bluuebunny/crossref_metadata_2025 huggingface dataset:
Seizure‐related Injuries in Children with Newly Diagnosed and Untreated Epilepsy
Authors: Appleton Richard E.
Published: March 2003

Summary: Purpose:Patients with epilepsy are reported to have an increased risk of physical injury. One of clinicians' concerns for diagnosing epilepsy early is to try to prevent such injuries and also to allay parental anxiety that seizures may cause injuries. The purpose of this study was to investigate injuries in children with newly diagnosed epilepsy and before starting antiepileptic medication.

Methods:A prospective study was undertaken of all newly diagnosed and untreated patients with at least two unprovoked, afebrile seizures of any type, aged 1–16 years, presenting consecutively to seven paediatric/paediatric neurology outpatient departments over a 12‐month period. Information was collected on the duration of epilepsy before diagnosis, the epilepsy syndrome, the seizure type causing the injury, how and the age at which the injury was sustained, and whether hospital treatment was required for the injury.

Results:One hundred ninety‐eight patients (116 boys) were surveyed. No patient died as a result of an injury. Twenty‐five (12.6%) children experienced an injury before the diagnosis of epilepsy was established. Only four of the 25 patients (2% of all 198 patients) required medical attention for the injury. The injuries occurred at a mean age of 10.3 years (range, 4–15.1 years), and epilepsy was diagnosed at a mean age of 11.1 (range, 4.2–15.8) years. Fifteen patients were injured at home, six at school, and four outside the home. The seizures causing the injuries were tonic–clonic (17), complex partial (four), myoclonic (one), and of uncertain type (three). None of the 32 patients with childhood‐onset typical absence epilepsy had accidental injuries.

Conclusions:Injuries caused by epileptic seizures were uncommon in this newly diagnosed and untreated, consecutive paediatric outpatient series. These unique data could help to reassure clinicians that the diagnosis of epilepsy should not be influenced by any concern that accidental injuries caused by seizures are common in children before starting medication.
Physical and Hormonal Profile of Male Sexual Development in Epilepsy
Authors: El‐Khayat Hamed A. , Shatla Hamed M. , Ali Gihan K. H. , Abdulgani Mohammad O. , Tomoum Hoda Y. , Attya Hussein A.
Published: March 2003

Summary:  Purpose: This study was designed to investigate the effect of epilepsy and antiepileptic drugs (AEDs) on both the physical and hormonal aspects of the sexual development of male patients with epilepsy.

Methods: One hundred thirty male subjects with epilepsy, their age ranging between 8 and 18 years (mean, 14 ± 2.9 years), entered the study; all were taking AEDs. Anthropometric measurements [height, weight, and body mass index (BMI)], testicular volume, penile length, and pubarche were assessed in the studied groups, as well as measurement of the levels of testosterone (T), free testosterone (FT), estradiol (E2), lutenizing hormone (LH), follicle‐stimulating hormone (FSH), and prolactin (PRL), and the results were compared with those of a control group.

Results: In this study, male patients older than 16 years were significantly shorter than their matched controls. The mean values of testicular volume and penile length were significantly lower in the patients in the different age subgroups, and the pubic hair staging (pubarche) was delayed in the patients older than 16 years. The mean values of total testosterone, estradiol, LH, and FSH serum levels were significantly higher, whereas the mean values of free testosterone, total‐T/E2, total. T/LH, and FT/E2 ratios were lower in the patient subgroups compared with their age‐matched controls. There were no significant changes in the mean basal PRL serum levels in the patients compared with the controls. The present study demonstrated a reduction in the testicular volume and penile length, significantly lower mean values of free testosterone and total‐T/E2, and a higher mean value of E2 in the patients receiving polytherapy in the age subgroup older than 16 years compared with those on monotherapy; however, there was no demonstrable effect of seizure control or the duration of illness in any of the studied parameters.

Conclusions: There is a delay in the sexual development of male patients with epilepsy in the different age subgroups, with endocrine changes in the form of increase in the total testosterone, but the free testosterone is lower, and an increase in estradiol, with lower T/LH levels. Patients receiving polytherapy, especially those older than 16 years, were more likely to have delayed gonadarch and disturbances in their hormonal profile.
Tonic–Absence Seizures: An Underrecognized Seizure Type
Authors: Shih Tina T. , Hirsch Lawrence J.
Published: March 2003

Summary:  Purpose: The individual electroclinical patterns—tonic seizures with generalized paroxysmal fast activity (GPFA, activity >13 Hz), and absence seizures with generalized slow spike‐and‐wave activity (GSS&W, <3 Hz)—have been extensively described in the literature. However, only passing reference was made to the pattern of GPFA followed by GSS&W. In addition, these descriptions were formulated in the pre‐EMU (Epilepsy Monitoring Unit) era, without benefit of video/clinical correlation. We now characterize this underrecognized seizure type.

Methods: We retrospectively reviewed the data from eight patients with seizures that demonstrated this stereotyped EEG and clinical pattern.

Results: We identified eight patients (six female patients; age 6–29 years; age at seizure onset, neonate to 10 years) who were evaluated at the Columbia University Epilepsy Monitoring Units between 1993 and 2002. All eight had an International League Against Epilepsy (ILAE) diagnosis of symptomatic generalized epilepsy, with six of eight manifesting multiple seizure types, six of eight with mild static encephalopathy, and two with normal cognition. A total of 29 seizures of this pattern was recorded; 26 of 29 seizures demonstrated GPFA (frequency between 14 and 30 Hz, lasting 2–8 s) followed by GSS&W (frequency range between 1 and 2 Hz, lasting 3–50 s). The predominant clinical correlate was bilateral tonic activity followed by a period of inattentiveness. In general, these seizures were differentiated from the patient's typical tonic seizures by this protracted period of impaired attentiveness.

Conclusions: We describe a heretofore underrecognized and poorly characterized seizure type in patients with symptomatic generalized epilepsy, which we have termed tonic–absence seizures. Clinically and electrographically, this consists of a tonic seizure with GPFA followed by an absence seizure with GSS&W.
Economic Evaluation of Epilepsy Treatment: A Review of the Literature
Authors: Heaney Dominic C. , Begley Charles E.
Published: March 2003

Summary:This article provides an overview of methods used and findings from economic analyses in epilepsy. Cost‐effectiveness studies have evaluated different drugs for monotherapy and add‐on therapy, and compared alternative treatment modalities for refractory epilepsy. The methodological characteristics of these studies are examined, and their results are compared and interpreted. Health outcome measures are defined and data sources described. Methods for assessing the direct and indirect costs, and/or cost savings, with a treatment's use, are explored. Directions for future research are identified and discussed.
Glutamatergic Modulation of GABAergic Signaling Among Hippocampal Interneurons: Novel Mechanisms Regulating Hippocampal Excitability
Authors: Kullmann Dimitri M. , Semyanov Alexey
Published: March 2003

Summary:  Purpose: Because interneurons play a central role in regulating the excitability of the hippocampal formation, it is important to understand the mechanisms that modulate γ‐aminobutyric acid (GABA)ergic signaling among them. This study addresses the modulation of GABA release from interneuron terminals by presynaptic glutamate receptors.

Methods: Whole‐cell recordings were obtained from CA1 stratum radiatum interneurons in guinea pig hippocampal slices. Selective agonists and blockers of glutamate receptors were used to study modulation of GABAergic transmission by group III metabotropic receptors or kainate receptors. Antidromic action‐potential initiation also was analyzed by stimulating the axons of interneurons.

Results: Agonists of group III metabotropic glutamate receptors attenuated monosynaptic GABAergic signals in interneurons, but not in pyramidal neurons, in agreement with anatomic evidence on the distribution of these receptors. Submicromolar kainate enhanced the frequency and amplitude of spontaneous GABAergic signals in interneurons. Kainate also depolarized the axons of hippocampal interneurons, and triggered spontaneous ectopic action potentials in axons. Synaptically released glutamate reproduced many of the effects of both agonists, implying that these receptors can sense the ambient glutamate concentration, and therefore indirectly respond to the excitatory traffic in the hippocampus. When the two classes of receptors were stimulated simultaneously, complex interactions were obtained.

Conclusions: Group III metabotropic receptors and kainate receptors profoundly affect GABAergic signaling among interneurons of the hippocampus. Glutamatergic modulation of GABAergic signaling among interneurons represents a novel class of mechanisms that potentially plays a major role in determining the initiation, propagation, and termination of seizures.
Short‐Term Effects of Pilocarpine on Rat Hippocampal Neurons in Culture
Authors: Priel M. R. , Albuquerque E. X.
Published: March 2003

Summary:  Purpose: Status epilepticus (SE) has been considered an epileptogenic factor in humans. In the pilocarpine (PILO) model, after a brief period marked by SE, the rats exhibit recurrent spontaneous seizures, mimicking the clinical features of temporal lobe epilepsy. The aim of our study was to identify the molecular actions of PILO that could account for its ability to induce SE.

Methods: Whole‐cell mode of the patch‐clamp technique was applied to cultured hippocampal neurons (2–3 weeks old) in the absence and in the presence of PILO (1–10 μM), to study the spontaneous activity, the evoked, and the miniature postsynaptic currents. The postsynaptic currents were isolated pharmacologically.

Results: PILO (1 and 10 μM) caused an initial increase followed by a decrease in the frequency of spontaneous activity. The increase in the frequency of excitatory postsynaptic currents (EPSCs) and inhibitory PSCs (IPSCs) was blocked by atropine (1 μM), indicating that this effect is mediated through muscarinic receptors. PILO also promoted a brief increase of the amplitude of IPSCs indirectly evoked by stimulation of a neuron synaptically connected to the neuron under study. Conversely, PILO promoted a sustained increase on the amplitude of electrically evoked EPSCs. In presence of tetrodotoxin (TTX; 300 nM), PILO (1 μM) increased the frequency of miniature EPSCs and IPSCs without changing their amplitude during the first 3 min of application.

Conclusions: These results indicate that PILO acting through muscarinic receptor causes an imbalance between excitatory and inhibitory transmission that can result in the generation of SE observed in animals acutely treated with PILO.
Upregulation of Cystatin C Expression in the Rat Hippocampus During Epileptogenesis in the Amygdala Stimulation Model of Temporal Lobe Epilepsy
Authors: Lukasiuk Katarzyna , Pirttilä Terhi J. , Pitkänen Asla
Published: March 2003

Summary:  Purpose: Cystatin C is a cysteine proteinase inhibitor with widespread distribution in body fluids and tissues, abundant in the cerebrospinal fluid and in brain tissue. There is an implied role for cystatin C in several neurologic disorders, but the actual function of cystatin C in the brain remains unknown. Moreover, the reports on the distribution of cystatin C in the brain are controversial. We present the data on the distribution of cystatin C in normal brain tissue and during epileptogenesis.

Methods: Epileptogenesis was triggered by inducing self‐sustained status epilepticus (SSSE) with a 20‐ to 30‐min electrical stimulation of the amygdala in rats. Animals were monitored continuously for 2 weeks with video‐EEG to ascertain that they were in an epileptogenic phase.

Results: Analysis of double‐stained immunopreparations indicated that in normal brain, cystatin C is expressed mainly in microglia. In epileptogenic animals, immunostaining was increased in the microglia as well as in the neuropil at 4 days, 1 week, and 2 weeks after SSSE. Moreover, the density of cystatin C‐positive microglia was associated with the severity of neuronal damage in the CA1 subfield of the hippocampus.

Conclusions: This is the first report linking cystatin C with epileptogenesis and epilepsy. Further studies will explore the potential neuroprotective functions of this protein during epileptogenesis and whether the manipulation of its expression or function will have therapeutic implications.
Clinical and Genetic Heterogeneity in Familial Temporal Lobe Epilepsy
Authors: Santos N. F. , Sousa S. C. , Kobayashi E. , Torres F. R. , Sardinha J. A. F. , Cendes F. , Lopes‐Cendes I.
Published: March 2003

Summary:  Purpose: Familial forms of temporal lobe epilepsy have been described recently. A locus on ch 10q has been linked to partial epilepsy with auditory symptoms. We investigated the proportion of families segregating temporal lobe epilepsy (TLE) linked to ch 10q and sought to establish genotype–phenotype correlations.

Methods: We studied 15 unrelated families segregating TLE. A total of 153 individuals, including 79 patients, were analyzed in this study. Family members were genotyped for four polymorphic dinucleotide repeat markers: D10S185, D10S574, D10S577, and D10S192, which flank the 15‐cM candidate interval on ch 10q. Two‐point lod scores were calculated for each family separately.

Results: Fourteen of our families had ictal semiology of mesial temporal onset of seizures and magnetic resonance imaging (MRI) abnormalities in the mesial structures; only one family, with seven affected individuals, reported auditory symptoms and had normal MRIs. Pedigree analysis showed an autosomal dominant transmission with 0.75 penetrance. Only two families had informative lod scores. A large family, with 22 affected individuals segregating mesial TLE, had negative lod scores for all four markers genotyped. The lod scores were significantly negative (less than –2.00) up to 0.05 for D10S185, 0.10 for D10S574, 0.25 for D10S577, and 0.15 for D10S192. The single family with auditory symptoms had positive lod scores for all markers genotyped, with a Z max of 1.52 at 0.0 for D10S574.

Conclusions: We identified two different clinical groups of families segregating TLE. Most families identified in this study had mesial TLE. Only one single family segregating lateral TLE was found. We significantly excluded linkage between familial mesial TLE and the locus on ch 10q. In addition, we showed evidence for linkage between one family with lateral TLE and markers on ch 10q. This is strong evidence for clinical and genetic heterogeneity among familial forms of TLE.
Behavioral, Morphologic, and Electroencephalographic Evaluation of Seizures Induced by Intrahippocampal Microinjection of Pilocarpine
Authors: De A. Furtado Marcio , Braga Glaucia K. , Oliveira José A. C. , Del Vecchio Flavio , Garcia‐Cairasco Norberto
Published: March 2003

Summary:  Purpose: We studied, by means of video‐EEG and neo‐Timm histochemistry, the behavioral, electrophysiologic, and structural characteristics of seizures induced by intrahippocampal microinjection of pilocarpine (HIP‐PILO), a selective model of temporal lobe epilepsy (TLE).

Methods: We investigated the behavioral and electrophysiologic (hippocampus and amygdala EEG) evaluation of status epilepticus (SE) induced by HIP‐PILO and the consequent spontaneous recurrent seizures (SRSs). We evaluated hippocampal structural rearrangements after SE by means of neo‐Timm staining.

Results: HIP‐PILO induced SE in 17 (71%) of 24 animals. Although three animals displayed spontaneous remission of SE (not used in analysis) before the established SE duration (90 min), none of those undergoing SE died. Of SE animals, 10 (71%) of 14 had SRSs. All animals with SE had clear‐cut mossy fiber sprouting (MFS) in the inner molecular layer of the dentate gyrus and epileptiform activity in hippocampus and amygdala.

Conclusions: HIP‐PILO rats displayed SE, SRS, MFS, and limbic epileptiform activity, without animal loss after SE. Thus, our data support this as a selective and efficient model of TLE.
Zinc and Epileptogenesis
Authors: Dudek F. Edward
Published: March 2003

Zinc is concentrated in the hippocampus, particularly in the mossy fiber axons of the dentate gyrus, and has been hypothesized to be important in neurodegeneration and epilepsy. Previous studies have suggested that activity-dependent release of zinc from reorganized mossy fibers leads to collapse of granule-cell inhibition. Synaptically released zinc has been proposed to depress the function of the new “epileptic” GABAA receptors, which have subunits that are zinc-sensitive. Recent experiments by Molnar and Nadler have replicated the previous data, and further tested this hypothesis. Their work suggests that activated mossy fibers in hippocampal slices do not release adequate zinc to depress GABAA receptor function at nearby inhibitory synapses. These studies point to the complexity of this hypothesis, particularly in regard to zinc release in vitro versus in vivo and the diffusion of zinc in the extracellular space.
Impact of Left Ventricular Function on the Pulmonary Vein Doppler Spectrum:
Authors: Wu Chih‐Cheng , Lee Wen‐Shin , Yu Wen‐Chung , Huang Wen‐Pin , Lin Yao‐Ping , Hsu Tsei‐Lieh , Ding Philip Yu‐An , Chen Chen‐Huan
Published: March 2003

Pulmonary vein Doppler spectrum is highly load‐dependent and thus has been used to estimate left ventricular (LV) filling pressure. However, the impact of LV function on pulmonary vein Doppler spectrum remains obscure because only load‐sensitive indices were studied previously. In the present study, measurements of the pulmonary vein Doppler spectrum were correlated with load‐insensitive LV systolic (end‐systolic elastance [Ees]) and diastolic (relaxation time constant [tau] and beta coefficient of the end‐diastolic pressure volume relationship) function indices obtained from an invasive catheterization study nonsimultaneously. The peak velocity, velocity time integral, and duration of systolic forward spectrum were significantly correlated with Ees (

r = 0.35, r = 0.36

, and

r = 0.41

, respectively;

P < 0.05

). The pulmonary vein diastolic velocity time integral (PVDVTI) and duration of the diastolic forward spectrum were significantly correlated with Ees (

r = 0.51

and

r = 0.57

, respectively;

P < 0.01

). PVDVTI was correlated with tau and the end‐diastolic pressure‐volume relationship (EDPVR) (

r = 0.42

and

r = 0.40

respectively,

P < 0.05

). On the other hand, the systolic fraction of the forward spectrum was significantly correlated with ejection fraction (for peak velocity,

r = 0.63, P < 0.01

; for velocity time integral,

r = 0.37, P < 0.05

) but not with Ees, and the diastolic fraction of the forward spectrum was significantly correlated with minimum pressure derivative over time (for peak velocity,

r = 0.48, P < 0.05

; for velocity time integral,

r = 0.44, P < 0.05

, respectively) but not with tau or EDPVR. In summary, the systolic and diastolic components of the pulmonary vein Doppler spectrum are affected variably by LV systolic and diastolic function, independent of the loading condition. The systolic and diastolic fraction of pulmonary vein Doppler spectrum appears to depend more on the loading condition than the LV systolic or diastolic function. (ECHOCARDIOGRAPHY, Volume 20, January 2003)
Color Doppler Tissue Imaging to Evaluate Left Atrial Appendage Function in Mitral Stenosis
Authors: Eryol Namık Kemal , Topsakal Ramazan , Kıranatlı Burhanettin , Abacı Adnan , Çiçek Yüksel , Oǧuzhan Abdurrahman , Başar Emrullah , Ergin Ali , Çetin Servet
Published: March 2003

Two‐dimensional color Doppler tissue imaging (CDTI) has so far been used, in general, to evaluate ventricular function. This study examined if the left atrial appendage tissue velocity could reproducibly be measured with CDTI and if they have any predictive value for left atrial appendage (LAA) function and former thromboembolism. Thirty‐six patients (24 women, 12 men; mean age 45 ± 12 years; 18 AF; 11 former thromboembolic stroke) with mitral stenosis undergoing transesophageal echocardiography were examined with CDTI. Peak systolic tissue velocity (m/sec, peak systolic velocity [PSV]) was measured at the tip of the LAA in the basal short‐axis view. LAA flow emptying (LAAEV) and filling (LAAFV) velocities (m/sec) were also recorded 1 cm immediately below the orifice of the appendage. Interobserver and intraobserver variabilities were determined for the PSV. LAA ejection fraction was measured by Simpson's method. Mitral regurgitation, AF, transmitral mean gradient, left ventricular ejection fraction, mitral valve area, and left atrial diameter were used as a covariant for adjustment. The intraobserver and interobserver correlation coefficients for the PSV using CDTI was 0.64 and 0.60, respectively (both

P = 0.01

). LAAEV

(0.29 ± 0.09 vs 0.19 ± 0.04, P = 0.001)

and LAA ejection fraction

(44 ± 12 vs 29 ± 14, P = 0.004)

were found to be significantly decreased in the patients with decreased PSV (<0.05 m/sec), even after adjustment. The decreased PSV was positively correlated with the low LAAEV (<0.25 m/sec) and history of thromboembolism (

r = 0.59, r = 0.38

, respectively), and remained a significant determinant of the low LAAEV (OR 50.03, CI 1.46–1738.11,

P = 0.02

), but not of history of thromboembolism (OR 4.29, CI 0.52–35.01,

P = 0.08

) after adjustment. In conclusion, these results suggest that CDTI provides a reproducible method for quantification of contraction at the tip of the LAA. Decreased PSV may be predictive of poor LAA function. (ECHOCARDIOGRAPHY, Volume 20, January 2003)
Assessment of Myocardial Perfusion with Intravenous Contrast Echocardiography:
Authors: Palagi Caterina , Mengozzi Giovanna , Rovai Daniele , Volterrani Duccio , Dell'Anna Rita , Giorgi Davide , Petronio Anna Sonia , Bello Vitantonio Di , Mariani Mario
Published: March 2003

The aim of the study was to evaluate the accuracy of intermittent, harmonic power Doppler (HPD) during intravenous Levovist infusion in identifying myocardial perfusion abnormalities in patients with recent infarction. Fifty‐five patients with first acute myocardial infarction, successfully treated by primary PTCA, were studied after 1 month by myocardial contrast echocardiography (MCE), 99mTc tetrofosmin single photon emission computed tomography (SPECT), and low dose dobutamine echocardiography (DE). Scoring myocardial perfusion as normal, moderately, or severely reduced; MCE and SPECT were in agreement in 71% of segments

(k = 0.414)

. Discordance was mainly due to ventricular walls with normal enhancement by MCE and moderate perfusion abnormalities by SPECT. Scoring perfusion as present or absent, the agreement significantly improved up to

86% (k = 0.59)

. Sensitivity and specificity of HPD for identifying SPECT perfusion defects were 63% and 93%, respectively. The agreement between MCE and SPECT was higher

(85%, k = 0.627)

in patients with anterior infarction. An improvement in regional contractile function was noted after dobutamine in 79 dysfunctional segments. A normal perfusion or a moderate perfusion defect by MCE were detected in 71 of 79 of these segments, while a severe perfusion defect was observed in 59 of 85 ventricular segments without dobutamine‐induced wall‐motion improvement. Sensitivity and specificity by HPD in detecting segments with contractile reserve were 90% and 69%, respectively. Thus, intermittent HPD during Levovist infusion allows myocardial perfusion abnormalities to be detected in patients with recent infarction. This method has a limited sensitivity but a high specificity in detecting SPECT perfusion defects, and a good sensitivity but a limited specificity in detecting contractile reserve. (ECHOCARDIOGRAPHY, Volume 20, January 2003)
Three‐Dimensional Echocardiographic Determination of Cardiac Output at Rest and Under Dobutamine Stress:
Authors: Handke Michael , Heinrichs Gudrun , Magosaki Etsuko , Lutter Georg , Bode Christoph , Geibel Annette
Published: March 2003

Determination of cardiac output is a potentially important clinical application of three‐dimensional (3‐D) echocardiography since it could replace invasive measurements with the Swan‐Ganz‐catheter. To date, there are no studies available to determine whether cardiac output measured by thermodilution can be predicted reliably under changing hemodynamic conditions. Fifteen pigs with ischemic myocardium were examined under four hemodynamic conditions at rest and under pharmacological stress with 5, 10, and 20 μg/kg/min dobutamine. The 3‐D datasets were recorded by means of transesophageal echocardiography. The endocardial definition was enhanced by administering the contrast agent FS069 (Optison). Cardiac output was calculated as the product of stroke volume (end‐diastolic – end‐systolic volume) and heart rate. The invasive measurements were performed with a continuous thermodilution system. In general, there was moderate correlation between 3‐D echocardiography and thermodilution

(r = 0.72, P < 0.001)

. At rest, the 3‐D echocardiographic measurements were slightly but significantly lower than the invasive measurements (mean difference

0.6 ± 0.5

L/min,

P < 0.001

). Under stress with 5, 10, and 20μg/kg/min dobutamine, there was a marked increase in the deviation (

1.3 ± 0.5

L/min,

P < 0.001; 1.6 ± 0.7

L/min,

P < 0.001

; and

2.1 ± 1.1

L/min,

P < 0.001

, respectively). The deviation was based on two factors: (1) Under stress, the decreasing number of frames per cardiac cycle acquired with 3‐D echocardiography led to imprecise recording of end‐diastolic and end‐systolic volumes, and thus to an underestimation of cardiac output. At least 30 frames per cardiac cycle are needed to eliminate this effect. (2) There is a systematic difference between 3‐D echocardiographic and invasive measurements, which is independent of the imaging rate. This is based on an overestimation of the true values by thermodilution. In conclusion, cardiac output can be determined correctly by 3‐D echocardiography for normal heart rates at rest. At elevated heart rates, the temporal resolution of 3‐D systems currently available is not adequate for reliable determination. In performing and evaluating future clinical comparative studies, the systematic difference between 3‐D echocardiography and thermodilution, based on overestimation by thermodilution, must be taken into account. (ECHOCARDIOGRAPHY, Volume 20, January 2003)
Update on Echocardiography of Coronary Sinus Anatomy and Physiology
Authors: D'Cruz Ivan A. , Shirwany Arsalan
Published: March 2003

The coronary sinus (CS) can be imaged echocardiographically as a small tubular sonolucency in the posterior atrioventricular groove. To date, its importance to echocardiographers has been that CS dilatation usually signifies a persistent left superior vena cava. Recently, we developed a technique to image CS caliber over the duration of the cardiac cycle. CS contraction accompanies the P wave on the electrocardiogram, in sinus rhythm or in various arrhythmias. CS contraction is always absent in atrial fibrillation. In sinus rhythm, CS contraction may be attenuated or absent if congestive heart failure, with marked venous congestion, is present. Thus, this attenuation is a potentially valuable echocardiographic sign of elevated central venous pressure. We demonstrate the echo visualization of CS‐related structures, such as tributary veins and the Thebesian valve. The potentially useful concept of the CS as a “miniventricle” is discussed. CS blood flow can be recorded by interrogation in the right heart inflow view. The pattern of CS antegrade flow and the exceptional situation of retrograde systolic CS flow from a posteriorly directed tricuspid regurgitant jet are demonstrated. (ECHOCARDIOGRAPHY, Volume 20, January 2003)
Serum Creatine Kinase Elevation in a Medical Department
Authors: Kodatsch Irmgard , Finsterer J. , Stöllberger Claudia
Published: March 2003

Summary: Serum creatine kinase (CK) levels are diagnostic markers for acute myocardial infarction. Many other causes however, including neuromuscular disorders, may induce serum CK elevation as well. Aim of the study was to investigate the prevalence of potential causes for serum CK elevation in a medical department. In particular we were interested in the recognition of patients in whom serum CK elevation was due to a neuromuscular disorder.  Included in this prospective study were 100 consecutive patients in whom the CK level, determined at admission, was increased (> 70 IU/l in female, > 80 IU/l in male patients). After admission we looked for the presence of causes known to induce CK elevation. Patients with no potential cause for CK elevation were invited for follow‐up investigations three months later. If no potential cause could be found and if CK was elevated again on this occasion, the patient was referred for a comprehensive neurological investigation.  The prevalence of patients with CK elevation was 11.2 %. The 100 patients (44 female, 56 male) were aged from 23 to 94 (mean 67) years. In 95 % CK elevation was only up to 500 IU/l. The most frequent cause for serum CK elevation was acute myocardial infarction in 32 %. Further frequent causes were drug intake (32 %), fall (24 %), haematoma (17 %), intramuscular injection (16 %) and malignancy (11 %). In 61 % of the cases at least two potential causes for serum CK elevation could be detected. Neuromuscular disorders were found in only 2 %.  This study shows that serum CK elevation occurs in 11 % of patients admitted to a medical department and can be explained by acute myocardial infarction in only 32 %. In almost two thirds of the patients, more than one potential cause for serum CK elevation can be found thus making CK elevation a rather unspecific finding. Neuromuscular disorders are rarely found as a cause of serum CK elevation in a medical department.
Erythrocyte Mean Cellular Volume and its Relation to Serum Homocysteine, Vitamin B12 and Folate
Authors: Haltmayer M. , Mueller T. , Poelz W.
Published: March 2003

Summary: Cobalamin (B12) and folate deficiency is related to both increased erythrocyte mean cellular volume (MCV) and raised serum total homocysteine (tHcy) values. Furthermore, there are indications that B12 and folate serum values do not represent the tissue status of the two vitamins exactly. Therefore, a direct relationship between MCV and tHcy, if demonstrated, could support the hypothesis that tHcy is a better indicator for the cited vitamin status than the serum levels of B12 and folate. We studied MCV, gamma glutamyl transferase (GGT), serum B12, folate and tHcy values in 200 hospitalized patients. There was a significant correlation of MCV with GGT (r = 0.266, P < 0.001) and with tHcy (r = 0.248, P < 0.001), but not with serum B12 and folate. Stepwise multiple linear regression with MCV as dependent and GGT, B12, folate and tHcy as independent variables, respectively, revealed significant associations of MCV with GGT (B = 2.18, 95 % CI 0.95 – 3.42, P = 0.001) and tHcy (B = 3.33, 95 % CI 1.26 – 5.39, P = 0.002). By removing tHcy from this model, serum B12 became a significant predictor of MCV (B = –1.70, 95 % CI –3.25 to –0.15, P = 0.032). Serum folate was not significantly associated with MCV in multivariate analysis. In conclusion, the present study confirms indications that serum B12 and folate values lack clinical sensitivity and specificity in diagnosing vitamin deficiency states by showing MCV was better associated to tHcy, than to B12 or folate serum levels. This observation demonstrates that tHcy may be useful in diagnosing patients with B12 and/or folate deficiency.
Antithrombin and Near‐Fatal Exertional Heat Stroke
Authors: Pechlaner Ch. , Kaneider Nicole C. , Djanani Angela , Sandhofer A. , Schratzberger P. , Patsch J. R.
Published: March 2003

Summary: Heat waves result in excess deaths, excess emergency department visits, and intensive care unit admissions for heat stroke. We describe the clinical features and 3‐month outcome of a patient with near‐fatal heat stroke, admitted to our intensive care unit in July, 2001. After heavily working for hours at a construction site during a heat wave, the 28‐year‐old male presented with 41.4 °C body temperature and multiorgan failure, consisting of neurological impairment, rhabdomyolysis, acute renal failure, disseminated intravascular coagulation, and acute respiratory distress syndrome (ARDS). In the first week there was no evidence of infection. Treatment included cooling, aggressive volume resuscitation, administration of antithrombin‐III concentrates and steroids. The patient survived and recovered normal neurological, renal, respiratory and haematological function, and no disability persisted. This case illustrates survival and complete recovery after multiorgan failure in heat stroke with vigorous intensive care. Treatment with antithrombin and steroids and may well have contributed to the favourable outcome. Correction of reduced antithrombin III levels to supranormal by therapeutic administration of antithrombin III concentrate in disseminated intravascular coagulation of heat stroke was not associated with any bleeding complications.
Palliative Treatment of Unresectable Bile Duct Tumours
Authors: Mayer Ramona , Stranzl Heidi , Prettenhofer Ulrike , Quehenberger F. , Stücklschweiger G. , Winkler P. , Hackl A.
Published: March 2003

Summary: Purpose
: Report on outcome of intraluminal high‐dose‐rate iridium‐192 (HDR‐Ir
192
) brachytherapy with or without external radiotherapy in patients with unresectable bile duct tumours suffering from symptoms of malignant obstructive jaundice.
Material and methods
: Fourteen patients (mean age: 63 years) who were unsuitable for surgical resection on preoperative evaluation/laparotomy or inoperable due to poor general condition were referred for palliative radiotherapy. After percutaneous transhepatic drainage, HDR‐Ir
192
brachytherapy was performed with a single dose of 2.5 Gy. Brachytherapy was given twice a day with at least a 6‐h interval for 2 days, 2 or 3 days apart, up to a total dose of 10 Gy. Five patients received small‐volume external radiotherapy (RT) (45 – 50.4 Gy/1.8 Gy) additionally.
Results
: Palliation with relief of the aggravating symptoms of obstructive jaundice was achieved in all patients. The actuarial 2‐year survival rate of all patients was 11.9 % with a median survival of 6.5 months. Patients treated with brachytherapy alone had a median survival of 4.5 months as compared with 6.5 months after combined internal and external irradiation (log rank,
P
= 0.95).
Conclusion : Patients with advanced unresectable bile duct cancer face a dismal prognosis; however, biliary drainage, and intraluminal brachytherapy with or without external RT, seem to be able to improve quality of life in the remaining time span.
DRGs in der Dermatologie: Erlösoptimierung durch Sicherung der Kodierqualität
Authors: Hensen Peter , Fiori Wolfgang , Juhra Christian , Irps Sebastian , Bunzemeier Holger , Schwarz Thomas , Luger Thomas , Roeder Norbert
Published: March 2003

Hintergrund: Die sachgerechte Abbildung der Behandlungsfälle im DRG‐System stellt die Grundlage der Vergütung für die durchgeführte Behandlung in deutschen Krankenhäusern dar. Dies kann nur über eine ausreichend gute Kodierung der medizinischen Daten ermöglicht werden. Ziel der vorliegenden Studie war, den Einfluß einer kontrollierten Leistungsdokumentation auf die klinischen Patientendaten zu untersuchen und die Auswirkungen einer verbesserten Kodierqualität auf die theoretischen Ertragsvolumina im australischen AR‐DRG‐System zu ermitteln.

Patienten und Methodik: Im Rahmen einer prospektiven Studie sind 1 914 Patientendatensätze einer dermatologischen Universitätsklinik nach Anwendung unterschiedlicher Dokumentationsstandards auf der Basis des AR‐DRG‐Systems V4.1 gruppiert und analysiert worden. Zur besseren Differenzierung des dermatologischen Behandlungsspektrums wurden die Patienten in elf Behandlungsgruppen eingeteilt, um gezielter Schwerpunkte aufzeigen zu können.

Ergebnisse: Durch eine kontrollierte Leistungsdokumentation konnten Steigerungen von Casemix, Casemix‐Index und mittlerem PKKS‐Wert erzielt werden. Ebenso zeigte sich, daßüber gesteuerte Maßnahmen zur Optimierung der Kodierqualität langfristig die tatsächliche durchschnittliche Fallschwere einer Klinik abgebildet werden kann.

Schlußfolgerungen: Unterschiedliche Dokumentationsstandards können drastische Auswirkungen auf die Erlössituation eines Krankenhauses haben. Unvollständige Leistungsdokumentation, Fehl‐ und Überkodierung stellen ein großes ökonomisches Risiko für ein Krankenhaus dar. Nur die Sicherstellung und Überwachung einer hohen Kodierqualität kann eine kostendeckende Erlössituation garantieren.
Treatment of scleromyxoedema with hydroxychloroquine
Authors: Terheyden Patrick , Becker Jürgen C. , Lurz Christa , Kahaly George J. , Bröcker Eva‐B.
Published: March 2003

Background: Scleromyxoedema is a rare disease of unknown aetiology that is characterized by deposition of mucin and sclerotic induration of the skin; it is associated with paraproteinaemia. Patients suffer from progressive disability due to immobilization and cosmetic disfigurement. Treatment of scleromyxoedema is a therapeutic challenge. The antimalarial hydroxychloroquine has a rapid and reliable effect in reticular erythematous mucinosis.

Patients and methods: Four consecutive patients (two women, two men; median age: 50 years) with scleromyxoedema, three of them with IgG λ paraprotein, were treated with hydroxychloroquine. Treatment was initiated with 600 mg p. o. for 10 days, followed by 400 mg for at least 4 weeks, and 200 mg thereafter.

Results: Complete remission of skin manifestations was achieved in one patient, whereas three patients achieved a partial remission of 61+, 5 and 25 months' duration. Notably, three patients felt increased mobility and reduced firmness of skin during the first week of treatment, which was reflected in a rapid reduction in dermal thickness. In one patient, dysphagia was reverted as evidenced by normalization of oesophageal clearance. Paraproteinaemia was not influenced at all. Side effects included one case of electroretinogram abnormalities after 19 months of therapy and one case of leucopenia after 3 months.

Conclusion: Hydroxychloroquine is an effective form of therapy for scleromyxoedema, leading to rapid and prolonged alleviation of symptoms.
The effect of solution heat‐treatment time on the fatigue properties of an Al‐Si‐Mg casting alloy
Authors: DAVIDSON C. J. , GRIFFITHS J. R. , MACHIN A. S.
Published: March 2003

Abstract Experiments have been carried out to investigate whether reducing the solution heat‐treatment time of Al‐7Si‐0.6Mg castings from the currently recommended values adversely affects their fatigue properties. Fatigue endurance tests have been carried out in zero‐tension (R=0) and measurements made of the casting defects that initiated the fatigue cracks. The work has been limited to stresses that produce a fatigue life of ~105 cycles and to two solution–treatment times (8 and 4 h). Two statistical techniques have been applied to the fatigue life data and no effect of solution heat‐treatment time was detected at a confidence level of better than 95%. Similarly, no effect of cyclic test frequency could be detected for tests carried out at 1 and 60 Hz. The conclusions are confirmed by an analysis of the relation between fatigue life and the size of the casting defects that initiated fatigue failure. The scatter in fatigue lives is related to the scatter in the sizes of casting defects in the specimens. It is clear that there is a potential for considerable savings in heat‐treatment costs for castings of the size and shape chosen for the study.
Mutant Proinsulin That Cannot Be Converted Is Secreted Efficiently from Primary Rat β-Cells via the Regulated Pathway
Authors: Halban Philippe A. , Irminger Jean-Claude
Published: March 2003

Prohormones are directed from the trans-Golgi network to secretory granules of the regulated secretory pathway. It has further been proposed that prohormone conversion by endoproteolysis may be necessary for subsequent retention of peptides in granules and to prevent their release by the so-called “constitutive-like” pathway. To address this directly, mutant human proinsulin (Arg/Gly32:Lys/Thr64), which cannot be cleaved by conversion endoproteases, was expressed in primary rat islet cells by recombinant adenovirus. The handling of the mutant proinsulin was compared with that of wild-type human proinsulin. Infected islet cells were pulse labeled and both basal and stimulated secretion of radiolabeled products followed during a chase. Labeled products were quantified by high-performance liquid chromatography. As expected, the mutant proinsulin was not converted at any time. Basal (constitutive and constitutive-like) secretion was higher for the mutant proinsulin than for wild-type proinsulin/insulin, but amounted to <1% even during a prolonged (6-h) period of basal chase. There was no difference in stimulated (regulated) secretion of mutant and wild-type proinsulin/insulin at any time. Thus, in primary islet cells, unprocessed (mutant) proinsulin is sorted to the regulated pathway and then retained in secretory granules as efficiently as fully processed insulin.
Isoprenylcysteine Carboxyl Methyltransferase Activity Modulates Endothelial Cell Apoptosis
Authors: Kramer Kristina , Harrington Elizabeth O. , Lu Qing , Bellas Robert , Newton Julie , Sheahan Kerri L. , Rounds Sharon
Published: March 2003

Extracellular ATP, adenosine (Ado), and adenosine plus homocysteine (Ado/HC) cause apoptosis of cultured pulmonary artery endothelial cells through the enhanced formation of intracellularS-adenosylhomocysteine and disruption of focal adhesion complexes. Because an increased intracellular ratio ofS-adenosylhomocysteine/S-adenosylmethionine favors inhibition of methylation, we hypothesized that Ado/HC might act by inhibition of isoprenylcysteine-O-carboxyl methyltransferase (ICMT). We found thatN-acetyl-S-geranylgeranyl-l-cysteine (AGGC) andN-acetyl-S-farnesyl-l-cysteine (AFC), which inhibit ICMT by competing with endogenous substrates for methylation, caused apoptosis. Transient overexpression of ICMT inhibited apoptosis caused by Ado/HC, UV light exposure, or tumor necrosis factor-α. Because the small GTPase, Ras, is a substrate for ICMT and may modulate apoptosis, we also hypothesized that inhibition of ICMT with Ado/HC or AGGC might cause endothelial apoptosis by altering Ras activation. We found that ICMT inhibition decreased Ras methylation and activity and the activation of the downstream signaling molecules Akt, ERK-1, and ERK-2. Furthermore, overexpression of wild-type or dominant active H-Ras blocked Ado/HC-induced apoptosis. These findings suggest that inhibition of ICMT causes endothelial cell apoptosis by attenuation of Ras GTPase methylation and activation and its downstream antiapoptotic signaling pathway.
The Fission Yeastspo14+Gene Encoding a Functional Homologue of Budding Yeast Sec12 Is Required for the Development of Forespore Membranes
Authors: Nakamura-Kubo Michiko , Nakamura Taro , Hirata Aiko , Shimoda Chikashi
Published: March 2003

The Schizosaccharomyces pombe spo14-B221 mutant was originally isolated as a sporulation-deficient mutant. However, thespo14+gene is essential for cell viability and growth. spo14+is identical to the previously characterizedstl1+gene encoding a putative homologue of Saccharomyces cerevisiae Sec12, which is essential for protein transport from the endoplasmic reticulum (ER) to the Golgi apparatus. In the spo14 mutant cells, ER-like membranes were accumulated beneath the plasma membrane and the ER/Golgi shuttling protein Rer1 remained in the ER. Sec12 is a guanine nucleotide exchange factor for the Sar1 GTPase. Overproduction ofpsr1+coding for an S. pombe Sar1 homologue suppressed both the sporulation defect ofspo14-B221 and cold-sensitive growth of newly isolatedspo14-6 and spo14-7 mutants. These results indicate that Spo14 is involved in early steps of the protein secretory pathway. The spo14-B221 allele carries a single nucleotide change in the branch point consensus of the fifth intron, which reduces the abundance of the spo14 mRNA. During meiosis II, the forespore membrane was initiated near spindle pole bodies; however, subsequent extension of the membrane was arrested before its closure into a sac. We conclude that Spo14 is responsible for the assembly of the forespore membrane by supplying membrane vesicles.
Lund University Libraries and the move to Virtua in a networked environment
Authors: Dahl Kerstin
Published: March 2003

The reason for moving from one library system to another or from one generation of a library system to the next must be to improve the library’s ability to serve its users in a better and more effective way. An integrated library system, today, is very complex and multi‐moduled, which makes it difficult to distinguish one system from another. The article describes the long and bumpy road from the first generation VTLS classic library management system to the third generation VTLS Virtua at Lund University Libraries in Sweden.
PalletPicker‐3D, the solution for picking of randomly placed parts
Authors: Saldner Henrik
Published: March 2003

It is now possible to pick randomly placed parts from a bin automatically. SVIA have developed a patented bin‐picking system that is general and easy for the operator to teach. It is possible because of the combination of a high precision optical 3D‐measuring technique, modern image processing and six‐axis robot technology.
GM creates flexible assembly line at its Ellesmere Port plant in the UK
Authors: Kochan Anna
Published: March 2003

GM's Vauxhall plant at Ellesmere Port is now building not only the Astra model but also the Vectra. Turning this plant into a flex plant that was also lean and efficient involved major changes to the assembly line operations. In particular, the logistics organisation was reviewed, which resulted in new and extended roles for logistics partners.
Designing for task oriented grasps in robotic assembly
Authors: Lowe Gordon , Shirinzadeh Bijan
Published: March 2003

The objective is to develop a flexible robot assembly system capable of economically switching between a wide range of product assemblies. Towards this goal, this paper introduces grasping as a principle issue in designing for flexibility in a robot system. The task, sensing, and certainty about actions are the primary factors in grasp decisions and not where to grasp the part. Identifying finger features, which satisfy a broad range of tasks reduces the likelihood of re‐tooling, and improves certainty about part location and relative orientation. Aided by the ability to address a broad range of tasks, design rules are established which assimilate grasps to part design.