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The effect of lumbar flexion and extension on disc contour abnormality measured quantitatively on magnetic resonance imaging.

STUDY DESIGN: Experimental study with subjects as their own control. OBJECTIVE: To determine if lumbar disc contour abnormality dimensions, measured quantitatively, differ in flexed, neutral or extended positions. SUMMARY OF BACKGROUND DATA: MRIs obtained lying supine are used to determine the degree of lumbar disc contour abnormality (bulging or herniation). Variations in positioning are suspected to influence this assessment. METHODS: Lumbar MR images for 26 male volunteers (24-74 years of age), with or without low back pain, were obtained with the subjects lying in neutral, maximal flexion, and maximal extension positions allowable within a conventional 1.5T MR scanner. Quantitative measures of anterior and posterior disc contour abnormality were obtained for each position. RESULTS: Statistically significant differences in disc angles were obtained between positions (2-5 degrees) for all levels. Posterior contour abnormality was significantly smaller in flexion and extension than in the neutral position (9.5%-30.1%). Posterior contour abnormality in extension was similar or smaller than in flexion. Anterior contour abnormality was significantly smaller in extension than flexion and smaller in the neutral position than flexion. CONCLUSION: Spine position should be standardized when assessing disc contour abnormality with MRI. The largest measured disc contour abnormalities when lying supine in a standard MR scanner are observed in the neutral position, as opposed to flexion or extension.

Adult↗

Incidence and spectrum of chromosome abnormalities in spontaneous abortions: new insights from a 12-year study.

PURPOSE: Despite advances in harvesting and culturing techniques, analysis of the impact of these improvements on the observed frequency of chromosomal abnormalities in spontaneous abortions (SAB) has not been determined. We sought to evaluate the effect of these refinements on the success rate of our cultures and on the resulting frequency of detected chromosomal abnormalities. METHODS: Between 1990 and 2002, 2301 specimens obtained from the products of conception (POC) of SABs were submitted to our laboratory for cytogenetic analysis. Due to refinements in specimen processing and culture techniques introduced at the end of 1997, our data were analyzed for two periods: Period A from 1990 through 1997 with 907 eligible specimens and Period B from 1998 through 2002 with 1273 eligible specimens. RESULTS: Modifications in physician communication and sample processing contributed to significant improvements in the culture success rate and in the ratio of male-to-female cases with normal karyotypes. Additionally, increased detection of trisomic, triploid, and multiple aneuploid cases in Period B resulted in a significant increase in the percentage of cases with abnormal karyotypes (42.8% in Period A vs. 65.8% in Period B). Monosomy X accounted for < 10% of all abnormalities in Period B. Eighty five multiple aneuploid karyotypes, including 57 double trisomies, comprised 7.7% of our 1099 abnormal cases. These karyotypes were detected predominantly in POCs from the older women in our study. This collection of multiple aneuploidies is the largest published to date and includes abnormalities not reported in prior studies. We also present a table empirically derived from the data in Period B that indicates the likelihood of a specific abnormal karyotype based on maternal age. The table can be utilized by health care providers, who counsel patients after a spontaneous miscarriage. CONCLUSION: Improvements in laboratory technique have led to reduced contamination and growth failure of POCs, irrespective of maternal age. This in turn has led to a more balanced male-to-female ratio and to the detection of an increased number of abnormal cases.

Abortion, Spontaneous↗

Abnormal cortical cells and astrocytomas in the Eker rat model of tuberous sclerosis complex.

PURPOSE: In patients with tuberous sclerosis complex (TSC), a wide range of neurologic abnormalities develop, including mental retardation and seizures. Brains from TSC patients are characterized by the presence of cortical tubers, large dysmorphic neurons, and abnormal cytomegalic cells. Although analysis of human TSC brain samples led to the identification of these abnormal cell types, very little is known about how these cells function. In an effort to model TSC-associated CNS abnormalities (and ultimately to analyze the electrophysiologic properties of abnormal cells), we examined Eker rats carrying a Tsc2 mutation. Anatomic studies, including standard histologic stains and immunocytochemistry, were performed on young Eker rats exposed to a carcinogen in utero or aged untreated Eker rats (18-24 months old). METHODS: Pregnant TSC2+/- females were injected once a day with hydroquinone (HQ), and offspring were killed at postnatal day P14 or P28. Coronal tissue sections throughout the CNS were prepared and stained for cresyl violet. In separate studies, brains of old untreated Eker rats were sectioned for anatomic analysis by using standard immunohistochemical techniques. RESULTS: Tissue sections stained with cresyl violet did not reveal any gross differences between HQ-treated Eker (Tsc2Ek/+) rats and siblings (Tsc2+/+). However, two classes of abnormal giant cells were observed in brain sections from untreated aged Eker rats: (a) large dysmorphic pyramid-like cells immunoreactive for NeuN, tuberin, and EAAC-1 in layers IV-VI; and (b) abnormal cytomegalic cells immunoreactive for glial fibrillary acidic protein (GFAP), vimentin, and nestin in deep cortical layers or along the white matter. In addition, large subependymal astrocytomas were observed in four animals. CONCLUSIONS: Our data suggest that cortical tuber formation in Eker rats is a rare event and that prenatal exposure to a nongenotoxic carcinogen such as HQ is not sufficient to induce tuber formation. However, with advanced age, an increased likelihood of astrocytoma formation and the emergence of dysmorphic neurons and cytomegalic cells in the Eker rat brain might exist; each of these abnormalities mimics those seen clinically and could contribute to neurologic problems associated with TSC. Further analysis of this rodent model may be warranted.

Animals↗

Clonal karyotype abnormalities and clinical progress in the myelodysplastic syndrome.

Clonal karyotype abnormalities in 124 patients with myelodysplastic syndrome are reviewed. 36% of patients had abnormalities at referral, the most common being 5q-, +8 and lesions of chromosomes 7 and 20. Reduced survival was associated with the presence of either single or multiple clonal abnormalities at referral, abnormalities of chromosome 7 or 8 (either alone or with other lesions) and exclusively abnormal metaphases. The presence of 5q- alone did not appear to affect survival. Sequential studies were carried out in 77 patients of whom 12 showed karyotypic evolution. Reduced survival was observed in patients with an evolving karyotype but appeared to be due almost entirely to evolution in those patients whose initial karyotype was normal. Leukaemic transformation occurred more commonly in patients with an abnormal karyotype, particularly those with multiple abnormalities, and in patients with an evolving karyotype. Although the first appearance of an abnormal karyotype or an apparent evolution are important phenomena, it is probable that in some cases they merely represent expansion of a previously existing clone that has escaped detection. The distinction between true karyotypic evolution or clonal expansion and statistical variations due to small sample size and variability of samples may be difficult but needs to be taken into account in considering clinical significance.

Adult↗

Ultrasonography in detection of single and multiple abnormal parathyroid glands in primary hyperparathyroidism: comparison with radionuclide scintigraphy and surgery.

BACKGROUND: Among the parathyroid imaging techniques, ultrasonography (USG) has the advantage of convenience, easy availability and low cost. OBJECTIVE: To study the role of USG in localization (side and/or site) of abnormal parathyroid glands in primary hyperparathyroidism (PHPT) and to compare with radionuclide scintigraphy and the 'gold standard', surgery. METHODS: Forty-six consecutive patients undergoing USG of the anterior neck for a diagnosis of PHPT in whom a nuclear scan (technetium-99m sestamibi and/or thallium-201/technetium-99m pertechnetate scintigraphy) was also performed, were studied. The results of imaging were independently interpreted and correlated with reference to surgical findings. RESULTS: Forty-six patients had 52 abnormal parathyroid glands on surgical exploration and surgery was successful in all but one. Forty-one patients had a single adenoma, four had multigland disease and one had a paraganglioma. USG correctly localized the abnormal gland in 30 (73%) and scintigraphy was positive in 40 (98%) out of 41 patients with a single adenoma as confirmed on surgical exploration. Scintigraphy showed a positive concordant test in all 30 patients with a single abnormal gland detected on USG and picked up 10 out of 11 abnormal glands where USG was negative. The sensitivity and positive predictive value of USG for detecting a single abnormal gland was 73% and 100%, respectively, whereas the sensitivity and positive predictive value for scintigraphy was 98%. In patients with multigland disease, USG missed 3 (30%) out of 10 and scintigraphy missed 6 (60%) out of 10 abnormal parathyroid glands as confirmed on surgical exploration (P < 0.05). However, in two patients who had ectopic parathyroid gland, both the modalities localized the lesion in one (paraganglioma), whereas in the other neither test was helpful (left retro-esophageal). CONCLUSION: USG is a convenient, affordable and useful modality to localize abnormal enlarged parathyroid glands in the majority of patients with PHPT. However, when USG is negative, scintigraphy is complementary to it.

Adenoma↗

Hand abnormalities are strongly associated with the duration of diabetes mellitus.

OBJECTIVES: To study the prevalence of hand abnormalities in diabetic patients and to evaluate associations between the hand abnormalities and diabetic variables, ergonomic factors and smoking habits. DESIGN: Cross-sectional study of 100 patients selected at random. Setting. Out-patient clinic, Department of Internal Medicine, Orebro Medical Centre Hospital in Sweden. MAIN OUTCOME MEASURES: Presence and extent of carpal tunnel syndrome (CTS), Dupuytren's contracture (DC), flexor tenosynovitis (FTS), and limited joint mobility (LJM). Duration of diabetes, metabolic control, chronic diabetic complications, blood pressure, ergonomic factors and smoking habits. RESULTS: Carpal tunnel syndrome, DC, FTS and LJM were each present in about 20% of the patients. Hand abnormalities were observed in 50 patients and more than one abnormality was found in 26 of the patients. The hand abnormalities were associated with the duration of diabetes but not with the metabolic control or with other diabetic complications. However, the diabetic complications were associated with bad metabolic control and with the duration of diabetes. Hand abnormalities correlated with heavy manual work but not with smoking habits. Twenty-five of the 50 patients with hand syndromes were disabled to such an extent that surgery was recommended. CONCLUSION: The prevalence of hand abnormalities in diabetic patients is high and increases with the duration of diabetes. In many cases patients with hand abnormalities can be helped by surgery.

Adult↗

Counselling implications of chromosomal abnormalities other than trisomy 21 detected through a maternal serum screening programme.

OBJECTIVE: To identify counselling requirements, we reviewed the frequency and type of non-trisomy 21 chromosome abnormalities found at amniocentesis after maternal serum screening for Down's syndrome. DESIGN: The study involved a review of the cytogenetic results of amniocenteses performed because of a raised maternal serum screening risk. SETTING: The maternal serum screening and amniocenteses were performed at hospitals in the Yorkshire region. SAMPLE: 1715 amniocenteses were performed as a result of a raised maternal serum screening risk for the period 1990 to 1993. METHODS: The cytogenetic results were classified into the main categories of numerical and structural chromosomal abnormalities. MAIN OUTCOME MEASURES: The nature and frequency of abnormal cytogenetic results were identified in which parental samples were required in order to determine if the abnormal finding was de novo or familial and/or for which specialist genetic counselling was required. RESULTS: Sixty-nine pregnancies of 1715 amniocenteses were identified with a chromosomal abnormality (4.0%): 35 (2.0%) with trisomy 21 and 34 (2.0%) with another chromosomal abnormality. For 20 of these 34 abnormalities, parental karyotypes were required and in 29 of the 34 specialist genetic counselling was required. CONCLUSIONS: Women undergoing maternal serum screening and, in particular, those proceeding to amniocentesis, should be informed that there is an equal chance that a chromosomal abnormality other than trisomy 21 will be found at amniocentesis, the nature of which usually requires parental samples and specialist counselling.

Amniocentesis↗

A six year study of the antenatal detection of fetal abnormality in six Scottish health boards.

OBJECTIVE: To assess the sensitivity of prenatal diagnosis by ultrasound and biochemical methods, to evaluate the reasons for non-detection and to make appropriate recommendations. DESIGN: Six year observational study, during which biochemical screening for trisomy 21 was introduced and there was an increase in routine ultrasound scanning at 18-22 weeks. SETTING: Six health boards in Scotland. POPULATION: 264,481 pregnancies, of which 862 were terminated because of fetal abnormality, and 2123 delivered with prenatally detectable major fetal abnormalities. MAIN OUTCOME MEASURES: The prenatal detection of trisomies 13, 18 and 21, and 12 major structural abnormalities, which the average ultrasonographer with average skills using average equipment would be expected to detect. RESULTS: Serum biochemical screening improved detection of trisomy 21 from 33% to 57%. The detection rate for the major abnormalities was 62% (815/1320) and 73% (598/818) when the trisomies were excluded. 18-22 weeks scanning yielded a 92% detection rate. Of the 505 undetected cases, 15% declined prenatal screening, 46% were unscreened because they were ineligible for testing, unbooked, booked too late or scanned too early for a diagnosis to be made, 2% had findings suspicious of a chromosomal abnormality but testing was not undertaken and 37% had a negative scan at a gestation when the abnormality was potentially detectable. CONCLUSIONS: A policy of first trimester scanning followed by serum alpha-fetoprotein screening and additional scanning as clinically indicated is effective in detecting major structural abnormalities, but scanning at 18-22 weeks and serum biochemical screening for trisomy 21 improved the detection rates. Supervised training and adequate equipment are essential. Present prenatal diagnostic tests will not detect all abnormalities and patients must be made aware of this.

Biomarkers↗

Poor patient comprehension of abnormal mammography results.

BACKGROUND: Screening mammography for women 50 to 69 years of age may lead to 50% having an abnormal study. We set out to determine the proportion of women who understand their abnormal mammogram results and the factors that predict understanding. METHODS: We surveyed 970 women age 40 to 80 years identified with abnormal mammograms from 4 clinical sites. We collected information on demographic factors, language of interview, consultation with a primary care physician, receipt of follow-up tests, and method of notification of index mammogram result. This study examines the following outcomes: the participant's report of understanding of her physician's explanation of results of the index mammogram, and a comparison of the radiology report to the participant's report of her index mammogram result. Multivariate models controlled for age, education, income, insurance status, and clinical site. RESULTS: The majority (70%) reported a "full understanding" of their physician's explanation of their abnormal mammogram, but a significant minority (30%) reported less than a full understanding (somewhat, not at all, did not explain). Among women of Asian ethnicity, only 63% reported full understanding. Asian ethnicity was a negative predictor (odds ratio [OR], 0.4; 95% confidence interval [CI], 0.3 to 0.7), and consultation with a primary care physician was a positive predictor (OR, 2.3; 95% CI, 1.7 to 3.3) of reported full understanding. Of the 304 women with a suspicious abnormality, only 51% understood their result to be abnormal. Women notified in person or by telephone were more likely than women notified in writing to understand their result to be abnormal (OR, 2.3; 95% CI, 1.2 to 4.8). CONCLUSION: Almost half of women with the most suspicious mammograms did not understand that their result was abnormal. Our data suggest that direct communication with a clinician in person or by phone improves comprehension.

Adult↗

"Benign" imaging abnormalities in children and adolescents with headache.

OBJECTIVE: To study the frequency of "benign" abnormalities on brain imaging in children with headache, compare it with the frequency of imaging findings that dictate a change in patient management, and determine the association of benign findings with headache. METHODS: A database of 681 headache patients from the pediatric outpatient neurology department over 2 years was reviewed. Patients with benign imaging abnormalities were compared to those with nonbenign findings. Benign abnormalities were defined as those that did not result in a change in patient management. Using literature review, we discuss the benign findings and their possible association with headache. RESULTS: Two-hundred and forty-one patients (35.4%) had imaging at our facility. Two-hundred and eighteen had brain magnetic resonance imaging and 23 had brain computed tomography (CT) only. Twenty-two patients had CT of the sinuses in addition to brain imaging. Forty-six (19.1%) were found to have 50 benign abnormalities including 13 sinus disease, 11 Chiari I malformations, 7 nonspecific white matter abnormalities, 5 venous angiomas, 5 arachnoid cysts, 4 enlarged Virchow-Robin spaces, 2 pineal cysts, 1 mega cisterna magna, 1 fenestration of the proximal basilar artery, and 1 periventricular leukomalacia. Twenty-three patients (9.5%) had findings requiring a change in management. These included 5 sinus disease, 4 tumors, 4 old infarcts, 3 Chiari I, 2 moyamoya, 1 intracranial vascular stenosis, 1 internal jugular vein occlusion, 1 arteriovenous malformation, 1 demyelinating disease, and 1 intracerebral hemorrhage. When excluding sinusitis, which was evident clinically prior to imaging, 3 patients had absence of abnormal neurologic symptoms and signs and imaging findings that resulted in a change in management. CONCLUSIONS: Approximately 20% of pediatric headache patients with brain imaging have benign abnormalities that do not result in a change in headache management. Imaging findings that require a change in management are rare in patients with an absence of abnormal neurologic symptoms and signs, occurring in 1.2% of patients imaged in this study.

Adolescent↗

Clinical significance of EEG abnormalities during photic stimulation in patients with photosensitive epilepsy.

PURPOSE: The continued presence of EEG abnormalities in patients with a history of photosensitive seizures is used to signify the persistence of photosensitive epilepsy. The extent to which this approach places patients at risk of seizures is unclear, however. We describe those EEG abnormalities that may be tolerated with low risk of further seizures, and those that are indicative of poor seizure control. METHODS: Fifty patients with EEG evidence of persistent photosensitive epilepsy underwent photosensitivity testing with diffuse and patterned light; 58% of patients continued to experience seizures, and 42% were seizure free. The incidence of EEG abnormalities to diffuse and patterned intermittent photic stimulation (IPS) was analysed as a function of recent seizures. RESULTS: All patients showed EEG abnormalities to patterned IPS; there was no significant association between patterned IPS and poor seizure control. EEG abnormalities to diffuse IPS occurred in 58% of patients, and 76% of these patients had experienced a seizure within the previous year. These patients were more than twice as likely to be poorly controlled than those who showed abnormalities only to patterned IPS. These results were consistent for both medicated and unmedicated patients. CONCLUSIONS: EEG abnormalities to patterned IPS can be used to signify the persistence of photosensitive epilepsy, but abnormalities to diffuse IPS are more likely to indicate the patient is poorly controlled and at risk of further seizures.

Adolescent↗

Prevalence and significance of electroencephalographic abnormalities in patients with suspected organic mental syndromes.

OBJECTIVE: To determine the prevalence of electroencephalogram (EEG) abnormalities at different levels of cognitive impairment and to assess the possible diagnostic usefulness of the test. DESIGN: Combined prospective assessment of subjects receiving EEGs and retrospective chart review of symptoms and medications. SETTING: Academic geriatric psychiatry service. PATIENTS: 350 adults age 50 and above; 312 were patients being evaluated for possible organic mental syndrome and 38 were normal controls. MEASUREMENTS: All subjects had EEGs and Mini-Mental State Examinations (MMSE) performed at the time of the EEG. EEGs were rated for the presence and type of abnormality, and subjects were stratified according to the severity of impairment. Charts were reviewed by a person blinded to EEG results to determine clinical diagnosis and medications received. MAIN RESULTS: Abnormal EEGs were significantly more common among all patients (67%) in the study than among controls (11%), and the prevalence of abnormality increased with increasing impairment. Many demented patients with equivocal impairment (42%), and most with mild-to-moderate impairment (65%) had abnormal EEGs. An abnormal EEG was not indicative of dementia even when clear cognitive impairment was present, since patients with depression frequently also had abnormal EEG results. CONCLUSIONS: These findings suggest that the EEG is a moderately sensitive but non-specific indicator of brain dysfunction in the elderly. The significance of abnormalities among patients with equivocal impairment should be more fully assessed by longitudinal follow-up to determine if greater cognitive impairment develops.

Aged↗

T-wave abnormalities are a better predictor of cardiovascular mortality than ST depression on the resting electrocardiogram.

BACKGROUND: ST depression and T-wave amplitude abnormalities are known to be independent predictors of cardiovascular (CV) death, but a direct comparison between them has not been described. METHODS: Analyses were performed on the first electrocardiogram (ECG) digitally recorded on 46,950 consecutive patients at the Palo Alto Veterans Affairs Medical Center since 1987. Females and patients with electrocardiograms exhibiting bundle branch block, left ventricular hypertrophy, electronic pacing, diagnostic Q waves, or Wolff-Parkinson-White syndrome were excluded, leaving 31,074 male patients for analysis (mean age 55 +/- 14). There were 1878 (6.0%) cardiovascular deaths (mean follow-up of 6 +/- 4 years). Electrocardiograms were classified using Minnesota code according to the degree of ST depression and T-wave abnormality, and the nine possible combinations of ST segment and T-wave abnormalities were recoded for analysis. RESULTS: The combination of major abnormalities in ST segments and T-waves carried the greatest hazard [3.2 (CI 2.7-3.8)]. Minor ST depression combined with more severe T-wave abnormalities carried a hazard of 3.1 (CI 2.5-3.7), whereas minor T-wave abnormalities combined with more severe ST depression carried a hazard of only 1.9 (CI 1.6-2.3). CONCLUSION: While both ST segment depression and abnormal T-wave amplitude are clinically important, T-wave abnormalities appear to be greater predictors of cardiovascular mortality.

Aged↗

Clinical correlates of abnormal brain-stem auditory evoked responses in multiple sclerosis.

Brain-stem auditory evoked responses (BAERs) were examined in 178 patients with multiple sclerosis (MS) and compared to the frequency of abnormalities in visually evoked responses (VERs) and in CSF electrophoresis. In clinically definite MS, BAERs were abnormal in 61% and a significant relationship was noted between disability due to MS and the frequency and severity of BAER abnormalities. In suspected MS, BAERs showed evidence of a second lesion in 14% whereas VERs indicated a second lesion in 24%. Abnormal BAERs in patients with suspected MS with brain-stem signs were significantly associated with the presence of truncal and limb ataxia. In progressive possible MS, abnormal BAERs were found in 49% but indicated a second lesion in 35% of patients and were significantly related to the duration of illness. In progressive possible MS, abnormal VERs but not abnormal BAERs, were significantly associated with the presence of CSF oligoclonal IgG banding. Normal BAERs in association with clinical brain-stem abnormalities were found in 24% of patients with clinically definite MS, 50% with suspected MS and 33% with progressive possible MS.

Brain Stem↗

Autoantibodies in normal and abnormal pregnancy.

Abnormal autoimmune function has been associated with reproductive failure for decades. In fact, all medical conditions historically associated with pregnancy loss (and on occasion infertility) are now recognized to have an autoimmune etiology. It is therefore quite surprising that only less than a decade ago a correlation between the presence of abnormal autoantibodies and pregnancy loss was reported for the first time. Since reproductive failure, similar to other abnormal autoimmune states, is not a monoclonal event, we have established that affected patients demonstrate polyclonal autoantibody abnormalities including a variety of nonorganospecific as well as organspecific autoantibody groupings. For example, patients with repeated pregnancy loss will exhibit abnormal levels of anti-phospholipid antibodies (PA). In normal pregnancy natural autoantibodies do not follow the standard immunoglobulin (Ig) pattern, characterized by a decrease in levels despite a probably mild increase in production, which is excessively compensated by the vasodilatation of pregnancy. PA, especially, demonstrate a mild increase during pregnancy, though levels only in the peripartal period may reach abnormally high titers (in comparison to nonpregnant controls). This dichotomy between total Ig and natural autoantibodies is interesting since it suggests that autoantibodies may be under distinct control. In fact, we have suggested that this observed elevation of autoantibodies may be the result of an antigenic stimulus by self-like antigen, represented by the maternal growth of the parasitic fetus. In abnormal pregnancies, especially those associated with maternal hypertension and fetal growth retardation (IUGR), autoantibody levels do reach highly abnormal levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Habitual↗

Prevalence of abnormal Pap smears in rural family practice.

The purpose of this study was to examine the prevalence of abnormal Pap smears in rural family practice, to compare this to the published literature, and to determine if the prevalence of abnormalities is higher in the younger age group (<=35 years of age). A retrospective chart audit was performed on all Pap smears from four rural family practice sites during a 12-month period. Data collected were Pap smear result, patient's age, and interval since previous Pap smear. Statistical analysis was used to determine if the prevalence of abnormal Pap smears was consistent among the practices as well as similar to the three larger published studies. Also, chi-square analysis was used to compare the prevalence of abnormal Pap smears in the younger (<=35 years of age) versus the older (>35 years of age) age groups. There were 2,891 Pap smears reviewed, with 782 (27%) recorded as abnormal. The prevalence of cervical intraepithelial neoplasia (CIN) (76 or 2.6%) was compared to the published literature and was found to be statistically significantly higher (chi square=772.194, P=0.000). The prevalence of abnormal Pap smears was higher in the younger than age 35 group when compared to the older than age 35 age group (chi square=20.953, P=0.000). Pap smear interval and age varied between the four practice sites, but the prevalence of CIN was not statistically different (chi square=3.154, P=0.368). The results of this study suggest that rural family physicians may encounter abnormal Pap smears at rates similar to those reported in the literature. This study also suggests that the prevalence of abnormal Pap smears may be higher in the younger groups in this population.

Adult↗

Abnormal metabotropic glutamate receptor expression and signaling in the cerebral cortex in diffuse Lewy body disease is associated with irregular alpha-synuclein/phospholipase C (PLCbeta1) interactions.

Diffuse Lewy body disease (DLBD) is a degenerative disease of the nervous system, involving the brain stem, diencephalic nuclei and cerebral cortex, associated with abnormal a-synuclein aggregation and widespread formation of Lewy bodies and Lewy neurites. DLBD presents as pure forms (DLBDp) or in association with Alzheimer disease (AD) in the common forms (DLBDc). Several neurotransmitter abnormalities have been reported including those of the nigrostriatal and mesocorticolimbic dopaminergic system, and central noradrenergic, serotoninergic and cholinergic pathways. The present work examines metabotropic glutamate receptor (mGluR) expression and signaling in the frontal cortex of DLBDp and DLBDc cases in comparison with age-matched controls. Abnormal L-[3H]glutamate specific binding to group I and II mGluRs, and abnormal mGluR1 levels have been found in DLBD. This is associated with reduced expression levels of phospholipase C beta1 (PLCbeta1), the effector of group I mGluRs following protein G activation upon glutamate binding. Additional modification in the solubility of PLCbeta1 and reduced PLCbeta1 activity in pure and common DLBD further demonstrates for the first time abnormal mGluR signaling in the cerebral cortex in DLBD. In order to look for a possible link between abnormal mGluR signaling and a-synuclein accumulation in DLBD, immunoprecipitation studies have shown alpha-synuclein/PLCbeta1 binding in controls and decreased alpha-synuclein/PLCbeta1 binding in DLBD. This is accompanied by a shift in the distribution of a-synuclein, but not of PLCbeta1, in DLBD when compared with controls. Together, these results support the concept that abnormal a-synuclein in DLBD produces functional effects on cortical glutamatergic synapses, which are associated with reduced alpha-synuclein/PLCbeta1 interactions, and, therefore, that mGluRs are putative pharmacological targets in DLBD. Finally, these results emphasize the emergence of a functional neuropathology that has to be explored for a better understanding of the effects of abnormal protein interactions in degenerative diseases of the nervous system.

Aged↗

Significance of abnormal rabbit ileal histology in the pathogenesis of diarrhea.

In spite of several macroscopic criteria for predicting the presence of histological abnormalities in rabbit ileum, microscopic ileal abnormalities still can escape detection. The effect of histologically abnormal rabbit ileum was evaluated on basal intestinal absorption, on basal absorption, on basal adenylate cyclase activity, and on cholera toxin-induced secretion and cholera toxin-induced stimulation of adenylate cyclase activity. Compared to histologically normal rabbit ileum, the presence of histological abnormalities was associated with decreased basal intestinal water, Na, Cl, and glucose absorption, absent glucose-dependent water absorption, and elevated basal adenylate cyclase activities. However, histologically abnormal rabbit ileum responded to inoculation of purified cholera toxin with stimulation of intestinal water secretion and adenylate cyclase activity similar to that in histologically normal ileum. These data have implications concerning the design of experiments that attempt to study the pathogenesis of diarrheal diseases by correlating changes in ileal transport with changes in ileal mucosal adenylate cyclase activity. In spite of abnormal ileal histology, studies of intestinal secretory states which attempt to define the role of adenylate cyclase in secretory processes can be performed provided animals are used as their own controls. However, when groups of animals are compared, the presence of an histologically abnormal ileum can cause changes in basal and intestinal secretagogue-stimulated ileal water and electrolyte transport and in basal and intestinal secretagogue-stimulated mucosal adenylate cyclase activity which can lead to erroneous conclusions if the presence of the abnormal ileal histology is not considered.

Adenylyl Cyclases↗