifetime occurrence rate of 8.0% and a current (past month) occurrence of 3.8%. Onset preceded the onset of cocaine dependence in 72.0% of the patients (and preceded onset of opiate dependence in 44.4%). Patients with pathological gambling (lifetime or current) did not differ significantly from other patients in length of treatment or proportion of cocaine-positive urine samples. Those with lifetime pathological gambling were significantly more likely to have tobacco dependence (84.0% versus 61.1%) and antisocial personality disorder (56.0% versus 19.8%), to be unemployed (84.0% versus 49.3%), to have recently engaged in illegal activity for profit (64.0% versus 38.5%), and to have been incarcerated (62.5% versus 33.9%). CONCLUSIONS: Pathological gambling is substantially more prevalent among cocaine-dependent outpatients than in the general population. Patients with pathological gambling differ from other cocaine-dependent outpatients in some sociodemographic characteristics but not in short-term outcome of treatment for cocaine dependence.

Adolescent↗
PubMed2005

Does sustained-release lithium reduce impulsive gambling and affective instability versus placebo in pathological gamblers with bipolar spectrum disorders?

OBJECTIVE: Selective serotonin reuptake inhibitors may be effective for some patients with pathological gambling, but those with comorbid conditions, such as bipolar spectrum disorders, may relapse during treatment. To the authors' knowledge, this is the first placebo-controlled treatment study in pathological gamblers with bipolar spectrum disorders; it compares sustained-release lithium carbonate to placebo. METHOD: Forty pathological gambling patients with bipolar spectrum disorders entered a 10-week randomized, double-blind, placebo-controlled treatment study of sustained-release lithium carbonate. Outcome measures included gambling severity, mood, anxiety, and impulsivity scales. RESULTS: Pathological gambling patients with bipolar spectrum disorders significantly improved while taking sustained-release lithium carbonate compared to placebo on total pathological gambling scores on the Yale-Brown Obsessive Compulsive Scale, including both thoughts/urges and behavior, as well as on the Clinical Global Impression severity of pathological gambling scale. Affective instability (the Clinician-Administered Rating Scale for Mania score) was also lower in the group treated with sustained-release lithium carbonate compared to placebo. Ten (83%) of 12 completers were rated as responders in the sustained-release lithium group versus five (29%) of 17 in the placebo group. Of note, improvement in gambling severity was significantly correlated with improvement in mania ratings. CONCLUSIONS: Sustained-released lithium may be an effective treatment in reducing both gambling behavior and affective instability in pathological gamblers with bipolar spectrum disorder. This study highlights the need to identify subgroups of pathological gambling patients with bipolar spectrum conditions because this may have important treatment implications.

Adult↗
PubMed1975

Degree of pathology as related to readiness to accept labels in process and reactive schizophrenics.

Two experiments were performed in order to determine whether readiness to accept deviant labels, as measured by acquiescence set, interacts with type of schizophrenia (process vs. reactive) to influence level of pathology. It was found on both a behavioral measure and a psychometric measure of psychopathology that high acquiescent process schizophrenics manifested more pathology than did either low acquiescent process or reactive schizophrenics, both of whom showed more pathology than high acquiescent reactive schizophrenics. The results suggest that one's acceptance of deviant labels as well as one's past history of being assigned social and evaluative labels may influence the patient's level of pathology. Scheff (1966), in viewing the mental patient from a sociological perspective, suggests that an important determinant of mental disorder is the acceptance by the deviant individual of the various labels which stigmatize him as mentally ill. If this is the case, then individual differences in readiness to accept or agree with labels about oneself may be related to the degree of pathology manifested in a psychiatric population. The present authors sought to determine if acquiescence set, as measured by the Agreement Response Scale (Couch & Keniston, 1960), is related to degree of pathology in schizophrenic patients. The Agreement Response Scale was used as a measure of the general tendency to acquiesce to or agree with personality statements or labels. The investigators performed two experiments, in Experiment 1 a behavioral measure of pathology was used and in Experiment 2 a psychometric measure of pathology was used. In addition, the schizophrenic Ss were grouped according to the process-reactive distinction as the reactive schizophrenic may be expected to have a more favorable history of labeling than would the process schizophrenic.

Adult↗
PubMed2003

Education modifies the relation of AD pathology to level of cognitive function in older persons.

OBJECTIVE: To test the hypothesis that years of formal education modifies the relation of AD pathology to level of cognitive function. METHODS: A total of 130 older Catholic clergy participating in the Religious Orders Study underwent annual cognitive function testing and brain autopsy at the time of death. Individual cognitive function tests were z-scored and averaged to yield a global measure of cognitive function and summary measures of five different cognitive abilities. Neuritic and diffuse plaques and neurofibrillary tangles were counted in separate 1 mm(2) areas of maximal density. Counts were converted to standard scores by dividing by their SD, and combined to yield a global AD pathology score and summary scores of each postmortem index. Linear regression was used to examine the relation of education and AD pathology scores to level of cognitive function proximate to death, controlling for age and sex. Subsequent analyses tested the interaction between education and each AD pathology score to determine whether education modified the relation of AD pathology to level of cognitive function. Additional analyses examined these associations on five specific cognitive abilities. RESULTS: Both years of formal education (regression coefficient = 0.073, p = 0.0001) and the global AD pathology score (regression coefficient = -0.689, p < 0.0001) were related to level of cognitive function. When an interaction term between education and AD pathology was added to the model, the association between a unit of AD pathology and level of cognitive function was 0.088 (p = 0.0078) standard unit less for each year of education than the level predicted from the model without the interaction term. Whereas neuritic plaques, diffuse plaques, and neurofibrillary tangles were all strongly related to cognitive function, education only modified the relation of neuritic plaques (p = 0.002) and diffuse plaques (p = 0.03) to cognition, but not neurofibrillary tangles. In analyses examining five different cognitive abilities, the interaction between education and the neuritic plaque score was strongest for perceptual speed and weakest for episodic memory. CONCLUSIONS: These data provide strong evidence that the relation between senile plaques and level of cognitive function differs by years of formal education.

Aged↗
PubMed2004

Cerebral infarctions and the likelihood of dementia from Alzheimer disease pathology.

BACKGROUND: Alzheimer disease (AD) is the most common cause of dementia. The effect of cerebral infarctions on the likelihood of dementia from AD pathology is not well understood. METHODS: The study included 153 deceased Catholic clergy who participated in the Religious Orders Study. Annual evaluations, including 19 tests of cognitive function, were performed to determine a diagnosis of dementia and level of cognitive abilities proximate to death. At autopsy, neuritic and diffuse plaques and neurofibrillary tangles were counted and combined into a standardized summary measure of AD pathology. Number, volume, side, and distribution of old macroscopic infarctions were recorded. Analyses included logistic and linear regression, adjusting for age, sex, and education. RESULTS: The AD pathology score ranged from 0 to 2.93 units, and 54 persons had infarctions. There was no relationship between AD pathology and infarctions (r = 0.04, p = 0.56). Each unit of AD pathology increased the odds of dementia by 4.40-fold (95% CI = 2.33 to 8.32), and this was essentially unchanged after accounting for infarctions. The presence of one or more infarctions independently increased the odds of dementia by 2.80-fold (95% CI = 1.26 to 6.21). There was no interaction between AD pathology and infarctions to further increase the likelihood of dementia (p = 0.39). The number, size, and distribution of infarctions added to the odds of dementia but also did not show an interaction with AD pathology. Similar results were found in analyses with global cognitive function and five different cognitive systems. CONCLUSION: Cerebral infarctions independently contribute to the likelihood of dementia but do not interact with AD pathology to increase the likelihood of dementia beyond their additive effect.

Aged↗
PubMed2005

The pathology of the substantia nigra in Alzheimer disease with extrapyramidal signs.

BACKGROUND: Extrapyramidal signs (EPS) are common in Alzheimer disease (AD) and increase in prevalence as AD advances. The neuropathologic substrate responsible for EPS in AD remains to be fully characterized. METHODS: Subjects had a clinical diagnosis of AD confirmed by neuropathologic examination. EPS during life were documented by clinical methods assessing bradykinesia, cogwheel rigidity, rest tremor, and parkinsonian gait. Subjects with EPS and previous neuroleptic exposure were excluded. Twenty-eight subjects were in the EPS group and 104 subjects were without EPS. Neuron loss, alpha-synuclein (ASYN)-labeled pathology, and tau-labeled pathology in the substantia nigra were measured using semiquantitative techniques such that higher scores represented increased pathologic burden. RESULTS: Presence of nigral ASYN-labeled pathology was more common (50 vs 28.9%; p < 0.05) in the EPS group than in those without EPS. There was more nigral neuron loss in the EPS group (1.50 vs 1.11 in no-EPS group; p < 0.05). Tau-labeled burden was not different by group comparisons; however, EPS onset at later stages of dementia severity was associated with increased tau-labeled pathology (Kendall tau-B = 0.48, p < 0.01) and this association remained after controlling for dementia severity at death. Additionally, moderate to severe tau burden was more common in the subgroup with "pure AD" (definite AD without other neuropathology) with EPS (81.8%) than cases without EPS (49.0%; p < 0.05). Four subjects with EPS (14.3%) had little to no significant nigral pathologic changes. CONCLUSIONS: Clinically detected extrapyramidal signs (EPS) in Alzheimer disease (AD) are associated with substantia nigra pathology including alpha-synuclein aggregation, hyperphosphorylated tau accumulation, and neuron loss that may account for the increasing prevalence of EPS as AD progresses. In some cases, limited nigral pathology suggests extranigral factors in the clinical symptoms of EPS.

Aged↗
PubMed1998

Pathological gambling and substance misuse: a review of the literature.

This paper reviews research conducted on the link between pathological gambling and substance misuse. We first examine the phenomenon of "pathological gambling," including similarities between pathological gambling and substance misuse, instruments used to measure pathological gambling, and the prevalence of pathological gambling in the United States and internationally. We then examine research on substance misuse among pathological gamblers, pathological gambling among substance misusers, and the treatment of the pathological gambler-substance misuser. We conclude with a discussion of future research needs.

Female↗