bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropathologic Findings in Postmortem Studies of Sudden Death in Epilepsy
Authors: Thorn M.
Published: November 2007

Summary: Death in patients with epilepsy may occur suddenly and unexpectedly. When no anatomic or chemically demonstrable cause for such a death is found at postmortem examination, the death may remain unexplained. Previous studies of general autopsy features in cases of sudden unexpected death in epilepsy (SUDEP) have reported increased lung and liver weights, pulmonary edema, hepatic fatty change, and small increases in heart weights. Neuropathologic findings include cerebral edema, lighter brain weights compared with agematched controls, and various other structural brain lesions in 34% to almost 50% of cases. In an ongoing United Kingdom study, brains from 25 cases of SUDEP have been examined. Macroscopic abnormalities were identified in 70% of cases and included contusions, old infarcts, hippocampal sclerosis, cortical dysgenesis, vascular malformation, oligodendroglioma, neurodegenerative brain disease, and microcephaly. Histopathologic findings include evidence of acute neocortical and brainstem hypoxic neuronal changes. Similar changes in hippocampal and basal ganglia neurones have also been observed. These changes indicate a cerebral event occurring at least 4–6 h before death and are at odds with a “sudden” death which, by definition, occurs within 1 h. Because many SUDEP cases are unwitnessed, the exact time sequence of events is often unknown. This study confirms the high incidence of structural brain lesions in SUDEP cases.
Rectal Use of Benzodiazepines
Authors: Dooley Joseph M.
Published: November 2007

Summary: A number of antiepileptic drugs (AEDs) can be given rectally for either acute seizure control or maintenance therapy. In particular, rectal AED therapy may enable physicians who are not expert in the treatment of status epilepticus (SE) to administer appropriate early therapy. It can also empower parents to provide emergency care when medical help is not available. Rectal administration of parenteral diazepam (DZP) or of specific rectal formulations has been reported effective for aborting and preventing seizures. Adverse events associated with this treatment tend to be rare and mild, although it is important to note the risk for respiratory depression. Lorazepam can also be administered rectally and can produce rapid seizure cessation. It is also associated with fewer side effects than DZP. Although valproate is relatively slowly absorbed after rectal administration, this route has been used to treat SE and for maintenance therapy when oral therapy is not possible. Other AEDs that may be administered rectally include clonazepam, paraldehyde, and carbamazepine.
Long‐Term Course of West Syndrome Associated with Tuberous Sclerosis
Authors: Fukushima Katsuyuki , Inoue Yushi , Fujiwara Tateki , Yagi Kazuichi
Published: November 2007

Summary: We retrospectively analyzed the long‐term clinical profiles of 47 patients with West syndrome (WS) associated with tuberous sclerosis (TS) the follow‐up study for >10 years showed that WS developed into epilepsies of various types in all patients. Their final diagnoses were symptomatic generalized epilepsy (SGE: 29 patients, 62%), symptomatic partial epilepsy (PE: 14 patients, 30%), and undetermined epilepsy (UE: 4 patients, 8%). Eighty‐five percent of all patients continued to show the same types of epilepsy that they had at their first examination; but in 15% the diagnosis had to be revised at the end of the follow‐up period. The outcome of seizures was unfavorable for the SGE group. In the PE group, however, seizures were controlled in 9 (64%) of the 14 patients, and disturbances of daily activity were mild. In patients with WS associated with TS, the seizure outcome and social activity varied depending on the type of epilepsy or epileptic syndrome that developed from WS. The complicated clinical developments from WS with TS multiple cortical tubers related to epileptogenesis in addition to impairment of brain development.
Surgical Outcome in a Group of Low‐IQ Patients with Focal Epilepsy
Authors: Gleissner Ulrike , Johanson Karin , Helmstaedter Christoph , Elger Christian E.
Published: November 2007

Summary: Purpose: Because a low IQ score indicates global brain damage, several authors consider it a contraindication for resective epilepsy surgery. This study reports the postoperative results of a small group of subaverage‐intelligence patients with epilepsy who underwent focal resections.

Methods: We report on 16 patients who underwent focal resections (no callosotomy or hemispherectomy). All had IQ's <85 and were >13 years of age at the time of surgery. Low IQ was psychometrically assessed (mean IQ = 70) and confirmed by the patients' educational/occupational status. Clinical characteristics, findings from the preoperative workup, and the surgical treatment are described in detail. Postoperative outcome was evaluated with respect to seizure relief and cognitive/ socioeconomic development.

Results: Three months after surgery, 14 (87%) of 16 patients were completely seizure free, and nine (64%) of 14 were seizure free at the 1‐year follow‐up. Patients' cognitive abilities and socioeconomic status were mostly unchanged and in some cases improved. Seizure outcome was not related to IQ level. and there was no evidence of multiple epileptic foci in the patients with continued seizures.

Conclusions: A low IQ level does not entail the presence of extended epileptogenic regions or multiple epileptic foci. Seizure‐relief rates in our group concurred with the rates in patients of average intelligence, and the cognitive/socioeconomic outcome was favorable. We conclude that focal surgery in intellectually impaired patients can be recommended if the preoperative diagnostics confirm a circumscribed seizure onset.
Confirmation of Two Magnetoencephalographic Epileptic Foci by Invasive Monitoring from Subdural Electrodes in an Adolescent with Right Frontocentral Epilepsy
Authors: Otsubo Hiroshi , Sharma Roy , Elliott Irene , Holowka Stephanie , Rutka James T. , III O. Carter Snead
Published: November 2007

Summary: Purpose: To report our evaluation of interictal two epileptic spike fields on magnetoencephalography (MEG) by using invasive intracranial monitoring in a patient without lesion on magnetic resonance imaging (MRI).

Methods: A 15‐year‐old left‐handed boy with a 9‐year history of refractory simple partial seizures, secondarily generalized, and a normal MRI, was studied with MEG to define magnetic spike sources, followed by invasive intracranial monitoring with subdural electrodes to delineate the epileptogenic zone and eloquent function pursuant to focal cortical excision.

Results: MEG demonstrated two spike foci on the right middle frontal and inferior rolandic areas adjacent to the st sory area. Ictal recordings during prolonged invasive monit ing from subdural electrodes revealed two epileptogenic zoi in the same locations as those defined by MEG. Focal corti excision was performed of each epileptogenic zone. The patii has been seizure free for 24 months without neurologic deficit

Conclusions: Magnetic source imaging is a valuable adjui in the planning of subdural grid placement in epilepsy surge particularly in patients in whom conventional imaging fails reveal a lesion.
Prevalence and Pattern of Epilepsy in India
Authors: Sridharan R. , Murthy B. N.
Published: November 2007

Summary: Purpose: To estimate the prevalence of epilepsy in India by meta‐analysis of previously published and unpublished studies and to determine patterns of epilepsy by using community‐based studies.

Methods: We attempted to identify as many previously published and unpublished studies as possible on the prevalence of epilepsy in India. The studies were assessed with regard to methods and definitions. The prevalence rates for rural and urban populations and for men and women were calculated with a 95% confidence interval (CI). The studies that provided details on age structure, age‐specific rates, and patterns of epilepsy were chosen for meta‐analysis. Both crude values and age‐standardized prevalence rates were calculated after accounting for heterogeneity.

Results: Twenty studies were found involving a sample population of 598,910, among whom 3,207 had epilepsy. This resulted in a crude prevalence of 5.35/1,000. After a correction for heterogeneity due to interstudy variation, the overall prevalence per 1,000 (and its 95% CI) was 5.33 (4.25‐6.41); with urban areas at 5.11 (3.49‐6.73); rural areas, 5.47 (4.04–6.9); men, 5.88 (3.89‐7.87); and women 5.51 (3.49‐7.53). After correction for Ihe variability in estimates of heterogeneity, agestandardized rates (from five studies) revealed that the prevalence rates per 1,000 (and the 95% CI), were as follows: overall, 5.59 (4.15‐7.03); men, 6.05 (3.79‐8.31); women, 5.18 (3.04–7.32); urban, 6.34 (3.43‐9.25); rural, 4.94 (3.12‐6.76). Urban men and women had a higher prevalence of epilepsy compared with rural ones, however the difference was not statistically significant. Age‐specific prevalence rates were higher in the younger age group, with the onset of epilepsy reported mostly in the first three decades of the sample population's lives. The treatment gap (i.e., the percentage of those with epilepsy who were receiving no or inadequate treatment) was more than 70% in the rural areas.

Conclusions: Based on the total projected population of India in the year 2001, the estimated number of people with epilepsy would be 5.5 million. Based on a single study on the incidence of epilepsy, the number of new cases of epilepsy each year would be close to half a million. Because rural population constitutes 74% of the Indian population, the number of people with epilepsy in rural areas will be 4.1 million, three fourths of whom will not be getting any specific treatment as per the present standard.
Opercular Reflex Seizures: A Case Report with Stereo‐Electroencephalographic Demonstration
Authors: Biraben A. , Scarabin J. M. , de Toffol B. , Vignal J. P. , Chauvel P.
Published: November 2007

Summary: Reflex epileptic seizures of opercular origin have been described previously based on video‐electroencephalo‐graphic monitoring, but very few patients have been explored with depth electrodes. We report a woman with late‐onset epilepsy who had intractable seizures despite trials of several an‐tiepileptic drugs. At the time of the depth‐electrode recordings, seizures were usually continuous and occurred either spontaneously or were induced by movements of the jaw and mouth. The seizures originated in the deep central opercular cortex; localization was confirmed by a good surgical outcome.
Design of an Intensive Epilepsy Monitoring Unit
Authors: Scott Catherine A. , Fish David R. , Allen Phillip J.
Published: November 2007

SummaryVideo‐electroencephalography (EEG) telemetry is a crucial component in the comprehensive evaluation of patients with epilepsy. The reasons for patients needing to be monitored fall broadly into three groups: presurgical assessment (36% of our patients), diagnostic assessment (52%), and sleep disorders (12%). Video EEG can be used to differentiate unusual epilepsies from pseudo seizures or other causes of paroxysmal neurological events. The design of a unit depends on the case mix of patients expected to be referred. The key elements to a successful unit are a reliable, flexible, easy‐to‐use recording system and a team of dedicated, experienced staff, both nursing and technical. The unit at the National Hospital is a six‐bed ward with 7 nurses to provide 24‐hour coverage, 5 technicians working in shifts, and physics support. A minimum of two staff are on duty at all times. It operates on a five‐day week with a throughput of approximately 500 patients per year. It is vital that investigations are performed as efficiently and effectively as possible, and the patient's safety and wellbeing is paramount at all times. Drug reduction is likely to be used to precipitate seizures, especially in those being considered for epilepsy surgery, and this poses a risk of provoked secondary generalized seizures. Continuous supervision of patients, and the ability to respond rapidly to a seizure, are therefore essential. We adopt a standardized easy‐to‐follow drug‐reduction protocol, similar to that used by other centers.
What is nonconvulsive status epilepticus, and what are its subtypes?
Authors: Shorvon Simon
Published: October 2007

Summary

Prolonged nonconvulsive seizures have been recognized at least since the 19th century, although their inclusion within the rubric of status epilepticus was only formalized by Gastaut and colleagues after the Xth Marseilles Colloquium, held in 1962 (Gastaut et al., 1967). This was the first ever large meeting devoted to the topic of status epilepticus, and the concept that there were status forms for every seizure type was formulated there. The classification of status epilepticus derived from the 1962 colloquium thus mirrored exactly the newly evolved International Classification of Seizure Type (Gastaut, 1970). The main disadvantage of a classification based on seizure type is that it does not take into account the broader range of phenomenology of epilepsy, which is especially significant in regard to nonconvulsive seizures. A seizure type classification does not do justice to the variety of forms and to their widely varying pathophysiological basis, prognosis, or clinical setting.
Intensive care unit management of patients with status epilepticus
Authors: Bleck Thomas P.
Published: October 2007

Summary

The intensive care unit management of status epilepticus focuses on patients who are refractory to initial treatment, who have an underlying condition that require critical care management, or who experience respiratory or cardiovascular complications of their therapies. The available data suggest that failure of a first‐line anticonvulsant agent to terminate status should lead to the use of a definitive therapy in general anesthetic doses. Midazolam, propofol, and phenobarbital have been used most frequently; the place of newer agents (e.g., valproate, levetiracetam, or topiramate) remains to be determined.
Mechanisms of drug resistance in status epilepticus
Authors: Löscher Wolfgang
Published: October 2007

Summary

Refractory status epilepticus (RSE) is a major medical emergency, defined as severe form of SE that does not respond to first (benzodiazepines) and second (phenytoin, phenobarbital) treatment efforts with antiepileptic drugs (AEDs). Understanding the mechanisms of RSE is important to prevent or reverse its development. Based on both clinical experience and data from rat models of SE, seizures that last more than 30 min become very hard to control by AEDs. Experimental studies have shown that the prolonged seizures of SE lead to progressive alterations of GABAA receptors, including reduced surface expression of these receptors by receptor trafficking, which would explain the loss of efficacy of benzodiazepines. In addition to AED target alterations, SE‐induced overexpression of drug efflux transporters, such as P‐glycoprotein (Pgp), in the brain may be involved in the resistance to AEDs (including phenytoin and phenobarbital) that are Pgp substrates. However, recent experiments of our group did not indicate that Pgp plays any important role in drug resistance of SE. Improved understanding the molecular mechanisms underlying AED resistance in SE will ultimately provide new treatment options for RSE.
The epidemiology of convulsive and nonconvulsive status epilepticus
Authors: Rosenow Felix , Hamer Hajo M. , Knake Susanne
Published: October 2007

Summary

Epidemiologic studies of status epilepticus (SE) depend on clear definitions of terms. Such a definition is available for convulsive generalized SE, but clear definitions of nonconvulsive SE (NCSE) are lacking. This as well as clinical difficulties to diagnose NCSE are one source of underascertainment. The minimal incidence of SE in the Caucasian population of industrialized countries is about 20/100,000/year. It depends on age, ethnic background and possibly gender. Case fatality rates lie between 1.9 and 40% depending on age, etiology and duration of the SE. Effective treatment can improve and focal SE itself may impair case fatality. Clearly increased rates of long term case fatality in patients with symptomatic SE suggest that these patients should be considered a population at high risk.
Lower Risk of Hypoglycemia with Insulin Detemir than with Neutral Protamine Hagedorn Insulin in Older Persons with Type 2 Diabetes: A Pooled Analysis of Phase III Trials
Authors: Garber Alan J. , Clauson Per , Pedersen Claus B. , Kølendorf Klaus
Published: October 2007

OBJECTIVES: To compare the safety and efficacy of insulin detemir with that of neutral protamine Hagedorn (NPH) insulin in older (aged ≥65) and younger (aged 18–64) persons with type 2 diabetes mellitus (DM).

DESIGN: Pooled, post hoc analysis of data from three open‐label, randomized studies.

SETTING: Three multinational Phase III trials.

PARTICIPANTS: Four hundred sixteen older and 880 younger persons with DM, treated for 22 to 26 weeks with basal insulin plus mealtime insulin or oral agents.

MEASUREMENTS: Hemoglobin A1c (HbA1c), fasting plasma glucose, glucose variability, hypoglycemic episodes.

RESULTS: Mean treatment difference for HbA1c (insulin detemir–NPH insulin) indicated that insulin detemir was not inferior to NPH insulin for both age groups (0.035%, 95% confidence interval (CI)=−0.114–0.183 and 0.100%, 95% CI=−0.017–0.217, for older and younger persons, respectively). Relative risk of all hypoglycemic episodes (insulin detemir/NPH insulin) was 0.59 (95% CI‐0.42–0.83) for older persons and 0.75 (95% CI‐0.59–0.96) for younger persons. Adverse events were similar between treatments. Fasting plasma glucose was similar between treatments (mean treatment difference 0.97 mg/dL, 95% CI=−8.01–9.95, and 4.69 mg/dL, 95% CI=−2.30–11.67, for older and younger persons, respectively). Mean treatment difference for weight was −1.02 kg (95% CI −1.61 to −0.42) and −1.13 (95% CI −1.58 to −0.69) for older and younger persons, respectively.

CONCLUSION: Previously reported benefits of insulin detemir, particularly less hypoglycemia and less weight gain, compared with NPH insulin, were the same for older and younger persons with DM at similar levels of HbA1c.
Association Between Apolipoprotein E4 and Cognitive Decline in Elderly Adults
Authors: Packard Chris J. , Westendorp Rudi G.J. , Stott David J. , Caslake Muriel J. , Murray Heather M. , Shepherd James , Blauw Gerard J. , Murphy Michael B. , Bollen Edward L.E.M. , Buckley Brendan M. , Cobbe Stuart M. , Ford Ian , Gaw Allan , Hyland Michael , Jukema J. Wouter , Kamper Adriaan M. , Macfarlane Peter W. , Jolles Jellemer , Perry Ivan J. , Sweeney Brian J. , Twomey Cillian ,   for the Prospective Study of Pravastatin in the Elderly at Risk Group
Published: October 2007

OBJECTIVE: To determine the influence of apolipoprotein E on cognitive decline in a cohort of elderly men and women.

DESIGN: Prospective study.

SETTING: Scotland, Ireland, and the Netherlands.

PARTICIPANTS: Five thousand eight hundred four subjects aged 70 to 82 from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER).

MEASUREMENTS: Subjects were assessed at baseline and over a mean 3.2‐year (range 0.7–4.2) follow‐up for memory (Picture‐Word Recall), speed of information processing (Stroop and Letter‐Digit Coding), global cognitive function (Mini‐Mental State Examination), and activities of daily living.

RESULTS: At baseline, subjects with apolipoprotein E4 versus those without E4 had poorer memory performance (mean score difference −0.20 (95% confidence interval (CI)=−0.31 to −0.09) for immediate recall and −0.32 (95% CI=−0.48 to −0.16) for delayed recall and slower information processing (difference in Stroop, 2.79 seconds, (95% CI=1.20–4.28); Letter‐Digit score, −0.36, (95% CI=−0.77–0.05). Subjects with apolipoprotein E4 showed a greater decline in immediate (−0.22, 95% CI=−0.33 to −0.11) and delayed (−0.30, 95% CI=−0.46 to −0.15) memory scores but no significant change in speed of information processing (Stroop, P=.17; Letter‐Digit, P=.06). Memory scores decreased 2.5% from baseline in those without E4, 4.3% in E4 heterozygotes (P=.01 for immediate and P=.03 for delayed, vs no E4) and 8.9% to 13.8% in E4 homozygotes (P=.04 for immediate and P=.004 for delayed, vs heterozygotes). Apolipoprotein E4 was associated with greater decline in instrumental activities of daily living (P<.001). Cognitive decline was not associated with lipoprotein levels.

CONCLUSION: Findings in PROSPER indicate that E4 is associated with more‐rapid cognitive decline and may, therefore, predispose to dementia.
The Relationship Between Glycemic Control and Falls in Older Adults
Authors: Nelson Joan M. , Dufraux Kimberly , Cook Paul F.
Published: October 2007

OBJECTIVES: To determine whether glycemic control contributes to fall risk in frail and nonfrail elderly adults with diabetes mellitus.

DESIGN: Retrospective, case‐controlled design.

SETTING: Health maintenance organization in the Denver, Colorado, metropolitan area.

PARTICIPANTS: One hundred eleven community‐dwelling adults aged 75 and older who receive care through Kaiser Permanente of Colorado. All subjects had been diagnosed with diabetes mellitus, had at least one hemoglobin A1C (HbA1c) measurement in the previous 12 months, and were using oral hypoglycemic medication or insulin to control their diabetes mellitus.

MEASUREMENTS: Measurements of risk factors (Vulnerable Elders Survey (VES‐13) with a cutpoint of 3 to determine frailty status, self‐reported number of falls over the prior 12‐month period, HbA1c, fasting low‐density lipoprotein cholesterol, average blood pressure, and other factors related to fall risk) were obtained through telephone interview and medical chart review. The outcome measure was falls.

RESULTS: Bivariate analyses to assess correlations between falls and risk factors determined that only HbA1c, frailty, and peripheral neuropathy were significantly associated with falls. A stepwise logistic regression determined that fall risk markedly increased when HbA1c was 7 or below, regardless of frailty status.

CONCLUSION: In this retrospective study of a convenience sample of frail older adults with diabetes mellitus, tighter glycemic control was associated with greater risk of falling. Prospective studies that further evaluate the risks and benefits of relaxed glucose control in high‐risk older adults are needed to confirm this finding.
Using Assessing Care of Vulnerable Elders Quality Indicators to Measure Quality of Hospital Care for Vulnerable Elders
Authors: Arora Vineet M. , Johnson Martha , Olson Jared , Podrazik Paula M. , Levine Stacie , DuBeau Catherine E. , Sachs Greg A. , Meltzer David O.
Published: October 2007

OBJECTIVES: To assess the quality of care for hospitalized vulnerable elders using measures based on Assessing Care of Vulnerable Elders (ACOVE) quality indicators (QIs).

DESIGN: Prospective cohort study.

SETTING: Single academic medical center.

PARTICIPANTS: Subjects aged 65 and older hospitalized on the University of Chicago general medicine inpatient service who were defined as vulnerable using the Vulnerable Elder Survey‐13 (VES‐13), a validated tool based on age, self‐reported health, and functional status.

MEASUREMENTS: Inpatient interview and chart review using ACOVE‐based process‐of‐care measures referring to 16 QIs in general hospital care and geriatric‐prevalent conditions (e.g., pressure ulcers, dementia, and delirium); adherence rates calculated for type of care process (screening, diagnosis, and treatment) and type of provider (doctor, nurse).

RESULTS: Six hundred of 845 (71%) older patients participated. Of these, 349 (58%) were deemed vulnerable based on VES‐13 score. Three hundred twenty‐eight (94%) charts were available for review. QIs for general medical care were met at a significantly higher rate than for pressure ulcer care (81.5%, 95% confidence interval (CI)=79.3–83.7% vs 75.8%, 95% CI=70.5–81.1%, P=.04) and for delirium and dementia care (81.5%, 95% CI=79.3–83.7 vs 31.4% 95% CI=27.5–35.2%, P<.01). According to standard nursing assessment forms, nurses were responsible for high rates of adherence to certain screening indicators (pain, nutrition, functional status, pressure ulcer risk; P<.001 when compared with physicians), although in patients with functional limitations, nurse admission assessments of functional limitations often did not agree with reports of limitations by patients on admission.

CONCLUSION: Adherence to geriatric‐specific QIs is lower than adherence to general hospital care QIs. Hospital care QIs that focus on screening may overestimate performance by detecting standard nursing or protocol‐driven care.
Postacute Care for Older People in Community Hospitals: A Multicenter Randomized, Controlled Trial
Authors: Young John , Green John , Forster Anne , Small Neil , Lowson Karin , Bogle Sue , George James , Heseltine David , Jayasuriya Tilak , Rowe Jed
Published: November 2007

OBJECTIVES: To compare the effects of community hospital care on independence for older people needing rehabilitation with that of general hospital care.

DESIGN: Randomized, controlled trial.

SETTING: Seven community hospitals and five general hospitals in the midlands and north of England.

PARTICIPANTS: Four hundred ninety patients needing rehabilitation after hospital admission with an acute illness.

INTERVENTION: Multidisciplinary team care for older people in community hospitals.

MEASUREMENTS: The primary outcome was the Nottingham extended activities of daily living scale (NEADL); secondary outcomes were the Barthel Index, Nottingham Health Profile, Hospital Anxiety and Depression Scale, mortality, discharge destination, 6‐month residence status, and satisfaction with services.

RESULTS: Loss of independence at 6 months was significantly less likely in the community hospital group (mean adjusted NEADL change score group difference 3.27; 95% confidence interval 0.26–6.28; P=.03). The results for the secondary outcome measures were similar for the two groups.

CONCLUSION: Postacute community hospital rehabilitation care for older people is associated with greater independence.
Consistency of Labial Finish Line Preparation for Metal Ceramic Crowns: An Investigation of a New Bur
Authors: Seymour Kevin G. , Cherukara George P. , Samarawickrama Dayananda Y.D. , Zou Lifong
Published: October 2007

Purpose: Previous studies have reported on the difficulties inherent in preparing the labial aspect of teeth for metal ceramic crowns with consistency and also the implications for the definitive restoration of underprepared and overangled finish lines. In this study, a bur designed to prepare a 1.2‐mm deep chamfer was tested and compared with two other bur kits.

Materials and Methods: Seventy‐two teeth were prepared to receive metal ceramic crowns in vitro by students using one of the two bur kits or the new bur. Using a coordinate measuring machine (CMM), replicas of the prepared teeth were scanned in the mid‐labial plane, and shoulder width and cavosurface angles were measured.

Results: The new bur produced preparations with a mean shoulder width and cavosurface angle of 1.146 ± 0.241 mm and 108 ± 11°, respectively, compared with 0.626 ± 0.234 mm and 128 ± 14° produced by a commercially available standardized crown cutting bur system and 0.626 ± 0.218 mm and 124 ± 15° produced by the bur kit in use at our center at the time of the study. These differences were statistically significant at the 5% level, using Tukey's comparison of means.

Conclusions: Teeth prepared by the new bur had wider shoulders and lower cavosurface angles than teeth prepared either with a standardized crown cutting system or locally selected bur kit. The quality of labial preparations produced by the new bur in terms of closeness to the postulated “ideal” width and angulation warrants further investigation.
Guidelines for Maxillary Incisal Edge Position—A Pilot Study: The Key Is the Canine
Authors: Misch Carl E.
Published: October 2007

Purpose: The purpose of this pilot study was to evaluate the relationship between the vertical position of the maxillary central incisal edge and the maxillary canine relative to the maxillary lip line in repose of dentate patients. This may be beneficial for clinicians in establishing guidelines for the rehabilitation of edentulous patients.

Materials and Methods: One hundred and four Caucasian dentate patients (59 men and 45 women) between the ages of 30 and 59 years were evaluated. A millimeter ruler was used to measure the maxillary right central incisor edge and the maxillary right canine tip to the maxillary lip in repose. Data were collected in reference to sex and age.

Results: For the female group, average central incisor exposure in relation to the relaxed maxillary lip line was 3.8 mm, and the range of exposure was –1 to +8 mm. In the 30‐ to 39‐year olds (17 patients), the average was 4.1 mm with a range of 0 to 8 mm. The average in the 40‐ to 49‐year‐old group (16 patients) was 2.8 mm with a range of –1 to +6 mm. In 50‐ to 59‐year olds (12 patients), the average was 1.8 mm with a range of –1 to +5 mm. In the male group, the average central incisor exposure was 2.5 mm, and the range was –3 to +7 mm. The average for the 30‐ to 39‐year‐old group (20 patients) was 3.2 mm with a range of 0 to 7 mm. For the 40‐ to 49‐year group (18 patients), the average was 2.4 mm and for 50 to 61 years (21 patients), it was 1.4 mm with a range of –3 to +5 mm in both latter age groups. The canine position for the female group average exposure was 0 mm, with a range of –2 to +2 mm. For the 30‐ to 39‐year old group, average exposure was 1 mm with a range of –1 to +2 mm. The 40‐ to 49‐year‐old group exposed an average of 0.4 mm with a range of –1 to +2 mm. For the 50‐ to 59‐year old group, canine exposure was –0.5 mm with a range of –2 to +1 mm. The male average canine exposure was –0.5 mm, and the range was –3 to +2 mm. For the 30‐ to 39‐year old group, the average was 0.9 mm with a range of –1 to +2 mm. The 40‐ to 49‐year‐old group exposed an average of 0.2 mm, with a range of –1 to +2 mm. For the 50‐ to 59‐year old group, average was –0.9 mm with a range of –2 to +1 mm.

Conclusions: There was a large range of maxillary central incisal exposure in relation to the maxillary lip line. The average dimension of central incisor exposure represented less than 30% of the subjects in the study and could not be used predictably to assess incisal edge position. The range of canine exposure was narrower. The average dimensions of canine exposure to the lip were within 1 mm for both men and women in all age groups. Further studies are needed to confirm these preliminary results. The average dimensions for the different sex and age groups related to canine exposure represented a greater proportion of the subjects. Therefore, it is suggested that the average canine exposure dimension can be used clinically to assess anterior incisor edge position when restoring edentulous patients.
Influence of Microwave Polymerization Method and Thickness on Porosity of Acrylic Resin
Authors: Pero Ana Carolina , Barbosa Débora Barros , Marra Juliê , Ruvolo‐Filho Adhemar Colla , Compagnoni Marco Antonio
Published: October 2007

Purpose: This study evaluated the influence of polymerization cycle and thickness of maxillary complete denture bases on the porosity of acrylic resin.

Materials and Methods: Two heat‐activated denture base resins—one conventional (Clássico) and one designed for microwave polymerization (Onda‐Cryl)—were used. Four groups were established, according to polymerization cycles: A (Onda‐Cryl, short microwave cycle), B (Onda‐Cryl, long microwave cycle), C (Onda‐Cryl, manufacturing microwave cycle), and T (Clássico, water bath). Porosity was evaluated for different thicknesses (2.0, 3.5, and 5.0 mm; thicknesses I, II, and III, respectively) by measurement of the specimen volume before and after its immersion in water. The percent porosity data were submitted to Kruskal–Wallis for comparison among the groups.

Results: The Kruskal–Wallis test detected that the combinations of the different cycles and thicknesses showed significant differences, and the mean ranks of percent porosity showed differences only in the thinnest (2.0 mm) microwave‐polymerized specimens (A = 53.55, B = 40.80, and C = 90.70). Thickness did not affect the results for cycle T (I = 96.15, II = 70.20, and III = 82.70), because porosity values were similar in the three thicknesses.

Conclusions: Microwave polymerization cycles and the specimen thickness of acrylic resin influenced porosity. Porosity differences were not observed in the polymerized resin bases in the water bath cycle for any thickness.
Influence of Educational Background on Stated Retreatment Choices for Suboptimal Fixed Prosthodontic Conditions
Authors: Akeel Riyadh
Published: October 2007

Purpose: The aim of this study was to compare the stated retreatment choices for defined, suboptimal fixed prosthodontic scenarios among groups of dental professionals with differing levels of education.

Materials and Methods: The study population (n = 75) comprised interns (n = 27), various categories of graduate students (n = 32), and specialist staff (n = 16) from the same institution. Participants were required to record their choices of retreatment or no retreatment for 22 suboptimal fixed prosthodontic scenarios.

Results: Participants' choices varied within and between groups, with regard to specific scenarios. Intergroup differences that were statistically significant were for faulty occlusion (p= 0.013), open margin (p= 0.019), defective root filling (p= 0.001), periapical radiolucency (p= 0.011), and improper pontic design (p= 0.005), when no signs and symptoms, no caries, or no inflammation were present. The results confirm the widely‐acknowledged variability in decision making that exists among dental professionals in general.

Conclusion: The tendency for a significantly more interventive approach by those on a training pathway focused on imparting primarily clinical/technical skills than those enrolled in more conventional, academically‐based programs, suggests that an educational dimension cannot be overlooked in the characterization of dentists' stated retreatment decision choices.
Aortic Stenosis: Assessment of the Patient at Risk
Authors: YEO KHUNG KEONG , LOW REGINALD I.
Published: October 2007

The true incidence of aortic stenosis among the general population is unknown but aortic sclerosis, its precursor, has been estimated to affect about 25% of people over age 65, while an estimated 3% of the population over age 75 have severe aortic stenosis. Severe aortic stenosis, when accompanied by symptoms of angina, syncope, or heart failure, is associated with high mortality rates. Two‐dimensional and Doppler echocardiography are cornerstone tools for the evaluation and monitoring of aortic stenosis. Echocardiography helps identify the patient at risk of death and guide timing of aortic valve replacement. Other important diagnostic tools include cardiac catheterization, treadmill stress testing, and dobutamine stress echocardiography, although their use is limited to specific patient populations. Aortic valve replacement carries a significant operative risk of approximately 4.0%. However, risk of operative mortality varies according to comorbidities and disease presentation. There are many risk models that guide estimation of the risk of operative mortality. Understanding operative risk is important in patient care and the selection of patients for aortic valve replacement.
ADAM8 expression is associated with increased invasiveness and reduced patient survival in pancreatic cancer
Authors: Valkovskaya N. , Kayed H. , Felix K. , Hartmann D. , Giese N. A. , Osinsky S. P. , Friess H. , Kleeff J.
Published: October 2007

ADAM8 belongs to a family of transmembrane proteins implicated in cell–cell interactions, proteolysis of membrane proteins, and various aspects of carcinogenesis. In the present study, we aimed to evaluate the expression and function of ADAM8 in pancreatic cancer. ADAM8 mRNA levels were analysed by quantitative RT‐PCR and correlated to patient survival. Immunohistochemistry was performed to localize ADAM8 in pancreatic tis‐sues. Silencing of ADAM8 expression was carried out by transfection with specific siRNA oligonucleotides. Cell growth and invasion assays were used to assess the functional consequences of ADAM8 silencing. SELDI‐TOF‐MS was performed to detect the proteolytic activity of ADAM8 in pancreatic cancer cells. ADAM8 mRNA was significantly overexpressed in pancreatic ductal adenocarcinoma (PDAC) compared with normal pancreatic tissues (5.3‐fold increase; P= 0.0008), and high ADAM8 mRNA and protein expression levels correlated with reduced survival time of PDAC patients (P= 0.048 and P= 0.065, respectively). Silencing of ADAM8 expression did not significantly influence pancreatic cancer cell growth but suppressed invasiveness. In addition, decreased proteolytic activity was measured in cell culture supernatants following silencing of ADAM8. In conclusion, ADAM8 is overexpressed in PDAC, influences cancer cell invasiveness and correlates with reduced survival, suggesting that ADAM8 might be a potential target in pancreatic cancer therapy.
Increased VEGFR2 expression during human late endothelial progenitor cells expansion enhances in vitro angiogenesis with up‐regulation of integrin α6
Authors: Smadja David M. , Bièche Ivan , Helley Dominique , Laurendeau Ingrid , Simonin Ghislaine , Muller Laurent , Aiach Martine , Gaussem Pascale
Published: October 2007

In vitro expansion of late endothelial progenitor cells (EPCs) might yield a cell therapy product useful for myocardial and leg ischaemia, but the influence of EPC expansion on the angiogenic properties of these cells is unknown. In the present study, we investigated the effect of in vitro EPC expansion on vascular endothelial growth factor (VEGF) receptor expression. EPCs were obtained from CD34+ cord blood cells and expanded for up to 5 weeks. Real‐time quantitative reverse‐transcription polymerase chain reaction (RT‐PCR) showed that VEGFR2 expression, contrary to VEGFR1 and VEGFR3 expression, was significantly higher on expanded EPCs than on freshly isolated CD34+ cells or on human umbilical vein endothelial cells (HUVECs). Quantitative flow cytometry confirmed that VEGFR2 density on EPCs increased during the expansion process and was significantly higher than on HUVECs. The impact of VEGFR2 increase was studied on the three theoretical steps of angiogenesis, i.e., EPC proliferation, migration and differentiation. VEGFR2 up‐regulation had no effect on VEGF‐induced cell proliferation, but significantly enhanced EPC migration and pseudotubes formation dependent on integrin α6 subunit overexpression. In vitro expansion of late EPCs increases the expression of VEGFR2, the main VEGF receptor, with possible implications for EPC‐based angiogenic therapy.
Issues affecting molecular staging in the management of patients with melanoma
Authors: Palmieri G. , Casula M. , Sini M.C. , Ascierto P.A. , Cossu A.
Published: October 2007

Introduction

Role of the RT‐PCR in prognostic prediction

Molecular complexity of melanomagenesis

Conclusions

Prediction of metastatic potential remains one of the main goals to be pursued in order to better assess the risk subgroups of patients with melanoma. Detection of occult melanoma cells in peripheral blood (circulating metastatic cells [CMC]) or in sentinel lymph nodes (sentinel node metastatic cells [SNMC]), could significantly contribute to better predict survival in melanoma patients. An overview of the numerous published studies indicate the existence of several drawbacks about either the reliability of the approaches for identification of occult melanoma cells or the clinical value of CMC and SNMC as prognostic factors among melanoma patients. In this sense, characterization of the molecular mechanisms involved in development and progression of melanoma (referred to as melanomagenesis) could contribute to better classify the different subsets of melanoma patients. Increasing evidence suggest that melanoma develops as a result of accumulated abnormalities in genetic pathways within the melanocytic lineage. The different molecular mechanisms may have separate roles or cooperate during all evolutionary phases of melanocytic tumourigenesis, generating different subsets of melanoma patients with distinct aggressiveness, clinical behaviour, and response to therapy. All these features associated with either the dissemination of occult metastatic cells or the melanomagenesis might be useful to adequately manage the melanoma patients with different prognosis as well as to better address the different melanoma subsets toward more appropriate therapeutic approaches.
Biomarkers of hepatic fibrosis, fibrogenesis and genetic pre‐disposition pending between fiction and reality
Authors: Gressner O.A. , Weiskirchen R. , Gressner A.M.
Published: October 2007

Introduction

Pathways, cells and molecular mediators in liver fibrogenesis

Classification of biomarkers of fibrosis

Class I biomarkers of fibrosis

Class II fibrosis biomarkers

Genetic pre‐disposition biomarkers

Future developments

Fibrosis is a frequent, life‐threatening complication of most chronic liver diseases. Despite major achievements in the understanding of its pathogenesis, the translation of this knowledge into clinical practice is still limited. In particular, non‐invasive and reliable (serum‐) biomarkers indicating the activity of fibrogenesis are scarce. Class I biomarkers are defined as serum components having a direct relation to the mechanism of fibrogenesis, either as secreted matrix‐related components of activated hepatic stellate cells and fibroblasts or as mediators of extracellular matrix (ECM) synthesis or turnover. They reflect primarily the activity of the fibrogenic process. Many of them, however, proved to be disappointing with regard to sensitivity and speci‐ficity. Up to now hyaluronan turned out to be the relative best type I serum marker. Class II biomarkers comprise in general rather simple standard laboratory tests, which are grouped into panels. They fulfil most criteria for detection and staging of fibrosis and to a lesser extent grading of fibrogenic activity. More than 20 scores are currently available, among which Fibrotest™ is the most popular one. However, the diagnostic use of many of these scores is still limited and standardization of the assays is only partially realized. Combining of panel markers in sequential algorithms might increase their diagnostic validity. The translation of genetic pre‐disposition biomarkers into clinical practice has not yet started, but some polymorphisms indicate a link to progression and outcome of fibrogenesis. Parallel to serum markers non‐invasive physical techniques, for example, transient elastography, are developed, which can be combined with serum tests and profiling of serum proteins and glycans.
Expression and sub‐cellular localization of human ABH family molecules
Authors: Tsujikawa Kazutake , Koike Kazuhisa , Kitae Kaori , Shinkawa Aina , Arima Hiroshi , Suzuki Takashi , Tsuchiya Mutsumi , Makino Yasutaka , Furukawa Tatsuhiko , Konishi Noboru , Yamamoto Hiroshi
Published: October 2007

AlkB is an Escherichia coli protein that catalyses the oxidative demethylation of 1‐methyladenine and 3‐methylcytosine in DNA and RNA. The enzyme activity of AlkB is dependent on a 2‐oxoglutarate‐ and Fe(II)‐dependent (2OG‐Fe[II]) oxygenase domain. Human AlkB homologues (hABH), hABH1, hABH2 and hABH3, which also possess the 2OG‐Fe(II) oxygenase domain, have previously been identified. Recent bioinformatics analysis suggests the existence of an additional five ABH genes in humans. In this study, we identified the hABH4–hABH7 mRNAs and determined their expression in human tissues. Moreover, an hABH2 splice variant lacking the 2OG‐Fe(II) oxygenase domain and a new gene, hABH8, were cloned from testis cDNA. hABH8 possesses not only the 2OG‐Fe(II) oxygenase domain but both an RNA‐binding motif and a methyl‐transferase domain. mRNA of the eight hABH molecules was detected in the 16 normal human tissues examined. The sub‐cellular localization of EmGFP‐hABH8 was restricted to the cytoplasm. EmGFP‐hABH1, 3, 4, 6 and 7 were localized in both the cytoplasm and nuclei. Interestingly, the EmGFP‐hABH2 splice variant localized in nucleoplasm with a dot‐like pattern. In some HeLa cells transfected with EmGFP‐hABH5, dot‐like fluorescence was also detected in the cytoplasm. These observations provide important information for the future annotation of the hABH family of molecules.
Plasma protein carbonyl levels and breast cancer risk
Authors: Rossner Pavel , Terry Mary Beth , Gammon Marilie D. , Agrawal Meenakshi , Zhang Fang Fang , Ferris Jennifer S. , Teitelbaum Susan L. , Eng Sybil M. , Gaudet Mia M. , Neugut Alfred I. , Santella Regina M.
Published: October 2007

To study the role of oxidative stress in breast cancer risk, we analysed plasma levels of protein carbonyls in 1050 cases and 1107 controls. We found a statistically significant trend in breast cancer risk in relation to increasing quartiles of plasma protein carbonyl levels (OR = 1.2, 95% CI = 0.9–1.5; OR = 1.5, 95% CI = 1.2–2.0; OR = 1.6, 95% CI = 1.2–2.1, for the 2nd, 3rd and 4th quartile relative to the lowest quartile, respectively, P for trend = 0.0001). The increase in risk was similar for younger (<50 years) and older women, more pronounced among women with higher physical activity levels (0.7 hrs/week for 4th quartile versus lowest quartile OR = 2.0, 95% CI = 1.4–3.0), higher alcohol consumption (≥15 grams/day for 4th quartile versus lowest quartile OR = 2.3, 95% CI = 1.1–4.7), and hormone replacement therapy use (HRT, OR = 2.6, 95% CI = 1.6–4.4 for 4th quartile versus lowest quartile). The multiplicative interaction terms were statistically significant only for physical activity and HRT. The positive association between plasma protein carbonyl levels and breast cancer risk was also observed when the analysis was restricted to women who had not received chemotherapy or radiation therapy prior to blood collection. Among controls, oxidized protein levels significantly increased with cigarette smoking and higher fruit and vegetable consumption, and decreased with alcohol consumption >30 grams per day. Women with higher levels of plasma protein carbonyl and urinary 15F2t‐isoprostane had an 80% increase in breast cancer risk (OR = 1.8, 95% CI = 1.2–2.6) compared to women with levels below the median for both markers of oxidative stress. In summary, our results suggest that increased plasma protein carbonyl levels may be associated with breast cancer risk.
Stem cell differentiation and expansion for clinical applications of tissue engineering
Authors: Guillot Pascale V. , Cui Wei , Fisk Nicholas M. , Polak Dame Julia
Published: October 2007

Introduction

The essentials of tissue engineering

Conclusions

This invited review discusses the latest advances stem cell biology, tissue engineering and the transition from bench to bedside. An overview is presented as to which the best cell source might be for cell therapy and tissue engineering applications, best biomaterials currently available and the challenges the field faces to translate basic research into therapies for a large number of human diseases.