CONGENITAL ANOMALIES, Issue 1 2005
Zoltán Kazy
ABSTRACT The objective of the study presented here was to check the effect of oral ketoconazole treatment on fetal development. Ketoconazole has been given a teratogenic classification of C by the US Food and Drug Administration, but human controlled epidemiological studies of the treatment's effects have not been reported. The occurrence of ketoconazole use in the second to third months of gestation was compared between cases with congenital abnormalities and their matched controls in the large population-based data set of the Hungarian Case,Control Surveillance of Congenital Abnormalities, 1980,1996. Birth weight and gestational age were evaluated in control newborn infants born to mothers with or without ketoconazole treatment. The case group comprised 22 843 cases with congenital abnormalities, while the control group contained 38 151 newborn infants without any defects. Six infants (0.03%) and 12 controls (0.03%) had mothers who had received oral ketoconazole treatment (prevalence odds ratio: with 95% confidence interval: 0.8, 0.3,2.2). No group of infants with congenital abnormalities had mothers with a higher incidence of use of the drug. The mean gestational age was somewhat longer while birth weight was somewhat larger in controls with ketoconazole treated mothers. Our study failed to demonstrate a higher rate of congenital abnormalities in infants with mothers who had received oral ketoconazole treatment during pregnancy. [source]

The Spectrum of Long-term Electrophysiologic Abnormalities in Patients with Univentricular Hearts

CONGENITAL HEART DISEASE, Issue 5 2009
Kathryn K. Collins MD
ABSTRACT Patients with univentricular hearts experience a wide range of electrophysiolgic abnormalities which tend to develop years after cardiovascular surgical interventions. Intra-atrial reentrant tachycardia (atrial flutter) in the Fontan population is the most common arrhythmia and, as such, has the largest body of literature addressing its cause and treatment. However, sinus node dysfunction, other atrial arrhythmias, ventricular arrhythmias, and cardiac dysynchrony also occur in this patient population. The purpose of this article is to review the prevalence, mechanisms, and treatment of these electrophysiologic abnormalities within the single ventricle and Fontan patient. [source]

Magnetic resonance imaging findings in a population-based cohort of children with cerebral palsy

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 1 2009
MARNIE N ROBINSON MBBS
The purpose of this study was to investigate the frequency and spectrum of magnetic resonance imaging (MRI) abnormalities in a population of children with cerebral palsy (CP) who were born in the years 2000 and 2001 in Victoria, Australia. In 2000 and 2001, 221 children (126 males, 95 females; mean age 6y [SD 7mo], range 5,7y) with CP, excluding those with CP due to postneonatal causes (6% of all cases), were identified through the Victorian Cerebral Palsy Register. All medical records were systematically reviewed and all available brain imaging was comprehensively evaluated by a single senior MRI radiologist. MRI was available for 154 (70%) individuals and abnormalities were identified in 129 (84%). The study group comprised 88% with a spastic motor type CP; the distribution was hemiplegia in 33.5%, diplegia in 28.5%, and quadriplegia in 37.6% of children. Overall, pathological findings were most likely to be identified in children with spastic hemiplegia (92%) and spastic quadriplegia (84%). Abnormalities were less likely to be identified in non-spastic motor types (72%) and spastic diplegia (52%). The most common abnormalities identified on MRI were periventricular white matter injury (31%), focal ischaemic/haemorrhagic lesions (16%), diffuse encephalopathy (14%), and brain malformations (12%). Dual findings were seen in 3% of patients. This is the first study to document comprehensively the neuroimaging findings of all children identified with CP born over a consecutive 24-month period in a large geographical area. [source]

Autism spectrum disorder and underlying brain mechanism in the oculoauriculovertebral spectrum

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 4 2007
Maria Johansson MD
As part of a multidisciplinary study, the rate of autism spectrum disorder (ASD), learning disability (LD), and brain abnormalities was examined in 20 participants (12 males, 8 females; age range 8mo-17y, mean age 8y 1mo) diagnosed as falling within the oculoauriculovertebral spectrum (OAV). A neuropsychiatric examination was performed, including standardized autism diagnostic interviews. Two individuals met diagnostic criteria for autism, one for autistic-like condition, and five for autistic traits. Four patients had mild LD, three severe LD, two profound LD, and two borderline intellectual functioning. Neuroimaging indicated cerebral abnormalities in more than half of the patients. Abnormalities of white/grey matter were found in more than half of examined individuals; enlargement of ventricles in more than a third. Results indicate that at least a subgroup of ASD may be associated with errors in early embryonic brain development. Awareness of the coexistence of OAV/ASD is important in habilitation care of individuals with OAV. [source]

Abnormalities in the coordination of respiration and swallow in preterm infants with bronchopulmonary dysplasia

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 7 2006
Ira H Gewolb MD
Individual rhythms of suck, swallow, and respiration are disrupted in preterm infants with bronchopulmonary dysplasia (BPD). Integration of respiration into suck-swallow efforts is critical for establishing coordinated suckle feeding. This study quantitatively assessed the coordination of respiration and swallow in infants with and without BPD. Thirty-four preterm infants of 26 to 33 weeks'gestational age were included: 14 participants with BPD (eight males, six females) and 20 comparison participants without BDP (10 males, 10 females). Participants were studied at postmenstrual age 32 to 40 weeks and postnatal age 2 to 12 weeks using digital recordings of pharyngeal pressure, nasal thermistor flow, and thoraco-abdominal plethysmography. The coefficients of variation (COV; standard deviation/mean) of the swallow-breath (SW-BR) and breath-breath (BR-BR) intervals during swallow runs, the percentage of,apneic swallows'(runs of ,3 swallows without interposed breaths), and phase relationships of respiration and swallow were used to quantify rhythmic coordination and integration of respiration into feeding episodes. Apneic swallows were significantly increased after 35 weeks in infants with BPD (mean 13.4% [SE 2.4]) compared with non-BDP infants (6.7% [SE 1.8];p < 0.05), as were SW-BR phase relationships involving apnea. The BPD cohort also had significantly higher SW-BR COV and BR-BR COV than non-BPD infants, indicating less rhythmic coordination of swallowing and respiration during feeding. Results emphasize the need for frequent rests and closer monitoring when feeding infants with respiratory compromise. Quantitative assessment of the underlying rhythms involved in feeding may be predictive of longer-term feeding and neurological problems. [source]

Abnormalities in cardiac and respiratory function observed during seizures in childhood

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 1 2005
Mary E O'Regan MRCP MRCPCH
The aim of this study was to observe any changes in cardiac and respiratory function that occur during seizures. Thirty-seven children (20 males, 17 females; median age 7y 6mo, range 1y 6mo to 15y 6mo) were studied. We recorded electroencephalograms, respiratory rate, heart rate, electrocardiograms, blood pressure, oxygen saturation, heart rate variability (time domain analysis), and cardiac vagal tone. A respiratory pause was defined as an interruption in respiration lasting more than 3s but less than 15s. Apnoea was defined as absence of respiration for more than 15s. Tachypnoea was defined as a 10% increase in respiratory rate from the pre-ictal baseline. Bradypnoea was defined as a 10% decrease in respiratory rate from the pre-ictal baseline. Significant hypoxia was defined as a saturation of less than 85%. A significant change in heart rate was taken as a 10% increase or decrease below the baseline rate. Data were obtained from 101 seizures: 40 focal seizures, 21 generalized seizures, and 40 absences. Focal seizures were frequently associated with significant respiratory abnormalities, tachypnoea in 56%, apnoea in 30%, frequent respiratory pauses in 70%, and significant hypoxaemia in 40%. The changes seen in respiratory rate were statistically significant. Changes in cardiac parameters, an increase or decrease in heart rate, were observed in only 26% of focal seizures and 48% of generalized seizures. We conclude that seizure activity can disrupt normal physiological regulation and control of respiratory and cardiac activity. [source]

The effects of lipid-lowering drug therapy on cardiovascular responsiveness in type 2 diabetic patients

DIABETES OBESITY & METABOLISM, Issue 1 2006
Laurence Guy HowesArticle first published online: 18 MAR 200
Type 2 diabetes is associated with a high prevalence of dyslipidaemia and a high incidence of cardiovascular disease. Lipid lowering therapy with HMG Co-A reductase inhibitors (statins) reduce the risk of cardiovascular events in type 2 diabetic and non-diabetic patients, effects which are believed to be partly due to improvements in vascular function. The aetiology of abnormal vascular function in type 2 diabetics is likely to be multifactorial and the pattern of vascular dysfunction in type 2 diabetes may differ from that which occurs in non-diabetic patients with dyslipidaemia. Abnormalities in endothelium derived hyperpolarising factor (EDHF) mediated vasodilation in resistance vessels may be more prominent in both type 1 and type 2 diabetes than in non-diabetic patients with endothelial dysfunction. The effects of lipid lowering therapy on vascular responsiveness may differ in type 2 diabetic patients from those found in non-diabetic patients. Statin therapy does not appear to improve responses to endothelial dependent vasodilators in type 2 diabetics, but may alter the ratio between nitric oxide (NO) and EDHF mediated responses. Fibrate therapy improves flow mediated dilation of brachial arteries in type 2 diabetic patients, but only appears to improve endothelium dependant vasodilator responses in resistance vessels when given in conjunction with co-enzyme Q. [source]

Effect of insulin infusion on electrocardiographic findings following acute myocardial infarction: importance of glycaemic control

DIABETIC MEDICINE, Issue 2 2009
R. M. Gan
Abstract Aims, To determine the effects of insulin infusion and blood glucose levels during acute myocardial infarction (AMI) on electrocardiographic (ECG) features of myocardial electrical activity. Methods, ECGs at admission and 24 h were examined in a randomized study of insulin infusion vs. routine care for AMI patients with diabetes or hyperglycaemia. Results were analysed according to treatment allocation and also according to average blood glucose level. Results, ECG characteristics were similar at admission in both groups. Patients allocated to conventional treatment had prolongation of the QT interval (QTc) after 24 h but those receiving infused insulin did not. In patients with a mean blood glucose in the first 24 h > 8.0 mmol/l, new ECG conduction abnormalities were significantly more common than in patients with mean blood glucose , 8.0 mmol/l (15.0% vs. 6.0%, P < 0.05). Conclusions, Prevention of QTc prolongation by administration of insulin may reflect a protective effect on metabolic and electrical activity in threatened myocardial tissue. Abnormalities of cardiac electrical conduction may also be influenced by blood glucose. [source]

Rapid review of liquid-based smears as a quality control measure

DIAGNOSTIC CYTOPATHOLOGY, Issue 3 2004
Sheryl Henderson M.Med.Sc.(Cytol.)
Abstract The objective of this study was to investigate the effectiveness of a standardized method of rapid review (RR) of monolayer preparations for the identification of abnormalities, the presence of an endocervical component and infectious agents. A total of 200 ThinPrep (Cytyc, Boxborough, MA) slides representing the spectrum of abnormalities commonly encountered in cervical/vaginal cytologic specimens was retrieved from archive. The study set comprised 129 cases within normal limits (WNL); 36 low-grade epithelial abnormalities (LGEA); 28 high-grade epithelial abnormalities (HGEA), including 2 endocervical adenocarcinomas in situ (AIS) and 7 carcinomas. Eighteen false negative (FN) cases were also included for study. Originally missed on initial review, these cases were found to be abnormal on quality control review (17 LGEA; 1 AIS). Commonly encountered infectious agents were represented and included Candida albicans, Trichomonas vaginalis, herpes simplex virus, and Actinomyces. The slides were reviewed using a standardized method of RR (turret technique, for 60 sec) by three experienced screeners masked to the original reference diagnosis. Median sensitivity for LGEA was 70% (range, 67,72%); HGEA, 69% (range, 54,80%); and FN, 65% (range, 56,78%). Specificity remained high, median specificity for LGEA was 95%; HGEA, 97%; and FN, 100%. There was no significant overcalling of any diagnostic category. The chi-square test at P < 0.05 showed no significant difference between RR and full manual rescreen of the ThinPrep smears in this study. While no statistical difference was proven, the sensitivity measurements for all categories of abnormality were moderate due to the high proportion of atypical cases included into the study set. Abnormalities on the monolayer preparations frequently displayed fewer, smaller groups of disaggregated cells with rounded cytoplasmic outlines that were difficult to discern on RR. Interobserver variation was noted. Monolayers with a paucity of diagnostic cells and those displaying subtle nuclear atypia were often overlooked. Diagn. Cytopathol. 2004;31:141,146. © 2004 Wiley-Liss, Inc. [source]

Role of Pap Test terminology and age in the detection of carcinoma invasive and carcinoma in situ in medically underserved California women

DIAGNOSTIC CYTOPATHOLOGY, Issue 4 2004
Lydia P. Howell M.D.
Abstract Our goals were to evaluate Pap Test findings classified by the Bethesda system, and follow up biopsies from participants in the California Breast and Cervical Cancer Control Program (Ca-BCCCP) for: 1) correlation in the detection of carcinoma in situ (CIS) and carcinoma invasive (CI), and 2) age-related trends, with discussion in the context of the 2001 ASCCP Management Guidelines. Women (n = 52,339) who had their initial screening Pap Tests with Ca-BCCCP between January 1995,December 1999 were followed for diagnostic services through December 2000. Descriptive and analytical methods were used in the analysis. Of the Pap results, 81.9% were negative, 10.6% showed infection, 4.7% showed an epithelial abnormality as defined by the Bethesda system (atypical squamous cells of undertermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL)), 0.1% showed squamous-cell cancer (SCC), and 2.7% showed other or unsatisfactory. Subsequent to the initial Pap Test, follow-up results of carcinoma in situ (CIS) and carcinoma invasive (CI) accounted for 0.36% and 0.05% of the population, respectively. Among HSIL Pap Tests (n = 285), 40.7% had follow-up showing CIS. Among SCC Pap Tests, 17.9% had follow-up results of CIS and 28.6% CI. Of the 191 patients with CIS as a follow-up finding, the initial Pap smear showed: HSIL 60.7%, SCC 2.6%, LSIL 10.5%, ASCUS 13.6%, and negative or infection 9.9%. Of the 27 patients with CI, the initial Pap Test showed: HSIL 40.7%, SCC 29.6%, LSIL 7.4%, ASCUS 7.4%, and negative or infection 11.1%. Pap diagnoses of other or unsatisfactory accounted for 2.6% of the Pap results from patients with CIS and 3.7% of Pap results from patients with CI. Except for LSIL, there was an increasing age trend in the number of cases in each of Pap results, with the exception of age 65+ yr. However, the ratio of LSIL and ASCUS to negative cases decreased with age. (P < 0.0001 and 0.0293, respectively). HSIL Pap results indicate a reasonably high probability of CIS and CI. However, approximately 1/3 of patients with CIS and 1/4 of patients with CI presented with Pap diagnoses of less severity than HSIL. When a negative Pap Test result is chosen as reference group, there is a negative age trend for LSIL and ASCUS, and no age trend for other results. These findings all have important implications in the design of follow-up strategies, and support the 2001 ASCCP Consensus Guidelines for the Management of Women with Cervical Abnormalities. Diagn. Cytopathol. 2004;30:227,234. © 2004 Wiley-Liss, Inc. [source]

Metals and oxidative homeostasis in Alzheimer's disease

DRUG DEVELOPMENT RESEARCH, Issue 3 2002
George Perry
Abstract Oxidative damage to every class of biological macromolecule has been characterized in Alzheimer's disease. Abnormalities in iron and copper metabolism are also being implicated as playing a crucial role in neurodegenerative disease pathogenesis. Metal homeostasis as it pertains to alterations in brain function in neurodegenerative diseases is reviewed here with its relationship to oxidative stress. While there is documented evidence for alterations in transition metal homeostasis, redox-activity, and localization, it is also important to realize that alterations in specific copper- and iron-containing metalloenzymes also contribute to the neurodegenerative process. These changes offer the opportunity to identify pathways where modification of the disease process can offer new routes for clinical efficacy, from gene therapy to use of antioxidant and chelating drugs. Drug Dev. Res. 56:293,299, 2002. © 2002 Wiley-Liss, Inc. [source]

Stress-Induced Wall Motion Abnormalities with Low-Dose Dobutamine Infusion Indicate the Presence of Severe Disease and Vulnerable Myocardium

ECHOCARDIOGRAPHY, Issue 7 2007
Stephen G. Sawada M.D.
Background: Patients with left ventricular (LV) systolic dysfunction due to coronary artery disease (CAD) may develop stress-induced wall motion abnormalities (SWMA) with low-dose (10 ,g/kg/min) dobutamine infusion. The clinical significance of low-dose SWMA is unknown. Objective: We investigated the clinical, hemodynamic and angiographic correlates of low-dose SWMA in patients with chronic ischemic LV systolic dysfunction. Methods: Seventy patients with chronic ischemic LV systolic dysfunction who had dobutamine stress echocardiography were studied. Clinical, hemodynamic, and angiographic parameters at rest and low-dose were compared between 38 patients (mean ejection fraction (EF) of 30 ± 8%) with low-dose SWMA and 32 patients (EF 30 ± 11%) without low-dose SWMA. Results: Multivariate analysis showed that the number of coronary territories with severe disease (stenosis ,70%)(P = 0.001, RR = 6.3) was an independent predictor of low-dose SWMA. An increasing number of collateral vessels protected patients from low-dose SWMA (P = 0.011, RR = 0.25). A higher resting heart rate was a negative predictor of low-dose SWMA (P = 0.015, RR = 0.92) but no other hemodynamic variables were predictors. In the patients with low-dose SMA, regions with low-dose SWMA were more likely to be supplied by vessels with severe disease than regions without low-dose SWMA (92% vs 58%, P < 0.001). Conclusion: In patients with ischemic LV systolic dysfunction, the extent of severe disease and a lower numbers of collaterals predict the occurrence of low-dose SWMA. Low-dose SWMA is a highly specific marker for severe disease. [source]

The Prevalence of Valvular Abnormalities in Patients Who Were Referred for Echocardiographic Examination With a Primary Diagnosis of "Heart Murmur"

ECHOCARDIOGRAPHY, Issue 5 2007
Mohammad-Reza Movahed M.D., Ph.D.
Introduction: The prevalence of valvular abnormality and innocent murmur in patients who are referred for echocardiographic evaluation with the diagnosis of "murmur" is not known. The goal of this study was to evaluate the prevalence of valvular abnormalities in such patients. Methods: We retrospectively reviewed the echocardiograms that were referred with the primary ordering diagnosis of "murmur," for the presence of valvular abnormalities. For comparison, we used other documented primary reasons for echocardiographic referral, such as chest pain, shortness of breath, etc. Results: In this cohort, 7,684 echocardiogram reports documented primary diagnostic reasons for echocardiographic referral. A total of 3,460 echocardiogram reports (45%) were coded "murmur" as the primary reason for the study referral. There was a higher prevalence of female patient referrals for heart murmur evaluation (61.8% vs. 38.2%). Although, patients with murmur had a higher prevalence of valvular abnormalities, compared to other reasons for echocardiographic examination, the prevalence of valvular abnormality was less than 50% (48.6% vs. 35.5%) in both groups. Despite the higher number of female patients referred with the diagnosis of murmur, the percentage of abnormal valves was lower in women (45.6% vs. 53.4% in men). Conclusion: The prevalence of valvular abnormalities in patients who were referred with the diagnosis of murmur for echocardiographic examination was less than 50%, with a lesser degree found in women. Routine utilization of echocardiography for evaluation of all murmurs may be unwarranted. [source]

Vasodilator Stress Induces Infrequent Wall Thickening Abnormalities Compared to Perfusion Defects in Mild-to-Moderate Coronary Artery Disease: Implications for the Choice of Imaging Modality with Vasodilator Stress

ECHOCARDIOGRAPHY, Issue 4 2004
M.R.C.P., Ph.D., Prem Soman M.D.
Background: Experimental evidence suggests that although vasodilator stress agents consistently induce regional flow disparity between stenosed and normal coronary vascular beds, the occurrence of functional myocardial ischemia is infrequent, especially in mild-to-moderate coronary artery stenosis. Thus, it is hypothesized that dipyridamole infusion, even at high doses, will result in a disproportionately higher frequency of perfusion defects compared to regional wall thickening abnormalities. Methods: We performed simultaneous high-dose (0.84 mg/kg) dipyridamole stress echocardiography (Echo) and Tc-99m sestamibi SPECT (MIBI, methoxyisobutyl isonitrile) in 46 patients with coronary artery diameter stenosis >50% and ,90% in one or two epicardial coronary arteries, and no previous myocardial infarction. Results: Of a total of 828 segments, MIBI showed 97 reversible defects while Echo showed only 23 reversible wall thickening abnormalities. Of the 97 segments with reversible MIBI defects, only 13 (13%) showed simultaneous reversible wall thickening abnormalities during dipyridamole infusion. There were 24 patients with MIBI defects, of whom 10 (41%) showed a corresponding wall thickening abnormality. The sensitivity of MIBI and Echo for the detection of coronary artery disease was 52% and 21%, respectively (P = 0.001). Conclusion: This suggests that vasodilator stress is not optimally suited for use with techniques that use regional wall thickening abnormality as a marker of ischemia for the diagnosis of coronary artery disease. (ECHOCARDIOGRAPHY, Volume 21, May 2004) [source]

Abnormalities in sexual development of the amphipod Gammarus pulex (L.) found below sewage treatment works

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2001
Melanie Yvette Gross
Abstract Increasing numbers of widely used industrial, agricultural, and natural chemicals are known to elicit endocrine-disrupting effects in a wide range of vertebrate and invertebrate species. The objective of this study was to determine whether the sexual development of the freshwater crustacean Gammarus pulex (L.) was affected below sewage treatment works (STW) previously known to contain endocrine-disrupting chemicals in their effluent. The gonadal structure, external sexual characteristics, and size of gammarids from exposed sites were compared to those of gammarids from a reference site. No significant difference was found in the gonadal structure of males collected below two STW. However, a highly significant number of females collected from a site known to elicit high estrogenic responses in vertebrates displayed an abnormal structure of oocytes in vitellogenesis. Body size was significantly shorter and male/female size differential was significantly reduced below one of the STW. Analysis of gnathopod and genital papillae length data suggests that different allometric relationships of these organs to body size exist between sample sites. [source]

Morphologic and Neurochemical Abnormalities in the Auditory Brainstem of the Genetically Epilepsy-prone Hamster (GPG/Vall)

EPILEPSIA, Issue 7 2005
Verónica Fuentes-Santamaría
Summary:,Purpose: This study was performed to evaluate whether audiogenic seizures, in a strain of genetically epilepsy-prone hamsters (GPG/Vall), might be associated with morphologic alterations in the cochlea and auditory brainstem. In addition, we used parvalbumin as a marker of neurons with high levels of activity to examine changes within neurons. Methods: Cochlear histology as well as parvalbumin immunohistochemistry were performed to assess possible abnormalities in the GPG/Vall hamster. Densitometry also was used to quantify levels of parvalbumin immunostaining within neurons and fibers in auditory nuclei. Results: In the present study, missing outer hair cells and spiral ganglion cells were observed in the GPG/Vall hamster. In addition, an increase was noted in the size of spiral ganglion cells as well as a decrease in the volume and cell size of the cochlear nucleus (CN), the superior olivary complex nuclei (SOC), and the nuclei of the lateral lemniscus (LL) and the inferior colliculus (IC). These alterations were accompanied by an increase in levels of parvalbumin immunostaining within CN, SOC, and LL neurons, as well as within parvalbumin-immunostained fibers in the CN and IC. Conclusions: These data are consistent with a cascade of atrophic changes starting in the cochlea and extending along the auditory brainstem in an animal model of inherited epilepsy. Our data also show an upregulation in parvalbumin immunostaining in the neuropil of the IC that may reflect a protective mechanism to prevent cell death in the afferent sources to this nucleus. [source]

Heart Rate Changes and ECG Abnormalities During Epileptic Seizures: Prevalence and Definition of an Objective Clinical Sign

EPILEPSIA, Issue 8 2002
Maeike Zijlmans
Summary: ,Purpose: To determine the prevalence of heart rate changes and ECG abnormalities during epileptic seizures and to determine the timing of heart rate changes compared to the first electrographic and clinical signs. To assess the risk factors for the occurrence of ECG abnormalities. Methods: We analyzed retrospectively 281 seizures in 81 patients with intractable epilepsy who had prolonged video-EEG and two-channel ECG. The nature and timing of heart rate changes compared to the electrographic and clinical seizure onset was determined. The ictal period (including one minute preictally and three minutes postictally) was analyzed for cardiac arrhythmias, conduction and repolarization abnormalities. Risk factors for cardiac abnormalities were investigated using parametric and non-parametric statistics. Results: There was an increase in heart rate of at least 10 beats/minute in 73% of seizures (93% of patients) and this occurred most often around seizure onset. In 23% of seizures (49% of patients) the rate increase preceded both the electrographic and the clinical onset. ECG abnormalities were found in 26% of seizures (44% of patients). One patient had an asystole for 30 seconds. Long seizure duration increased the occurrence of ECG abnormalities. No other risk factor was found. Conclusions: Heart rate changes occur frequently and occur around the time or even before the earliest electrographic or clinical change. The change can clarify the timing of seizure onset and the specific rate pattern may be useful for seizure diagnosis and for automatic seizure detection. ECG abnormalities occur often and repeatedly in several seizures of the same patient. [source]

Occipitoparietal Epilepsy, Hippocampal Atrophy, and Congenital Developmental Abnormalities

EPILEPSIA, Issue 1 2000
Article first published online: 19 SEP 200
First page of article [source]

CLINICAL STUDY: Abnormalities in cortical and transcallosal inhibitory mechanisms in subjects at high risk for alcohol dependence: a TMS study

ADDICTION BIOLOGY, Issue 3-4 2008
Kesavan Muralidharan
ABSTRACT Central nervous system (CNS) hyperexcitability and a resulting state of behavioral undercontrol are thought to underlie the vulnerability to early-onset alcohol dependence (AD). The aim of this study was to explore the differences in the functioning of cortical inhibitory systems, utilizing transcranial magnetic stimulation (TMS), in subjects at high risk (HR) and low risk (LR) for AD and to examine the relationship between CNS inhibition and behavioral undercontrol. Right-handed HR (n = 15) and LR (n = 15) subjects, matched for age, gender, height, weight and education, were assessed for psychopathology and family history of alcoholism using the Semi-Structured Assessment for the Genetics of Alcoholism and the Family Interview for Genetic Studies. Following single-pulse TMS, an electromyogram recorded from the right opponens pollicis muscle was used to measure the silent periods at different stimulus intensities. HR subjects had significantly shorter contralateral and ipsilateral (iSP) silent periods and a relatively higher prevalence of ,absent' iSP. They had significantly higher mean externalizing symptoms scores (ESS) than LR subjects, and there was a significant negative correlation between iSP duration and ESS. These preliminary findings suggest that HR subjects have relative impairments in corticocortical and transcallosal inhibitory mechanisms. The consequent state of CNS hyperexcitability may be etiologically linked to the excess of externalizing behaviors observed in this population, which is thought to be a predisposition to a higher risk of developing early-onset alcoholism. [source]

Abnormalities of prothrombin: a review of the pathophysiology, diagnosis, and treatment

HAEMOPHILIA, Issue 6 2008
S. L. MEEKS
Summary., Prothrombin (factor II) deficiency is a rare autosomal recessive coagulation disorder that occurs in approximately 1 in 1,2 million people. Prothrombin is activated to thrombin, which in turn proteolytically cleaves fibrinogen to fibrin and contributes to forming a stable fibrin clot. The haemostatic level of prothrombin is thought to be between 20 and 40%, and the half-life is approximately 3 days. There are more than 40 known mutations in prothrombin. Both hypoprothrombinemia and dysprothrombinemia have been described. Low prothrombin activity typically prolongs both the activated partial thromboplastin time and prothrombin time. Clinical manifestations are predominantly mucosal or surgical- or trauma-associated bleeding, but joint bleeding and intracranial haemorrhages have been reported. No purified prothrombin products are available for replacement therapy. Both fresh frozen plasma and prothrombin complex concentrates contain prothrombin and may be used for treatment. [source]

Genetics of Migraine: Possible Links to Neurophysiological Abnormalities

HEADACHE, Issue 5 2002
Peter S. Sándor MD
First page of article [source]

Electroencephalographic Abnormalities in Aseptic Meningitis and Noninfectious Headache.

HEADACHE, Issue 1 2001
A Comparative Study
Background.,The finding of abnormalities on electroencephalogram (EEG) during the course of aseptic meningitis is often considered to be indicative of parenchymal brain involvement, even in absence of clinical signs of encephalitis. Objective.,To investigate if patients with aseptic nonherpetic meningitis who have abnormal EEG recordings during the acute stage of the disease differ in clinical characteristics or cerebrospinal fluid findings from patients with aseptic meningitis and normal EEG recordings. Methods.,The EEG records of 82 patients with aseptic meningitis were reviewed. A comparative group consisted of 41 age-matched patients with severe headaches without evidence of meningeal inflammation. Results.,Significantly more patients with aseptic meningitis (28%) demonstrated abnormalities on EEG than controls (12%) (P = .048). Patients with aseptic meningitis and abnormal EEG findings (n = 23) did not differ in age, duration of symptoms, clinical course, cerebrospinal fluid cell count, or protein level from those with normal EEG findings (n = 59). However, all patients with aseptic meningitis who were confused (n = 5) also revealed EEG abnormalities (P<.00012). Patients with headache with normal EEG recordings did not differ from those with abnormal EEGs in age, sex, or duration of symptoms. Nevertheless, patients with common migraine (n = 9) showed abnormalities on EEG (P = .06) more frequently. Conclusions.,The finding of an abnormal EEG in patients with aseptic meningitis, clear mental state and absence of focal neurological signs should not be used as proof of encephalitis. Because pathological examination is usually not performed, it remains unclear if EEG abnormalities in patients with aseptic meningitis indicate a silent parenchymal inflammation, or reflect an infectious encephalopathy. [source]

Migraine-Associated Seizure: A Case of Reversible MRI Abnormalities and Persistent Nondominant Hemisphere Syndrome

HEADACHE, Issue 6 2000
Scott Friedenberg MD
The complex relationship between migraine and epilepsy is highlighted by the occurrence of a seizure during a migraine attack without aura. This phenomenon, referred to as migralepsy, suggests an inherent overlap in the underlying pathophysiology of these events. We report the case of a patient who had a generalized seizure, persistent nondominant hemisphere syndrome, and reversible magnetic resonance imaging abnormalities during a prolonged migraine attack without aura. [source]

Dynamic Assessment of Abnormalities in Central Pain Transmission and Modulation in Tension-type Headache Sufferers

HEADACHE, Issue 2 2000
Jonathan D. Neufeld PhD
Objective.,To examine and compare central pain processing and modulation in young tension-type headache sufferers with that of matched healthy controls using an induced headache "challenge" paradigm. Background.,Recent research has suggested that abnormalities in central pain processing and descending pain modulation may contribute to chronic tension-type headache. These abnormalities, if they contribute to headache pathogenesis, should be present in young adult tension-type headache sufferers. Recent research using static measures of physiological variables, such as muscle tenderness and exteroceptive suppression, has identified chronic muscle tenderness as a characteristic of young tension-type headache sufferers, but other central nervous system functional abnormalities may require a dynamic "challenge" to be observed. Methods.,Twenty-four young women meeting the International Headache Society diagnostic criteria for tension-type headache (headache-prone) and a matched group of 24 healthy women who reported fewer than 10 problem headaches per year (control) participated in a double-blind, placebo-controlled, crossover study. Subjects completed jaw clenching and a placebo condition on different days in counterbalanced order. Pericranial muscle tenderness, pressure-pain thresholds on the temporalis, and exteroceptive suppression periods were assessed before and after each procedure. Head pain was recorded for 12 to16 hours following each condition. Results.,Headache-prone subjects were more likely than controls to experience headaches after both the jaw clenching and placebo procedures, but neither group was significantly more likely to experience headaches following jaw clenching than placebo. In pretreatment measurements, headache-prone subjects exhibited greater muscle tenderness than controls, but pressure-pain detection thresholds and exteroceptive suppression periods did not differ in the two groups. Control subjects showed increases in muscle tenderness and exteroceptive suppression periods following both the clenching and placebo procedures, whereas headache-prone subjects exhibited no significant changes in any of the physiological measures following either experimental manipulation. Conclusions.,These results confirm previous findings indicating abnormally high pericranial muscle tenderness in young tension headache sufferers even in the headache-free state. In addition, the results suggest that the development of headaches following noxious stimulation is more strongly related to headache proneness and associated abnormalities in central pain transmission or modulation (indexed by pericranial muscle tenderness and exteroceptive suppression responses) than muscle strain induced by jaw clenching. [source]

Congenital dyserythropoietic anemia type II (CDAII) is caused by mutations in the SEC23B gene,

HUMAN MUTATION, Issue 9 2009
Paola Bianchi
Abstract Congenital dyserythropoietic anemia type II (CDAII) is an autosomal recessive disease characterized by ineffective erythropoiesis, hemolysis, erythroblast morphological abnormalities, and hypoglycosylation of some red blood cell (RBC) membrane proteins. Recent studies indicated that CDAII is caused by a defect disturbing Golgi processing in erythroblasts. A linkage analysis located a candidate region on chromosome 20, termed the CDAN2 locus, in the majority of CDAII patients but the aberrant gene has not so far been elucidated. We used a proteomic-genomic approach to identify SEC23B as the candidate gene for CDAII by matching the recently published data on the cytoplasmic proteome of human RBCs with the chromosomic localization of CDAN2 locus. Sequencing analysis of SEC23B gene in 13 CDAII patients from 10 families revealed 12 different mutations: six missense (c.40C>T, c.325G>A, c.1043A>C, c.1489C>T, c.1808C>T, and c.2101C>T), two frameshift (c.428_428delAinsCG and c.1821delT), one splicing (c.689+1G>A), and three nonsense (c.568C>T, c.649C>T, and c.1660C>T). Mutations c.40C>T and c.325G>A were detected in unrelated patients. SEC23B is a member of the Sec23/Sec24 family, a component of the COPII coat protein complex involved in protein transport through membrane vesicles. Abnormalities in this gene are likely to disturb endoplasmic reticulum (ER)-to-Golgi trafficking, affecting different glycosylation pathways and ultimately accounting for the cellular phenotype observed in CDAII. Hum Mutat 30:1,7, 2009. © 2009 Wiley-Liss, Inc. [source]

A review of the possible relevance of inositol and the phosphatidylinositol second messenger system (PI-cycle) to psychiatric disorders,focus on magnetic resonance spectroscopy (MRS) studies

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 5 2005
Hyeonjin Kim
Abstract Myo -inositol is an important part of the phosphatidylinositol second messenger system (PI-cycle). Abnormalities in nerve cell myo -inositol levels and/or PI-cycle regulation has been suggested as being involved in the pathophysiology and/or treatment of many psychiatric disorders including bipolar disorder, major depressive disorder, panic disorder, obsessive-compulsive disorder, eating disorders and schizophrenia. This review examines the metabolism and biochemical importance of myo -inositol and the PI-cycle. It relates this to the current in vivo evidence for myo -inositol and PI-cycle involvement in these psychiatric disorders, particularly focusing upon the magnetic resonance spectroscopy (MRS) findings in patient studies to date. From this review it is concluded that while the evidence suggests probable relevance to the pathophysiology and/or treatment of bipolar disorder, there is much less support for a significant role for the PI-cycle or myo -inositol in any other psychiatric disorder. More definitive investigation is required before PI-cycle dysfunction can be considered specific to bipolar disorder. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Regional cerebral blood flow after recovery from anorexia or bulimia nervosa

INTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 6 2007
Guido K. Frank MD
Abstract Objective: Abnormalities of regional cerebral blood flow (rCBF) have been found in individuals who are ill with anorexia (AN) or bulimia nervosa (BN). Little is known about whether rCBF normalizes after recovery from AN and BN. Method: Eighteen control women (CW), 10 recovered restricting type AN, 8 recovered AN with a binging history, and 9 recovered BN participants without a history of AN were studied using positron emission tomography and [15O]water in order to assess rCBF. Results: Partial volume corrected rCBF values in cortical and subcortical brain regions were similar between groups. Neither current body mass index nor age correlated with rCBF values. Conclusion: The results from this study indicate that rCBF normalizes with long-term recovery. Thus, altered rCBF is unlikely to confound functional imaging studies in AN or BN after recovery. © 2007 by Wiley Periodicals, Inc. Int J Eat Disord 2007. [source]

Inactivation of Pten in Osteo-Chondroprogenitor Cells Leads to Epiphyseal Growth Plate Abnormalities and Skeletal Overgrowth,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2007
Alice Fiona Ford-Hutchinson
Abstract To study the role of the Pten tumor suppressor in skeletogenesis, we generated mice lacking this key phosphatidylinositol 3,-kinase pathway regulator in their osteo-chondroprogenitors. A phenotype of growth plate dysfunction and skeletal overgrowth was observed. Introduction: Skeletogenesis is a complex process relying on a variety of ligands that activate a range of intracellular signal transduction pathways. Although many of these stimuli are known to activate phosphatidylinositol 3,-kinase (PI3K), the function of this pathway during cartilage development remains nebulous. To study the role of PI3K during skeletogenesis, we used mice deficient in a negative regulator of PI3K signaling, the tumor suppressor, Pten. Materials and Methods:Pten gene deletion in osteo-chondrodroprogenitors was obtained by interbreeding mice with loxP-flanked Pten exons with mice expressing the Cre recombinase under the control of the type II collagen gene promoter (Ptenflox/flox:Col2a1Cre mice). Phenotypic analyses included microcomputed tomography and immunohistochemistry techniques. Results: ,CT revealed that Ptenflox/flox:Col2a1Cre mice exhibited both increased skeletal size, particularly of vertebrae, and massive trabeculation accompanied by increased cortical thickness. Primary spongiosa development and perichondrial bone collar formation were prominent in Ptenflox/flox:Col2a1Cre mice, and long bone growth plates were disorganized and showed both matrix overproduction and evidence of accelerated hypertrophic differentiation (indicated by an altered pattern of type X collagen and alkaline phosphatase expression). Consistent with increased PI3K signaling, Pten-deficient chondrocytes showed increased phospho-PKB/Akt and phospho-S6 immunostaining, reflective of increased mTOR and PDK1 activity. Interestingly, no significant change in growth plate proliferation was seen in Pten-deficient mice, and growth plate fusion was found at 6 months. Conclusions: By virtue of its ability to modulate a key signal transduction pathway responsible for integrating multiple stimuli, Pten represents an important regulator of both skeletal size and bone architecture. [source]

Connexin40-Deficient Mice Exhibit Atrioventricular Nodal and Infra-Hisian Conduction Abnormalities

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2000
BRIAN A. VANDERBRINK B.S.
AV Nodal and Infra-Hisian Conduction in Cx40 Mice. Introduction: Previous electrophysiologic investigations have described AV conduction disturbances in connexin4(Cx40)-deficient mice. Because expression or(Cx40 occurs predominantly in the atria and His-Purkinje system of the mouse heart, the AV conduction disturbances were thought to be secondary to disruption in His-Pnrkinje function. However, the lack of a His-bundle electrogram recording in the mouse has limited further investigation of the importance of Cx40. Using a novel technique to record His-bundle recordings in Cx40-deficient mice, we define the physiologic importance of defciencies in Cx40. Methods and Results: Ten Cx40 -/- mice and 11 Cx40+/+ controls underwent a blinded, in vivo, closed chest electrophysiology study at 9 to 12 weeks of age. In the Cx40+/+ mice, the PR interval was significantly longer compared with Cx40+/+ mice (44.6 ± 6.4 msec vs 36.0 ± 4.1 msec, P = 0.002). Not only the HV interval (14.0 ± 3.0 msec vs 10.4 ± 1.2 msec, P = 0.003) but also the AH interval (33.2 ± 4.8 msec vs 27.1 ± 3.7 msec, P = 0.006), AV Wenckebach cycle lengths, and AV nodal effective and functional refractory periods were prolonged in Cx40 -/- compared with Cx40+/+ mice. Conclusion: Cx40-deficient mice exhibit significant delay not only in infra-Hisian conduction, as would be expected from the expression of Cx40 in the His-Purkinje system but also in the electrophysiologic parameters that reflect AV nodal conduction. Our data suggest a significant role of Cx40 in atrionodal conduction and/or in proximal His-bundle conduction, [source]

Abnormalities of whole body protein turnover, muscle metabolism and levels of metabolic hormones in patients with chronic heart failure

JOURNAL OF INTERNAL MEDICINE, Issue 1 2006
H. NØRRELUND
Abstract. Objective., It is well known that chronic heart failure (CHF) is associated with insulin resistance and cachexia, but little is known about the underlying substrate metabolism. The present study was undertaken to identify disturbances of basal glucose, lipid and protein metabolism. Design., We studied eight nondiabetic patients with CHF (ejection fraction 30 ± 4%) and eight healthy controls. Protein metabolism (whole body and regional muscle fluxes) and total glucose turnover were isotopically assayed. Substrate oxidation were obtained by indirect calorimetry. The metabolic response to exercise was studied by bicycle ergometry exercise. Results., Our data confirm that CHF patients have a decreased lean body mass. CHF patients are characterised by (i) decreased glucose oxidation [glucose oxidation (mg kg,1 min,1): 1.25 ± 0.09 (patients) vs. 1.55 ± 0.09 (controls), P < 0.01] and muscle glucose uptake [a , v diffglucose (,mol L,1): ,10 ± 25 (patients) vs. 70 ± 22 (controls), P < 0.01], (ii) elevated levels of free fatty acids (FFA) [FFA (mmol L,1): 0.72 ± 0.05 (patients) vs. 0.48 ± 0.03 (controls), P < 0.01] and 3-hydroxybutyrate and signs of elevated fat oxidation and muscle fat utilization [a , v diffFFA (mmol L,1): 0.12 ± 0.02 (patients) vs. 0.05 ± 0.01 (controls), P < 0.05] and (iii) elevated protein turnover and protein breakdown [phenylalanine flux (,mol kg,1 h,1): 36.4 ± 1.5 (patients) vs. 29.6 ± 1.3 (controls), P < 0.01]. Patients had high circulating levels of noradrenaline, glucagon, and adiponectin, and low levels of ghrelin. We failed to observe any differences in metabolic responses between controls and patients during short-term exercise. Conclusions., In the basal fasting state patients with CHF are characterized by several metabolic abnormalities which may contribute to CHF pathophysiology and may provide a basis for targeted intervention. [source]