bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic Human Papillomavirus Vaccination
Authors: Albers Andreas E. , Kaufmann Andreas M.
Published: August 2009

Despite impressive progress in prevention and therapy of premalignant and malignant dysplasia the worldwide burden of cancer is relatively unchanged. Supplementation of the therapeutic arsenal by immunotherapeutic methods would have the potential to make a significant impact. Dysplastic lesions and cancer of the cervix show strong association with human papillomaviruses (HPV), as do tumours of other mucosal epithelia like squamous cell carcinoma of the head and neck. Such tumours are distinct from most other malignancies in that they harbour foreign antigens derived from the virus. The expression of viral oncogenes is necessary to maintain the cancerous phenotype. Therefore, these antigens are unique to the tumour and very attractive targets for ‘proof of concept’ studies in the development of therapeutic vaccinesshowing the general applicability of tumour vaccination and prove the correlation of immune response and clinical response. To date numerous clinical trials have been performed with candidate vaccines predominantly for cervical cancer and its precursors. Although a naturally induced anti-HPV T cell response in patients can be shown, the success of therapeutic vaccines has so far been limited. This can probably be attributed to immunosuppression, immunoselection and immunoediting of the tumour cells and other, mostly unknown, factors of the individual contributing to the failure of autonomous clearance of the infection. Overriding this failure, reversing immunosuppression and application in early stages of the disease are the key tasks for future development of therapeutic vaccines. This review will summarize the basis and recent developments of therapeutic vaccines and discuss obstacles that hinder their success.
Integrating Human Papillomavirus Vaccination in Cervical Cancer Control Programmes
Authors: Franco Eduardo L. , Coutlée François , Ferenczy Alex
Published: August 2009

Screening with Pap cytology has substantially reduced cervical cancer morbidity and mortality during the last 50 years in high-income countries. Unfortunately, in resource-poor countries, Pap screening has either not been effectively implemented or has failed to reduce cervical cancer rates. Cervical cancer in these countries thus remains a major public health problem. Infection with certain human papillomavirus (HPV) types is now recognized as a necessary cause of this disease and has led to new preventive strategies for cervical cancer. Testing for HPV DNA of oncogenic types is gaining increasing interest and application in cervical cancer screening. It has much greater sensitivity and only slightly lower specificity than Pap cytology. Molecular-based screening will be of particular clinical value in the post-vaccine era in which cervical disease will be a rare event and may escape cytology-based detection. As a primary screening test followed by Pap triage of HPV-positive cases, HPV testing has the potential to improve the overall quality of screening programmes, thus allowing for increased testing intervals, which would lower program costs with acceptable safety. Prophylactic vaccines against the 2 leading oncogenic HPV types (16 and 18) have been recently licensed. In large clinical trials, they have shown excellent safety and nearly 100% efficacy in preventing persistent infections and the cervical pre-cancers due to vaccine HPV types 16 and 18. Combining modern screening techniques and universal prophylactic HPV vaccination is likely to produce the most advanced and cost-effective preventive strategy to fight cervical cancer worldwide.
Sex Determination Diversity and Sex Chromosome Evolution in Poeciliid Fish
Authors: Schultheis C. , Böhne A. , Schartl M. , Volff J.N. , Galiana-Arnoux D.
Published: August 2009

Poeciliids, a family of live-bearing freshwater fish, including among others platyfish, swordtails and guppies, fully illustrate the diversity of genetic sex determination mechanisms observed in teleosts. Besides unisexuality, a variety of sex-determining systems has been described in this group of fish, including male and female heterogamety with or without autosomal influence, as well as more complicated situations such as multichromosomal and polyfactorial sex determination. Due to the presence of different mechanisms in closely related species or even between populations within a same species, poeciliids are a very attractive model to study the evolutionary dynamics of sex determination. For one species, the Southern platyfish Xiphophorus maculatus, positional cloning of the master sex-determining gene has been initiated through the construction and sequencing of bacterial artificial chromosome contigs covering the region differentiating the X from the Y chromosome. Initial analysis revealed a high plasticity of the sex-determining region and the absence of synteny with other fish and vertebrate sex chromosomes, indicating an independent evolutionary origin.
The Sex Determining Loci and Sex Chromosomes in the Family Salmonidae
Authors: Davidson W.S. , Huang T.-K. , Fujiki K. , von Schalburg K.R. , Koop B.F.
Published: August 2009

Salmonids are descended from a common ancestor that underwent an autotetraploidization event. After a whole genome duplication species could deal with sex determination by deleting one copy of SEX, the sex determining locus, or by recruiting a duplicated transcription factor to become a novel sex determining gene. It is not known which if any of these strategies salmonids adopted, but it appears that they all have primarily a genetic mechanism of sex determination with male heterogamety. The sharing of sex-linked markers on the X and Y chromosomes and the difficulty in identifying Y-specific markers indicate that X and Y chromosomes in salmonids have a large pseudoautosomal region and a small sex determining region. Linkage analyses suggest that either SEX differs in different lineages or else has remained the same and moved by transposition to different chromosomes. The identification of the sex chromosomes in salmonid species has not resolved this issue. It is clear that salmonids are at an early stage in sex chromosome differentiation and therefore provide a wonderful opportunity to study the evolution of sex determination. The availability of a reference salmonid genome sequence would provide an important resource for research in this area.
Effects of Endocrine Disrupters on Sexual, Gonadal Development in Fish
Authors: Scholz S. , Klüver N.
Published: August 2009

Steroid sex hormones play an important role in the sexual differentiation of fish. Thus, it is not surprising that chemical contaminants with steroid-like activities were considered as responsible for the unusual occurrence of gonadal intersex conditions and other gonadal aberrations in feral fish. In this review, we give an overview about field data and summarise and categorise experimental evidence that links disruption of gonadal development in gonochoristic fish to contaminations by endocrine disrupting chemicals. A comprehensive overview on laboratory studies using water-borne exposures and histopathological analysis is given. Parameters ranging from simple quantitative characteristics such as sex ratio, number of sex reversed fish, and gonadosomatic index (GSI) to detailed morphometric analyses have been considered. Categorisation of the data indicates 2 major groups of chemicals with apparently conserved effects across species, i.e. estrogenic/anti-androgenic or androgenic/anti-estrogenic compounds. Since gross morphological parameters and histological analysis are often the first parameters measured in field campaigns for sampling of feral fish, the review supports the critical evaluation of present and future field studies and the confirmation or rejection of causative links to exposure with endocrine disrupting chemicals. Furthermore, in combination with the analysis of molecular endpoints the processed data will be useful to deduce mechanistic information on potential endocrine disrupting compounds.
Erythropoietin Sustains Cognitive Function and Brain Volume after Neonatal Stroke
Authors: Gonzalez Fernando F. , Abel Regina , Almli C. Robert , Mu Dezhi , Wendland Michael , Ferriero Donna M.
Published: August 2009

Neonatal stroke leads to mortality and severe morbidity, but there currently is no effective treatment. Erythropoietin (EPO) promotes cytoprotection and neurogenesis in the short term following brain injury; however, long-term cognitive outcomes and optimal dosing regimens have not been clarified. We performed middle cerebral artery occlusion in postnatal day 10 rats, which were treated with either a single dose of EPO (5 U/g, i.p.) immediately upon reperfusion, or 3 doses of EPO (1 U/g, i.p. each) at 0 h, 24 h, and 7 days after injury. At 3 months after injury, rats treated with 3 doses of EPO did not differ from shams in the Morris water maze, and generally performed better than either rats treated with a single dose or vehicle-treated injured rats. These multiple-dose-treated rats also had increases in hemispheric volume and its subregions. These results suggest that additional, later doses of EPO may be required for cell repair, proliferation, and long-term incorporation into neural networks after neonatal brain injury.
Expression of MMP-12 after Neonatal Hypoxic-Ischemic Brain Injury in Mice
Authors: Svedin Pernilla , Hagberg Henrik , Mallard Carina
Published: August 2009

Matrix metalloproteinase-12 (MMP-12) is expressed in the brain and is important for myelin formation in the developing brain, while MMP-12 deficiency protects against spinal cord injury in the adult, suggesting a role for MMP-12 after brain injury. However, the role of MMP-12 in neonatal hypoxic-ischemic brain injury is not known. The purpose of this study was to investigate the expression of MMP-12 in the brain after neonatal hypoxia-ischemia (HI). HI was induced by unilateral ligation of the left carotid artery followed by hypoxia (10% O2, 36°C) for 50 min in postnatal day 9 C57/Bl6J mice. At 24 and 72 h after HI, the mRNA and protein expression of MMP-12 were measured by real-time PCR and Western blot, respectively. Distribution and cellular expression of MMP-12 were examined by immunohistochemistry. At 72 h after HI, both MMP-12 mRNA and protein expression were significantly increased in the ipsilateral hemisphere compared to the contralateral hemisphere and sham-operated animals (p < 0.05). The extent of tissue loss in the ipsilateral hemisphere at 72 h after HI was positively correlated with the degree of MMP-12 protein expression (r = 0.900, p < 0.05). In nonischemic animals, immunohistochemical analysis demonstrated weak cytoplasmic MMP-12 immunoreactivity throughout the brain in cells which resembled neurons and stronger immunoreactivity was observed in blood vessels. After HI, the MMP-12 staining became more prominent in the ipsilateral hemisphere and immunohistochemical double-labeling experiments identified the MMP-12-positive cells as neurons, isolectin and Olig2-positive cells. This study demonstrates that MMP-12 is upregulated after HI, suggesting that MMP-12 may contribute to injury in the immature brain, similar to that seen in the adult.
Astrocytic Demise in the Developing Rat and Human Brain after Hypoxic-Ischemic Damage
Authors: Gelot Antoinette , Villapol S. , Billette de Villemeur Thierry , Renolleau Sylvain , Charriaut-Marlangue Christiane
Published: August 2009

In order to approach the physiopathological mechanism underlying the selective susceptibility of the immature brain to hypoxia-ischemia (HI), we have compared the lesions experimentally induced in postnatal day 7 rats using a model of neonatal stroke with those occurring in human fetal and neonatal brains. We first observed that gray and white matter lesions demonstrated a similar organization (core with cell loss and/or cavity and penumbra) and evolutionary pattern between experimental and human HI lesions. We then observed that, in the intermediate white matter, GFAP- and vimentin-positive astrocytes exhibited clasmatodendrosis and represent a major cell population involved in cell death in human brains (56.3 and 67.9%, respectively). In rat brains, GFAP- and TUNEL-positive astrocytes were also highly vulnerable, increasing between 6 (31%) and 72 (58%) hours after ischemia. Together, these results indicate that astroglial dysfunction may play a critical role in determining the progress and outcome of acute hypoxic-ischemic injury particularly in the developing brain.
SNAP-II and SNAPPE-II and the Risk of Structural and Functional Brain Disorders in Extremely Low Gestational Age Newborns: The ELGAN Study
Authors: Dammann Olaf , Naples Mary , Bednarek Francis , Shah Bhavesh , Kuban Karl C.K. , O’Shea T. Michael , Paneth Nigel , Allred Elizabeth N. , Leviton Alan
Published: August 2009

Background: Illness severity measures predict death and illnesses in the newborn. It is unknown how well they predict brain lesions evident on ultrasound scans or neurodevelopmental dysfunctions in preterm infants. Methods: A total of 1,399 inborn infants born before the 28th week of gestation were given Scores for Neonatal Acute Physiology (SNAP-II and SNAPPE-II) based on data collected within the first 12 h of admission to the intensive care unit and had a protocol brain ultrasound scan read independently by 2 sonologists. Of the surviving 1,149 infants, 1,014 (88%) had a neurologic examination at approximately 24 months post-term equivalent, and 975 (85%) had a Bayley Scales of Infant Development assessment. SNAP-II and SNAPPE-II were dichotomized at arbitrary cut-offs (30 for SNAP-II and 45 for SNAPPE-II), using the highest quartile and decile of the week of gestation as a cut-off, and at a Z score of >1 standard deviation from an external mean. Results: After adjustment for gestational age, high SNAP-II and SNAPPE-II scores predicted intraventricular hemorrhage, moderate/severe ventriculomegaly and echodense lesions in cerebral white matter. Only 2 SNAP-II extremes, the highest decile for gestational age and a Z score >1, also predicted echolucent lesions in the white matter. Neither SNAP-II nor SNAPPE-II predicted any statistically significant diagnosis of cerebral palsy. MDI and PDI scores <55 were consistently predicted by both high SNAP-II and SNAPPE-II, whereas scores in the 55–69 range were inconsistently predicted. High SNAP-II and SNAPPE-II inconsistently predicted a positive screen for autism spectrum disorder and small head circumference at 24 months. Conclusion: The physiologic instability in the first 12 post-natal hours identified by illness severity scores conveys information about the risks of brain damage and neurodevelopmental dysfunctions. This risk information might reflect postnatal characteristics in the causal chain. On the other hand, high SNAP scores might be indicators of immaturity and vulnerability.
Inhibition of Human Mesangial Cell Proliferation by Targeting T-Type Calcium Channels
Authors: Mulgrew Christopher J. , Cove-Smith Andrea , McLatchie Linda M. , Brooks Gavin , Shattock Michael J. , Hendry Bruce M.
Published: August 2009

Background: Aberrant glomerular mesangial cell (MC) proliferation is a common finding in renal diseases. T-type calcium channels (T-CaCN) play an important role in the proliferation of a number of cell types, including vascular smooth muscle cells. The hypothesis that T-CaCN may play a role in the proliferation of human MC was investigated. Methods: The presence of T-CaCN in primary cultures of human MC was examined using voltage clamping and by RT-PCR. The effect of calcium channel inhibitors, and of siRNA directed against the Cav3.2 T-CaCN isoform, on MC proliferation was assessed using the microculture tetrazolium assay and nuclear BrdU incorporation. Results: Human MC express only the Cav3.2 T-CaCN isoform. Co-incubation of MC with a T-CaCN inhibitor (mibefradil, TH1177 or Ni2+) results in a concentration-dependent attenuation of proliferation. This effect cannot be attributed to direct drug-induced cytotoxicity or apoptosis and is not seen with verapamil, an L-type channel blocker. Transfection of MC with siRNA results in knockdown of T-CaCN Cav3.2 mRNA and a clear attenuation of MC proliferation. Conclusions: These results demonstrate for the first time an important role for T-CaCN in human MC proliferation. This could potentially lead to a novel therapy in the treatment of proliferative renal diseases.
β-Blocker Prescription and Outcomes in Hemodialysis Patients from The Japan Dialysis Outcomes and Practice Patterns Study
Authors: Nakao Kazushi , Makino Hirofumi , Morita Satoshi , Takahashi Yoshimitsu , Akizawa Tadao , Saito Akira , Asano Yasushi , Kurokawa Kiyoshi , Fukuhara Shunichi , Akiba Takashi
Published: August 2009

Background/Aims: Given the clear benefits of mortality reduction observed for most β-blockers in clinical trials, they are relatively underused in hemodialysis patients. Since the outcomes associated with the use of β-blockers are not fully known, we investigated their effect on mortality among a cohort of hemodialysis patients. Methods: Data were analyzed from the Dialysis Outcomes and Practice Patterns Study phase II for 2,286 randomly selected patients on hemodialysis in Japan. Treatment with β-blockers was the major predictor variable. The main outcome measure was all-cause mortality. Cox regression analysis was used to assess an association between treatment with β-blockers and the risk of death. Results: 247 patients (11.9%) were administered β-blockers and 1,828 patients (88.1%) were not. Whereas patients treated with β-blockers had a higher prevalence of hypertension and coronary heart disease, Kaplan-Meier analysis revealed that all-cause mortality rates were significantly (p < 0.007) decreased in patients treated with β-blockers compared to those without. In multivariable, fully adjusted models, treatment with β-blockers was also independently associated with reduced all-cause mortality (hazard ratio = 0.48; p = 0.02). Conclusion: This study indicated a possible association between the use of β-blockers and reduced risk of mortality in hemodialysis patients. These results should be confirmed in further randomized controlled trials.
Albuminuria and Renal Function in Obese Adults Evaluated for Obstructive Sleep Apnea
Authors: Agrawal Varun , Vanhecke Thomas E. , Rai Baroon , Franklin Barry A. , Sangal R. Bart , McCullough Peter A.
Published: August 2009

Background: Obstructive sleep apnea (OSA) is associated with hypertension, obesity and metabolic syndrome that are risk factors for cardiovascular and chronic kidney disease. Few data are available regarding renal parameters in patients with OSA. Methods: We conducted a cross-sectional study of 91 obese adults who had routine polysomnography before bariatric surgery. Presence and severity of OSA were determined by the apnea-hypopnea index (AHI <5 = no OSA and AHI ≥5 = OSA). Clinical and laboratory data were available within a month of polysomnography. Results: Mean ± SD age was 44.9 ± 9.9 years. There were 66 women. Mean ± SD body mass index was 48.3 ± 8.9 kg/m2 with hypertension and type 2 diabetes present in 55 and 31 subjects, respectively. There were 36 subjects with no OSA and 55 with OSA. The two groups had similar demographic characteristics, blood pressure (BP), lipid profile and medication use except for difference in mean ± SD hemoglobin A1c (5.6 ± 0.6% in no OSA, 6.0 ± 0.8% in OSA; p = 0.029) and use of renin-angiotensin system blocking agents (22.2% in no OSA, 46.4% in OSA; p = 0.024). Median (interquartile range) urine albumin:creatinine ratio (ACR) was not different between the two groups [6 (4–14.5) mg/g in no OSA, 8 (5–16) mg/g in OSA; p = 0.723], while significant difference existed in serum creatinine (0.8 ± 0.2 mg/dl in no OSA, 0.9 ± 0.2 mg/dl in OSA, p = 0.013). Age- and gender-adjusted correlations were observed between log-log ACR and systolic BP (r = 0.265; p = 0.016), log-log ACR and diastolic BP (r = 0.245; p = 0.026) and between serum creatinine and log AHI (r = 0.188, p = 0.089). Multiple linear regression analysis demonstrated log-log ACR to be associated with diastolic BP (p = 0.046), while serum creatinine was associated with log AHI (p = 0.044). Conclusion: In obese adults, increasing severity of OSA is associated with higher serum creatinine but not greater degree of albuminuria.
Presence of Foam Cells in Kidney Interstitium Is Associated with Progression of Renal Injury in Patients with Glomerular Diseases
Authors: Wu Yan , Chen Yan , Chen Dan , Zeng Caihong , Li Leishi , Liu Zhihong
Published: August 2009

Background: Renal interstitial foam cells (FCs) are occasionally observed in various renal diseases. The goal of the present study was to determine the relationship between the formation of renal interstitial FCs and the degree of proteinuria and hyperlipidemia, as well as the progression of these diseases. Methods: 125 patients with Alport syndrome (AS), 192 patients with idiopathic membranous nephropathy (IMN), 388 patients with IgA nephropathy (IgAN), and 137 patients with focal segmental glomerulosclerosis (FSGS) were investigated retrospectively. Results: FCs were observed in various glomerular diseases. The frequency of interstitial FCs was 64.8% in AS, 21.4% in MN, 12.4% in IgAN, and 36.5% in FSGS. Regardless of the pathologic diagnosis of the glomerular disease, segmental glomerular sclerosis occurred more frequently in patients with FCs than in patients without FCs. In the AS or IgAN group, interstitial fibrosis was more severe, and levels of proteinuria and serum lipids were significantly higher in FC-positive patients than in patients without FCs. Conclusion: FC formation in renal interstitium is associated with the degree of proteinuria and hyperlipidemia in patients with AS and IgAN. The presence of FCs in renal interstitium may contribute to the progression of glomerular diseases.
Lack of Correlation between Calcium Intake and Serum Calcium Levels in Stable Haemodialysis Subjects
Authors: Byrne Fiona N. , Kinsella Sinead , Murnaghan Dermot J. , Kiely Mairead , Eustace Joseph A.
Published: August 2009

Background: The relationship between calcium intake and serum calcium level in hemodialysis patients is poorly understood. Methods: We quantify total oral calcium intake using detailed 7-day food diaries with 294 patient days of observation in 42 stable, non-diabetic hemodialysis subjects. Results: Mean (SD) albumin-corrected serum calcium was 9.84 mg/dl (0.8). The albumin-corrected serum calcium was low (<8.4 mg/dl) in 2 patients, low-normal (8.4–9.49) in 9 patients, high-normal (9.5–10.2) in 18 patients and high (>10.2) in 13 patients. Mean (SD) total (diet plus binder) oral calcium intake was 1996 mg/day (1,020); 16 patients (38%) had a total calcium intake >2,000 mg/day. Calcium intake and serum calcium were poorly correlated (Spearman rank method), r = 0.14, p = 0.39. Median calcium intakes were similar in those with normal (1,990 mg/day), high-normal (1,926 mg/day) and high calcium groups (1,713 mg/day), p = 0.73 (Kruskal-Wallis), p = 0.29 (linear test for trend). Forty-one percent (11/27) of patients who had serum calcium in the normal range had a calcium intake greater than 2 g/day, while 11.5% had a calcium intake greater than 3 g/day. In subjects with a parathyroid hormone (PTH) concentration <300 pg/ml (n = 20), the correlation between calcium intake and either uncorrected serum calcium or albumin-corrected serum calcium was stronger, r = 0.45, p = 0.05 and r = 0.38, p = 0.10, respectively, though there remained wide variability in calcium intake. Conclusion: Serum calcium is not a reliable indicator of calcium intake, especially at PTH ≥300 pg/ml. An excessive calcium intake may coexist with a normal serum calcium level.
A Randomized Controlled Clinical Trial Comparing the Efficacy of Dead Sea Mineral-Enriched Body Lotion versus Two Types of Placebo in the Treatment of Cutaneous Dryness, Itching, Peeling and Tightness in Hemodialysis Patients (EDIT)
Authors: Boaz Mona , Shtendik Larisa , Oron Miriam , Portugal-Cohen Meital , Kohen Ron , Biro Alexander , Cernes Relu , Barnea Zvi , Maor Zeevi , Katzir Ze’ev
Published: August 2009

Background/Aims: The present study was designed to investigate the short-term safety and efficacy of topical application with body lotion enriched with minerals from the Dead Sea versus 2 different placebo treatments in reducing symptoms of uremic pruritus. Methods: In this single-center, randomized, double placebo-controlled clinical trial, 78 hemodialysis patients with self-reported uremic pruritus were randomized to twice-daily topical treatment with body lotion enriched with minerals from the Dead Sea (DS) or to each of 2 types of placebo: (1) lotion with no Dead Sea minerals but otherwise identical to DS (P1) or (2) lotion with no active ingredients (P2). Symptoms of uremic pruritus (itching, dryness, peeling, tightness) were evaluated at baseline and 2 weeks (14 days) after treatment intervention using a 5-point Likert scale. Results: Following treatment, significant differences in symptom severity scores between DS and P1 and, separately, between group DS and P2, were not detected. Additionally, when DS was compared to the combined placebo groups (P1 and P2 together), significant post-treatment differences in symptom severity scores were not observed. Symptoms were less severe post-treatment regardless of treatment assignment. Conclusions: DS was not superior to either of the placebo treatments in the symptomatic relief of uremic pruritus.
Pregnancy and Delivery in Patients with Portal Vein Cavernoma
Authors: Ducarme Guillaume , Plessier Aurelie , Thuillier Claire , Ceccaldi Pierre François , Valla Dominique , Luton Dominique
Published: August 2009

Background: Portal vein cavernoma (PVC) is a rare disease resulting from extrahepatic portal vein thrombosis and development of collateral venous circulation. The management of pregnancy and delivery in woman with PVC has rarely been described. Cases: Two primiparous women are presented to illustrate the management of PVC during pregnancy and discuss the delivery route according to the symptoms and the PVC complications. The first patient presented PVC associated with large jejunal varices and high anticardiolipid antibodies. She was treated with β-blocker therapy and low molecular weight heparin during pregnancy, and delivered by cesarean section. The second patient presented protein S deficiency complicated by PVC and thrombocytopenia and delivered vaginally without complications. Conclusion: Many issues should be considered when counseling women with PVC, including the management before and during pregnancy according to symptoms and PVC complications. A multidisciplinary approach seems to be key to the management of delivery. Our advice to caregivers is that elective cesarean section seems necessary in cases with digestive varices. Vaginal delivery, with a passive second stage, seems to be relatively safe and less morbid in women without digestive varices, when maternal and fetal tolerance permits.
Comparison of Patient and Clinician Perspectives in the Assessment of Antipsychotic Medication Adherence
Authors: Barbui Corrado , Kikkert Martijn , Mazzi Maria Angela , Becker Thomas , Bindman Jonathan , Schene Aart , Nosè Michela , Helm Hedda , Thornicroft Graham , Tansella Michele
Published: August 2009

Background: Factors influencing patient and clinician perspectives in the assessment of medication adherence have never been compared. Method: This study used baseline and 12-month follow-up data from the QUATRO study, an international multicentre study. At baseline, information on patient sociodemographic characteristics, treatment factors, psychopathology, functioning and experience of antipsychotic side effects was gathered. After 12 months of follow-up, psychopathology, functioning and patient experience of antipsychotic side effects were measured once more, and a patient and clinician rating of adherence was obtained by means of the Medication Adherence Rating Scale (MARS) and the Compliance Rating Scale (CRS). Results: During the recruitment period, 409 subjects with a diagnosis of schizophrenia were recruited. Patients were more often men and single. Mean age was 41.5 years. At the time of the assessment, more than 40% were unemployed and on average had been on antipsychotic treatment for more than 10 years. Nearly 70% were receiving second-generation antipsychotics, and 50% received adherence therapy during the 12 months after enrolment. The relationship between the MARS and the CRS scores showed only a small overlap (correlation coefficient = 0.26). In the multivariate model, the only factor significantly associated with both patient and clinician ratings of adherence was psychopathology. Unemployment and poor subjective tolerability of antipsychotics were significantly associated with low levels of patient ratings of adherence. Conversely, length of treatments and use of newer antipsychotics were significantly associated with better clinician ratings of adherence. Conclusion: Patient and clinician ratings of adherence do not measure the same dimension. Factors that may positively affect adherence in terms of compliance with prescribed medication regimens may not affect patients’ views on adherence, and this should be taken into consideration when planning and negotiating treatment modalities with each individual patient suffering from schizophrenia.
A Comparative Study of Axis I Antecedents before Age 18 of Unipolar Depression, Bipolar Disorder and Schizophrenia
Authors: Rubino I. Alex , Frank Ellen , Croce Nanni Roberta , Pozzi Daniela , Lanza di Scalea Teresa , Siracusano Alberto
Published: August 2009

Background: Despite a large scientific literature on early clinical precursors of schizophrenia, bipolar disorder and unipolar depression, few data are available on axis I disorders preceding the adult onset of these illnesses. Sampling and Methods: Disorders before the age of 18 years were retrospectively assessed with a structured interview in 3 groups of consecutive adult inpatients with DSM-IV diagnoses of schizophrenia (n = 197), major depressive disorder (n = 287) and bipolar disorder (n = 132). Only patients with adult onset of schizophrenia and of mania/hypomania were included. A sample of the general population served as control group (n = 300). Results and Conclusion: The clinical groups significantly outnumbered the control sample on the majority of early axis I diagnoses. Schizophrenia was significantly associated (1) with attention deficit hyperactivity disorder (ADHD), ADHD inattentive subtype, ADHD hyperactive subtype and primary nocturnal enuresis, compared to unipolar depression, and (2) with social phobia and ADHD inattentive subtype, compared to bipolar disorder. Oppositional defiant disorder was significantly associated with bipolar disorder, compared to the other clinical and control groups. The ADHD hyperactive subtype predicted the adult onset of bipolar disorder compared to unipolar depression. Externalizing disorders seem of special importance as regards the clinical pathways toward schizophrenia.
Early Mood Swings as Symptoms of the Bipolar Prodrome: Preliminary Results of a Retrospective Analysis
Authors: Özgürdal Seza , van Haren Elisabeth , Hauser Marta , Ströhle Andreas , Bauer Michael , Assion Hans-Jörg , Juckel Georg
Published: August 2009

Background/Aims: Temperament and mood swings are promising indicators for the characterization of mood spectrum vulnerability. The aim of this study was to investigate the relationship between affective temperament and mood swings in bipolar disorder. We explored these clinical features retrospectively. Methods: Patients who met the criteria for bipolar I disorder were enrolled in the study. Exclusion criteria were partial remittance and a full affective or psychotic episode. Data concerning illness and family history, mood swings (semistructured interview for mood swings) and depression (Beck, Depression Inventory) were obtained. We examined premorbid temperament with the validated German version Temps-M of the original version Temps-A. Patients with and without mood swings were compared with respect to the dominant temperament. Results: Out of 20 bipolar patients, 6 subjects reported mood swings prior to the onset of affective disorder. Subjects with mood swings prior to the onset of bipolar disorder significantly correlated with a positive family history of affective disorders. Concerning cyclothymic and irritable temperament, bipolar affective patients with mood swings had higher scores. No differences were found between males and females. Conclusion: Our findings go in line with previous results that mood swings, as represented by the cyclothymic temperament, are present prior to the first onset of bipolar disorder in a subset of patients. These traits may represent vulnerability markers and could presumably be used to identify individuals at high risk for developing bipolar disorder in order to prevent this illness. Further studies are indicated to clarify the correlation with genetic risk factors.
Cardiac Repolarization Indices in Epilepsy Patients
Authors: Neufeld Gregory , Lazar Jason M. , Chari Geetha , Kamran Haroon , Akajagbor Edesiri , Salciccioli Louis , Kassotis John , Stewart Mark
Published: August 2009

Objectives: Although epilepsy may be associated with an increased risk for sudden cardiac death, its effects on Q-T intervals has not been established. Methods: To determine whether changes in Q-T interval duration (QTmax c, QTmin c) and dispersion (QTD c) occur in epileptic patients, we retrospectively studied 40 consecutive patients (age: 36.1 ± 22.2 years) who have had a seizure disorder for 14.0 ± 12.2 years and were seen in the Epilepsy Monitoring Unit, and 60 age-matched non-epileptic controls (age: 38.0 ± 15.6 years). Q-T intervals were calculated from a single 12-lead ECG. Results: QTmax c (425 ± 30 vs. 410 ± 36 ms, p = 0.040) and QTD c (63.1 ± 22.4 vs. 31.0 ± 17.2 ms, p = 0.000) were higher, and QTmin c (362 ± 36 vs. 379 ± 33 ms, p = 0.040) was lower in epilepsy patients. QTmax c was significantly correlated with disease duration (r = –0.35, p = 0.028) before, but not after age correction (r = –0.31, p = 0.053). Neither age nor reported recent seizure frequency was correlated with any repolarization index. Conclusions: QTmax c and QTD c are higher in epilepsy patients as compared to control subjects. While Q-T interval appears to be related to disease duration, particularly over the early history of disease, it is unrelated to patient age or recent reported seizure frequency.
Effectiveness of Combination Use of Antibiotic-Loaded PerOssal® with Spinal Surgery in Patients with Spondylodiscitis
Authors: von Stechow D. , Rauschmann M.A.
Published: August 2009

Degradable composites of calcium sulphate and nanoparticulate hydroxyapatite (PerOssal®) have shown promising results in vitro. Here we investigated the handling, efficacy and compatibility of PerOssal when loaded with gentamicin or vancomycin in 19 patients with spondylodiscitis in vivo. So far, 12 patients who were followed up over at least 1 year have shown a normalization of the infection parameters, no more bone loss in the affected regions and a bony fusion after 3–6 months postoperatively. No revision surgery was related to the use of PerOssal. Locally there were no signs of an ongoing infection. This study demonstrates encouraging results regarding handling, resorption, biocompatibility and antibiotic release using PerOssal pellets in vivo.
Activation of Basophils and Mast Cells for Mediator Release
Authors: Ishizaka Teruko , White John R. , Saito Hirohisa
Published: August 2009

Biochemical events involved in both IgE-dependent and IgE-independent mediator release from basophils and mast cells were analyzed. The results revealed that bridging of IgE receptors activates a variety of membrane-associated enzymes, such as serine protease, phospholipase C, methyltransferases and adenylate cyclase, resulting in the stimulation of phosphatidylinositol (PI) turnover and a transient increase in both phospholipid methylation and intracellular cAMP. Mobilization of intracellular Ca2+ monitored by Quin-2 fluorescence is detected within 5 s after antigen challenge and appears to be the earliest intracellular change detectable after receptor bridging. Stimulation of PI turnover results in the generation of inositol 1,4,5-triphosphate (IP3) and of 1,2-diacylglycerol (DAG), which in turn activates protein kinase C. Evidence was obtained that the guanyl nucleotide (GTP)-binding protein Ni is not involved in the transduction of IgE-mediated triggering signals for mediator release. Although the sequence of enzyme activation following receptor bridging is not clear, the results suggest that the mobilization of intracellular Ca2+ is a crucial initial signal in the IgE-mediated activation of basophils and mast cells. In the mediator release induced by IgE-independent stimuli, enzymes involved in the mediator release are different from one stimulus to another. The results indicate the presence of multiple biochemical pathways for mediator release from basophils and mast cells.
Nonsteroidal Antiinflammatory Drugs Induce UV-Dependent Histamine and Leukotriene Release from Peripheral Human Leukocytes
Authors: Ring Johannes , Przybilla Bernhard , Ruzicka Thomas
Published: August 2009

The effect of UV-A radiation on the in vitro release of vasoactive mediators from human peripheral leukocytes incubated with different nonsteroidal antiinflammatory drugs (NSAIDs) was studied in the newly developed photo basophil histamine release test (PBHRT). Washed peripheral leukocytes were incubated with 10––6 to 10––3M of various NSAIDs and exposed to 1–100 J/cm2 UV-A. Maximum histamine release was 4% with acetylsalicylic acid, 10% with benoxaprofen, 20% with thiophene, 28% with diclofenac, 39% with tiaprofenic acid, 40% with carprofen, 55% with ketoprofen and not demonstrable with indoprofen. Maximal reactions occurred at UV-A doses of 25 or 50 J/cm2. Leukotriene B4 (LTB4) generation in the supernatants of cells treated with UV-A or NSAID alone was below or close to the detection limit (145 pg/ml). On the contrary, UV-A irradiation of cells incubated with NSAID led to marked LTB4 generation (up to 1,000 pg/ml). The results indicate that many NSAIDs can induce photosensitization in vitro, the PBHRT being a promising new method for identification of possibly phototoxic compounds. Release of vasoactive mediators like histamine or leukotrienes may be involved in the in vivo development of phototoxic or photoallergic side reactions.
Eosinophil Chemotactic Activity in Allergic Patients during the Birch Pollen Season: The Effect of Immunotherapy
Authors: Rak Sabina , Håkansson Lena , Venge Per
Published: August 2009

Recently, heat-labile eosinophil chemotactic activity (ECA) has been found in serum after challenge of allergic asthmatic patients. In this study, we investigated changes in ECA in 40 birch-allergic patients during the birch pollen season; 20 of them had been treated with immunotherapy of birch pollen extract before the season. ECA raised significantly (p <0.001) in the untreated birch pollen-allergic patients during the season. Immunotherapy completely abolished this activity.
Sawmill Alveolitis in Sweden
Authors: Belin Lars
Published: August 2009

Short-lasting alveolitis-like symptoms are described in Swedish sawmill workers who are trimming and sorting moldy planks. Precipitating antibodies to Rhizopus antigen are demonstrated by double diffusion analyses in more than 50% of the wood trimmers, who are exposed to >106 Rhizopus colony-forming units/m3 (Rcfu/m3). Febrile reactions with muscular pain and malaise occur in 10–20% at peak exposure levels above 107Rcfu/m3. Sawmill workers with repeated acute symptoms have high titres of precipitating antibodies and are mainly non-smokers. The prevalence of this disease in the total Swedish wood trimmer population is estimated at 5–10%. Less typical symptoms from upper and lower airways and a mild, reversible decrement of forced vital capacity over one week’s work shift is also suspected to be caused by this airborn mold. The pathogenetic mechanism is assumed to be identical with the wood mold reactions in wood chip burners, where a more complete picture of typical allergic alveolitis is seen. Identification of the cases and preventive measurements seem to have reduced the incidence rate of both these wood mold diseases.
Physicochemical Characterization of a Major Protein Allergen, Derp I, from the House Dust Mite, Dermatophagoides pteronyssinus
Authors: Stewart G.A. , Simpson R.J. , Thomas W.R. , Turner K.J.
Published: August 2009

A major house dust mite allergen, Der p I, was isolated from spent growth medium and physico-chemically characterized. These studies show that the allergen is monomeric, contains approximately 216 residues and 4 intra-chain disulphide bonds. The N-terminal amino acid is threonine. Circular dichroism studies show that the allergen contains 10% α-helical, 50% β-pleated sheet and 40% random structures.
Immunohistochemical Study of Nasal Mucosa in Patients with Common Variable Immunodeficiency
Authors: Karlsson Göran , Brandtzaeg Per , Hansson Göran , Petruson Björn , Björkander Janne , Hanson Lars Å.
Published: August 2009

The presence of immunoglobulin (Ig)-producing cells was studied immunohistochemically in nasal mucosa obtained from adult patients with common variable immunodeficiency. In 11 of 19 biopsy specimens no such cells could be detected and with one exception very few appeared in the others. Distinct sign of epithelial IgM transport mediated by secretory component (SC) was seen in three specimens although the epithelial distribution of SC appeared normal in all cases. All patients had recurrent lower respiratory tract infections and 16 had recurrent infections of the upper respiratory tract. The localization of the infections primarily to the respiratory tract might be explained by the fact that the immunodeficiency, as reflected by the low serum Ig concentrations, was still more severely expressed at the B cell level in the nasal mucosa.
Immunohistochemical Study of Nasal Mucosa in Patients with Selective IgA Deficiency
Authors: Brandtzaeg Per , Karlsson Göran , Hansson Göran , Petruson Björn , Björkander Janne , Hanson Lars Å.
Published: August 2009

Fifteen nasal biopsy specimens from adult patients with selective IgA deficiency were examined in a ‘blind’ immunohistochemical study for the presence of immunocytes producing various immunoglobulin (Ig) classes. Three groups of patients could be identified. One group had a predominance of IgG- and IgM-producing cells in their nasal mucosa, a second group revealed mainly IgG- and IgD-producing cells, and a third group had very few mucosal immunocytes. The clinical examinations showed that upper respiratory tract infections were most common in patients with few immunocytes while such infections were least common in patients with predominance of IgG and IgM immunocytes. Our results indicated that IgM, in contrast to IgD, acts as a compensatory secretory Ig in some patients with selective IgA deficiency.
Pharmacology of Upper Airways Challenge
Authors: Proud David , Kagey-Sobotka Anne , Naclerio Robert M. , Lichtenstein Lawrence M.
Published: August 2009

We have used a model of nasal provocation to study the effects of pharmacologic interventions upon various types of inflammatory reactions of the upper airways. Pretreatment of allergic individuals with aspirin reduces the levels of prostaglandins in nasal secretions during the immediate allergic response but has no effect on symptoms. Theophylline and azatadine both reduce symptoms and the levels of mast cell mediators during the allergic response. By contrast, azatadine has no effect on symptoms or mediator levels during the response to challenge with cold, dry air, suggesting different mechanisms of mast cell activation in response to allergen and cold, dry air. Both topical and systemic steroids are effective in reducing symptoms and mediators during the late allergic response, but topical steroids also significantly inhibit the immediate response. Nasal challenge provides a convenient, relatively noninvasive method to study inflammatory reactions of the upper airways.
Mast Cell Differentiation in Cultures of T Cell-Depleted Mesenteric Lymph Node Cells from Nippostrongylus brasiliensis-lnfected Mice
Authors: Huff Thomas F. , Justus David E.
Published: August 2009

Lymphoid and bone marrow cells from normal and horse serum-immunized mice and lymphoid cells from Nippostrongylus brasiliensis-infected mice were cultured on monolayers of embryonic skin fibroblasts to analyze the factors which regulate the differentiation and proliferation of mast cells in vitro. Our results indicate that T cells can regulate the development of mast cells in vitro by either enhancement or suppression. In cultures of horse serum-immune spleen cells, inducer T cells are required for mast cells to develop. However, in cultures of mesenteric lymph node cells from N. brasiliensis-infected mice, inducer T cells are not required for mast cell development. This suggests that the development of mast cells may occur at discrete interleukin-3 (IL-3)-dependent and IL-3-independent stages. Mast cell precursors in the mesenteric lymph nodes of N. brasiliensis-infected mice may have already been acted on by inducer cells in vivo to become mast cell committed. While IL-3 does not appear to be required for mast cell development, these precursors do require the presence of a connective tissue microenvironment such as embryonic skin. The precursors can be inhibited from development by interferon preparations.
Detection in Allergic Individuals of IgE Specific for the Australian Paralysis Tick, Ixodes holocyclus
Authors: Gauci M. , Stone B.F. , Thong Y.H.
Published: August 2009

Three techniques were developed to detect IgE specific to Ixodes holocyclus. The radioimmunoas-say (RIA) was found to be superior to both radioallergosorbent test and enzyme immunoassay techniques. Validation of the RIA technique was provided by dilution experiments and by a blind study involving 13 volunteers; the RIA graph was linear over a wide range of concentrations. The RIA ratio clearly discriminated between those volunteers with and without systemic allergic reactions and helped to identify borderline cases showing local or cutaneous allergic reactions. It appears to be suitable for diagnostic and research applications.
Antiphagocytic and Antioxidant Properties of Plant Alkaloid Tetrandrine
Authors: Seow W.K. , Ferrante A. , Si-ying Li , Thong Y.H.
Published: August 2009

The effects of tetrandrine, a benzylisoquinoline alkaloid useful in the treatment of silicosis, on a broad range of human neutrophil activities was examined in vitro. Random movement, chemotaxis and phagocytosis were significantly suppressed. There was minimal but significant inhibition of lysosomal enzyme secretion from specific (secondary) but not azurophil (primary) granules. The same concentration of tetrandrine (10 μg/ml) caused marked depression of hexose-monophosphate shunt activity and hydrogen peroxide production, but inhibition of superoxide anion generation was observed even at a concentration of 0.1 μg/ml. This discrepancy was attributed to the capacity of tetrandrine to scavenge oxygen radicals, as shown by experiments using hypoxanthine-xanthine oxidase to generate superoxide. These potent antiphagocytic and antioxidant properties of tetrandrine may account for some of its remarkable anti-inflammatory effects.