bluuebunny/crossref_metadata_2025 huggingface dataset:
Pilot Cluster-Randomised Trial of Adjunctive Motivational Interviewing to Reduce Crack Cocaine Use in Clients on Methadone Maintenance
Authors: Mitcheson Luke , McCambridge Jim , Byrne Suzanne
Published: December 2006

This pilot trial explored the effectiveness of an adjunctive single session of motivational interviewing (MI) to reduce crack cocaine use in a methadone maintenance treatment population. Twenty-nine participants were cluster randomised by clinician to MI or a crack information control condition as part of treatment as usual. The intervention had a modest impact on one crack cocaine measure but was not statistically significant in this small sample. A large and statistically significant reduction in heroin use amongst those in the MI condition was observed. This pilot study demonstrated that it was feasible to incorporate a psychosocial intervention within a busy outpatient methadone maintenance programme and the findings support the value of undertaking a larger trial.
RamA, the Transcriptional Regulator of Acetate Metabolism in Corynebacterium glutamicum, Is Subject to Negative Autoregulation
Authors: Cramer Annette , Eikmanns Bernhard J.
Published: December 2006

The RamA protein represents a LuxR-type transcriptional activator of genes involved in acetate metabolism of Corynebacterium glutamicum. Here we analyze the expression of the respective ramA gene and its regulation. Transcription was found to start 71 nucleotides upstream of the translational start codon and to be two- to threefold up-regulated in the presence of acetate in the growth medium. Accordingly, about twofold higher amounts of RamA were observed in C. glutamicum cells grown on acetate instead of glucose. Using cell extracts of C. glutamicum and employing DNA affinity chromatography, we found RamA itself as the main protein which binds to the ramA promoter region. By electrophoretic mobility shift analysis with the ramA promoter region and His-tagged RamA protein, multiple RamA-binding sites were identified in front of the ramA transcriptional start site. Transcriptional cat fusion experiments revealed that ramA promoter activity was about threefold higher in a RamA-deficient mutant of C. glutamicum than in the wild-type, however, acetate-dependent up-regulation of ramA expression was not affected in the RamA-negative mutant. These results indicate that RamA negatively controls the expression of its own gene, but is not involved in acetate-dependent up-regulation of ramA expression.
Transcriptome Analysis of Temporal Regulation of Carbon Metabolism by CcpA in Bacillus subtilis Reveals Additional Target Genes
Authors: Lulko Andrzej T. , Buist Girbe , Kok Jan , Kuipers Oscar P.
Published: December 2006

The pleiotropic regulator of carbon metabolism in Gram-positive bacteria, CcpA, regulates gene expression by binding to so-called cre elements, which are located either upstream or in promoter regions, or in open-reading frames. In this study we compared the transcriptomes of Bacillus subtilis 168 and its ccpA deletion mutant during growth in glucose-containing rich medium. Although growth was similar, glucose was completely consumed by the wild-type strain in the stationary phase, while it was still present in the culture of the mutant. At that stage, direct and indirect effects on gene expression were observed. During exponential growth, CcpA mainly influences the carbohydrate and energy metabolism, whereas from transition phase onwards its function expands on a broader range of physiological processes including nucleotide metabolism, cell motility and protein synthesis. A genome wide search revealednew putative cre sites, which could function in vivo according to our transcriptome data. Comparison of our data with published transcriptome data of ccpA mutant analysis in the exponential growth phase confirmed earlier identified CcpA regulon members. It also allowed identification of potential new CcpA-repressed genes, amongst others ycgN and the ydh operon. Novel activated members include opuE andthe opuAABC, yhb and man operons, which all have a putative cre site that appears to be dependent on helical topology. A comparative analysis of these genes with the known activated genes i.e.ackA and pta revealed the presence of a possible upstream activating region (UAR) as has been shown to be functional for the activation of ackA. The data suggest that at later growth phases CcpA may regulate gene expression by itself or complexed with other, yet unknown cofactors.
Effect of Ultraviolet B Radiation on the Absorption Characteristics of Various Intraocular Lenses
Authors: Kocak Nilufer , Kaynak Suleyman , Ilknur Turna , Ozkan Sebnem , Erdogan Gokhan , Cıngıl Guray
Published: December 2006

Background: The aim of this study was to determine the effect of ultraviolet B (UVB) exposure on UV filters of various intraocular lenses (IOLs). Methods: Eight samples each of the hydrophobic acrylic, hydrophilic acrylic and silicone IOLs were used. Four IOLs of each type was selected randomly as the control group while the remaining four IOLs of each type were exposed to a UVB dose of 1.4 J/cm2 (2.40 mW/cm2) for 9.45 min, two times with a 4-week interval. IOLs were evaluated for any sign of opacification under microscope weekly. After a follow-up period of 16 weeks, spectrometry for UV filter absorption rates, scanning electron microscopy for deposit formation and energy dispersive X-ray analysis for elemental composition were performed for all IOLs, and findings of the control group IOLs were compared with those of the UVB-exposed IOLs. All these procedures were done at the Department of Ophthalmology, Faculty of Medicine, Dokuz Eylul University. Results: All the IOLs were free of any opacification during the follow-up period. Spectrometric analysis of their UV filters revealed a change in absorption rates in the hydrophilic acrylic and silicone IOLs compared to the control IOLs of the same type. Only the hydrophobic acrylic IOLs preserved the same UV absorption curve after UVB exposure. Conclusion: The pathogenesis of IOL opacification is still undetermined. Some reports claimed that the UV light was the responsible factor. Our experimental study revealed that high doses of UVB did not cause any opacification though they impaired the function of UV filters of the hydrophilic acrylic and silicone IOLs.
Antiphospholipid Antibodies in Ocular Arterial and Venous Occlusive Disease
Authors: Palmowski-Wolfe Anja M. , Denninger Elke , Geisel Jürgen , Pindur Gerhard , Ruprecht Klaus W.
Published: December 2006

Purpose: It was the aim of this study to evaluate antiphospholipid antibodies (APA), i.e. lupus anticoagulants (LA) and anticardiolipin (ACA) IgG and IgM, in ophthalmic occlusive disease. Methods: Over a 3.5-year period, APA were evaluated in 368 patients. Results: Eighty-six patients (23.4%), compared to 5% in the general population, tested positive for APA. APA did not differ significantly between patients with venous (20.6%) or arterial (25.5%) occlusive disease. This included 93 patients with central retinal vein occlusion (18% APA positive), 67 with retinal branch vein occlusion (24% APA positive), 41 with central retinal artery occlusion (22% APA positive), 53 with retinal branch artery occlusion (32% APA positive), 71 with anterior ischemic optic neuropathy (23% APA positive), 12 with posterior ischemic optic neuropathy (33% APA positive) and 31 patients with amaurosis fugax (23% APA positive). Excluding patients with accepted main risk factors, APA were positive in 15.3% of 85 patients. Conclusion: The high APA prevalence confirms its relevance in ocular occlusive disorders.
Changes in Colour Discrimination during the Menstrual Cycle
Authors: Giuffrè Giuseppe , Di Rosa Luigi , Fiorino Fabio
Published: December 2006

A group of normal women of reproductive age were recruited to investigate colour discrimination during the various phases of the menstrual cycle. Colour vision was tested with the Farnsworth-Munsell 100-hue arrangement test, and the test was administered at 3 time points: the beginning of the cycle, ovulation, and the end of the cycle. We found that colour discrimination was better at ovulation than at the other 2 time points. It is possible that psychological as well as hormonal factors could contribute to improved colour vision performance at ovulation.
Pneumatic Displacement of Submacular Hemorrhage due to Age-Related Macular Degeneration
Authors: Ron Yonina , Ehrlich Rita , Axer-Siegel Ruth , Rosenblatt Irit , Weinberger Dov
Published: December 2006

Purpose: Subretinal hemorrhage is one of the most serious complications of exudative age-related macular degeneration (AMD). Treatment with vitreous surgery with or without plasminogen activator, fluid-gas exchange, or perfluorocarbon yields only a small improvement in visual acuity. Patients and Methods: The files of 24 patients with submacular hemorrhage secondary to AMD who were treated by injection of perfluoropropane gas (C3F8) (11 patients) or sulfur hexafluoride (SF6) (13 patients) were reviewed for visual acuity before and after the procedure and time of treatment from onset of symptoms. Results: For the whole sample, pneumatic displacement led to a statistically significant improvement in mean visual acuity (p = 0.015). A significant difference between pre- and postoperative visual acuity was found for the patients treated with SF6 (p = 0.034), but not for the patients treated with C3F8 (p = 0.245). Conclusion: The use of gas injection to displace submacular hemorrhage can significantly improve visual acuity.
Swallowing Difficulties Reported by Adults Infected with HIV/AIDS Attending a Hospital Outpatient Clinic in Gauteng, South Africa
Authors: Bladon Kerry L. , Ross Eleanor
Published: December 2006

Objective: Swallowing difficulties can exert a profound effect on quality of life, may result in reduced nutritional intake and place individuals at risk of aspiration. However, there is little data available on the swallowing difficulties occurring within the HIV/AIDS population in South Africa. A descriptive study was therefore conducted to document the presence of reported swallowing difficulties in a sample of adults with HIV. Patients and Methods: One-to-one semi-structured interview schedules were administered to 120 adults with HIV attending a clinic in Gauteng, and medical records were evaluated to document the presence of reported swallowing difficulties. Results: Participants described a range of swallowing difficulties and the number of swallowing difficulties reported by participants was negatively correlated with CD4 count. Swallowing difficulties were significantly associated with various opportunistic diseases and related medical pathologies. Prescribed medications were associated with reported swallowing difficulties. Treatment of swallowing difficulties was mainly medical in nature. Swallowing difficulties had affected quality of life. Conclusions: From the results it was concluded that speech therapists have a role to play in the assessment and treatment of swallowing difficulties in individuals with HIV/AIDS.
ECCA Grading Scale: An Original Validated Acne Scar Grading Scale for Clinical Practice in Dermatology
Authors: Dreno B. , Khammari A. , Orain N. , Noray C. , Mérial-Kieny C. , Méry S. , Nocera T.
Published: December 2006

Introduction: The ECCA grading scale (échelle d’évaluation clinique des cicatrices d’acné) is a tool designed to help dermatologists to assess the severity of acne scars and to standardize the discussions about the treatments of scars. Methods: We developed an acne scar clinical grading scale called ECCA, which consists of 6 items designed to assess easily and quickly the severity of acne scars by a global score. The interobserver reliability of the ECCA grading was statistically validated. Results: The statistical analysis showed the interinvestigator reliability of the ECCA grading scale among 7 dermatologists who used it on the same group of 10 acne patients. Conclusion: ECCA is a new tool which will now be available for dermatologists to use in their everyday practice and for clinical trials evaluating the efficacy of treatments on acne scars.
Scleromyxedema: Successful Treatment with Thalidomide in Two Patients
Authors: Amini-Adle Mona , Thieulent Nadege , Dalle Stéphane , Balme Brigitte , Thomas Luc
Published: December 2006

Background: Scleromyxedema is an unusual skin disease characterized by mucinous infiltration of the skin. There is no satisfactory treatment for this disorder. Case Report: We report 2 cases of scleromyxedema, both associated with an IgG-λ paraprotein. Treatment with thalidomide was started and great improvement of the lesion was noted as shown by a quality of life questionnaire similar to those used in rheumatoid arthritis. TNF-α value was elevated in both cases during this treatment. Discussion: We hypothesize that the efficiency of thalidomide could be mediated by its costimulatory effect on T cytotoxic lymphocytes.
Morphometric Assessment of the Impact of Serum Thymulin Immunoneutralization on Pituitary Cell Populations in Peripubertal Mice
Authors: Camihort Gisela , Luna Georgina , Vesenbeckh Silvan , Ferese Celia , Dardenne Mireille , Goya Rodolfo , Cónsole Gloria
Published: December 2006

Thymulin is a thymic hormone involved in several aspects of intra- and extrathymic T-cell differentiation. Thymulin also possesses hypophysiotropic activity which suggests that this metallopeptide may play an important role in thymus-pituitary communication, particularly during early life. The aim of the present study was to evaluate the impact of serum thymulin suppression from birth to peripuberty on the morphology of different pituitary cell populations in prepubertal C57Bl/6 mice. Animals were submitted to immunoneutralization of circulating thymulin from postnatal day 1 to the end of the study (age 32 days). From their 1st day of life, the animals were submitted to a protocol of intraperitoneal injections of rabbit anti-thymulin serum (α-FTS) and normal rabbit serum (NRS) in the controls. On their 33rd day of life, the animals were killed and their pituitaries were immediately dissected, fixed and immunostained using the EnVision system with primary antibodies against growth hormone, thyrotropin, corticotropin, gonadotropins and prolactin. Morphometry was performed by means of an image analysis system. The following parameters were calculated: volume density = Σ cell area/reference area (RA); cell density (CD) = number of cells/RA, and cell size (expressed in µm2). Serum thymulin was measured by a rosette bioassay while pituitary hormones were assayed by radioimmunoassay. Serum prolactin, luteinizing hormone, follicle-stimulating hormone, growth hormone and thyroid-stimulating hormone were significantly lower in the α-FTS animals of either sex compared with the corresponding NRS counterparts. The somatotrope, lactotrope and corticotrope populations showed a significant decrease in CD, while cell hypertrophy was observed in some of the pituitary cell populations of the α-FTS group compared to the NRS group. In the α-FTS group, there were sex differences in the morphometric changes observed. Our results suggest that serum thymulin plays a significant role during early life in the postnatal maturation of endocrine cells of the mouse anterior pituitary gland.
Children’s Production of Word Accents in Swedish Revisited
Authors: Ota Mitsuhiko
Published: December 2006

The two word accents in Stockholm Swedish (Accent I and Accent II) are distinguishedby a consistent falling pitch contour on the stressed syllable of AccentII words. The current study presents new types of evidence that this feature ofword accent can be systematically found in words produced by 16- to 18-montholdSwedish-speaking children. Compared to other disyllabic productions, thestressed syllable in Accent II words have a larger F0 decline, more sequences ofhigh-low turning points identified by a stylized contour algorithm and an earlier F0peak. In addition, a negative correlation is found between the value of F0 peak andF0 change in the stressed syllable. Taken together, these findings indicate that childrenlearning Swedish have internalized a subtle but lexically relevant pitch contourby a very early stage of word production.
Syringomyelia in Infants Secondary to Mobile Congenital Atlantoaxial Dislocation
Authors: Goel A. , Muzumdar D. , Dange N.
Published: December 2006

We report a characteristic pattern of ‘waist-like’ syringomyelia observed in three infants having mobile and reducible congenital atlantoaxial dislocation. The syringomyelia in at least two of these cases was diagnosed to be an intramedullary tumor. Following atlantoaxial fixation, all three patients had long-term recovery of their symptoms.
MR Demonstration of Complete Cerebellar and Corpus Callosum Agenesis
Authors: Gupta Arun , Malik G.K. , Gupta Amit , Saksena Sona , Gupta Rakesh K.
Published: December 2006

Complete cerebellar agenesis is a very rare entity, which occurs during the early period of embryogenesis and is usually associated with severe motor dysfunction. We report a case of complete cerebellar agenesis with complete corpus callosum agenesis diagnosed on magnetic resonance imaging (MRI). These anomalies were also associated with rudimentary pons.
Cyclic GMP Synthesis by Human Retinal Pigment Epithelial Cells Is Mainly Mediated via the Particulate Guanylyl Cyclase Pathway
Authors: Diederen Roselie M.H. , La Heij Ellen C. , Markerink-van Ittersum Marianne , Kijlstra Aize , Hendrikse Fred , de Vente Jan
Published: December 2006

Background/Aims: Cyclic 3′,5′-guanosine monophosphate (cGMP), a central molecule in the phototransduction cascade, is also involved in a number of other physiological processes in the retina, like stimulating the absorption of subretinal fluid by activating the retinal pigment epithelium (RPE) cell pump. The aim of this study was to quantify cGMP synthesis by RPE cells and to investigate the role of two separate enzymatic pathways (soluble versus particulate guanylyl cyclase) in its production. Methods: cGMP expression was evaluated by immunochemistry and radioimmunoassay following culture of the D407 RPE cell line in the presence of a nonselective phosphodiesterase inhibitor (IBMX), in combination with the particulate guanylyl cyclase stimulator atrial natriuretic peptide (ANP) or the soluble guanylyl cyclase stimulator sodium nitroprusside (SNP). Results: Stimulation of the particulate guanylyl cyclase in RPE cells with ANP resulted in high intra- and extracellular cGMP levels. Stimulation of the soluble guanylyl cyclase by SNP resulted in a slight elevation of cGMP levels compared to controls. Conclusions: These results show that cultured human RPE cells are capable of producing cGMP and that most cGMP is generated following stimulation of the particulate guanylyl cyclase pathway.
Hypertension and Sensorimotor Peripheral Neuropathy in Type 2 Diabetes
Authors: Jarmuzewska E.A. , Ghidoni A. , Mangoni A.A.
Published: December 2006

Background: The mechanisms responsible for the onset of sensorimotor peripheral diabetic neuropathy (SMPN) remain largely unknown. To address this issue, we studied the relationship between traditional cardiovascular risk factors, parameters of metabolic control, and the presence of SMPN in patients with type 2 diabetes of relatively short duration. Methods: Blood pressure, glycated hemoglobin, lipid profile, and the presence of micro- and macrovascular complications were assessed and monitored in 31 consecutive ambulatory patients with type 2 diabetes (age 60.7 ± 7.5 years, mean ± SD) within 10 years of diagnosis (mean diabetes duration 6.0 ± 2.3 years). Results: Clinical and neurophysiological features of SMPN were present in 10 patients (SMPN+, 32%). There were no significant differences in age, gender distribution, diabetes duration, body mass index, metabolic control, and serum cholesterol between SMPN– and SMPN+ patients. However, the prevalence of hypertension (i.e. blood pressure ≧140/90 mm Hg) was higher in SMPN+ patients (10/10 vs. 13/21, χ2 = 5.13, p = 0.025). Regression analysis showed that, after correcting for age, gender, duration of diabetes, glycated hemoglobin, and cholesterol, the presence of hypertension was independently associated with SMPN (R2 = 0.17, p = 0.023). Conclusions: There is a strong association between hypertension and SMPN in type 2 diabetic patients with relatively short duration of disease. This relationship is independent of other risk factors.
Activation of Serum Response Element by D2 Dopamine Receptor Is Governed by Gβγ-Mediated MAPK and Rho Pathways and Regulated by RGS Proteins
Authors: Ho Guyu , Wang Yuren , Jones Philip G. , Young Kathleen H.
Published: December 2006

In this study, we investigated the activation of the serum response element (SRE) by the D2 dopamine receptor (D2R) agonist quinpirole. Stimulation of CHO cells expressing the D2R by quinpirol evoked a dose-dependent SRE activation, which was completely blocked by overnight treatment of pertussis toxin or by co-expression of the β-adrenergic receptor kinase C-terminus, implicating the involvement of Gαi and Gβγ in the signal transduction. Furthermore, using MEK inhibitors and dominant negative mutants of RhoA, Rac1, and Cdc42, we showed that the Gβγ-mediated activation of the SRE in CHO cells utilizes both MAPK and Rho pathways. Expression of either regulator of G protein signaling 2 or 4 (RGS2 or RGS4) proteins significantly attenuated the quinpirole-induced SRE activation. These results delineate the signaling pathways which couple D2 receptor to the transcriptional activation of SRE and demonstrate a modulatory role for RGS proteins in these processes.
High-Fat- and Lipid-Induced Insulin Resistance in Rats: The Comparison of Glucose Metabolism, Plasma Resistin and Adiponectin Levels
Authors: Li Ling , Yang Gangyi , Li Qingming , Tang Yi , Li Ke
Published: December 2006

Aims: In animal models, both an acute elevation in plasma free fatty acid (FFA) via intravenous infusion of a lipid emulsion and a chronic elevation in plasma FFA via high-fat feeding have been shown to induce skeletal muscle and liver insulin resistance. However, there have been very few studies comparing the effects of high-fat- and lipid-induced insulin resistance on glucose metabolism and adipocytokines. Methods: In the current study, we used lipid infusion and a high-fat feed in combination with the hyperinsulinemic-euglycemic clamp technique to assess the impact of acute and chronically elevated FFA levels on overall glucose metabolism and insulin action; two adipocytokines, resistin and adiponectin, were used. Results: At baseline, plasma FFA levels were significantly increased in the high-fat diet (HF) group compared to the control group (p < 0.05). During clamp steady-state, the FFA levels were reduced by ∼25% in the control and ∼48% in the HF groups. In contrast, there was a significant increase in the plasma FFA level in the lipid-infused group (from 0.82 ± 0.03 to 2.87 ± 0.18 mmol/l). The glucose infusion rates (GIRs) in the HF and lipid groups were obviously lower than in the control group (p < 0.01). Moreover, GIR was lower in the lipid group compared with the HF group (p < 0.05). The rate of glucose disappearance (GRd) was significantly lower in the lipid group compared with the control group. Hepatic glucose production in the control group was suppressed by ∼15% compared with the HF and lipid groups where it was suppressed by only ∼72 and ∼91%, respectively. The resistin level of muscle tissues in the lipid group was significantly higher compared with the control and HF groups (both p < 0.05). After the insulin clamp, the circulating adiponectin level was significantly decreased in the lipid group compared with the control and HF groups (p < 0.05). Conclusions: Lipid infusion, which was more effective than a high-fat diet, can induce peripheral and hepatic insulin resistance in rats. Insulin-induced resistance might be associated with elevated resistin and decreased adiponectin.
Distribution of Anemia Associated with Micronutrient Deficiencies Other than Iron in a Probabilistic Sample of Mexican Children
Authors: Villalpando Salvador , Pérez-Expósito Ana Beatriz , Shamah-Levy Teresa , Rivera Juan A.
Published: December 2006

Background: This investigation aims to explore the association among anemia and vitamins A, C, and folate deficiencies in a probabilistic sample of Mexican children. Methods: Data on hemoglobin, serum vitamins A and C and folate concentrations and percent transferrin saturation (PTS) in children 0.5–11 years (n = 1,770) were extracted from the database of the probabilistic Mexican National Nutrition Survey 1999 (NNS-99). Results: Overall, 16.6% of children were anemic. Iron deficiency children with or without anemia had more frequent low serum retinol (40.6 vs. 16% and 27.7 vs. 11.9%, p < 0.05, respectively) and lower hemoglobin folate (11.5 vs. 22%, p < 0.05) than their non-iron deficiency counterparts. Mean concentrations of serum iron (p < 0.01), folate (p < 0.001) and retinol (p < 0.0001), but not ascorbic acid (p < 0.6), were significantly lower in anemic than in nonanemic children. In a linear regression model, 15% of hemoglobin variation in children was explained by retinol, folate and PTS, but not vitamin C (p <0.0001). Conclusion: Anemia was mostly associated with iron deficiency and with a lesser proportion of folate and vitamin A deficiencies. Vitamin A deficiency might be overestimated since iron deficiency may lower serum retinol concentrations. Interventions aimed to reduce anemia in this population must consider interactions between those micronutrients in designing strategies.
Dietary Supplementation with Chickpeas for at Least 5 Weeks Results in Small but Significant Reductions in Serum Total and Low-Density Lipoprotein Cholesterols in Adult Women and Men
Authors: Pittaway J.K. , Ahuja K.D.K. , Cehun M. , Chronopoulos A. , Robertson I.K. , Nestel P.J. , Ball M.J.
Published: December 2006

Aim: To compare the effects of a chickpea-supplemented diet and those of a wheat-supplemented diet on human serum lipids and lipoproteins. Methods: Forty-seven free-living adults participated in a randomized crossover weight maintenance dietary intervention involving two dietary periods, chickpea-supplemented and wheat-supplemented diets, each of at least 5 weeks duration. Results: The serum total cholesterol and low-density lipoprotein cholesterol levels were significantly lower (both p < 0.01) by 3.9 and 4.6%, respectively, after the chickpea-supplemented diet as compared with the wheat-supplemented diet. Protein (0.9% of energy, p = 0.01) and monounsaturated fat (3.3% of total fat, p < 0.001) intakes were slightly but significantly lower and the carbohydrate intake significantly higher (1.7% of energy, p < 0.001) on the chickpea-supplemented diet as compared with the wheat-supplemented diet. Multivariate analyses suggested that the differences in serum lipids were mainly due to small differences in polyunsaturated fatty acid and dietary fibre contents between the two intervention diets. Conclusions: Inclusion of chickpeas in an intervention diet results in lower serum total and low-density lipoprotein cholesterol levels as compared with a wheat-supplemented diet.
Molecular Pathogenesis of Kallmann’s Syndrome
Authors: Cadman Steven Mark , Kim Soo-Hyun , Hu Youli , González-Martínez David , Bouloux Pierre-Marc
Published: December 2006

Hypogonadotrophic hypogonadism (HH) is characterized by delayed or absent pubertal development secondary to gonadotrophin deficiency. HH can result from mutations of the gonadotrophin-releasing hormone receptor 1, the gonadotrophin β-subunits, or various transcription factors involved in pituitary gland development. HH occurs in DAX1 mutations when associated with adrenal insufficiency (adrenal hypoplasia congenita), and is also linked with obesity in patients with mutations of leptin and its receptor, as well as mutations in prohormone convertase 1. Rarely, HH has resulted from kisspeptin receptor (GPR54) mutations, a gene implicated in the regulation of pubertal onset. When occurring with anosmia (a lack of sense of smell), HH is referred to as Kallmann’s syndrome (KS). Two KS-related loci are currently known: KAL1, encoding anosmin-1, responsible for X-linked KS, and KAL2, encoding the fibroblast growth factor receptor 1 (FGFR1), mutated in autosomal dominant KS. Anosmin-1 is an extracellular glycoprotein with some unique structural characteristics; it interacts with both urokinase-type plasminogen activator and FGFR1. It has previously been shown that anosmin-1 enhances FGFR1 signalling in a heparan sulphate-dependent manner, and proposed that anosmin-1 fine-tunes FGFR1 signalling during olfactory and GnRH neuronal development. Here, we review the known normosmic causes of HH, and discuss novel developmental and molecular mechanisms underlying KS; finally, we introduce three novel genes (NELF, PKR2, and CHD7) that may be associated with some phenotypic features of KS.
Macrosomic Newborns of Diabetic Mothers Are Associated with Increased Aortic Intima-Media Thickness and Lipid Concentrations
Authors: Akcakus Mustafa , Koklu Esad , Baykan Ali , Yikilmaz Ali , Coskun Abdulhakim , Gunes Tamer , Kurtoglu Selim , Narin Nazmi
Published: December 2006

Background/Aims: Exposure to diabetes in utero has been established as a significantrisk factor for some of components of metabolic syndrome. A few studies have examined relationship between the metabolic syndrome and echocardiographic left ventricular (LV) mass. We aimed to investigate relationship between abdominal aortic intima-media thickness (aIMT), LV mass and lipid profile in macrosomic newborns. Methods: Abdominal aIMT was measured in 30 macrosomic neonates of diabetic mothers (group A), 30 macrosomic neonates of healthy mothers (group B) and 30 healthy neonates (group C). Lipid profile and LV mass were determined. Result: Mean aIMT was significantly higher in groups A and B (0.489 ± 0.015, 0.466 ± 0.019 mm, respectively) than in controls (0.375 ± 0.024 mm). Weight-adjusted aIMT in group A was significantly higher than in groups B and C. Macrosomia was associated with increased lipid concentrations. Both LV mass indexed for BSA (body surface area) and birth weight measurements were significantly increased in group A compared with control. Conclusions: Macrosomic neonates of diabetic mothers have significant aIMT and LV mass indexed for BSA and birth weight with lipid alterations. It might play a role in the pathogenesis of atherosclerosis in adult life.
Effect of SP-B Peptides on the Uptake of Liposomes by Alveolar Cells
Authors: Poelma D.L. , Walther F.J. , Waring A.J. , Haitsma J.J. , Zimmermann L.J. , Lachmann B. , van Iwaarden J.F.
Published: December 2006

Background: Exogenous surfactant has been accepted worldwide as a therapy of RDS in premature and term infants. Exogenous surfactant is usually derived from lung extracts containing phospholipids and the surfactant proteins SP-B and SP-C. Synthetic peptides of SP-B and SP-C are being tested with the aim to develop a completely synthetic surfactant preparation. Nevertheless, the effects of these peptides on the endogenous surfactant metabolism remain unknown. Objectives: The effect of synthetic SP-B peptides on uptake of surfactant-like liposomes was investigated in alveolar cells. Native SP-B and seven SP-B peptides were included: monomeric and dimeric SP-B1–25 (Cys-11 → Ala-11), SP-B63–78and Ala-SP-B63–78 (Cys-71 → Ala-71;Cys-77 → Ala-77)and their serine mutants. Methods: In vitro, alveolar macrophages (AM) and alveolar type II cells (ATII) were incubated with liposomes containing SP-B or one of its peptides. In vivo, rats received intratracheally various SP-B peptides (SP-B/lipid ratio 1:33 w/w) incorporated in fluorescent surfactant-like liposomes. One hour after instillation, AM and ATII were isolated and cell-associated fluorescence was determined using flow cytometry. Confocal laser microscopy was performed to ensure internalization of the liposomes. Results: In vitro uptake by AM or ATII was not influenced by the SP-B peptides. In vivo, SP-B1–25 and Ser-SP-B1–25 increased the uptake by AM whereas dSP-B1–25 decreased the uptake. Neither SP-B1–25 nor dSP-B1–25 affected total uptake by ATII. The overall uptake by SP-B63–78 variants was not changed. Conclusions: Surface-active synthetic SP-B peptides do not interfere with the normaluptake of surfactant by ATII.
Clinical Outcomes in Methicillin-Resistant Staphylococcus aureus-Colonized Neonates in the Neonatal Intensive Care Unit
Authors: Kim Young Hee , Chang Sung Soo , Kim Yang Soo , Kim Ellen Ai-Rhan , Yun Sung Cheol , Kim Ki Soo , Pi Soo Young
Published: December 2006

Background: Methicillin-resistent Staphylococcus aureus (MRSA) colonization can persist for prolonged periods, and patient-related factors are associated with persistent carriage in adults. However, such knowledge is lacking among neonates. Objectives: To better understand the outcome of MRSA-colonized neonates in the neonatal intensive care unit (NICU), we prospectively followed all colonized neonates until decolonization over 39 months and determined the incidence, duration of colonization, clinical outcomes and risk factors associated with prolonged carriage of MRSA. Methods: Nasal and inguinal cultures were obtained from all newly admitted neonates following an outbreak of MRSA. Weekly and 1–2 monthly cultures were obtained from all hospitalized and discharged neonates colonized with MRSA, respectively, until 2 consecutive cultures were negative. Results: 152 of 1,456 (10.4%) neonates became colonized. The mean time to acquire MRSA colonization was 17.1 ± 40.7 (range 1–471) days. The median time to decolonization was 36 days. About 20% of decolonized patients had been colonized for a prolonged period of ≧160 days. 47.5% of colonized patients were sent home colonized, and none with prolonged carriage developed MRSA-related infections in the following 6 months in contrast to 6 infants (3.9%) who developed MRSA sepsis during hospitalization. The only risk factor associated with prolonged carriage was the concurrent colonization of both the inguinal and nasal areas on admission. Conclusion:Nearly all neonates with acquired colonization became decolonized either prior to or after discharge from NICU. A significant percentage failed to decolonize prior to hospital discharge, but almost all decolonized by 30 months in the community without evidence of systemic or local infections.
Severe Transient Cardiac Failure Caused by Placental Chorangiosis
Authors: Schmitz Thomas , Opgen-Rhein Bernd , Kroschwald Peter , Schroeder Gunnar , Weber Sven , Czernik Christoph , Obladen Michael
Published: December 2006

Background: Chorangiomas are villous capillary tumors of the placenta with high impact on neonatal morbidity and mortality. Cardiac complications have occasionally been reported. Objective: To elucidate clinical features, diagnosis and treatment of cardiac failure caused by chorangiomas. Method:We report a case of a newborn, in whom massive chorangiomas were associated with severe cardiac failure, anemia, and thrombocytopenia. Results: Chorangiosis was not diagnosed prenatally. The pre-existing cardiac failure of the infant deteriorated soon after birth. Despite the severe stage, cardiac failure was reversible with intensive medical treatment including phosphodiesterase inhibitor. Complete recovery with no signs of cardiomyopathy was confirmed at the age of 5 months. Conclusions: Severe cardiac failure in the neonate can be caused by chorangiosis. The time of diagnosis and treatment seems to be critical for the outcome of the infant. Prenatal treatment interventions should be considered.
Fractal Analysis of the Maternal Surface of the Placenta: Preliminary Report
Authors: Shiba Masahiro , Kikuchi Akihiko , Hara Kikue , Sunagawa Sorahiro , Yoshida Shiro , Takagi Kimiyo , Ogiso Yoshifumi
Published: December 2006

Aims: The objective of this study was to determine whether the maternal surface of the placenta is fractal, and whether the mean fractal dimension differs according to the gestational age and clinically or pathologically different conditions. Methods: Using digitized images of the maternal surface of 75 placentas, fractal dimensions were measured with a fractal analysis software. Results: The mean fractal dimension of the maternal surface of the placentas significantly exceeded the topological dimension of a surface (= 2). This means that the morphological pattern of the maternal surface fulfills the mathematical definition of fractal structures. Among the three different groups of gestational age, the mean fractal dimension in 22–29 weeks was significantly lower than that in 30–36 and 37–41 weeks (p = 0.022 and 0.014, respectively). Although not significantly different (p = 0.149), in 30–36 weeks the mean fractal dimension of the placentas complicated by pregnancy-induced hypertension (PIH) was greater than that without PIH. Conclusion: Fractal geometry, a vocabulary of irregular shapes, can be useful for describing quantitatively the architecture of the maternal surface of the placenta and become a useful tool for analyzing physiological and pathological placental formation mathematically.
Oral Sensitization to Peanut Is Highly Enhanced by Application of Peanut Extracts to Intact Skin, but Is Prevented when CpG and Cholera Toxin Are Added
Authors: Adel-Patient Karine , Ah-Leung Sandrine , Bernard Hervé , Durieux-Alexandrenne Coralie , Créminon Christophe , Wal Jean-Michel
Published: December 2006

Background: CpG oligonucleotides might offer an alternative to conventional immunotherapy in preventing and potentially reversing Th2-biased immune deregulation which leads to allergy. However, non-invasive ways of administration, especially in peanut-allergic patients, should be explored. Methods: One hundred micrograms of whole peanut protein extract (PE) alone, or mixed with cholera toxin (CT, 50 µg) plus CpG (100 µg) as adjuvant, was applied on intact skin of mice (40 min, twice). Initiation of an immune response was monitored by detection of specific antibodies in sera. The effect of this pretreatment on a further oral sensitization by PE was then evaluated by assaying antibodies and cytokines specific for PE and purified allergens. Cytokine production in liver 40 min after skin application was also assayed. Results: Two brief skin applications of PE alone highly potentiated further oral sensitization, as demonstrated by very intense specific IgE, IL-4 and IL-5 productions. Conversely, skin pretreatment with PE and CT + CpG efficiently prevented further sensitization via gastro-intestinal exposure. In both cases, the specificity of the antibodies and cytokines was the same as in control mice. CT + CpG treatment allowed the rapid production of IL-12 and TGFβ in liver and of specific IgG2a in sera, suggesting the activation of Th1 and/or regulatory T cells. Conclusions: Oral sensitization to peanut is highly enhanced by a previous short exposure of allergens to intact skin. Conversely, the use of CT + CpG adjuvant for skin application efficiently prevents further oral sensitization. The potential of such treatment in specific immunotherapy needs to be evaluated.
The Synergistic Interaction of Interferon Types I and II Leads to Marked Reduction in Severe Acute Respiratory Syndrome-Associated Coronavirus Replication and Increase in the Expression of mRNAs for Interferon-Induced Proteins
Authors: Scagnolari Carolina , Trombetti Simona , Alberelli Alessia , Cicetti Simona , Bellarosa Daniela , Longo Roberta , Spanò Alberto , Riva Elisabetta , Clementi Massimo , Antonelli Guido
Published: December 2006

Interferon (IFN)-α, -β and -γ have been shown to be only marginally effective against severe acute respiratory syndrome coronavirus (SARS-CoV) replication in Vero cell lines. We investigated the combination of type I IFNs (IFN-α or -β) and IFN-γ for antiviral activity and found that such combinations synergistically inhibited SARS-CoV replication in Vero cells, using yield reduction assay and the isobologram and combination index methods of Chou and Talalay for evaluation. The highly synergistic anti-SARS-CoV action of type I IFNs and IFN-γ parallels the marked increase in 2′-5′-oligoadenylate synthetase and p56 mRNAs following exposure in Vero cells to either IFN-α or -β and IFN-γ compared with the transcriptional levels obtained after stimulation with either IFN alone. These results demonstrate that SARS-CoV, although only moderately sensitive to the antiviral action of the individual types of IFN, is highly sensitive to a combination of type I and II IFNs, which suggests that such combinations may have potential in the treatment of SARS-CoV infections.
Prevalence and Antimicrobial Resistance Patterns of Aeromonas Strains Isolated from Drinking Water Samples in Istanbul, Turkey
Authors: Koksal F. , Oguzkurt N. , Samastı M. , Altas K.
Published: December 2006

The aim of this study was to determine the prevalence and the resistance patterns of Aeromonas spp. in drinking water in Istanbul, Turkey. We investigated a total of 1,680 drinking water samples (840 tap water and 840 domestic water tank samples) for Aeromonas strains between June 2002 and October 2005. A total of 147 Aeromonas strains were isolated from 49 (6%) of 840 tap water samples and from 98 (12%) of 840 domestic water tank samples. Antibiotic susceptibility of Aeromonas strains was determined by the disc diffusion method, according to the CLSI (Clinical Laboratory Standards Institute) recommendation. Among the 147 Aeromonas strains, the prevalence was: A. hydrophila 68 (46%), A. sobria 50 (34%), A. caviae 11 (8%), A. salmonicida 9 (6%), A. veronii 5 (3%) and A. jandaei 4 (3%). Approximately 55% of the strains were resistant to ampicillin, 48% to erythromycin, 41% to amoxicillin-clavulanic acid, 28% to ceftazidime, 27% to cefoxitin, 26% to ceftriaxone and cefotaxime, 22% to piperacillin, 14% to trimethoprim-sulfamethoxazole, 12% to tetracycline, 11% to aztreonam, 8% to meropenem, 6% to imipenem, 2% to nalidixic acid, 1% to ciprofloxacin, tobramycin and gentamicin. None of the strains were resistant to amikacin and netilmicin. In conclusion, Aeromonas spp. isolated from drinking water in Istanbul have a resistance potential and the antibiotic resistance rates of A. hydrophila, A. sobria and A. caviae were usually higher than those of other Aeromonas strains. It should be kept in mind that these microorganisms in drinking water might be a potential risk for public health.
Time Course of Hyperosmolar Opening of the Blood-Brain and Blood-CSF Barriers in Spontaneously Hypertensive Rats
Authors: Al-Sarraf Hameed , Ghaaedi Firuz , Redzic Zoran
Published: December 2006

The time course of blood-brain barrier (BBB) and blood-CSF barrier (BCSFB) responses to hyperosmolar mannitol infusion (HMI; 1.6 M) during chronic hypertension was investigated using 14C-sucrose as a marker of barrier integrity. 14C-sucrose entry into CSF of both spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats 2 min after HMI increased ∼7-fold compared to their respective control. The volume of distribution (Vd) of 14C-sucrose into brain cortex of SHR increased 13-fold 2 min after HMI while that in WKY rats increased only 4-fold. After HMI Vd of 14C-sucrose into the cortex of WKY, and CSF of both SHR and WKY remained steadily greater than their corresponding control for up to 30 min (p < 0.01), whereas in the cortex of SHR the Vd of 14C-sucrose reached control values 20 min after HMI (p > 0.05), indicating that after HMI the increase in paracellular diffusion of 14C-sucrose into SHR cortex was not persistent, in contrast to WKY rats and CSF of both SHR and WKY rats. Electron microscopy of the brain cortex after HMI showed capillary endothelial cell shrinkage and perivascular swellings in the brain cortex, and in the choroid plexus opening of tight junctions were observed. Our results indicate disruption of both the BBB and the BCSFB after HMI in both SHR and WKY rats. The disruption remained persistent up to 25 min after HMI at the BBB of WKY rats and BCSFB in both animal groups, while in SHR the protective function of the BBB returned to control values 20 min after HMI.
Hemorrhagic Complications After Off-Label Thrombolysis for Ischemic Stroke
Authors: Aleu Aitziber , Mellado Patricio , Lichy Christoph , Köhrmann Martin , Schellinger Peter D.
Published: December 2006

Background and Purpose—

Only 2% to 4% of patients with acute ischemic stroke receive thrombolytic therapy resulting from the current strict inclusion criteria among other issues. Safety of intravenous and intraarterial thrombolysis in off-label situations is controversially discussed. We sought to review the reports on such patients regarding intra- and extracranial hemorrhage.

Summary of Review—

A MEDLINE search for off-label uses of thrombolysis revealed reports on 273 patients treated with intraarterial or intravenous thrombolysis for ischemic stroke. Symptomatic intracranial hemorrhage occurred in 19 of 273 patients (6.95%) and extracranial hemorrhage in 17 of 273 (6.22%).

Conclusions—

These data suggest that the overall bleeding risk in off-label thrombolysis may not be as high as presumed. However, the small number of patients in each group and the likely underreporting of worse outcomes preclude drawing any conclusion as to specific treatment recommendations. Selected patients might benefit, however, from thrombolysis in situations not currently considered in the inclusion criteria. To obtain a meaningful database, a registry for off-label thrombolysis should be created.
Atherosclerotic Renovascular Disease in Older US Patients Starting Dialysis, 1996 to 2001
Authors: Guo Haifeng , Kalra Philip A. , Gilbertson David T. , Liu Jiannong , Chen Shu-Cheng , Collins Allan J. , Foley Robert N.
Published: December 2006

Background—

Temporal trends regarding the epidemiology of atherosclerotic renovascular disease (ARVD) in dialysis populations are poorly defined.

Methods and Results—

United States Renal Data System data were used to identify patients aged 67 years or older at dialysis inception between 1996 and 2001 (n=146 973). Medicare claims in the preceding 2 years were used to identify ARVD and revascularization procedures. Prior ARVD rose from 7.1% to 11.2% between 1996 and 2001 (adjusted odds ratio [AOR], 1.68). Other associations included hypertensive end-stage renal disease (ESRD; AOR, 2.21), ESRD network (AOR, 0.44 in network 17 versus 1.00 in network 1), peripheral vascular disease (AOR, 1.65), black race (AOR, 0.44), urologic cause of ESRD (AOR, 0.57), age >85 years (AOR, 0.58), substance dependency (AOR, 0.62), and inability to ambulate or transfer (AOR, 0.67). The proportion of ARVD patients undergoing revascularization rose from 14.6% to 16.7% between 1996 and 2001 (AOR, 1.27). Other associations included hypertension (AOR, 2.10), ESRD network (AOR, 2.07 for network 13 versus 1.00 in network 1), age >85 years (AOR, 0.53), and black race (AOR, 0.54). The rise in ARVD was not reflected in the proportion of patients with renovascular disease listed as cause of ESRD on the Medical Evidence Report at dialysis inception (5.5% in 1996, 5.0% in 2001).

Conclusions—

ARVD diagnoses have become more common in older patients beginning dialysis therapy. The association of demographic factors including age, race, and geographic residence with utilization patterns suggests possible barriers to care.