bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a 12-Lead Digital Holter System for 24-Hour QT Interval Assessment
Authors: Molnar Janos , Ranade Vassant , Cvetanovic Ivana , Molnar Zita , Somberg John C.
Published: May 2006

Background: Drug induced QT prolongation may precipitate life threatening cardiac arrhythmias. Evaluation of the QT prolonging effect of new pharmaceutical agents in a ‘thorough QT/QTc study’ is being mandated by FDA. The purpose of this study was to evaluate an automated 12-lead digital Holter system for a thorough QT/QTc study. Methods: Five healthy volunteers underwent 24-hour digital Holter monitoring. Each recording underwent a fully automated QT analysis (AQA) followed by an onscreen complete manual over read (MOR). Each recording was analyzed twice at least 2 weeks apart. The effect of data sampling (5-min segment/hour), the system sensitivity to detect 5-ms increase in QT, and the ability to assess circadian variation were evaluated. Results: The AQA resulted in identical QT for the first and second analyses, but with obvious errors in QT measurements. Compared to the complete onscreen MOR, the mean QT was longer with AQA (416 ± 41 vs. 387 ± 30 ms, p < 0.001), correlation; r = 0.3. The reproducibility of AQA with complete MOR was very good (QT: 387 ± 30 vs. 387 ± 30 ms, coefficient of variation: 0.2%, r = 0.986. The 5-min mean QT intervals correlated well with the hourly mean QT intervals (r = 0.994, p < 0.001, coefficient of variation = 1 ms) and both showed a similar circadian variation. The system was sensitive to detect a 5-ms change in QT intervals (5 ± 2 ms, coefficient of variation = 0.6%, r = 0.998, p < 0.001). Conclusions: The AQA is not an acceptable method, while the automatic analysis with complete MOR is a highly sensitive and reproducible method. Data sampling by analyzing 5-min segments per hour is sensitive and reproducible.
Perception of Emotional Facial Expressions at Different Intensities in Early-Symptomatic Huntington’s Disease
Authors: Montagne Barbara , Kessels Roy P.C. , Kammers Marjolein P.M. , Kingma Elselijn , de Haan Edward H.F. , Roos Raymund A.C. , Middelkoop Huub A.M.
Published: May 2006

Background: While there is abundant evidence that patients with Huntington’s disease (HD) have an impairment in the recognition of the emotional facial expression of disgust, previous studies have only examined emotion perception using full-blown facial expressions. Objective: The current study examines the perception of facial emotional expressions in HD at different levels of intensity to investigate whether more subtle deficits can be detected, possible also in other emotions. Method: We compared early symptomatic HD patients with healthy matched controls on emotion perception, presenting short video clips of a neutral face changing into one of the six basic emotions (happiness, anger, fear, surprise, disgust and sadness) with increasing intensity. Overall face perception ability as well as depressive symptoms were taken into account. Results: A specific impairment in recognizing the emotions disgust and anger was found, which was present even at low emotion intensities. Conclusion: These results extend previous findings and support the use of more sensitive emotion perception paradigms, which enable the detection of subtle neurobehavioral deficits even in the pre- and early symptomatic stages of the disease.
The Pathogenesis of Autosomal Dominant Polycystic Kidney Disease
Authors: Sutters Michael
Published: May 2006

In individuals with autosomal dominant polycystic kidney disease (ADPKD), renal function deteriorates as the kidneys become replaced by multitudes of fluid-filled cysts. Although the PKD genes were identified a decade ago, the pathway(s) leading from mutation to disease remain the subject of intense investigation. As a result of this work, it has become apparent that the polycystins are multifunctional proteins that, in the broadest sense, appear to be involved in the transduction of a number of environmental cues into appropriate cellular responses. It is likely that the central pathogenetic pathway for cystogenesis stems from de-differentiation of tubular epithelial cells. Available evidence indicates that loss of polycystin activity leads to subtle derangements of cell calcium regulation through several possible pathways. Abnormal cell calcium homeostasis might then lead to altered differentiation in affected cells. The study of the polycystins has revealed some entirely novel insights into fundamental cell biology but these have not yet been satisfactorily integrated into a verified pathogenetic pathway for the development of ADPKD.
Blood Lipids in Brain Infarction Subtypes
Authors: Amarenco Pierre , Labreuche Julien , Elbaz Alexis , Touboul Pierre-Jean , Driss Fathi , Jaillard Assia , Bruckert Éric
Published: May 2006

Background: Little is known about the relationship between hypercholesterolaemia and specific aetiological subtypes of brain infarction (BI). Methods: In a cross-sectional study of 492 pairs of patients with a BI proven by MRI and matched hospital controls, we determined the blood levels of triglycerides, total, HDL and LDL cholesterol, and apolipoprotein A1 and B, in the same centralized laboratory. We performed aetiological BI subtype classification. Results: Except for triglycerides, the risk of BI increased continuously with the lipid levels, without any heterogeneity between the main BI subtypes or the group on lipid-lowering therapy. The adjusted odds ratio per standard deviation in LDL cholesterol (0.93 mmol/l) was 1.74 (95% confidence interval, 1.02–2.98) in atherothrombotic strokes (n = 109) and 2.71 (95% confidence interval, 1.60–4.55) in lacunar strokes (n = 105). Eighty percent of patients were above the ATP-III guideline threshold LDL cholesterol of 2.59 mmol/l (100 mg/dl), with a major contribution of both atherothrombotic and lacunar stroke subtypes to this group. Conclusions: These findings suggest that blood lipids, particularly total and LDL cholesterol levels, are associated with all subtypes of BI, and that LDL above 2.59 mmol/l is highly prevalent.
Modulation of Atopy Patch Test and Skin Prick Test by Pretreatment with 1% Pimecrolimus Cream
Authors: Weissenbacher Stephanie , Traidl-Hoffmann Claudia , Eyerich Kilian , Katzer Kerstin , Braeutigam Matthias , Loeffler Helena , Hofmann Heidelore , Behrendt Heidrun , Ring Johannes , Darsow Ulf
Published: May 2006

Background: In a subgroup of patients with atopic eczema (AE), aeroallergens are relevant eliciting factors. The atopy patch test (APT) was proposed as inflammation model for AE. Objective: It was the aim of this study to investigate the effect of pretreatment with 1% pimecrolimus cream (Elidel®) on the APT and skin prick test (SPT). Methods: In a randomized, controlled, double-blind study, 20 patients with AE and positive SPT and APT screening reaction to house dust mite Dermatophagoides pteronyssinus, cat dander, grass or birch pollen were enrolled (age 20 ± 11 years, 55% males). For 2 weeks, patients twice daily applied pimecrolimus and vehicle control to marked fields on their backs and forearms. Then, APT was performed (200 index of reactivity/g extracts in petrolatum; Stallergènes, France) on both fields on the back and SPT was performed on the pretreated forearms. Results: Including only patients with different readings (n = 13), stronger APT suppression of at least 1 ETFAD (European Task Force on Atopic Dermatitis) grade in the pimecrolimus area versus intraindividual control was observed in 10 of these patients after 48 and 72 h (p < 0.05; 90% CI 50.5–93.4). Including all 20 subjects, the analysis still showed a borderline significance compared with the vehicle (p = 0.0564). SPT with histamine and aeroallergens showed a median 7.5–10% reduction in actively pretreated areas (p = 0.086). Immunohistochemical analysis in 2 patients revealed an induction of interferon-γ in primecrolimus-pretreated skin. Conclusion: APT can be used as a model for AE skin inflammation. It was shown for the first time that pimecrolimus pretreatment has a potential to suppress the development of lesions induced by aeroallergen exposure in patients with AE.
Long-Term Immunologic Effects of Broad-Spectrum Aeroallergen Immunotherapy
Authors: Limb Susan L. , Brown Kathryn C. , Wood Robert A. , Eggleston Peyton A. , Hamilton Robert G. , Adkinson Jr. N. Franklin
Published: May 2006

Background: Limited data exist regarding extended, long-term immunologic effects of immunotherapy in polysensitized individuals. To study possible long-term effects, skin tests and specific IgE levels were obtained from subjects who had previously received broad-spectrum aeroallergen immunotherapy years before. Methods: Eighty-two subjects (78% male, mean age 23 years) previously enrolled in a randomized, placebo-controlled trial of immunotherapy for treatment of childhood allergic asthma were reevaluated in adulthood (mean follow-up interval, 10.8 years) by puncture skin tests and CAP-RAST levels for major aeroallergens. All completed at least 18 months (median 27 months) of maintenance active treatment or placebo injections without subsequent immunotherapy. Results: At adult follow-up, 36% of all skin tests to treatment allergens among subjects who received immunotherapy (n = 41) had significantly reduced intensity versus 26% of skin tests among placebo recipients (n = 41; p = 0.03). No significant differences were noted for individual treatment allergens. No significant differences were observed in the long-term changes of serum-specific IgE antibody levels for all treatment allergens between immunotherapy treatment and placebo groups (p = 0.43). The treatment and placebo groups had a similar acquisition of new skin test sensitivities from time of randomization in the original childhood trial to debriefing (15 vs. 20%; p = 0.28) and to adult follow-up (30 vs. 31%; p = 0.75). Conclusions: Immunotherapy suppresses skin test sensitivity 8–16 years after discontinuation of treatment, but long-term effects on specific IgE levels in serum are not observed. Broad-spectrum immunotherapy does not appear to affect the acquisition of new inhalant sensitivities.
Effect of Isolation Measures on the Incidence and Prevalence of Hepatitis C Virus Infection in Hemodialysis
Authors: Gallego Eduardo , López Aurora , Pérez Juan , Llamas Francisco , Lorenzo Inmaculada , López Esperanza , Illescas Maria Luisa , Andrés Elena , Olivas Emilio , Gómez-Roldan Carmen
Published: May 2006

Background: Nosocomial transmission of hepatitis C virus (HCV) in hemodialysis (HD) units is well established. In units with a high prevalence of HCV infection, the implementation of universal precautionary measures may not suffice in order to decrease the incidence and prevalence of HCV. In this setting strict isolation practices can be useful in order to achieve this goal. Methods: The incidence and prevalence of HCV infection amongst all HD and peritoneal dialysis (PD) patients from the province of Albacete, Spain, have been studied from 1992 to 2003.Through the 1993–1995 period chronic HD patients were treated either in a room exclusively for HCV– patients or in a room shared by HCV+ and HCV– patients. Complete separation of HCV+ and HCV– patients was implemented in 1995. Acute patients have been separated since 1992. The implementation of universal precautions was applied throughout the period. Results: There has not been a single seroconversion in the rooms where only HCV– patients were dialyzed during the 11 years of follow-up. There were two seroconversions in the rooms shared for 3 years by both HCV+ and HCV– patients. In 1995 the prevalence of HCV+ cases in HD and PD was 21.6 and 23.2%, respectively. Since then it has decreased steadily and in parallel for both therapies, and the current prevalence is 6.8% in HD and 5.7% in PD. Conclusions: In HD units with a high prevalence of HCV+ patients, strict isolation in combination with implementation of universal prevention measures can eliminate nosocomial transmission and obtain a long-term reduction in prevalence.
Trojan Horse Meets Magic Bullet to Spawn a Novel, Highly Effective Drug Delivery Model
Authors: Lacko Andras G. , Nair Maya , Paranjape Sulabha , Mooberry Linda , McConathy Walter J.
Published: May 2006

Because of their physicochemical properties and the selective receptor-mediated uptake of their core components, reconstituted high-density lipoproteins have unique advantages over conventional formulations to serve as targeted drug delivery agents.
Estradiol, but Not Dehydroepiandrosterone, Decreases Parasitemia and Increases the Incidence of Cerebral Malaria and the Mortality in Plasmodium berghei ANKA-Infected CBA Mice
Authors: Libonati Rosana M.F. , Cunha Maristela G. , Souza José M. , Santos Marcos V.N. , Oliveira Salma G. , Daniel-Ribeiro Claudio T. , Carvalho Leonardo J.M. , do Nascimento José L.M.
Published: May 2006

Objective: The effect of castration and subsequent replacement of dehydroepiandrosterone (DHEA) or estradiol on parasitemia, mortality and incidence of cerebral malaria (CM) was evaluated in CBA mice infected with Plasmodium berghei ANKA. Methods: Female mice were castrated, and groups of 12–15 animals received daily injections of DHEA, estradiol or saline. Four days after the start of treatment, mice were inoculated with 1 × 106P. berghei ANKA-parasitized erythrocytes. DHEA treatment was continued during the 5 days after infection, and estradiol was administered during the follow-up. Parasitemia was evaluated daily in Giemsa-stained blood smears. Signs of CM were determined by the manifestation of coma, limb paralysis and/or convulsions. Plasma TNF-α levels were evaluated by sandwich ELISA. Nitric oxide synthase (NOS) activity in the brain of moribund mice was measured by the method of Bredt and Snyder. Results: In non-castrated infected mice, the incidence of CM was 50%, and plasma TNF-α increased and brain NOS activity decreased compared to non-infected controls. Castration had no major effect on the parameters analyzed (parasitemia, mortality, CM incidence, TNF-α levels or NOS activity). Estradiol replacement caused a decrease in parasitemia but resulted in higher CM incidence and faster mortality, with an increase in NOS activity. Conclusions: Estradiol modulated the immune response of P. berghei ANKA-infected CBA mice, decreasing parasitemia and increasing NOS activity, and impacted negatively on survival and CM incidence, showing that neuroimmunoendocrine interactions are important in the physiopathogenesis of malaria infections.
Chronic Inhibition of Nitric Oxide Production Aggravates Diabetic Nephropathy in Otsuka Long-Evans Tokushima Fatty Rats
Authors: Kamijo Hiroshi , Higuchi Makoto , Hora Kazuhiko
Published: May 2006

Background: Nitric oxide (NO) is known to play a role in diabetic nephropathy, but the molecular basis for this effect remains unclear. Method: Otsuka Long-Evans Tokushima Fatty spontaneous diabetic rat models were used along with Long-Evans Tokushima Otuska rat models as age-matched controls. Either L-arginine (a NO precursor) or L-NAME (a nitric oxide synthase inhibitor) was administered from the age of 22 weeks. Clinical parameters and serum and urinary NO2+NO3 levels were measured, in addition to renal histological findings and ED-1-positive cell counts in glomeruli. Results: There were no significant differences in creatinine clearance between any of the groups at any point. The levels of urinary NO2+NO3 in the diabetic group were significantly lower than those in the control groups after 40 weeks; that in the L-NAME diabetic group was significantly lower than in the other diabetic groups at 52 weeks. Compared with the other diabetic groups, the L-NAME diabetic group had significantly higher urinary protein excretion levels, histological scores, and numbers of ED-1-positive cells in glomeruli. Diabetic rats administered L-arginine excreted more urinary protein than the diabetic controls. Conclusion: Diabetic nephropathy was exacerbated drastically by a nitric oxide synthase inhibitor and mildly by a NO precursor. These data suggested that NO may modify type 2 diabetic nephropathy in Otuska Long-Evans Tokushima Fatty rats through factors other than hemodynamics.
Thiopurine S-Methyltransferase Pharmacogenetics: Genotype to Phenotype Correlation in the Slovenian Population
Authors: Milek M. , Murn J. , Jaksic Z. , Lukac Bajalo J. , Jazbec J. , Mlinaric Rascan I.
Published: May 2006

The toxicity of thiopurine drugs has been correlated to the activity of thiopurine S-methyltransferase (TPMT), whose interindividual variation is a consequence of genetic polymorphisms. We have herein investigated the relevance of some genetic markers for the prediction of thiopurine-related toxicities and to determine the genotype to phenotype correlation in the Slovenian population. The most prevalent mutant allele in the Slovenian population is TPMT*3A (4.1%), followed by TPMT*3C (0.5) and TPMT*3B (0.3), while the TPMT*2 allele was not found in any of the examined samples. TPMT enzyme activity distribution in the subgroup sample was bimodal and as such correlated with genetic data. Using a cutoff value of 9.82 pmol/107 RBC per h, the genetic data correctly predicted TPMT enzyme activity in 91.6% of the examined individuals. Pharmacogenetic TPMT analyses have therefore proved to have significant clinical implications for prediction of individuals’ responses to treatment with thiopurine drugs in order to avoid possible life-threatening therapy-related toxicities.
Retropatellar Chondromalacia Associated with Medial Osteoarthritis after Meniscus Injury
Authors: Burger C. , Kabir K. , Mueller M. , Rangger C. , Minor T. , Tolba R.H.
Published: May 2006

Background/Aims: In an ovine meniscal repair model, the patellofemoral (PF) osteoarthritis due to a non-sutured tear or failed repair was investigated. Methods: A radial meniscus tear was either sutured with polydioxanone (PDS), with a slow degrading polylactide long-term suture(LTS) or left without treatment. Knee joint cartilage in the PF and medial compartment was evaluated compared to normal knees (healthy controls). Results: Retropatellar osteoarthritis in the non-sutured and sutured animals was intense in contrast to the control knees after 6 months in all groups (p < 0.001), and after 12 months in the PDS group (p < 0.001), LTS group and non-sutured animals (p < 0.05). Conclusion: Non-sutured meniscus tears and failed repair lead fast to intense PF osteoarthritis corresponding with tibial damage of the injured compartment.
Allergen-Specific Polyclonal Antibodies Reduce Allergic Disease in a Mouse Model of Allergic Asthma
Authors: Moerch Ulrik , Haahr Hansen Margit , Vest Hansen Nils Jakob , Rasmussen Lone Kjær , Oleksiewicz Martin B. , Frandsen Torben P. , Haurum John S. , Bregenholt Søren
Published: May 2006

Background: Recombinant allergen-specific immunoglobulin G (IgG) antibody therapy can reduce allergic asthma symptoms by inhibiting the immunoglobulin E (IgE)-mediated allergic response. This study investigated the effect of intranasally administered allergen-specific monoclonal (mAb) and polyclonal (pAb) antibody on airway inflammation and hyperresponsiveness (AHR) in a mouse model of human asthma. Methods: Ovalbumin (OVA)-specific IgG2b antibodies were generated by phage display using spleens from OVA-immunized mice, and screening against OVA and finally expressed in CHO cells. Sensitized mice were treated intranasally with either a recombinant anti-OVA mAb (gc32) or a polyclonal preparation comprising seven selected antibodies (including gc32). Control mice received diluent only, OVA only, a control polymeric IgG or dexamethasone. Following challenge with nebulized OVA, investigators assessedairway inflammation by histology and cellular composition of the bronchoalveolar fluid, and methacholine-induced airway hyperresponsiveness (AHR). Serum levels of total and OVA-specific IgE were measured by ELISA. Results: Sensitized mice developed airway inflammation and AHR in response to OVA challenge. Intranasally administered OVA-specific murine polyclonal or monoclonal IgG2b antibodies both reduced OVA-induced lung inflammation. Polyclonal, but not anti-OVA mAb, also reduced AHR and eosinophil influx into the airway lumen. Both anti-OVA antibody preparations reduced levels of specific IgE with no effect on total IgE levels. Conclusions: Intranasal treatment with allergen-specific pAb reduces pulmonary inflammation and AHR in a mouse model of allergic asthma, but allergen-specific mAb reduces inflammation only. Allergen-specific recombinant pAb offers a potentially valuable therapeutic approach to the management of allergic asthma.
Delayed Energy Protection of Ischemic Preconditioning on Hepatic Ischemia/Reperfusion Injury in Rats
Authors: Ofluoglu E. , Kerem M. , Pasaoglu H. , Turkozkan N. , Seven I. , Bedirli A. , Utku Yilmaz T.
Published: May 2006

Background: Hepatic ischemia/reperfusion (IR) injuries associated with hepatic resections are unresolved problems in the clinical practice. The aim of this study is to elucidate the effect of ischemic preconditioning (IPC) on the energy charge (EC) and related mechanisms at the late phase of hepatic IR injury. Methods: 30 Wistar rats were randomly divided into sham, IR and IPC groups. The model of partial hepatic IR was used. The rats were subjected to 60 min hepatic ischemia, pretreated by IPC (10/15 min) or not. After 24 h of reperfusion, serum alanine aminotransferase (ALT), nitrite/nitrate (NOx), malondialdehyde (MDA), hepatic tissue arginase activity, adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP) and EC of the liver were measured. Results: Liver injury reduced by IPC is measured by liver tissue arginase activity and serum ALT. Tissue NOx levels in rats pretreated with IPC were significantly higher than levels in the IR group (p < 0.001). Tissue levels of MDA in the liver of the IPC group were found to be significantly lower than the levels in the IR group (p < 0.001). ATP and EC levels 24 h after hepatic ischemia in rats pretreated with IPC were higher than the levels in the IR (p < 0.05). All groups had similar ADP and AMP levels in the liver tissues. The IPC procedure significantly reduced the hepatic necrosis (p < 0.001). Conclusion: The results of this study demonstrated that pretreatment with IPC improved tissue ATP, EC, and hepatic necrosis at late stages of ischemia reperfusion injury of the liver. Increased nitric oxide, reduced MDA and arginase activity seemed to play a regulatory role in this delayed protective effect of IPC.
Increase in Linkage Information by Stratification of Pedigree Data into Gold-Standard and Standard Diagnoses: Application to the NIMH Alzheimer Disease Genetics Initiative Dataset
Authors: Gordon Derek , Haynes Chad , Finch Stephen J. , Brown Abraham M.
Published: May 2006

Patients diagnosed with a standard clinical method (subject to misclassification error) are often combined with patients diagnosed with a gold-standard method (with zero or very small misclassification error) in family-based studies of complex disease. For example, non-autopsied patients (NAP) are often included along with autopsy-proven (AP) patients in family-based studies of complex diseases, such as Alzheimer’s disease (AD). Theoretical and simulation studies suggest that certain misclassification errors can result in severe reduction of power in genetic linkage and association analyses and that phenotype (or diagnostic) error can produce misleading results. Morton’s test for heterogeneity can identify genomic regions where error may have led to loss in power. We applied this test to pedigree data from the NIMH Alzheimer’s Disease Genetics Initiative Database separated into AP and NAP pedigrees. Morton’s test identified one highly significant region of heterogeneity on chromosome 2. The source of the heterogeneity was due to significant indication of linkage in the AP pedigrees at position 109 cM (p value = 6.68 × 10–5) with no indication in the NAP pedigrees. Furthermore, Morton’s test showed no evidence for heterogeneity on chromosome 19 in early-onset pedigrees that showed highly significant evidence for linkage in other published reports. These results suggest that supplementing linkage analysis with Morton’s test can be usefully applied to genetic data sets that have AP and NAP samples, or other sample mixtures that include a ‘gold standard’ subgroup with reduced error rate, to increase power to detect linkage in the presence of diagnostic misclassification.
Effect of Insulin on the Brain Activity Obtained during Visual and Memory Tasks in Healthy Human Subjects
Authors: Benedict Luke , Nelson Charles A. , Schunk Emily , Sullwold Kristin , Seaquist Elizabeth R.
Published: May 2006

Insulin receptors are found throughout the brain, particularly in the hippocampus, although the impact of insulin on memory is unclear. The purpose of this study was to examine the effect of insulin on event-related potentials in response to a standard memory task and visual evoked potentials (VEPs) during exposure to a reversing checkerboard. We hypothesized that insulin would decrease P300 magnitude and latency during the presentation of previously observed stimuli, but would have no effect on VEPs. Sixteen humans participated in two euglycemic clamp studies with somatostatin performed in random order in which serum insulin levels were either suppressed (14 ± 1 pmol/l) or increased by insulin infusion (433 ± 40 pmol/l). At steady state, event-related potentials and then VEPs were collected using a 32-electrode cap. The major finding was that the P300 amplitude measured during the identification of an object as old was significantly smaller over parietal regions when insulin was infused than when no insulin was provided. Insulin was without effect on the VEPs. We conclude that insulin has region- and task-specific effects on neuronal activation. While the P300 amplitude measured during the presentation of an old object was reduced during insulin infusion, the hormone was without effect on VEPs.
Inheritance of Olfactory Preferences III. Processing of Pheromonal Signals in the Antennal Lobe of Heliothis subflexa × Heliothis virescens Hybrid Male Moths
Authors: Vickers Neil J.
Published: May 2006

Pheromone-responsive olfactory interneurons were studied to determine the extent to which their physiological and morphological properties complemented the behavior and peripheral olfactory neurobiology observed in hybrid male moths created by interbreeding two species of heliothine moth, Heliothis virescens and Heliothis subflexa. Complete recordings were made from a total of 33 neurons, and 16 projection neurons (PNs) were subsequently stained with a fluorescent dye. Stained PNs tuned to pheromonal odorants had dendritic arborizations restricted to one of four olfactory glomeruli that together constituted the macroglomerular complex (MGC). As in parental males, PNs tuned to (Z)-11-hexadecenal always had an arbor in the cumulus, the largest of the MGC glomeruli. Previous neurophysiological investigations revealed that PNs with dendritic arbors restricted to the dorso-medial glomerulus (DM) of the MGC responded specifically to either (Z)-9-tetradecenal (Z9–14:Ald; H. virescens males) or (Z)-9-hexadecenal (Z9–16:Ald; H. subflexa males). Hybrid males, which responded equally well in wind tunnel tests to blends containing either Z9–14:Ald or Z9–16:Ald, had DM PNs that responded to both odorants. PNs specific for a third compound, (Z)-11-hexadecenol, required by hybrid males for behavioral activity were localized to the antero-medial MGC glomerulus (AM). Thus, neuronal activity across the cumulus, DM and AM glomeruli represented an attractive blend in hybrid males. Neurons tuned to (Z)-11-hexadecenyl acetate and Z9–14:Ald were restricted to a fourth, ventro-medial glomerulus. The across-glomerular pattern of activity associated with attractive pheromone blends was most similar to that of H. subflexa males, signifying a dominant effect of H. subflexa genes. These results indicate that the behavioral phenotype of hybrid males can be linked to underlying central olfactory characteristics.
Clinical Course of Progressive Multiple Sclerosis in Brazilian Patients
Authors: Vasconcelos C.C.F. , Miranda-Santos C.M. , Alvarenga R.M.P.
Published: May 2006

Objective: To describe the clinical course and outcome of multiple sclerosis with progressive onset in Brazilian patients. A total of 238 medical records were reviewed, 26 cases (10.9%) fulfilled Thompson criteria (2000), and 5.80% classified as primary progressive and 5.04% relapsing progressive according to Lublin and Reingold. Study Population: 19 Caucasians and 7 non-Caucasians; male:female ratio 1.2:1, mean age at onset was 34 ± 7.9 years. Results: Non-Caucasian patients had earlier onset of disease. The most common manifestations at onset were pyramidal and cerebellar (89% and 34.6%). After 11.3 ± 6.35 years of disease more than 50% of the patients had involvement of most of their functional systems. No statistically significant differences were observed between the subgroups. Conclusion: The clinical course and outcome of progressive multiple sclerosis in Brazil, a tropical country with low prevalence, were very similar to those in the multiple sclerosis high prevalence areas.
Lipoma of the Deep Lobe of the Parotid Gland: Report of 3 Cases
Authors: Gooskens Ivette , Manni Johannes J.
Published: May 2006

Since lipomas are common soft-tissue neoplasms in other regions of the body, they are found only rarely in the parotid gland and are, therefore, often not considered in the initial differential diagnosis of parotid gland tumours. Even rarer are lipomas arising in the deep lobe of the parotid gland with only 6 cases presented in the literature. Lipomas originating in the parapharyngeal space are also extremely rare. When there is any suspicion, computed tomography and especially magnetic resonance imaging are of high diagnostic value. Fine-needle aspiration cytology seems not to contribute much to an accurate diagnosis. None of these preoperative examinations allows an absolute reliable distinction between a lipoma and a liposarcoma. The preferred treatment is complete surgical excision which will minimize the possibility of a recurrence and will also lead to a definitive diagnosis. We report 3 patients with a lipoma of the deep lobe of the parotid gland, extending into the parapharyngeal space, and discuss differential diagnosis and radiological features of lipomas in this rare location.
Non-Invasive Resting Magnetocardiographic Imaging for the Rapid Detection of Ischemia in Subjects Presenting with Chest Pain
Authors: Tolstrup Kirsten , Madsen Bo E. , Ruiz Jose A. , Greenwood Stephen D. , Camacho Judeen , Siegel Robert J. , Gertzen H. Caroline , Park Jai-Wun , Smars Peter A.
Published: May 2006

Background: Early diagnosis of ischemia is complicated by the poor sensitivity of standard tests and contraindication for stress testing in unstable angina patients. Magnetocardiography (MCG) imaging can be used for the rapid, non-invasive detection of ischemia at rest. Methods: We studied 125 patients with presumed ischemic chest pain. All were chest pain free at the time of scanning. A 6-minute resting MCG scan (CardioMag Imaging, Inc., New York, 9-channel system) was performed. Following the MCG scan, automated software data analysis was performed, and quantitative scores were automatically calculated for each subject. The presence of ischemia was determined after testing with serial troponins, stress testing, and/or coronary angiography. Results: The mean age was 59.4 ± 13.6 years. Most patients (86.4%) had non-ischemic 12-lead ECG and normal troponin (86.2%). Fifty-five patients (44.0%) were determined to be ischemic. The MCG sensitivity, specificity, positive and negative predictive value was 76.4, 74.3, 70.0 and 80.0%, respectively, for the detection of ischemia (p < 0.0001). Conclusions: MCG is a new rapid, non-invasive imaging tool able to detect repolarization abnormalities at rest consistent with ischemia in patients presenting with chest pain syndrome and normal or non-specific 12-lead ECG and normal troponin.
Obestatin, Acylated and Total Ghrelin Concentrations in the Perinatal Rat Pancreas
Authors: Chanoine Jean-Pierre , Wong Alfred C.K. , Barrios Vicente
Published: May 2006

Background: Ghrelin and obestatin are encoded by the preproghrelin gene and originate from posttranslational processing of the preproghrelin peptide. The fetal rat pancreas contains acylated and desacylated ghrelin peptides, as well as growth hormone secretagogue receptor -1a mRNA. Acylated ghrelin inhibits insulin secretion. We investigated the plasma and tissue ontogeny of ghrelin and obestatin in the rat. Methods: We measured obestatin and acylated and total ghrelin concentrations in plasma, pancreas and stomach from rat fetuses (F20) and neonates at postnatal day (PN) 1, 6, 12 and 21). Results: Overall, obestatin concentrations were markedly lower than total ghrelin concentrations. In plasma, total ghrelin concentrations decreased abruptly after birth (p < 0.05), contrasting with a 3 times increase in the concentration of acylated ghrelin between F20 and PN1 (p < 0.05). In pancreas, total ghrelin and obestatin concentrations decreased progressively from PN1 to PN21 but acylated ghrelin concentrations increased 6–7 times from F20 (18 [6] pg/ml) to PN6 (122 [59] pg/ml). The percent of acylated ghrelin increased from 1.8 (0.6) at F20 to 39.7 (13.0) % of total ghrelin immunoreactivity at PN12 (p < 0.05). There were significant positive correlations between postnatal obestatin, acylated or total ghrelin and insulin concentrations in the pancreas (all p < 0.02, r2 > 0.21) and between postnatal total ghrelin and obestatin (in pancreas, r2 = 0.37) or acylated ghrelin (in stomach, r2 = 0.27) (p < 0.001). Conclusion: Ghrelin and obestatin are present in the perinatal pancreas where they could potentially affect insulin secretion.
Normal Serum Alanine Concentration Differentiates Transient Neonatal Lactic Acidemia from an Inborn Error of Energy Metabolism
Authors: Morava Eva , Hogeveen Marije , De Vries Maaike , Ruitenbeek Wim , de Boode Willem-Pieter , Smeitink Jan
Published: May 2006

Background: Elevated blood lactate levels are common in the critically ill neonate; however, sometimes they are difficult to interpret. Persistent or recurrent lactic acidemia might point to an inborn error of metabolism, like disturbances of the oxidative phosphorylation. Chronic lactic acidemia results in increased serum alanine levels. Serum alanine levels in newborns with transient lactic acidemia have not yet been studied. Objective: We designed a pilot study to evaluate the use of serum alanine levels as an additional metabolic marker to differentiate the transient effect of circulatory failure from a possible mitochondrial dysfunction. Methods: We prospectively evaluated 10 newborns with transient lactic acidemia after mild dysoxia, and 10 newborns with recurrent lactic acidemia consecutively diagnosed with a disorder in oxidative phosphorylation. Results: No significant serum alanine level elevation was found in transient lactic acidemia. Increased serum alanine was a sensitive marker in mitochondrial dysfunction. Conclusions: We propose to measure the serum alanine level in hypotonic newborns with lactic acidemia to facilitate the decision making in further diagnostics and management.
Different Vascular Smooth Muscle Cell Apoptosis in the Human Internal Mammary Artery and the Saphenous Vein
Authors: Frischknecht Karin , Greutert Helen , Weisshaupt Christian , Kaspar Mathias , Yang Zhihong , Lüscher Thomas F. , Carrel Thierry P. , Tanner Felix C.
Published: May 2006

Background: The remarkable patency of internal mammary artery (MA) grafts compared to saphenous vein (SV) grafts has been related to different biological properties of the two blood vessels. We examined whether proliferation and apoptosis of vascular smooth muscle cells (VSMC) from human coronary artery bypass vessels differ according to patency rates. Methods and Results: Proliferation rates to serum or platelet-derived growth factor (PDGF)-BB were lower in VSMC from MA than SV. Surface expression of PDGF β-receptor was slightly lower, while that of α-receptor was slightly higher in MA than SV. Cell cycle distribution, expression of cyclin E, cdk2, p21, p27, p57, and cdk2 kinase activity were identical in PDGF-BB-stimulated cells from MA and SV. However, apoptosis rates were higher in MA than SV determined by lactate dehydrogenase release, DNA fragmentation, and Hoechst 33258 staining. Moreover, caspase inhibitors (Z-VAD-fmk, Boc-D-fmk) abrogated the different proliferation rates of VSMC from MA versus SV. Western blotting and GSK3-β kinase assay revealed lower Akt activity in VSMC from MA versus SV, while total Akt expression was identical. Adenoviral transduction of a constitutively active Akt mutant abrogated the different proliferation rates of VSMC from MA versus SV. Conclusions: Higher apoptosis rates due to lower Akt activity rather than different cell cycle regulation account for the lower proliferation of VSMC from MA as compared to SV. VSMC apoptosis may protect MA from bypass graft disease.
Insulin Resistance, Hyperinsulinemia, and Renal Injury: Mechanisms and Implications
Authors: Sarafidis Pantelis A. , Ruilope Luis M.
Published: May 2006

Most of the basic components of the metabolic syndrome, namely type 2 diabetes mellitus, hypertension, obesity, or low high-density lipoprotein cholesterol levels, apart from being major risk factors for cardiovascular disease have been also associated with an increased risk of chronic kidney disease. However, several epidemiologic studies conducted over the past years suggest that the central component of the syndrome, insulin resistance, as well as compensatory hyperinsulinemia are independently associated with an increased prevalence of chronic kidney disease. In addition, background studies support the existence of several pathways linking insulin resistance and hyperinsulinemia with kidney damage. Insulin per se promotes the proliferation of renal cells and stimulates the production of other important growth factors such as insulin-like growth factor-1 and transforming growth factor beta. Insulin also upregulates the expression of angiotensin II type 1 receptor in mesangial cells, thus enhancing the deleterious effects of angiotensin II in the kidney, and stimulates production and renal action of endothelin-1. Moreover, insulin resistance and hyperinsulinemia are associated with decreased endothelial production of nitric oxide and increased oxidative stress which have been also implicated in the progression of diabetic nephropathy. This review analyzes the above and other potential mechanisms, through which insulin resistance and hyperinsulinemia can contribute to renal injury.
Prevalence and Causes of Seizures at the Time of Diagnosis of Probable Alzheimer’s Disease
Authors: Lozsadi D.A. , Larner A.J.
Published: May 2006

Background/Aims: To investigate the frequency of epilepsy at the time of diagnosis of Alzheimer’s disease (AD). Methods: Observational study, Cognitive Function Clinic population, over a 6-year period (2000–2005 inclusive). Results: In a cohort of 177 patients with newly diagnosed clinically probable AD, 12 (6.8%) had a history of seizure disorder and/or were using anti-epileptic medications at the time of diagnosis. In 6 of these cases (3.4%), seizure onset was approximately concurrent with the onset of cognitive decline, and no symptomatic or provoking factor for seizures other than AD was identified. Conclusion: Although epileptic seizures are more common later in the course of AD, nonetheless they may accompany the onset of, and be symptomatic of, the disease, perhaps reflecting a shared pathogenesis.
Thrombin-Cofactor Interactions
Authors: Adams Ty E. , Huntington James A.
Published: May 2006

Precise modulation of thrombin activity throughout the hemostatic response is essential for efficient cessation of bleeding while preventing inappropriate clot growth or dissemination which causes thrombosis. Regulating thrombin activity is made difficult by its ability to diffuse from the surface on which it was generated and its ability to cleave at least 12 substrates. To overcome this challenge, thrombin recognition of substrates is largely controlled by cofactors that act by localizing thrombin to various surfaces, blocking substrate binding to critical exosites, engendering new exosites for substrate recognition and by allosterically modulating the properties of the active site of thrombin. Thrombin cofactors can be classified as either pro- or anticoagulants, depending on how substrate preference is altered. The procoagulant cofactors include glycoprotein Ibα, fibrin, and Na+, and the anticoagulants are heparin and thrombomodulin. Over the last few years, crystal structures have been reported for all of the thrombin-cofactor complexes. The purpose of this article is to summarize the features of these structures and to discuss the mechanisms and physiological relevance of cofactor binding in thrombin regulation.
Common Carotid Artery Intima-Media Thickness and the Risk of Stroke Recurrence
Authors: Tsivgoulis Georgios , Vemmos Konstantinos , Papamichael Christos , Spengos Konstantinos , Manios Efstathios , Stamatelopoulos Kimon , Vassilopoulos Demetrios , Zakopoulos Nikolaos
Published: May 2006

Background and Purpose—

Increased common carotid artery intima-media thickness (CCA-IMT) has been associated with an increased risk of myocardial infarction and stroke. We investigated the relationship between CCA-IMT and recurrent stroke in a cohort of ischemic stroke patients.

Methods—

High-resolution B-mode ultrasonographic measurements of the CCA-IMT were performed in a consecutive series of 238 patients hospitalized in our institution with first-ever ischemic stroke. Stroke risk factors and secondary prevention therapies were documented. Patients were followed-up prospectively and the outcome event of interest was recurrent stroke.

Results—

During a mean follow-up period of 28.9 months (range: 6 to 60 months), 27 recurrent strokes were documented. Patients who experienced recurrent cerebrovascular events had significantly (
P
=0.005) higher CCA-IMT values (1.01 mm, 95% CI:0.92 to 1.11 mm) than subjects who were free of stroke recurrence (0.88 mm, 95% CI:0.85 to 0.91 mm). After adjustment for baseline characteristics, risk factors and stroke subtypes and secondary prevention therapies increasing CCA-IMT was found to be an independent predictor of stroke recurrence. For each increment of 0.1 mm in CCA-IMT the probability of experiencing recurrent stroke increased by 18.0% (95% CI:2.0% to 36.0%,
P
=0.027).

Conclusions—

Increased CCA-IMT values are associated with a higher risk of long-term stroke recurrence.
Midlife Respiratory Function Related to White Matter Lesions and Lacunar Infarcts in Late Life
Authors: Guo Xinxin , Pantoni Leonardo , Simoni Michela , Gustafson Deborah , Bengtsson Calle , Palmertz Bo , Skoog Ingmar
Published: May 2006

Background and Purpose—

Increased evidence suggests that poor respiratory function increases risk of ischemic damage to the brain. Longitudinal studies on respiratory function and cerebral small-vessel disease are lacking. We examined midlife and late-life respiratory function in relation to small-vessel disease on computed tomography (CT) in women followed for 26 years.

Methods—

White matter lesions (WMLs) and lacunar infarcts were rated on brain CT scans in 2000 in 379 women 70 to 92 years of age from a longitudinal population study in Göteborg, Sweden. Respiratory function was measured by peak expiratory flow (PEF) in 1974 and 2000 and by forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV
1
) in 1980 and 2000.

Results—

Lower FVC and FEV
1
in 1980 and 2000 were associated with presence and severity of WMLs and lacunar infarcts in 2000. Per 1-SD decrease of FVC in 1980, odds ratios (95% CIs) were 1.49 (1.11 to 2.02) for presence of WMLs and 1.95 (1.34 to 2.84) for lacunar infarcts after adjustment for potential confounders. Per 1-SD decrease of FEV
1
in 1980, adjusted odds ratios were 1.46 (1.06 to 2.00) for presence of WMLs and 1.42 (1.02 to 1.97) for lacunar infarcts. PEF in 1974 and 2000 was not associated with WMLs or lacunar infarcts.

Conclusions—

WMLs and lacunar infarcts in elderly women were related to lower midlife respiratory function. Although our data may not establish causation between lower respiratory function and small-vessel disease, they imply the importance of good respiratory function in midlife.
Long-Term Risk Factors for Stroke
Authors: Harmsen Per , Lappas Georg , Rosengren Annika , Wilhelmsen Lars
Published: May 2006

Background and Purpose—

To estimate the predictive value of risk factors for stroke measured in midlife over follow-up extending through 28 years.

Methods—

A cohort of 7457 men 47 to 55 years of age and free of stroke at baseline year 1970 were examined. Risk of stroke was analyzed for the entire period and for 0 to 15, 16 to 21, and 22 to 28 years of follow-up using age-adjusted and multiple Cox regression analyses.

Results—

Age, diabetes, and high blood pressure were independently associated with increased risk of stroke for the entire 28 years and for each of the periods. Previous transient ischemic attacks, atrial fibrillation, history of chest pain, smoking, and psychological stress were independently related to stroke for the entire follow-up period and also during the first 1 or 2 successive periods. Family history of stroke or of coronary disease carried no independent prognostic information, nor did serum cholesterol. Elevated body mass index predicted stroke during the later part of the follow-up and so did (almost) low physical activity during leisure time, together with antihypertensive medication at baseline.

Conclusions—

High blood pressure and diabetes retain their importance as stroke risk factors also over an extended follow-up into old age. A family history of cardiovascular disease was not significantly related to outcome. Transient ischemic attacks, atrial fibrillation, stress, smoking, and a history of chest pain were associated with outcome only for the first or the first 2 periods. High body mass index and antihypertensive medication at baseline emerged as risk factors in the second and third decades.
Polymorphisms in the Advanced Glycosylation End Product–Specific Receptor Gene and Risk of Incident Myocardial Infarction or Ischemic Stroke
Authors: Zee Robert Y.L. , Romero Jose R. , Gould Jessica L. , Ricupero Dennis A. , Ridker Paul M
Published: May 2006

Background and Purpose—

Recent findings of an association between polymorphisms of advanced glycosylation end product–specific receptor (AGER) and risk of diabetic vasculopathy have generated great interest. However, to date, no genetic–epidemiological data are available on risk of atherothrombotic events among nondiabetic populations.

Methods—

Using DNA samples collected at baseline in a prospective cohort of 14 916 initially healthy American men, we evaluated 3 AGER genetic variants: −429T>C, −374T>A, and Gly82Ser, among 600 white individuals who subsequently developed atherothrombotic event (incident myocardial infarction or ischemic stroke) and among 600 age- and smoking-matched white individuals who remained free of reported vascular disease during follow-up (controls).

Results—

Genotype distributions for the polymorphisms tested were in Hardy–Weinberg equilibrium. Haplotype-based conditional logistic regression, adjusting for other potential confounders, showed that haplotype C-T-Gly (myocardial infarction: odds ratio [OR], 0.60; 95% CI, 0.41 to 0.90;
P
=0.01) and haplotype T-A-Gly (ischemic stroke: OR, 0.63; 95% CI, 0.40 to 0.99;
P
=0.05), compared with the reference haplotype T-T-Gly, were associated with reduced risk of atherothrombosis. Prespecified analysis limited to those without baseline history of diabetes showed similar significant findings.

Conclusions—

We found an association of specific AGER promoter gene haplotypes with reduced risk of incident myocardial infarction and ischemic stroke that was independent of the presence of diabetes.