bluuebunny/crossref_metadata_2025 huggingface dataset:
HIF-1α-Deficient Mice Have Increased Brain Injury after Neonatal Hypoxia-Ischemia
Authors: Sheldon R. Ann , Osredkar Damjan , Lee Christina L. , Jiang Xiangning , Mu Dezhi , Ferriero Donna M.
Published: August 2009

Evidence suggests that the activation of the transcription factor hypoxia-inducible factor 1α (HIF-1α) may promote cell survival in hypoxic or ischemic brain. To help understand the role of HIF-1α in neonatal hypoxic-ischemic brain injury, mice with conditional neuron-specific inactivation of HIF-1α underwent hypoxia-ischemia (HI). Mice heterozygous for Cre recombinase under the control of the calcium/calmodulin-dependent kinase II promoter were bred with homozygous ‘floxed’ HIF-1α transgenic mice. The resulting litters produced mice with a forebrain predominant neuronal deletion of HIF-1α (HIF-1αΔ/Δ), as well as littermates without the deletion. In order to verify reduction of HIF-1α at postnatal day 7, HIF-1αΔ/Δ and wild-type mice were exposed to a hypoxic stimulus (8% oxygen) or room air for 1 h, followed by immediate collection of brain cortices for determination of HIF-1α expression. Results of Western blotting of mouse cortices exposed to hypoxia stimulus or room air confirmed that HIF-1αΔ/Δ cortex expressed a minimal amount of HIF-1α protein compared to wild-type cortex with the same hypoxic stimulus. Subsequently, pups underwent the Vannucci procedure of HI at postnatal day 7: unilateral ligation of the right common carotid artery followed by 30 min of hypoxia (8% oxygen). Immunofluorescent staining of brains 24 h after HI confirmed a relative lack of HIF-1α in the HIF-1αΔ/Δ cortex compared to the wild type, and that HIF-1α in the wild type is located in neurons. HIF-1α expression was determined in mouse cortex 24 h after HI. Histological analysis for the degree of injury was performed 5 days after HI. HIF-1α protein expression 24 h after HI showed a large increase of HIF-1α in the hypoxic-ischemic cortex of the wild-type compared to the hypoxic only cortex. Histological analysis revealed that HI injury was increased in the neuronally deficient HIF-1αΔ/Δ mouse brain (p < 0.05) and was more severe in the cortex. Genetic reduction of neuronal HIF-1α results in a worsening of injury after neonatal HI, with a region-specific role for HIF-1α in the setting of neonatal brain injury.
The Validity, Reliability and Clinical Utility of the Hong Kong Montreal Cognitive Assessment (HK-MoCA) in Patients with Cerebral Small Vessel Disease
Authors: Wong Adrian , Xiong Yun Y. , Kwan Pauline W.L. , Chan Anne Y.Y. , Lam Wynnie W.M. , Wang Ki , Chu Winnie C.W. , Nyenhuis David L. , Nasreddine Ziad , Wong Lawrence K.S. , Mok Vincent C.T.
Published: August 2009

Background/Aims: To evaluate the psychometric properties of the Hong Kong Montreal Cognitive Assessment (HK-MoCA) in patients with cerebral small vessel disease (SVD). Methods: 40 SVD patients and 40 matched controls were recruited. Concurrent and criterion validity, inter-rater and test-retest reliability, internal consistency of the HK-MoCA were examined and clinical observations were made. Results: Performance on the HK-MoCA was significantly predicted by both executive (β = 0.23, p = 0.013) and non-executive (β = 0.64, p < 0.001) composite scores. It differentiated SVD patients from controls (area under the curve = 0.81, p < 0.001) with an optimal cutoff at 21/22. Reliability, internal consistency and clinical utility were good. Conclusion: The HK-MoCA is a useful cognitive screening instrument for use in SVD patients.
Drug Development: From Concept to Marketing!
Authors: Tamimi Nihad A.M. , Ellis Peter
Published: August 2009

Drug development is an expensive, long and high-risk business taking 10–15 years and is associated with a high attrition rate. It is driven by medical need, disease prevalence and the likelihood of success. Drug candidate selection is an iterative process between chemistry and biology, refining the molecular properties until a compound suitable for advancing to man is found. Typically, about one in a thousand synthesised compounds is ever selected for progression to the clinic. Prior to administration to humans, the pharmacology and biochemistry of the drug is established using an extensive range of in vitro and in vivo test procedures. It is also a regulatory requirement that the drug is administered to animals to assess its safety. Later-stage animal testing is also required to assess carcinogenicity and effects on the reproductive system. Clinical phases of drug development include phase I in healthy volunteers to assess primarily pharmacokinetics, safety and toleration, phase II in a cohort of patients with the target disease to establish efficacy and dose-response relationship and large-scale phase III studies to confirm safety and efficacy. Experience tells us that approximately only 1 in 10 drugs that start the clinical phase will make it to the market. Each drug must demonstrate safety and efficacy in the intended patient population and its benefits must outweigh its risks before it will be approved by the regulatory agencies. Strict regulatory standards govern the conduct of pre-clinical and clinical trials as well as the manufacturing of pharmaceutical products. The assessment of the new medicinal product’s safety continues beyond the initial drug approval through post-marketing monitoring of adverse events.
Interleukin-8 and Acute Kidney Injury following Cardiopulmonary Bypass: A Prospective Cohort Study
Authors: Liangos Orfeas , Kolyada Alexey , Tighiouart Hocine , Perianayagam Mary C. , Wald Ron , Jaber Bertrand L.
Published: August 2009

Background: Cardiopulmonary bypass (CPB) elicits an inflammatory response mediated partly by neutrophils, which are activated and recruited by interleukin-8 (IL-8). We hypothesized that acute kidney injury (AKI) following CPB might be mediated by IL-8 and examined the association of perioperative plasma IL-8 levels with AKI in a prospective cohort. Methods: Plasma IL-8 was measured before, and 2, 24 and 48 h following CPB. Two AKI definitions, a serum creatinine increase of ≥0.3 mg/dl or 50% (AKI Network [AKIN] stage-1) or ≥50% alone (AKI-50%), within the first 72 h, were used. Area under the receiver operator characteristic curves (AUCs) were generated and multivariable logistic regression analyses performed. Results: A total of 143 patients were enrolled. The baseline mean serum creatinine was 1.1 mg/ dl (SD = 0.3), the CPB perfusion time was 112 min (SD = 43). Twenty-nine percent of the patients developed AKIN stage-1 and 13% AKI-50%. The plasma IL-8 level 2 h after CPB was higher in AKIN stage-1 (p = 0.03) and AKI-50% (p < 0.01), and predicted AKIN stage-1 (AUC = 0.62; p = 0.02) and AKI-50% (AUC = 0.72; p < 0.01). On multivariable analysis, the 2-hour plasma IL-8 level was associated with 1.36- and 1.59-fold higher odds for AKIN stage-1 and AKI-50%, respectively (p = 0.05). Conclusion: Plasma IL-8 predicts the development of AKI following CPB, supporting a potential involvement for this chemokine in the pathogenesis of AKI.
Random Spot Urine Protein/Creatinine Ratio Is Unreliable for Estimating 24-Hour Proteinuria in Individual Systemic Lupus Erythematosus Nephritis Patients
Authors: Hebert Lee A. , Birmingham Daniel J. , Shidham Ganesh , Rovin Brad , Nagaraja H.N. , Yu Chack-Yung
Published: August 2009

Background: Recently the American Rheumatologic Association (ARA) recommended random spot urine protein/creatinine ratio (P/C) to monitor systemic lupus erythematosus (SLE) glomerulonephritis (GN). Shortly afterward, 2 works were published, designated Study 1 and Study 2, which are the only studies to test spot P/C in SLE GN. Here we evaluate Study 1 and Study 2, which came to different conclusions. Methods: Study 1 compared spot P/C to the P/C of intended 24-hour collections >50% complete, which reliably estimates 24-hour proteinuria. Study 2 compared spot P/C to the protein content of intended 24-hour collections >80% complete. To compare studies, Study 2 data were converted to P/C ratios. Results: Study 1 and Study 2 were found to be in agreement. Both showed that spot P/C and 24-hour P/C were highly correlated, but only when compared over the entire P/C range (0–8.0) (r = 0.842). Over the P/C range 0.5–3.0 (the most common P/C range encountered in SLE GN), correlation was present, but concordance was poor, rendering random P/C ratio unreliable. Conclusions: Random spot P/C ratio is unreliable for detecting moderate proteinuria change. For example, random spot P/C would not reliably diagnose British Isles Lupus Assessment Group (BILAG) Category A or B proteinuric flares.
Higher Survival Rates of Chronic Hemodialysis Patients on Anti-Hypertensive Drugs
Authors: Iseki K. , Shoji T. , Nakai S. , Watanabe Y. , Akiba T. , Tsubakihara Y.
Published: August 2009

Background: The effects of anti-hypertensive drugs on survival have not been examined in a large cohort of hemodialysis (HD) patients. Methods: We examined the relationship between blood pressure, anti-hypertensive drug therapy, and survival using the nationwide HD registry of the Japanese Society for Dialysis Therapy. Outcomes were confirmed using the coded ID numbers of the 2005 and 2006 registries. Logistic analyses were performed to determine the effect of anti-hypertensive drug therapy on survival. Results: A total of 163,668 patients (50.6% men; 31.5% with diabetes mellitus; mean age 63.6 years) on HD 3 times a week in 2005 were studied. Mean (SD) levels of systolic and diastolic blood pressure were 153.4 (24.1) and 78.7 (13.7) mm Hg, respectively, before the HD session. Two-thirds of the HD patients were prescribed anti-hypertensive drugs and the numbers of anti-hypertensive medications were: 1 in 26.8%, 2 in 24.4%, and 3 or more in 14.5% of the total patients. The 1-year mortality rate was 6.6% overall: 8.5% in patients not prescribed anti-hypertensive drugs and 5.6% among those prescribed anti-hypertensive drugs. The odds ratio (95% confidence interval) for the 1-year mortality rate was 0.724 (0.681–0.770, p < 0.0001) for patients prescribed anti-hypertensive drugs, after adjusting for age, sex, diabetes mellitus, body mass index, HD duration, serum albumin, and systolic blood pressure. Conclusion: Survival was better in patients prescribed anti-hypertensive drugs, particularly renin-angiotensin system inhibitors, than in those not prescribed anti-hypertensive drugs. The causality on this association remained to be determined and prospective studies on blood pressure target levels and the effects of anti-hypertensive drug class in HD patients are warranted.
Impact of Early Referral to Nephrologist on Mental Health among Hemodialysis Patients: A Dialysis Outcomes and Practice Patterns Study (DOPPS)
Authors: Yokoyama Yoko , Yamazaki Shin , Hasegawa Takeshi , Wakita Takafumi , Hayashino Yasuaki , Takegami Misa , Akiba Takashi , Akizawa Tadao , Asano Yasushi , Saito Akira , Kurokawa Kiyoshi , Fukuhara Shunichi
Published: August 2009

Background: Pre-dialysis early referral is associated with improved survival in patients on dialysis. Here, we examined the association between pre-dialysis early referral and post-dialysis Mental Health (MH) in hemodialysis patients. Methods: We examined data from the Dialysis Outcomes and Practice Patterns Study (DOPPS), a prospective and observational study of hemodialysis patients, by performing a cross-sectional and longitudinal analysis of DOPPS data from Japan. The outcome measure was analyzed from the MH subscale of the Medical Outcomes Study Short Form-36 Item Health Survey. Predictors of mean MH were identified using analysis of covariance. The variables evaluated in the multivariate models included age, sex, duration of dialysis and diabetes. Results: A total of 552 patients under hemodialysis participated in the study, with a late referral prevalence of 34.2% (189/552). The estimated mean MH score was 60.7 (95% confidence interval (CI) 57.5–63.8) and 65.6 (95% CI 63.2–68.1) in late and early referrals, respectively. A statistically significant difference in mean MH score of 4.9 was observed between late and early referral groups (p = 0.01). The mean MH score for late referral was significantly lower than that for early referral in the 6–12 and 12–18 month groups. Conclusions: Pre-dialysis early referral is a modifiable and important factor and is associated with improved MH of post-dialysis patients.
The Effect of Parity on Midgestational Uterine Artery Doppler Findings in Uncomplicated and Low-Risk Pregnancies
Authors: Goynumer G. , Yayla M. , Arisoy R. , Durukan B.
Published: August 2009

Background: To establish the effect of parity on uteroplacental Doppler findings during midgestation in uncomplicated and low-risk pregnancies. Methods: Color flow pulse Doppler imaging of uterine arteries was performed on 760 uncomplicated singleton pregnancies fulfilling the study criteria at 19–24 weeks of gestation. Pulsatility indices (PIs) and bilateral notching were compared in nulliparous and parous pregnant women during various gestational weeks. The effects of maternal age, gestational age and parity on abnormal Doppler findings were assessed. Results: We found a significant difference in the prevalence of bilateral diastolic notch between nulliparous and parous women. From 19 to 24 weeks of gestation, a significant decrease in the PI values was observed (p < 0.001). The decrease in the PI values was significant in nulliparous, in contrast to parous women (p < 0.001). Parity had no effect on the mean PI, but parity was found to decrease the risk of bilateral notching (p < 0.05, R2 = 0.031). Conclusion: The mean indices are similar when the first and subsequent pregnancies are compared, especially after the 21st gestational week. Notching is more prominent in the first pregnancy. Parity has an effect on PIs in earlier weeks, and this effect is more pronounced in the appearance of bilateral notches.
Development of Laser-Induced Choroidal Neovascularization in Rats after Retinal Damage by Sodium Iodate Injection
Authors: García-Layana Alfredo , Vásquez Gustavo , Salinas-Alamán Angel , Moreno-Montañés Javier , Recalde Sergio , Fernández-Robredo Patricia
Published: August 2009

Purpose: To determine the role of the retinal pigment epithelium (RPE) in the development of laser-induced choroidal neovascularization (CNV) by selective damage with sodium iodate (SI). Methods: In group 1, diode laser photocoagulation was applied to the right eye of Long-Evans rats (n = 11). In group 2 (n = 11), SI was administered intravenously at a dose of 40 mg/kg of body weight 2 days after photocoagulation. In group 3 (n = 10), SI was injected 2 days before laser was applied. In group 4 (n = 10), SI was injected immediately after photocoagulation. Results: CNV ingrowth developed in 42 of 93 burns (45%) of the laser group and in 46 of 75 burns (61%) when SI was administered 2 days after laser (p = 0.036). No CNV developed in the other groups. Conclusions: The angiogenic effect of the RPE is essential during the first hours after the onset of the laser-induced CNV process. When the RPE was damaged before or at the time of photocoagulation, CNV was not induced. These results suggest that RPE integrity is a decisive element in CNV formation.
A New Approach in the Surgical Management of Anterior Capsular Phimosis Syndrome
Authors: Panagopoulos A. , Chalioulias K. , Kirkby G.R.
Published: August 2009

Anterior capsular opacification and contraction syndrome is a well-recognised complication of uneventful phacoemulsification. It often results in a clinically significant reduction in vision secondary to central opacification, intraocular lens decentration and tilt. We report 3 cases of anterior capsular phimosis, which we treated using a new technique, where long, fine pointed scissors are used to cut the anterior capsule radially towards the edge of the lens optic and the edge is then grasped with capsulorrhexis forceps and the anterior capsule is torn away. The tear occurs at the edge of the optic because the anterior and posterior capsules are fused at this point. We believe that our technique offers a superior alternative for the effective, safe and quick management of anterior capsular phimosis, thereby improving the intraoperative fundus view for vitreoretinal surgery or delivery of laser treatment.
Targeting of Integrin-Linked Kinase with a Small Interfering RNA Inhibits Endothelial Cell Migration, Proliferation and Tube Formation in vitro
Authors: Guo Lili , Yu Wenzhen , Li Xiaoxin , Zhao Gang , He Peiying
Published: August 2009

Purpose: To investigate the role of integrin-linked kinase (ILK) in endothelial cell migration, proliferation and tube formation in vitro. Materials and Methods: Cultured RF/6A cells were knocked down for ILK using small interfering RNA (siRNA). Cellular ILK expression was quantified by real-time quantitative PCR and Western blot analysis. Cell migration was measured by cell counting in modified Boyden chambers, while microfilament dynamics were assessed by immunofluorescence analysis. Cell cycling was determined using a FACS Calibur flow cytometer, and the expression of cyclin D1 was also measured by the Western blot assay. The secretion of vascular endothelial growth factor (VEGF) in culture medium samples was assessed by ELISA, and capillary/tube-like network formation assays were performed using matrigel. Results: Both ILK mRNA and protein levels were vir- tually undetectable after transfection with ILK siRNA. In addition, there was a significant accumulation of cells in the G₀–G1 phase and a marked decrease in cell numbers in the S phase in ILK-specific siRNA-transfected cells, and the expression of cyclin D1 was decreased after transfection. The knockdown of ILK significantly inhibited cell migration ability by disturbing F actin assembly, and VEGF secretion in conditioned medium was also reduced by 33%. Furthermore, treatment with ILK siRNA suppressed tube formation in RF/6A cells and significantly reduced the overall length of the tubes. Conclusions: Knockdown of ILK with siRNA effectively inhibits endothelial cell migration, proliferation and tube formation in vitro.
Selective Deficit of Autobiographical Incident Memory in Subjects with Bipolar Disorder
Authors: Shimizu Mitsue , Kubota Yasutaka , Mason Richard , Baba Hisamitsu , Calabrese Joseph R. , Toichi Motomi
Published: August 2009

Background: Previous studies have suggested that episodic memory impairment is one of the trait-like markers of bipolar disorder (BD), and is also associated with the course of the illness. Autobiographical memory (AM) is a special type of episodic memory, and disruption of AM causes severe psychosocial dysfunctions in patients with various neuropsychiatric disorders. However, little is known about possible deficits in AM in BD. This study investigated AM performance of BD patients and the effect of aging on their memory function. Sampling and Methods: We assessed AM of particular incidents (incident AM) and AM of personal facts (semantic AM), focusing on 4 time periods in 31 BD patients and 38 normal controls. Each group was divided into younger and older subgroups. General episodic memory functioning was also assessed by a word list learning task. Results: While there were no impairments in semantic AM throughout the lifetime in either group, both the younger and older BD groups exhibited impairments in incident AM compared to controls, and this effect was more profound in the recent period in the older BD group. Performance on the word list learning test was not impaired in either subgroup of BD patients, indicating that general episodic memory function was preserved. Conclusions: We are the first group to report relatively selective AM impairments in BD, which have severer effects upon recent incident memory, and seemed to worsen with aging and/or clinical course.
Is the Stressor Criterion Dispensable?
Authors: Kraemer Bernd , Wittmann Lutz , Jenewein Josef , Maier Thomas , Schnyder Ulrich
Published: August 2009

Background: The stressor criterion (criterion A) in the DSM-IV diagnosis of posttraumatic stress disorder (PTSD) is frequently questioned. To explore the clinical and diagnostic usefulness of criterion A, we examined its value in predicting and capturing PTSD symptom clusters (criteria B–D) in a sample of trauma survivors. Method: We studied 342 adult German-speaking Swiss tourists affected by the 2004 tsunami. We analyzed sensitivity and specificity, predictive value and variance explanation of criterion A for evoking PTSD criteria B–D. Results: Sensitivity of criterion A for PTSD criteria B–D was 93.2%, while positive predictive value was 23.1%. Criterion A made a small, yet statistically significant contribution of 7.5% for PTSD symptom clusters B–D. Conclusion: The assessment of criterion A (A1 and A2) is not necessary for the identification of individuals suffering from PTSD symptoms according to DSM-IV. We suggest therefore that criterion A is a dispensable part of the diagnosis of PTSD.
Is There Still a Role for Measuring Serum Urea in an Age of eGFR? Evidence of Its Use when Assessing Patient Hydration
Authors: Shepherd John , Hatfield Steve , Kilpatrick Eric S.
Published: August 2009

Background: With the current practice of using estimated glomerular filtration rate (eGFR) for the assessment of renal function, serum urea is arguably a redundant test. However, with little evidence, it is purported that urea can be used as a marker to aid in the assessment of hydration status. The aim of this study was to compare serum urea and eGFR with urine specific gravity (USG) to establish how each compares with this surrogate marker of hydration status. Methods: The study subjects comprised 2,547 separate acute hospital attendances (1,489 female, 1,058 male; median age (IQR) 60 (39–81) years) where USG and serum urea and creatinine were measured immediately on admission. Results: A significant rise in the median serum urea concentration was observed with increasing categories of USG (p < 0.0001). In contrast, a significant trend was not observed for eGFR vs. USG (p = 0.65). Conclusion: Serum urea concentration is significantly affected by hydration status whereas eGFR is not.
Correlation of Retinal Sensitivity and Retinal Thickness in Central Serous Chorioretinopathy
Authors: Dinc Umut Aslı , Yenerel Melda , Tatlipinar Sinan , Gorgun Ebru , Alimgil Levent
Published: August 2009

Aim: To evaluate the correlation of microperimetry (MP) and optical coherence tomography (OCT) in eyes having acute onset of central serous chorioretinopathy (CSCR). Methods: After a detailed ophthalmological examination, all cases were evaluated by fundus fluorescein angiography, OCT and MP. Mean macular thickness was detected by OCT. Mean macular sensitivity (MS) and mean defect (MD) were determined by MP. The correlation between OCT and MP findings was analyzed by Spearman’s correlation test. Results: Fifteen eyes with CSCR of 15 patients with a mean age of 40.5 ± 6.7 years were recruited. The mean visual acuity was 0.7 ± 0.2, and the mean macular thickness was 348.9 ± 75.8 μm. Mean MS and MD were 13.9 ± 4.6 and –5.2 ± 4.1 dB, respectively. The mean macular thickness was significantly correlated with both mean MS and MD (p = 0.011 and p = 0.017, respectively). A significant correlation was also found between mean macualt thickness, MS and MD in the central 1 mm, superior 3 mm and nasal 3 mm of the macula (p < 0.05). Conclusions: Our results demonstrated a significant correlation between structural and functional changes in CSCR. MP provides quantitative measurements of central macular function in CSCR that may supplement OCT findings as well as the better understanding of visual functions during the acute stage of the disease.
Clinicopathologic Report of Uveal Melanoma with Persistent Exudative Retinal Detachment after Gamma Knife Radiosurgery
Authors: Song Won Kyung , Yang Woo Ick , Byeon Suk Ho , Koh Hyoung Jun , Kwon Oh Woong , Lee Sung Chul
Published: August 2009

Aims: Our purpose was to report the clinical and pathological findings from uveal melanoma patients with persistent exudative retinal detachment (RD) after Gamma Knife radiosurgery (GKR). Methods: A retrospective review was performed. Results: GKR was performed on 19 uveal melanoma patients from 2004 to 2006, and 5 of them developed persistent exudative RD. The mean initial largest basal tumor diameter in these 5 patients was 14.4 ± 1.9 mm, and the mean tumor height was 9.2 ± 1.0 mm. Marginal doses of 40–50 Gy radiation were administered. RD developed or had become aggravated an average of 3 (1–10) months after GKR. Two patients underwent enucleation, while the remaining 3 underwent tumor removal by endoresection with retinal reattachment surgery by vitrectomy and silicone oil tamponade. These procedures were undertaken an average of 6.3 (1.5–14) months after radiation and 3.3 (0.5–5) months after the onset or aggravation of RD. Histologically 4 tumors showed 50–100% necrosis without any mitotic activity. Thus local tumor control after GKR appeared sufficient regardless of RD. Conclusion: Aggravation or development of exudative RD after GKR does not necessarily entail treatment failure. Therefore, retinal reattachment surgery in persistent exudative RD may be an option to preserve the eye.
Learning Curve of the Scleral Buckling Operation: Lessons from the First 97 Cases
Authors: Sagong Min , Chang Woohyok
Published: August 2009

Background/Aims: To provide an insight into the learning curve associated with scleral buckling surgery for an ophthalmologist on a fellowship course and to evaluate risk factors affecting outcomes during this period. Methods: Retrospective data were collected on 97 consecutive scleral buckling procedures (divided into 3 consecutive groups) performed by one surgeon (W.C.) beginning his first fellowship year. We evaluated the anatomic results, operative times and complications, and sought to identify risk factors of anatomic failure. Results: The single-operation success rate was 71.9% (23 of 32 eyes) in the first group, which was lower than 87.5% (28 of 32 eyes) in the second and 84.8% (28 of 33 eyes) in the third. The operative time was 106.3 min in the first, which is longer than 86.5 min in the second and 73.8 min in the third group. Factors predictive of unfavorable anatomic outcome were multiple breaks and multiple buckling procedures in the first 32 cases, and multiple breaks and breaks located posterior to the equator in the latter 65. Conclusion: Surgical experience of approximately 30 cases was required to achieve stable clinical results. Thus, a retinal surgeon at the beginning of his career may increase his success rate by careful case selection avoiding high-risk groups until he reaches the level of experience indicated by the learning curve.
Content Quality of Ophthalmic Information on the Internet
Authors: Schalnus Rainer , Aulmann Georg , Hellenbrecht Anja , Hägele Michael , Ohrloff Christian , Lüchtenberg Marc
Published: August 2009

Purpose: Little is known whether information about eye conditions on the Internet is complete and accurate to support patient or layman decision making. Methods: Quality of content modules about age-related macular degeneration (AMD) was analyzed on 20 web sites. Content analysis covered 72 criteria in 11 groups. Each single criterion was rated with ‘1’ or ‘0’ (yes/no answer). Results: The interrater reliability between two observers was almost perfect (κ = 0.86). On average, 25.6% (±15.6) of the criteria were fulfilled. In the categories diagnostic procedures, therapy, preventive checkups, prevention and prognosis of AMD, only 12.7, 18.3, 20.0, 25.0 and 30.0%, respectively, of the required content was given. Conclusion: Our study shows, based upon the example of university eye hospitals, that the full potential to provide laymen with firsthand and up-to-date information has by far not yet been achieved. Further research is needed on how the Internet influences the communication between patient and ophthalmologist.
Survival of Corneal Allografts following Topical Treatment with the Immunomodulator Mycophenolate Mofetil
Authors: Bertelmann Eckart , de Ruijter Maurice , Gong Nianqiao , Knapp Sigrid , Pleyer Uwe
Published: August 2009

Aims: To evaluate the efficacy and safety of topically applied mycophenolate mofetil (MMF) for the prophylaxis of corneal graft rejection in an experimental keratoplasty model. Methods: A total of 12 female Lewis rats received 3.5-mm MHC I/II-incompatible corneal grafts from DA donors. Recipients were randomly assigned to receive either topical MMF + β-cyclodextrin therapy (1%), β-cyclodextrin therapy alone or to remain untreated. Therapy was applied every 2 h (over 24 h) during the first 3 postoperative days, then twice hourly during daytime. Grafts were graded every day based on a rejection score including the parameters transplant clarity and edema. Results: The mean survival time (MST) of the grafts in the MMF-treated group was 12 days, the MST in the vehicle-treated group was 14.3 days and the MST in the untreated group was 13.3 days. So, the survival curves of the 3 treatment groups did not differ significantly. Conclusion: Topical MMF is ineffective for prophylaxis of corneal graft rejection.
Transformed Alpha-Fetoprotein (t-AFP) Levels in Women with Threatened Preterm Labor
Authors: González-Bugatto Fernando , de los Ángeles Bailén María , Fernández-Macías Rosa , Fernández-Deudero Álvaro , Hervías-Vivancos Blas , Bartha José L.
Published: August 2009

Background/Aims: To evaluate maternal serum transformed α-fetoprotein (MSt-AFP) levels, a new molecular conformation of AFP was used in cases of threatened preterm labor (TPL). Methods: Prospective case-control study. Maternal serum levels of classical AFP and transformed AFP (t-AFP) were compared between 2 groups matched by gestational age: 25 women with TPL and 25 healthy pregnant women as controls. Results: There was no significant difference in classical maternal serum AFP (MSAFP) levels between the 2 groups. In contrast, MSt-AFP levels were significantly lower in cases of TPL than in the control group [7.64 (1.78–29.06) vs. 33.38 (13.80–190.50) ng/ml; p = 0.006]. Similarly, the t-AFP:AFP ratio was also decreased in the TPL group [0.04 (0.004–0.12) vs. 0.16 (0.05–0.80); p = 0.008]. There was no significant correlation between MSAFP and MSt-AFP levels. Conclusions: MSt-AFP levels are decreased in women with TPL.
Concentrations of Metals, β-Amyloid and Tau-Markers in Cerebrospinal Fluid in Patients with Alzheimer’s Disease
Authors: Gerhardsson Lars , Blennow Kaj , Lundh Thomas , Londos Elisabet , Minthon Lennart
Published: August 2009

Background/Aims: In this study, metal concentrations were related to the levels of well-known Alzheimer markers in cerebrospinal fluid (CSF), such as amyloid-beta (Aβ), total tau (T-tau) and phosphorylated-tau (P-tau). Methods: Concentrations of 19 metals (Mg, Ca, V, Mn, Fe, Co, Ni, Cu, Zn, Se, Rb, Sr, Mo, Cd, Sn, Sb, Cs, Hg and Pb by inductively coupled plasma-mass spectrometry) and the levels of Aβ, T-tau and P-tau in CSF were determined (xMAP technology) in 264 patients with Alzheimer‘s disease (AD), and in 54 healthy referents. Results: The AD subjects showed positive correlations between CSF-T-tau and CSF-P-tau versus CSF-Mn (rs = 0.22, p = 0.004; rs = 0.18, p = 0.021). CSF-T-tau, however, showed a negative correlation with CSF-Cs (rs = –0.17; p = 0.027). In subjects with severe AD, CSF-Aβ showed a strong positive correlation with CSF-Cs (rs = 0.49; p = 0.026), while CSF-T-tau showed a strong negative correlation with CSF-Cs (rs = –0.49; p = 0.026). Also, CSF P-tau was negatively associated with CSF-Cs (rs = –0.41; p = 0.06). Conclusion: The different relationships between the CSF-levels of Aβ and tau-markers versus the levels of CSF-Mn and CSF-Cs may be due to different binding affinity between these metals and metal binding proteins in the CSF and the surrounding brain.
Mesh Fixation with Autologous Platelet-Rich Fibrin Sealant in Inguinal Hernia Repair
Authors: de Hingh I.H.J.T. , Nienhuijs S.W. , Overdevest E.P. , Scheele K. , Everts P.A.M.
Published: August 2009

Background: Chronic pain is the main complication following inguinal hernia repair. A possible explanatory factor is the suture fixation of the mesh. Glue fixation might overcome this problem. Albeit at a very low frequency, human and bovine components of fibrin sealants currently available could contain blood-borne pathogens. Autologous platelet-rich fibrin sealant (P-RFS) eliminates this risk and has additional advantages such as hemostatic and antibacterial effects. Therefore, its feasibility was assessed in inguinal hernia repair, with a focus on pain. Methods: In 22 patients with primary inguinal hernia, the mesh was fixated with P-RFS. Data included operative variables, complications, pain scores and neurological examinations. Long-term follow-up was 22.2 months (SD 2.2) postoperatively. Results: After 2 weeks, visual analogue scale and disability pain scores were lower than they were preoperatively. Complications at 3 months were 1 recurrence, 1 chronic pain and 6 sensory disturbances. At the last clinical evaluation, the recurrence was planned for repair due to discomfort. No chronic pain, sensory disorders or discomfort was reported at long-term follow-up. Conclusion: Mesh fixation with autologous P-RFS is feasible. If there is a preference for autologous material, P-RFS is indicated. If glue fixation becomes standard, further randomized studies are warranted for this alternative.
Thromboxane B2 Synthesis in Human Platelets Induced by the Late Complement Components C5b-9
Authors: Betz Margarita , Seitz Michael , Hänsch Gertrud Maria
Published: August 2009

Sublytic doses of purified C5b6, C7, C8 and C9 induce the release of thromboxane B2 (TXB2) in human platelets. In the present study, we attempted to analyze the signal by which C5b-9 triggers the prostanoid synthesis in platelets. TXB2 release was accompanied by liberation of Ca++ from intracellular stores. Influx of Ca++ was not observed, indicating that C5b-9 did not form a channel large enough to permit passage of Ca++ ions. Therefore, channel formation is apparently not required for cell stimulation.
Contribution of Basophil/Mast Cell and Eosinophil Growth and Differentiation to the Allergic Tissue Inflammatory Response
Authors: Denburg Judah A. , Otsuka Hirokuni , Ohnisi Masaki , Ruhno John , Bienenstock John , Dolovich Jerry
Published: August 2009

The mechanisms underlying allergic tissue basophil/mast cell (BMC) or eosinophil (Eo) accumulation are unclear, especially since chemotaxis or IgE levels do not offer a sufficient explanation. We have found that a formaldehyde-blockable, steroid-responsive nasal metachromatic cell (NMC) population predominates in epithelium and correlates well with symptoms and signs in patients with allergic rhinitis. Circulating BMC and Eo progenitors (colony-forming cells in culture; CFU-c) are increased in atopic patients, inversely related to NMC counts, and fall as NMC numbers rise during seasonal allergen (ragweed pollen) stimulation. The metachromatic cell progeny of these CFU-c are also formaldehyde-blockable in their staining reaction and thus may correspond to NMC. Human nasal polyps yield BMC CFU-c. Nasal polyp epithelial scrapings or mononuclear cells, T lymphocytes or keratinocytes in vitro all produce potent BMC or Eo colony-stimulating activities (CSA) as well as an interleukin-3-like activity, each of which is partially separable from the others. Nasal epithelial cells cultured from scrapings of atopic, as opposed to nonatopic, patients also produce BMC or Eo CSA with an enhanced effect of the former on atopic peripheral blood CFU-c growth. These studies support the hypothesis that BMC and Eo accumulate in allergic inflammation as a result of in situ growth and differentiation of progenitors stimulated by soluble hemopoietic factors derived from mucosal cell populations.
Biochemical Characterization of the Human Basophil-Promoting Activity
Authors: Stadler Beda M. , Hirai Koichi , Brantschen Stefan , Nakajima Kazunori , de Weck Alain L.
Published: August 2009

Human T cells produce a factor that induces growth of metachromatically staining cells in human bone marrow cultures. These cultured cells contain metachromatically staining granules and release histamine upon triggering with IgE and anti-IgE antibody. Based on morphological criteria, these cultured cells were termed basophil-like cells. We have generated a human T hybridoma which produces this basophil-like cell-promoting activity (BaPA). BaPA has a molecular weight of approximately 20 kilodaltons and isoelectric points between pH 5.8 and 7.5, with a major peak at pH 7. BaPA is of protein nature and can be clearly separated from interleukin-1 (IL-1), IL-2, interferons, GM-CSF and M-CSF. BaPA is also clearly different from a human IL-3-like activity which by itself can induce growth of metachromatically staining cells containing lower histamine levels than the cells cultured in the presence of BaPA. The growth of human basophil/mast cell-like cells can furthermore be enhanced if human bone marrow cells are cultured in the presence of fibroblast feeder cells.
Mediator Release from Basophilic Cells Derived from Cultured Cord Blood Cells
Authors: Iikura Y. , Nagakura T. , Nakamura N. , Shichijo K. , Saito N.
Published: August 2009

Mononuclear cells from human umbilical cord blood were separately cultured either in the presence of phorbol ester-phytohemagglutin-leukocyte-conditioned medium (PE-PHA-LCM) or PHA-LCM. Cells cultured in PE-PHA-LCM released histamine following calcium ionophore and compound 48/80 challenge. However, there was a similar histamine release from cells cultured in the presence of PHA-LCM following calcium ionophore but not following compound 48/80 challenge. Neutrophil chemotactic activity (NCA), recognized to be one of the markers for mast cell activation, was detected following calcium ionophore and anti-IgE challenge from the supernatant of cells cultured in the presence of PHA-LCM, suggesting unique features in the cells studied.
Acid Anhydrides and Asthma
Authors: Newman Taylor A.J. , Venables K.M. , Durham S.R. , Graneek B.J. , Topping M.D.
Published: August 2009

We have studied asthma caused by inhaled acid anhydrides as a model of hapten-induced airway hyperresponsiveness. Inhalation tests with the relevant anhydride in sensitised individuals reproducibly provoked a significant increase in non-specific airway responsiveness identifiable 3 h after the test and prior to the development of the late asthmatic reaction. Seven cases of asthma caused by tetrachlorophthalic anhydride (TCPA) had specific IgE in their serum to a TCPA-human serum albumin conjugate. RAST inhibition studies showed the anhydride to be involved in the antibody-combining site. Survey of the factory population where these 7 cases worked allowed investigation of the determinants of the specific IgE response: its presence was associated with intensity of exposure and current cigarette smoking; in addition smoking interacted with atopy to increase the prevalence of specific IgE. During a 5-year period of avoidance of exposure to TCPA specific IgE declined exponentially with a half-life of one year, suggesting continuing IgE secretion. Five years after avoidance of exposure, airway hyperresponsiveness remained increased in several cases.
Level of Indoor Allergens in Dust from Homes of Allergic and Non-Allergic Individuals
Authors: Schwartz B. , Lind P. , Løwenstein H.
Published: August 2009

In a number of studies performed on different locations throughout the world and in homes inhabited both by healthy individuals as well as by patients allergic to the specific allergen, the content of the major allergens from the house dust mite (Der p I, m I and f I), cat (Fel d I) and dog (Ag 3, 13) was measured. The comparison between homes of allergies and non-allergies revealed a tendency to high levels of cat allergens in homes of non-allergies. The content of the mite allergens showed large variations both with respect to the total amount of mites and the species of the mites.
Antigenic Challenge via the Airway Alters the Permeability of the Trachea in Sensitized Rats
Authors: Carswell F. , Mukherjee S. , Heap P.
Published: August 2009

Inbred rats were sensitized by intraperitoneal injection of DNP19 ovalbumin (DNP-OA) or saline. The rats were subsequently challenged by exposure to an aerosol of DNP-OA or bovine gamma globulins (BGG) for 10 min. Tracheal tissue was processed immediately after challenge in fixative containing 1% lanthanum. Planimetry of transmission electron micrographs showed 59% of the intraepithelial membranes were stained with lanthanum in the DNP-OA-sensitized and DNP-OA-challenged group; 39% in the saline-sensitized, DNP-OA-challenged group, and 26% in the DNP-OA-sensitized, BGG-challenged group. X-ray static probe microanalysis confirmed that most lanthanum penetrated in the DNP-OA-sensitized and DNP-OA-challenged group. In this group, the magnitude of the mechanical response, measured by body plethysmography, correlated directly (r = 0.74) with the lanthanum penetration. Our results confirm that increased permeability of the intercellular spaces occurs in immediate pulmonary hypersensitivity. They suggest that this change in permeability may be involved in producing the mechanical response.
A Canine Model for the Study of Hapten-Specific Suppression of IgE-Mediated Bronchoconstriction and Anaphylaxis
Authors: Kepron W. , Jackson C.-J. , Sehon A.H.
Published: August 2009

Newborn mongrel dogs were sensitized with conjugates of ovalbumin (OA) and 2,4-dinitrophenol (OA-DNP3) in the presence of Al(OH)3 to produce high levels of anti-OA and anti-DNP IgE antibody. At 4–6 months of age, when anti-DNP and anti-OA antibody levels reached titers of 64 by passive cutaneous anaphylaxis, the dogs underwent separate inhalation and intravenous challenges with conjugates of DNP and bovine gamma globulin (DNP15-BGG) and OA. Inhalation challenge with DNP15-BGG and OA resulted in 5- and 10-fold increases in airflow resistance, respectively. Intravenous challenge with either DNP15-BGG or OA produced profound anaphylaxis with 60–80% decreases in blood pressure, cardiac output and regional blood flows in the carotid, superior mesenteric and renal arteries, and the distal aorta. Treatment of sensitized dogs with 5 doses of 20 mg of conjugates of DNP and polyvinyl alcohol (DNP2-PVA) on alternate days resulted in (1) suppression of anti-DNP IgE antibody production; (2) abrogation of established airway and vascular anaphylactic sensitivities; (3) no change in regional blood flows, and (4) no effect on sensitivities to challenge with OA.
Immunoglobulin G Subclass Deficiencies
Authors: Söderström T. , Söderström R. , Avanzini A. , Brandtzaeg P. , Karlsson G. , Hanson L.Å.
Published: August 2009

Low levels of single or multiple serum immunoglobulin G (IgG) subclasses is a common finding among patients with increased susceptibility to infections. In this investigation we summarize data from studies of 503 subclass-deficient individuals. Low IgG2 levels was the most common deficiency among children, and boys were more often deficient than girls. From the age of 16, females dominated, and the most frequent finding was low IgG3 levels. In vitro T or B lymphocyte dysfunction was demonstrated in 75% of the individuals, suggesting that low subclass levels may be indicators of an underlying defect at the B cell or possibly T cell level. Vaccinations and mucosal biopsies were performed to evaluate which patients may be helped by immunoglobulin substitution therapy.
Comparison of the Frequency of Atopic Diseases in Children with Severe and Partial IgA Deficiency
Authors: Plebani A. , Monafo V. , Ugazio A.G. , Monti C. , Avanzini M.A. , Massimi P. , Burgio G.R.
Published: August 2009

Similar frequencies of atopic diseases and of elevated total serum IgE levels were observed in 40 children with serum IgA levels below 5 mg/dl and absence of salivary IgA (severe selective IgA deficiency, SIgAD) and in 40 children with serum IgA levels above 5 mg/dl but below -2 SD of age-normal mean values and presence of salivary IgA (partial SIgAD). These findings suggest that the absence of secretory IgA, which has been postulated to play a protective role by excluding allergens at the mucosal level, does not appear to play a crucial role in the pathogenesis of atopic diseases.
Screening for Anti-HTLV-III/LAV Antibody in High-Risk Subjects: Sensitivity and Specificity of Commercial Tests
Authors: Lantin J.P. , Peitrequin R. , Frei P.C.
Published: August 2009

1,834 serum samples from high-risk subjects were tested for anti-HTLV-III/LAV antibody by using the enzyme immuno assay (EIA) of Abbott (A), or the EIA of Abbott and Pasteur (P), or those two EIA plus Western blot analysis (WB). 983 samples were negative in A, 766 were strongly positive when tested in duplicate with both A and P, and 85 were slightly positive in A (23 samples) or discordant (62 samples) when tested further in P and WB. Of 62 discordant samples, 38 were reproducible. The pattern A+P––WB–– was by far the most frequently encountered (26 samples) and interpreted as reflecting the higher incidence of positive results in the assay A. If one assumes that WB results are correct, the specificities of A and P are 93 and 100%, respectively (p <0.01), whereas the sensitivities are similar (98 and 99%).
Effect of Growth Factors on the Proliferation of Thymocytes in Different Functional and Anatomical Compartments
Authors: Sandberg G. , Ernström U. , Söder O. , Kölare S.
Published: August 2009

The intrathymic location of cells responding to the thymocyte growth peptide (TGP) was investigated in guinea pigs. Thymus cells were labelled by topical application of a fluorescein isothiocyanate solution, and the percentage of fluorescent cells analyzed by flow cytometry. Large cells forming rosettes with rabbit erythrocytes, known to respond to TGP, had a lower percentage of fluorescent cells than non-rosetting cells, which do not respond to TGP. If the TGP-responding cells are anatomically segregated in the guinea pig thymus, this might indicate that they are preferentially located in the deep, juxtamedullary part of the cortex, where one major proliferating compartment is situated.