bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing Novel Immunogens for an Effective, Safe Alzheimer’s Disease Vaccine
Authors: Maier Marcel , Seabrook Timothy J. , Lemere Cynthia A.
Published: February 2006

Active amyloid β (Aβ) vaccination has been shown to be effective in clearing cerebral Aβ and improving cognitive function in mouse models of Alzheimer’s disease. However, an Aβ vaccine clinical trial was suspended after meningoencephalitis was detected in a subset of subjects. Passive immunization has been suggested to be a safer alternative to active Aβ immunization but there are reports of increased risk of microhemorrhages associated with its administration in aged β-amyloid precursor protein transgenic mice bearing abundant vascular amyloid deposition. In addition, the cost may be prohibitive for large-scale clinical use. Therefore, we are designing novel Aβ immunogens that encompass the B cell epitope of Aβ but lack the T cell-reactive sites. These immunogens induced the production of Aβ-specific antibodies in the absence of an Aβ-specific cellular immune response in wild-type mice and are being tested in β-amyloid precursor protein transgenic mice. These data together with published reports from several other groups suggest that a safe, active Aβ vaccine is a tenable goal.
Clinical Observations with AN-1792 Using TAPIR Analyses
Authors: Hock Christoph , Nitsch Roger M.
Published: February 2006

Clinical observations with AN-1792 using tissue amyloid plaque immunoreactivity (TAPIR) analyses established for the first time evidence in humans that antibodies against β-amyloid-related epitopes are capable of slowing progression in Alzheimer’s disease. Antibodies derived upon TAPIR assay selection may specifically target the pathologic neoepitopes of aggregated Aβ species present in amyloid plaques and some of their aggregated, protofibrillar and low molecular weight oligomeric precursors. We briefly summarize here how the proof of concept was established and why it provides the basis for a potential cure for Alzheimer’s disease.
Complications of Ophthalmic Regional Blocks: Their Treatment and Prevention
Authors: Kumar Chandra M. , Dowd Timothy C.
Published: February 2006

Complications following ophthalmic regional anaesthesia are rare but are reported during both needle (intraconal and extraconal blocks) and blunt cannula (sub-Tenon’s block) techniques. At present there is no perfect technique of ophthalmic regional anaesthesia. This article reports on the complications, treatment and prevention of commonly used ophthalmic regional blocks. Thorough knowledge of the measures required to deal with complications when they occur are of paramount importance for safe clinical practice.
Endoscopy-Guided Subretinal Fluid Drainage in Vitrectomy for Retinal Detachment
Authors: Sonoda Yasushi , Yamakiri Keita , Sonoda Shozo , Uchino Eisuke , Doi Norihito , Sakamoto Taiji
Published: February 2006

Purpose: To study the usefulness of endoscopy-guided subretinal fluid drainage in pars plana vitrectomy (PPV) for rhegmatogenous retinal detachment (RRD). Participants/Methods: A prospective non-comparative study of a small number of RRD cases. The study involved examining 10 eyes of 10 patients with RRD that received PPV. Two eyes had hazy corneas, which hindered the observation by surgical microscopy. Fluid-gas exchange was performed and then subretinal fluid was drained through a primary retinal break guided by an endoscope. No drainage retinotomy was made. Each clinical feature was studied and the surgical outcome and complications were evaluated. Results: All eyes had retinal reattachment by a single operation. No serious complication related to surgery was experienced. Conclusions: Endoscopy-guided subretinal fluid drainage is the safe and effective procedure in PPV for RRD.
Myoneural Junctions of Extraocular Muscles: Distances from the Orbital Rim and Widths
Authors: Kakizaki Hirohiko , Zako Masahiro , Nakano Takashi , Asamoto Ken , Miyagawa Toshiaki , Iwaki Masayoshi
Published: February 2006

Purpose: To examine both the distances from the orbital rim to the myoneural junctions (MNJs) and the widths of the MNJs of all extraocular muscles. Methods: Six orbits of 3 post-mortem cadavers were used. The cadavers (1 female and 2 males) were all Japanese with an average age of 76.3 years. The MNJs of the extraocular muscles and their motor nerves were exposed, and then the distance from the orbital rim to each MNJ and the width of each MNJ were examined. Results: The distance from the orbital rim to each MNJ in the 6 extraocular muscles ranged from 24.4 to 33.6 mm and the width of each MNJ ranged from 5.0 to 8.5 mm. Conclusions: It is essential for orbital surgeons to understand both the distance from the orbital rim to MNJs and the widths of MNJs. This information not only aids the understanding of MNJ damage, but also prevents iatrogenic nerve impairment during orbital surgery.
Effect of the Background on the Disparity-Induced Ramp Vergence Response in Humans
Authors: Hayakawa Yuuki , Takagi Mineo , Iijima Atsuhiko , Bando Takehiko , Takada Ritsuko , Miki Atsushi , Usui Tomoaki , Hasegawa Shigeru , Abe Haruki
Published: February 2006

Purpose: Our purpose was to investigate the changes in the dynamic property of vergence eye movements caused by changes in the co-existing stationary background in the central visual field. Methods: Disparity-driven target movement was presented virtually by a head-mounted liquid-crystal display. Two targets were used: a bar-shaped target that moved between 2 and 0.5 m along the mid-sagittal line at a speed of 50 cm/s (vergence target) and a background image of a cross-shaped target that stayed at a distance of 2 m (background target). Eight normal subjects participated in the experiments. The subject was asked to follow the vergence target while the configuration of the background target was randomly changed among four conditions in each experiment: the length (experiment 1) or the width (experiment 2) of the horizontal and vertical lines composing the cross of the background target was each randomly changed among four conditions. A limbus tracker was used to measure eye movements. Results: In experiment 1, there was a negative correlation between the amplitude of the vergence eye movements and the lengths of the lines of the cross in each of five subjects (mean r = 0.018, n = 48 in each subject). Similarly, in experiment 2, there was a negative correlation between the amplitude of the vergence eye movements and the width of the lines of the cross in each of 8 subjects (mean r = –0.12, n = 48 in each subject). Conclusion: The vergence response to a target object significantly differs depending on the texture of background objects on the visual axis.
Periocular Microcystic Adnexal Carcinoma: Management and Outcome with Mohs’ Micrographic Surgery
Authors: Leibovitch Igal , Huilgol Shyamala C. , Richards Shawn , Paver Robert , Selva Dinesh
Published: February 2006

Purpose: To report a series of patients with periocular microcystic adnexal carcinoma (MAC) treated with Mohs’ micrographic surgery (MMS). Design: Prospective, interventional case series. Methods: This series included all patients treated with MMS for periocular MAC, who were monitored by the Skin and Cancer Foundation Australia between 1993 and 2002. Results: There were 5 patients (4 males, 1 female) with a mean age of 52 ± 12 years. Four tumors were located in the medial canthus and one in the lower lid.The tumor was initially misdiagnosed as basal cell carcinoma in 3 patients and squamous cell carcinoma in 1 patient. The average number of excision levels required for complete removal of the tumor during MMS was 2.2 (range 1–6). Perineural invasion was recorded in one patient.Five-year follow-up data was available for 3 patients, and there was no tumor recurrence in any of these cases. Conclusion: The low 5-year recurrence rate of periocular MAC with MMS emphasizes the importance of margin-controlled excision of this tumor.
Intravitreal Triamcinolone Acetonide for Exudative Age-Related Macular Degeneration among Japanese Patients
Authors: Ito Motoko , Okubo Akiko , Sonoda Yasushi , Yamakiri Keita , Sakamoto Taiji
Published: February 2006

Aim: To study the results of intravitreal triamcinolone acetonide (TA) for exudative age-related macular degeneration (AMD) among Japanese patients. Methods: 13 eyes of 12 Japanese patients (9 males and 3 females) with subfoveal choroidal neovascularization (CNV) of exudative AMD received intravitreal TA (8 mg). Visual acuity, size of CNV and serous retinal detachment, and complications related to treatment were evaluated for 6 months or longer. Results: Postoperative maximum visual acuity significantly improved (p < 0.05). Postoperative eyes had a greater probability of a reduced size of CNV and/or retinal detachment compared to preoperative eyes. Seven eyes showed increased intraocular pressure (21 mm Hg or over), which was controlled well by medication. Cataract development and advancement were observed in 90% of phakic eyes. No other serious complications were found. Conclusions: Intravitreal TA might be an effective treatment for subfoveal CNV of exudative AMD among Japanese as well as Caucasian patients for a comparatively short period.
Magnetic Resonance Imaging of the Brain in Patients with Pseudoexfoliation Syndrome and Glaucoma
Authors: Yüksel Nurşen , Anik Yonca , Altintas Özgül , Onur İnci , Caglar Yusuf , Demirci Ali
Published: February 2006

Purpose: To evaluate ischemic changes in brain magnetic resonance images in patients with pseudoexfoliation syndrome (PXS) and pseudoexfoliation glaucoma (PXG) and compare them with age- and sex-matched control subjects. Methods: This case-control study involved 16 consecutive patients with PXS, 21 patients with PXG and 18 healthy age- and sex-matched control subjects. Each subject underwent a comprehensive ophthalmological examination. In all participants, an axial T1-, T2- and proton-density-weighted and coronal cerebral 1.5-tesla magnetic resonance imaging (MRI) scan was made. White matter hyperintensities (WMH) were considered present if these were hyperintense on both proton-density- and T2-weighted images and not hypointense on T1-weighted images. White matter lesions were classified into two parts as the subcortical and periventricular regions. We used a validated rating scale of subcortical WMH: 0 = absent, 1 = punctuate foci, 2 = beginning confluence of foci and 3 = large confluent areas. Periventricular white matter lesions were classified on a scale of 0 (no white matter lesions), 1 (pencil-thin periventricular lining), 2 (thick lining) or 3 (large confluent white matter lesions). Results: The proportions of persons with WMH were 93.7% for patients with PXS, 95.2% for patients with PXG and 55.5% for control subjects. The numbers of white matter lesions in patients with PXS and PXG were significantly greater than in the control subjects (p < 0.05). White matter lesions at subcortical locations in patients with PXG were significantly more frequent than in the control subjects (80.9 vs. 33.3%; p < 0.05). The proportion of patients with subcortical WMH was 56.2% in PXS; no significant difference was found in subcortical WMH between PXS and controls. The proportions of patients with periventricular WMH were 93% in PXS, 90.4% in PXG and 44.4% in controls. White matter lesions at periventricular locations in patients with PXG and PXS were significantly more frequent than in the control subjects (p < 0.05). The difference between the pseudoexfoliation groups and controls with regard to the size of periventricular and subcortical white matter lesions was statically significant (p < 0.05). When patients with PXS were compared with PXG patients, there was no statistically significant difference in the number, size and scale of white matter lesions. Conclusion: We found a significantly higher prevalence of MRI-defined WMH in patients with a clinical diagnosis of pseudoexfoliation with or without glaucoma versus control subjects. We think that the findings in this study may shed light on a possible link between ischemic brain lesions and pseudoexfoliation, which is not related with the presence of glaucomatous optic neuropathy. Further investigations are required to resolve the underlying associations.
Orbital Tuberculoma Extending into the Cranium
Authors: Dewan Taru , Sangal Kartikeya , Premsagar Ishwar Chand , Vashishth Shashi
Published: February 2006

Orbital tuberculoma is not uncommon in the developing countries, but intracranial extension of orbital tuberculoma is extremely rare. Our case, a 14-year-old girl, presented with proptosis and progressive painless diminution of vision eventually leading to loss of vision. MRI showed a mass with peripheral enhancement of contrast, separate from the optic nerve and extending into the cranium through the optic foramen. Early decompression and chemotherapy resulted in marked visual recovery. Histopathology of the excised lesion confirmed tuberculosis. The case is reported to highlight both the rare presentation as well as remarkable visual recovery in a patient with orbital tuberculosis.
Mini Erythema Migrans – A Sign of Early Lyme Borreliosis
Authors: Weber Klaus , Wilske Bettina
Published: February 2006

Background: An erythema migrans (EM) remaining smaller than 5 cm in diameter, called mini EM by us, has not been addressed in detail. Objective: To study the significance of the mini EM as a sign of Lyme borreliosis. Methods: Patients with suspected mini EM were retrospectively selected out of 257 consecutive patients with EM. The diagnosis of mini EM rested on the cultivation of Borrelia burgdorferi. Species and subtype analysis of culture isolates was performed using outer surface protein A (OspA) polymerase chain reaction followed by restriction fragment length polymorphism and sequencing of the OspA gene. Results: There was one patient with definite (0.4%) and another patient with a questionable mini EM. Borrelia garinii OspA type 6 was identified in the patient with the definite and B. burgdorferi sensulato in the patient with the questionable mini EM. Conclusion: The mini EM represents an important and apparently uncommon sign of early Lyme borreliosis.
An Italian Study on Psoriasis and Depression
Authors: Esposito Maria , Saraceno Rosita , Giunta Alessandro , Maccarone Mara , Chimenti Sergio
Published: February 2006

Background: Psoriasis is often associated with the risk of physical disability, social discomfort and psychological disorders. Objectives: The aim of this study was to investigate the prevalence of depressive symptomatology among Italian patients with psoriasis vulgaris, in order to better evaluate the disease severity in this patient population. Methods: Five thousand Italian patients with psoriasis were mailed the Center for Epidemiological Studies-Depression Scale (CES-D) questionnaire, a 20-item instrument developed to perform epidemiological studies of depressive symptomatology in the general population. Questionnaires with responses to 16 or more items were considered evaluable. Results: We received evaluable questionnaires from 2,391 patients, including 1,528 men (63.9%) and 863 women (36.1%). Depressive symptomatology was observed in 1,482/2,391 patients (62% overall; females, 63%; males, 61%). Men <40 years of age were significantly more likely to report depressive symptoms than were men ≧40 years of age (67 vs. 58%, respectively; p = 0.002). Depressive symptomatology was more prevalent in psoriatic patients with only primary or secondary education than in psoriatic patients with higher education (51 vs. 32%, respectively; p < 0.02). Conclusion: Our results are consistent with previous studies showing that psoriasis is associated with profound psychological morbidity, in particular with depression in a large number of patients. It is important to consider this association in the overall management of psoriasis.
Low Levels of Emotional Awareness Predict a Better Response to Dermatological Treatment in Patients with Psoriasis
Authors: Consoli Silla M. , Rolhion Sophie , Martin Caroline , Ruel Karine , Cambazard Frédéric , Pellet Jacques , Misery Laurent
Published: February 2006

Background: Personality and emotional factors are thought to influence the onset of psoriasis, the occurrence of relapses, and the sensitivity of this condition to dermatological treatments. Objective:To explore the relationships between emotional disorders and emotional information processing in the one hand, and psoriasis severity and response to treatment on the other. Methods: We recruited 93 patients through an article in the local press. These patients attended three consultations. We evaluated psoriasis severity by Psoriasis Area and Severity Index (PASI) score and response to treatment by change in PASI score from baseline to the 3-month visit. We screened for comorbid mental disorders, using the Mini International Neuropsychiatric Interview. We used the Hospital Anxiety and Depression Scale to assess anxiety and depressive symptoms. Alexithymia (difficulty in identifying and expressing emotions) was evaluated with the 26-item version of the Toronto Alexithymia Scale (TAS-26) and the ability to integrate and differentiate emotions (emotional awareness) was assessed with the Lane and Schwartz Levels of Emotional Awareness Scale (LEAS). Results: Forty patients presented at least one psychiatric diagnosis and 33 were considered alexithymic (TAS ≧73). No psychological score was associated with baseline PASI score, which was higher in men and positively correlated with disease duration. Patients who considered their disease to be stress-reactive tended to have lower LEAS scores (p = 0.052). At the 3-month visit, PASI scores had significantly improved in the subset of patients (n = 67) presenting severe psoriasis at inclusion (PASI >2); emotional awareness and anxiety scores had also improved in these patients (p < 0.001), but dermatological and psychological changes were not statistically related. Dermatological improvement at 3 months with respect to baseline PASI was predicted by longer disease duration (>20 years) and lower baseline LEAS score (p = 0.044 and p = 0.021, respectively). Conclusion: This study demonstrates the value of assessing the ability of patients with psoriasis to process emotional information, as defined by emotional awareness. Patients with low LEAS scores appear to be more reactive to stress, but also to be more responsive to treatment, suggesting the activation of a particular stress physiology by negative affective states that are not experienced.
Autologous Whole Blood Injections to Patients with Chronic Urticaria and a Positive Autologous Serum Skin Test: A Placebo-Controlled Trial
Authors: Staubach P. , Onnen K. , Vonend A. , Metz M. , Siebenhaar F. , Tschentscher I. , Opper B. , Magerl M. , Lüdtke R. , Kromminga A. , Maurer M.
Published: February 2006

Background: Patients with chronic urticaria (CU) frequently exhibit positive skin test reactions to autologous serum (ASST). Therapies aimed at inducing tolerance to circulating histamine-releasing factors in ASST+ CU patients, e.g. by treatment with autologous whole blood (AWB), have not yet been tested. Objective: To test whether ASST+ CU patients can benefit from repeated low-dose intramuscular injections of AWB. Methods: We characterized CU severity and duration, anti-FcΕRI and anti-IgE expression, use of antihistamines, and quality of life in 56 CU patients (ASST+: 35, ASST–: 21) and assessed the therapeutic effects of 8 weekly AWB injections in a randomized, placebo-controlled, single-blind, parallel-group trial. Results: Numbers, size, intensity, and/or duration of CU symptoms, quality of life, as well as expression of anti-FcΕRI or anti-IgE were similar in ASST+ and ASST– CU patients. However, CU in ASST+ patients was of longer duration and required markedly more antihistaminic medication. Interestingly, ASST+ patients, but not ASST– patients, showed significantly (1) reduced CU activity, (2) decreased use of antihistamines, and (3) improved quality of life after AWB treatment. Placebo treatment was ineffective in both groups, but differences of AWB and placebo treatment responses did not achieve statistical significance in either group, most likely due to the limited number of patients treated. Conclusion: Our findings suggest that ASST+ CU is clinically different from other CU subforms and that ASST+ CU patients can benefit from AWB therapy.
Novel Mutation in ATP2C1 Gene in a Japanese Patient with Hailey-Hailey Disease
Authors: Ohtsuka Tsutomu , Okita Hiroshi , Hama Naoto , Yamazaki Soji
Published: February 2006

Hailey-Hailey disease (HHD) is an autosomal dominant disorder with recurrent eruption of vesicles and bullae involving predominantly the neck, groin and axillary regions. Histopathology shows suprabasal cleavage in epidermal cells. Recent studies have revealed that HHD is caused by mutations in the ATP2C1 gene encoding a novel Ca2+ pump. We analyzed mutations of the ATP2C1 gene in 2 Japanese patients with HHD. The diagnosis of HHD was made based on the characteristic clinical features and histopathological evidence. All 27 exons and flanking intron boundaries were amplified by polymerase chain reaction and products analyzed by sequencing. As a result, we identified a novel missense mutation (A1087G) in exon 13 of the ATP2C1 gene in a patient. This mutation led the amino acid change from Thrto Ala in the phosphorylation protein domain. Another patient showed no mutation of the gene. These results demonstrate that a spectrum of ATP2C1 gene mutations is present in Japanese HHD patients.
Genomics and Public Health in the United States: Signposts on the Translation Highway
Authors: Gwinn Marta , Khoury Muin J.
Published: February 2006

Successful completion of the Human Genome Project has raised public expectations that research findings will translate quickly into health benefits; however, the gap between biomedical research and clinical and public health application seems wider than ever. Public health scientists now have the opportunity to help create a broad concept of research translation that integrates genomic information into policies, programs and sevices benefiting the whole population. Important ’signposts’ along the translation highway include conducting population-based reearch in genomics, developing evidence on the clinical and public health value of genomic information, and integrating genomics into health practice.
PopGen: Population-Based Recruitment of Patients and Controls for the Analysis of Complex Genotype-Phenotype Relationships
Authors: Krawczak Michael , Nikolaus Susanna , von Eberstein Huberta , Croucher Peter J.P. , El Mokhtari Nour Eddine , Schreiber Stefan
Published: February 2006

Objective: Patient samples used for mapping complex human disease genes are unlikely to be representative of the phenotype spectrum of the respective population as a whole. On the other hand, most ongoing prospective studies are probably too small for evaluating polygenic disease markers. Design: Precise estimates of population-specific genotypic risks can be obtained efficiently through the complete ascertainment of patients in a geographically confined area. The PopGen project uses the most northern part of Germany as a target region for such a pursuit. Results: PopGen currently pursues recruitment, sampling and processing activities in close collaboration with a multitude of clinical partners, covering cardiovascular, neuropsychiatric and environmental diseases. Conclusion: PopGen has successfully established itself as a large-scale genetic epidemiological project of international recognition.
Getting Ready for the Future: Integration of Genomics into Public Health Research, Policy and Practice in Europe and Globally
Authors: Brand Angela , Schröder Peter , Brand Helmut , Zimmern Ron
Published: February 2006

The integration of genomics into public health research, policy and practice will be one of the most important future challenges that our health care systems will face. The next decade will provide a window of opportunity to establish infrastructures that will enable the scientific advances to be translated into evidence-based policies and interventions that improve population health. Approaches for national, European and international institutionalization of public health genomics are shown that aim to champion these challenges.
Comparison of 3′-End Encoding Regions of Turkey Coronavirus Isolates from Indiana, North Carolina, and Minnesota with Chicken Infectious Bronchitis Coronavirus Strains
Authors: Loa Chien Chang , Wu Ching Ching , Lin Tsang Long
Published: February 2006

Objective: To analyze the 3′-end structural protein-encoding region of turkey coronavirus (TCoV) isolates associated with outbreaks of acute enteritis in Indiana, North Carolina, or Minnesota. Methods: Four isolates of TCoV were sequenced over the entire 3′-end structural protein-encoding region and compared phylogenetically along with the corresponding sequences of infectious bronchitis virus (IBV) strains. Results: The sequence similarity between TCoV and IBV was lower than that among TCoV isolates or that among IBV strains. The variation of sequences between TCoV and IBV was mainly contributed by the S protein gene. The sequence similarity of S gene between TCoV and IBV was lower than that among TCoV isolates or that among IBV strains. The phylogenetic tree based on the S protein region was similar to that based on the entire 3′-end structural protein-encoding region with TCoV isolates and IBV strains grouped in two separate clusters. The phylogenetic tree based on other genes had a very different topology with TCoV isolates randomly forming groups with different IBV strains. Conclusions: These results suggested that TCoV probably shared the same origin with that of IBV and acquired sequences of S gene for turkey intestine tropism during the process of evolution in a separate environment.
Acute-Stage Evolution of Watershed Infarction Assessed on Diffusion-Weighted MR Imaging
Authors: Kim Sang Joon , Lee Choong Wook , Kim Hyun Jeong , Lee Jeong Hyun , Lee Deok Hee , Choi Choong Gon , Suh Dae Chul , Kang Dong-Wha
Published: February 2006

Background: To investigate acute stage (<5 days) evolution of the watershed infarction (WI) on diffusion-weighted (DW) magnetic resonance (MR) imaging and to evaluate the role of perfusion MR imaging in predicting the progression of watershed infarction. Methods: Twenty-eight patients with acute WI within 24 h after symptom onset were selected for this study. Criterion for WI was based on DW images. We assessed the infarct volume changes between the initial and follow-up (mean: 2.2 days) DW images. Perfusion images were obtained in 20 patients at the initial work-up and sensitivity, specificity, and accuracy of perfusion-diffusion mismatch in predicting severe infarct progression were evaluated. Clinical outcome was assessed by using National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). Results: Infarct volumes on initial and follow-up DW images were 8.6 ± 7.7 cm3 and 20.2 ± 27.0 cm3, respectively. Twenty-one cases showed no or slight increment (<15 cm3) of infarct volume on follow-up MR imaging and seven cases showed severe progression (>15 cm3 increment). Among 20 cases in which perfusion maps were obtained, 5 cases showed perfusion-diffusion mismatch: among those, 4 developed severe progression of infarction. Severe progression group showed higher follow-up NIHSS score and poor outcome by 90-day mRS score. Conclusion: WI usually begins as a small volume lesion, and progression of infarction during the acute stage is usually limited in most cases. Perfusion imaging may have an important role in predicting severe infarct progression in WI.
Feasibility of Follow-Up through E-Mail in Patients Discharged after Subarachnoid Hemorrhage
Authors: Greebe Paut , Rinkel Gabriel J.E.
Published: February 2006

Background: Long-term follow-up in patients with a subarachnoid hemorrhage (SAH) can be important in patients care and for clinical research, but outpatients’ visits or telephone interviews are time consuming. Methods: We studied the feasibility of follow up through e-mail in a prospectively collected series of patients with aneurysmal SAH. Results: Of the 97 patients who were discharged 58 (60%; 95% CI 49–70%) had e-mail, and all 58 provided their e-mail address. At 1 year 37 patients (64%; 95% CI 50–76%) responded to the first questionnaire sent by e-mail, 6 did so after an e-mail reminder. Fifteen responded after a telephone call, of which 12 had a new e-mail address. Conclusions: E-mail follow-up after SAH is feasible and for patients acceptable, but the proportion of patients with no or with changing e-mail address is considerable. The validity of the responses via e-mail has to be assessed in further studies.
Dexamethasone Impairs the Gastric Mucosal Integrity in Rats Treated with a Cyclooxygenase-1 but Not with a Cyclooxygenase-2 Inhibitor
Authors: Peskar Brigitta M. , Ehrlich Karlheinz , Egger Tamara , Sattler Wolfgang
Published: February 2006

In rats, neither the cyclooxygenase-1 inhibitor SC-560 nor the cyclooxygenase-2 inhibitor rofecoxib damages the gastric mucosa. Coadministration of dexamethasone induced injury in SC-560- but not in rofecoxib-treated rats. High levels of cyclooxygenase-1 protein occurred in the gastric mucosa of control rats, with no change after administration of SC-560. In contrast, the gastric cyclooxygenase-2 protein levels were low in control rats, but increased in a time-dependent manner after administration of SC-560. Dexamethasone prevented the increase in cyclooxygenase-2 protein levels. Our findings show that inhibition of cyclooxygenase-1 upregulates cyclooxygenase-2. When the upregulation is prevented by dexamethasone, gastric damage develops, suggesting that induction of cyclooxygenase-2 represents a compensatory mechanism that counteracts the injurious effect of cyclooxygenase-1 inhibition.
Puberty in Subjects with Complete Androgen Insensitivity Syndrome
Authors: Papadimitriou Dimitrios T. , Linglart Agnès , Morel Yves , Chaussain Jean-Louis
Published: February 2006

Background: Androgen receptor defects affect the regulation of the gonadotropic axis. However, little is known about the timing of pubertal maturation in complete androgen insensitivity syndrome (CAIS). Aims: To evaluate growth, skeletal maturation and gonadotropin and sex steroid secretion in patients with CAIS and intact gonads at puberty. Methods: Clinical, auxological and hormonal evaluation of 9 patients with CAIS from birth up to 17 years of age, prior to gonadectomy, in a single institution, retrospective study. Results: Breast development occurred at a median age of 11.1 years, thumb sesamoid appeared at 11.5 years, and peak height velocity at 12.3 years, all consistent with average female values. However, median adult male height (+1.2 SDS) was closer to the patients’ male target height (–0.3 SDS). Plasma testosterone levels rose early compared to normal boys. LH (basal and GnRH-stimulated) increased rapidly, above normal male values, in early puberty. Conclusions: This retrospective evaluation of a limited number of cases with a heterogeneous pattern of follow-up suggests that patients with CAIS may enter puberty at an age closer to female standards. These results imply a major role of direct androgen action, in utero or in early life, in determining the pattern of pubertal gonadotropin maturation.
Impact of del32–71-GH (Exon 3 Skipped GH) on Intracellular GH Distribution, Secretion and Cell Viability: A Quantitative Confocal Microscopy Analysis
Authors: Salemi Souzan , Yousefi Shida , Eblé Andrée , Deladoëy Johnny , Mullis Primus-E.
Published: February 2006

Background: Familial isolated growth hormone deficiency (IGHD) is a disorder with about 5–30% of patients having affected relatives. Among those familial types, IGHD type II is an autosomal dominant form of short stature, associated in some families with mutations that result in missplicing to produce del32–71-GH, a GH peptide which cannot fold properly. The mechanism by which this mutant GH may alter the controlled secretory pathway and therefore suppress the secretion of the normal 22-kDa GH product of the normal allele is not known in detail. Previous studies have shown variance depending on cell type, transfection technique used, as well as on the method of analysis performed. Aim: The aim of our study was to analyse and compare the subcellular distribution/localization of del32–71-GH or wild-type (wt)-GH (22-kDa GH), each stably transfected into AtT-20, a mouse pituitary cell line endogenously producing ACTH, employed as the internal control for secretion assessment. Methods: Co-localizationof wt- and del32–71 mutant GH form was studied by quantitative confocal microscopy analysis. Using the immunofluorescent technique, cells were double stained for GH plus one of the following organelles: endoplasmic reticulum (ER anti-Grp94), Golgi (anti-βCOP) or secretory granules (anti-Rab3a). In addition, GH secretion and cell viability were analysed in detail. Results/Conclusions: Our results show that in AtT-20 neuroendocrine cells, in comparison to the wt-GH, the del32–71-GH has a major impact on the secretory pathway not only affecting GH but also other peptides such as ACTH. The del32–71-GH is still present at the secretory vesicles’ level, albeit in reduced quantity when compared to wt-GH but, importantly, was secretion-deficient. Furthermore, while focusing on cell viability an additional finding presented that the various splice site mutations, even though leading eventually to the same end product, namely del32–71-GH, have different and specific consequences on cell viability and proliferation rate.
Effects of Nitrofen and Vitamins A, C and E on Maturation of Cultured Human H441 Pneumocytes
Authors: Gonzalez-Reyes Salome , Martinez Leopoldo , Martinez-Calonge Wenceslao , Fernandez-Dumont Virginia , Tovar Juan A.
Published: February 2006

Background/Aim: Nitrofen (2,4-dichloro-4´-nitrodiphenyl ether), a teratogen with oxidant properties, induces congenital diaphragmatic hernia (CDH) with lung hypoplasia and delayed lung development and maturation in rat embryos. Several phenotypic features of the alveolar epithelium including surfactant proteins A and B synthesis and its regulation by transcription factors are reproduced in cultured human H441 pneumocytes. The aim of the present study was to test whether vitamins A, E and C with anti-oxidant properties were able to recover the expression of such regulators in an in vitro setting. Materials and Methods: Cultured human H441 pneumocytes were treated with nitrofen with or without additional exposure to vitamins A, E and C. Thyroid transcription factor 1 (TTF-1), hepatocyte nuclear factor 3-β (HNF-3β) and hepatocyte nuclear factor 3-β surfactant protein B (SP-B) mRNAs were measured by real-time polymerase chain reaction (RT-PCR). The cells were also immunohistochemically stained for assessment of proliferation (PCNA) and apoptosis (bis-benzimide) status and SP-B and TTF-1 protein expressions. Results were compared by ANOVA with a significant threshold of 5%. Results: Nitrofen severely decreased TTF-1, HNF-3β and SP-B mRNA expression by H441 pneumocytes in culture. Addition of vitamin E normalized the levels of the three transcripts, while vitamin A normalized only those of TTF-1 and SP-B mRNA. Vitamin C was significantly beneficial only for SP-B transcript. Nitrofen decreased proliferation and TTF-1 and SP-B protein expressions with no apparent effect on apoptosis. Additional exposure to vitamins A, C or E rescued near normal values. Conclusions: The changes induced by nitrofen in cultured H441 human pneumocytes are reverted in part by anti-oxidant vitamins by upregulating TTF-1, HNF-3β and SP-B and stimulating proliferation and maturity in nitrofen-treated cells. These effects of anti-oxidant vitamins could be of some interest for developing new transplacental therapeutic strategies aimed at improving lung development and maturation in fetuses with CDH.
Giant Cell Interstitial Pneumonia in a 60-Year-Old Female without Hard Metal Exposure
Authors: Menon Balakrishnan , Sharma Amit , Kripalani Jai , Jain Sudhir
Published: February 2006

Giant cell interstitial pneumonia is a form of pulmonary fibrosis usually caused by exposure to hard metals. We report a case of giant cell interstitial pneumonia in a 60-year-old female office worker who was a non-smoker and did not have any exposure to hard metals.
Expression of IP-10/CXCL10 Is Upregulated by Double-Stranded RNA in BEAS-2B Bronchial Epithelial Cells
Authors: Taima Kageaki , Imaizumi Tadaatsu , Yamashita Koji , Ishikawa Akira , Fujita Takashi , Yoshida Hidemi , Takanashi Shingo , Okumura Ken , Satoh Kei
Published: February 2006

Background: Interferon (IFN)-γ-inducible protein of 10 kDa (IP-10/CXCL10) is a potent chemoattractant for activated T and NK cells, and elevated levels of IP-10 are identified in bronchoalveolar lavage fluids from patients with pulmonary disorders related to Th-1-type immunity, which is a prerequisite for elimination of viral pathogens. Bronchial epithelial cells play an important role in respiratory infections as the initiator of airway inflammation by releasing chemokines and expressing cell surface membrane molecules involved in leukocyte adhesion. Polyinosinic-polycytidylic acid (poly IC) is a synthetic double-stranded RNA (dsRNA) and induces antiviral reactions in cells. Objectives: We investigated the regulation of IP-10 in BEAS-2B bronchial epithelial cells in response to poly IC, and also addressed the possible role of retinoic-acid-inducible gene-I (RIG-I) and IFN-regulatory factor 3 (IRF-3), two genes involved in the signaling induced by viral infection. Methods: The expressions of IP-10 mRNA and protein were analyzed by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. The overexpression of RIG-I or IRF-3 was performed by transfection of BEAS-2B cells with each cDNA. Results: Poly IC enhanced the expression of IP-10 mRNA and protein in concentration- and time-dependent manners. Overexpression of RIG-I or IRF-3 potentiated the poly-IC-induced upregulation of IP-10. Conclusions: IP-10 may contribute to antiviral activity through the activation of Th-1-type immunity, and RIG-I and IRF-3 may be involved in this reaction.
Wall Shear Stress – an Important Determinant of Endothelial Cell Function and Structure – in the Arterial System in vivo
Authors: Reneman Robert S. , Arts Theo , Hoeks Arnold P.G.
Published: February 2006

It has been well established that wall shear stress is an important determinant of endothelial cell function and gene expression as well as of its structure. There is increasing evidence that low wall shear stress, as pres- ent in artery bifurcations opposite to the flow divider where atherosclerotic lesions preferentially originate, expresses an atherogenic endothelial gene profile. Besides, wall shear stress regulates arterial diameter by modifying the release of vasoactive mediators by endothelial cells. Most of the studies on the influence of wall shear stress on endothelial cell function and structure have been performed in vitro, generally exposing endothelial cells from different vascular regions to an average wall shear stress level calculated according to Poiseuille’s law, which does not hold for the in vivo situation, assuming wall shear stress to be constant along the arterial tree. Also in vivo wall shear stress has been determined based upon theory, assuming the velocity profile in arteries to be parabolic, which is generally not the case. Wall shear stress has been calculated, because of the lack of techniques to assess wall shear stress in vivo. In recent years, techniques have been developed to accurately assess velocity profiles in arterioles, using fluorescently labeled particles as flow tracers, and non-invasively in large arteries by means of ultrasound or magnetic resonance imaging. Wall shear rate is derived from the in vivo recorded velocity profiles and wall shear stress is estimated as the product of wall shear rate and plasma viscosity in arterioles and whole blood viscosity in large arteries. In this review, we will discuss wall shear stress in vivo, paying attention to its assessment and especially to the results obtained in both arterioles and large arteries. The limitations of the methods currently in use are discussed as well. The data obtained in the arterial system in vivo are compared with the theoretically predicted ones, and the consequences of values deviating from theory for in vitro studies are considered. Applications of wall shear stress as in flow-mediated arterial dilation, clinically in use to assess endothelial cell (dys)function, are also addressed. This review starts with some background considerations and some theoretical aspects.
Relationship of Patient and Medical Characteristics to Health Status in Children and Adolescents After the Fontan Procedure
Authors: McCrindle Brian W. , Williams Richard V. , Mitchell Paul D. , Hsu Daphne T. , Paridon Stephen M. , Atz Andrew M. , Li Jennifer S. , Newburger Jane W.
Published: February 2006

Background—

After the Fontan procedure, patients are at risk for suboptimal health status related to their complex healthcare experience, physiological limitations, medical complications, and guarded long-term prognosis.

Methods and Results—

In the Pediatric Heart Network cross-sectional study of Fontan survivors 6 to 18 years of age, parents completed the Child Health Questionnaire, and scores were related in multivariable analysis to patient and medical characteristics obtained from medical record review. For 537 patients (mean age at study, 11.9 years; 60% male) with a median age at Fontan of 2.8 years (range, 0.7 to 14.6 years), parent-reported patient morbidities included deficits in vision in 33%, speech in 27%, and hearing in 7%, as well as problems with attention in 46%, learning in 43%, development in 24%, behavior in 23%, anxiety in 17%, and depression in 8%. Child Health Questionnaire summary scores were significantly lower than the US population sample for Physical Functioning (mean Z score, −0.47±1.19;
P
<0.001) and Psychosocial Functioning (−0.28±1.08;
P
<0.001). Parent-reported medical conditions and long-term and current medical problems explained the greatest amount of variation in the Physical Functioning scores. Parent-reported patient conditions, including behavior, learning, anxiety, and attention problems and depression, explained the greatest amount of variation in the Psychosocial Functioning scores. Lower family income had a negative impact on both Physical and Psychosocial Functioning.

Conclusions—

There are deficits in health status in children and adolescents after the Fontan procedure. Strategies to address this problem might emphasize coordinated and effective prevention, detection, and management of noncardiac and psychosocial conditions, as well as specific targeting of patients from low-income households.
Achieving Rapid Door-To-Balloon Times
Authors: Bradley Elizabeth H. , Curry Leslie A. , Webster Tashonna R. , Mattera Jennifer A. , Roumanis Sarah A. , Radford Martha J. , McNamara Robert L. , Barton Barbara A. , Berg David N. , Krumholz Harlan M.
Published: February 2006

Background—

Fewer than half of patients with ST-elevation acute myocardial infarction (STEMI) are treated within guideline-recommended door-to-balloon times; however, little information is available about the approaches used by hospitals that have been successful in improving door-to-balloon times to meet guidelines. We sought to characterize experiences of hospitals with outstanding improvement in door-to-balloon time during 1999–2002.

Methods and Results—

We performed a qualitative study using in-depth interviews (n=122) with clinical and administrative staff at 11 hospitals that were participating with the National Registry of Myocardial Infarction and had median door-to-balloon times of ≤90 minutes during 2001–2002, representing substantial improvement since 1999. Data were organized with the use of NUD-IST 4 (Sage Publications Software) and were analyzed by the constant comparative method of qualitative data analysis. Eight themes characterized hospitals’ experiences: commitment to an explicit goal to improve door-to-balloon time motivated by internal and external pressures; senior management support; innovative protocols; flexibility in refining standardized protocols; uncompromising individual clinical leaders; collaborative teams; data feedback to monitor progress and identify problems and successes; and an organizational culture that fostered resilience to challenges or setbacks in improvement efforts.

Conclusions—

Several themes characterized the experiences of hospitals that had achieved notable improvements in their door-to-balloon times. By distilling the complex and diverse experiences of organizational change into its essential components, this study provides a foundation for future efforts to elevate clinical performance in the hospital setting.
Evolutionary conserved structures as indicators of medical risks: increased incidence of cervical ribs after ovarian hyperstimulation in mice
Authors: Steigenga Marc , Helmerhorst Frans , De Koning Jurien , Tijssen Ans , Ruinard Sebastiaan , Galis Frietson
Published: February 2006

The presence of a rib on the seventh cervical vertebra (a cervical rib) represents one of the most common intraspecific variations of the number of cervical vertebrae in mammals. Cervical ribs are highly associated with stillbirths, congenital abnormalities and embryonal tumours. These associations indicate strong stabilising selection against such a change to the highly conserved number of cervical vertebrae in humans. We propose, therefore, that the presence of variation for this highly conserved trait can be used as an indicator of medical risks. We have tested for prolonged effects of controlled ovarian hyperstimulation treatments (OHS) in mice by analysing the frequency of cervical ribs in the offspring of females that had received OHS treatment. We found that OHS treatment in mice had several significant effects on the offspring after adjusting for multiple pregnancy: these included an increase in cervical rib incidence, gestational period and nest size, and a decrease in birth weight and ossification, indicating growth retardation.The high incidence of cervical ribs in the OHS group compared to the control group (39.5% vs. 4.7%) indicates that the OHS treatment affects embryogenesis during a period that is highly sensitive to disturbance, the early organogenesis stage (phylotypic stage). This implies that in mice OHS treatment of the mother has a prolonged effect and continues during early pregnancy.
A comparative study of the functional morphology of parapodia and setae in nereids (Polychaeta: Nereididae)
Authors: Hesselberg  , Vincent
Published: February 2006

Errant polychaetes of the family Nereididae can be found in a wide range of sub- and intertidal habitats. They can burrow, crawl and swim. The latter two behaviours are primarily achieved by the use of parapodia and their attached setae. Here we compare the parapodia and setae of five species of atoke nereids living in either soft or hard substrate in a scanning electron microscopy (SEM) study. Three types of setae, found in all the worms examined, were consistently different across species, allowing us to compare setal distribution. However, neither distribution nor number of setae, or intersetal gap showed a clear dependence on substrate. Thus it appears that the morphology is not adapted to a specific substrate. This might be because both the parapodia and the setae serve multiple functions in the living animal. Location of the parapodium and the size of the intersetal gap showed some dependence on whether the atoke stage swims. However, neither the area of the parapodium nor of the setal bundles seems to relate to swimming. Phylogenetic relationships amongst the examined species, from three genera all in the subfamily Nereidinae, did not significantly influence either of the morphological parameters investigated. This study indicates that the morphology of the parapodia and setae of nereids is not adapted to any specific function, instead they are presumably important for a variety of tasks performed by the worms.