bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic effects of a 12‐week course of alefacept on nail psoriasis
Authors: Körver JEM , Langewouters AMG , Van De Kerkhof PCM , Pasch MC 
Published: September 2006

AbstractBackground and objectives  Nail psoriasis is a common finding in psoriatic patients and it affects the quality of life in a great proportion of patients. Topical or systemic treatments have limited effectiveness or have a serious toxicity potential. Biologicals such as alefacept are the most recent treatment modalities for psoriasis. In the present study we evaluated changes in nail pathology in patients with plaque psoriasis and nail involvement during treatment with alefacept.Patients and methods  Digital photographs from eight patients were produced, which were analysed using the nail psoriasis severity index (NAPSI). A minimal NAPSI of 15 was chosen to divide patients into a moderate to very severe nail psoriasis group and a group with no or mild nail psoriasis. A decrease in NAPSI of at least 25% was considered a significant response to therapy.Results  In the group with at least moderate nail psoriasis, two patients improved, in two patients the nail changes remained unchanged and in one patient the nail pathology was aggravated. The group with no or mild nail psoriasis showed variable results.Conclusions  Although alefacept showed some results in treating nail pathology in psoriasis, a more extensive study is required, covering both more patients and a more extensive time period. Furthermore, it would also be clinically relevant to compare the effects of alefacept on nail psoriasis with other biologicals.
Skin capacitance mapping of psoriasis
Authors: Xhauflaire‐Uhoda E , Piérard‐Franchimont C , Piérard GE 
Published: September 2006

AbstractBackground  The pathobiological dynamics of psoriatic lesions are complex and difficult to perceive by clinical inspection alone. Non‐invasive bioengineering methods may prove to be useful in this field.Objective  To identify some subtle capacitance variations in the stratum corneum of chronic psoriasis lesions.Method  The newly developed method of skin capacitance imaging was used to provide non‐optical images of the hydration of the superficial layers of the stratum corneum.Results  Compared to the uninvolved skin, psoriatic lesions usually showed an overall lowered capacitance, admixed with foci of moderately higher capacitance. Still other sharply circumscribed blotches with higher capacitance were present. The latter aspect corresponded to inflammatory areas. Sweating appeared markedly impaired inside the lesions. The fingerprint of some patients was altered, thus potentially interfering with the current biometric security procedures using the same method.Conclusion  Skin capacitance imaging is a non‐invasive, non‐optical method that distinguishes three contrasting levels of stratum corneum hydration in psoriatic lesions. The lowest capacitance level probably corresponded to xerotic orthokeratosis. The medium capacitance level presumably identified foci of parakeratosis and clumps of neutrophils. The highest capacitance level suggested exsudation at the site of prominent vessel dilation and dermal inflammation. Impaired sweating in the psoriatic lesions may potentially interfere with body thermoregulation.
Nefazodone: A Review of Its Neurochemical Mechanisms, Pharmacokinetics, and Therapeutic Use in Major Depressive Disorder
Authors: He Handan , Richardson J. Steven 
Published: September 2006

ABSTRACTNefazodone, an antidepressant agent with a phenylpiperazine structure, has a pharmacological profile that is distinct from other antidepressant drugs. Like many other antidepressants, nefazodone inhibits the reuptake of norepinephrine and serotonin from the synaptic cleft. Unlike other antidepressants, nefazodone is also a potent antagonist of 5‐HT2 serotonergic receptors. In addition, nefazodone is a weak antagonist of α1‐adrenergic receptors, but has little or no affinity for cholinergic, histaminergic, or dopaminergic receptors. In placebo‐controlled clinical trials, nefazodone has been found to be an effective antidepressant drug with minimal cardiovascular action and significantly fewer side effects than imipramine. Since nefazodone is an effective antidepressant with a low incidence of serious adverse effects, it may be particularly useful in major depressive disorder patients who are intolerant of the anticholinergic or serotonergic side effects of other antidepressants, or who do not respond to treatment with other antidepressant agents. In this paper, we review the mechanisms of action, the pharmacokinetics, and the antidepressant efficacy of nefazodone.
A Review of the Preclinical Development of Zaleplon, a Novel Non‐Benzodiazepine Hypnotic for the Treatment of Insomnia
Authors: Beer B. , Clody D. E. , Mangano R. , Levner M. , Mayer P. , Barrett J. E. 
Published: September 2006

SUMMARYZaleplon (N‐[3‐(3‐cyanopyrazolo[l,5‐a]pyrimidin‐7‐y l)phenyl)]‐N‐ethylacetamide) is a non‐benzodiazepine sedative‐hypnotic with benzodiazepine‐like sedative effects, but with less apparent liability for accompanying undesirable side effects. Zaleplon displaces [3H]flunitrazepam from rat cortical membranes with an IC50 value of 200 nM and enhances t‐butylbicyclophosphorothionate [35S]TBPS binding by 73%, suggesting pharmacological activity mediated by the GABAA benzodiazepine receptor complex. In various preclinical procedures such as motor activity, muscle relaxation, EEG, anticonvulsant activity, and vigilance, zaleplon produced effects similar to those of other sedative‐hypnotic compounds such as triazolam and flurazepam; furthermore, these effects, when evaluated, were reversed by the benzodiazepine receptor antagonist flumazenil. Zaleplon increased punished (conflict) responding in squirrel monkeys and rats and these effects were also antagonized by flumazenil. When established as a discriminative stimulus in rats at 3.0mg/kg i.p., zaleplon showed a dose‐related increase in drug‐appropriate responding up to the training dose and a correlated decrease in response rate. Triazolam (0.1 to 1.0 mg/kg), the benzodiazepine partial agonist Ro 17‐1812 (0.3 to 3.0mg/kg), and the triazolopyridine CL 218,872 (1.0 to 3.0 mg/kg) substituted consistently for zaleplon in all rats, whereas the imidazo‐pyridines zolpidem (3.0 to 10 mg/kg) and alpidem (10 to 30 mg/kg), the benzodiazepine partial agonist bretazenil (0.03 to 10 mg/kg) and the novel putative anxio‐lytic CL 273,547 (10 to 56 mg/kg) did not result in consistent drug‐appropriate responding in all rats. These results suggest that the effects of zaleplon are similar in many respects to other compounds acting at the benzodiazepine receptor complex but differ as well from both benzodiazepine and non‐ benzodiazepine drugs. This profile of activity, coupled with additional information in ancillary procedures, yields a pre‐clinical profile of a short‐acting sedative‐hypnotic non‐benzodiazepine that is currently in Phase III development for the treatment of sleep disturbances.
Diffusion Tensor Imaging in Children with Fetal Alcohol Spectrum Disorders
Authors: Wozniak Jeffrey R. , Mueller Bryon A. , Chang Pi‐Nian , Muetzel Ryan L. , Caros Lydia , Lim Kelvin O. 
Published: September 2006

Background: Prenatal alcohol exposure, which is associated with macrostructural brain abnormalities, neurocognitive deficits, and behavioral disturbances, is characterized as fetal alcohol syndrome (FAS) in severe cases. The only published study thus far using diffusion tensor imaging (DTI) showed microstructural abnormalities in patients with FAS. The current study investigated whether similar abnormalities are present in less severely affected, prenatally exposed patients who did not display all of the typical FAS physical stigmata.Methods: Subjects included 14 children, ages 10 to 13, with fetal alcohol spectrum disorders (FASD) and 13 matched controls. Cases with full‐criteria FAS, mental retardation, or microcephaly were excluded. Subjects underwent MRI scans including DTI.Results: Although cases with microcephaly were excluded, there was a trend toward smaller total cerebral volume in the FASD group (p=0.057, Cohen's d effect size =0.73). Subjects with FASD had greater mean diffusivity (MD) in the isthmus of the corpus callosum than controls (p=0.013, effect size =1.05), suggesting microstructural abnormalities in this region. There were no group differences in 5 other regions of the corpus callosum. Correlations between MD in the isthmus and facial dysmorphology were nonsignificant.Conclusions: These results suggest that even relatively mild forms of fetal alcohol exposure may be associated with microstructural abnormalities in the posterior corpus callosum that are detectable with DTI.
Spouse Abuse and Alcohol Problems Among White, African American, and Hispanic U.S. Army Soldiers
Authors: Bell Nicole S. , Harford Thomas C. , Fuchs Cara H. , McCarroll James E. , Schwartz Carolyn E. 
Published: September 2006

Background: Prior studies suggest racial/ethnic differences in the associations between alcohol misuse and spouse abuse. Some studies indicate that drinking patterns are a stronger predictor of spouse abuse for African Americans but not whites or Hispanics, while others report that drinking patterns are a stronger predictor for whites than African Americans or Hispanics. This study extends prior work by exploring associations between heavy drinking, alcohol‐related problems, and risk for spouse abuse within racial/ethnic groups as well as variations associated with whether the perpetrator is drinking during the spouse abuse incident.Methods: Cases (N=7,996) were all active‐duty male, enlisted Army spouse abusers identified in the Army's Central Registry (ACR) who had also completed an Army Health Risk Appraisal (HRA) Survey between 1991 and 1998. Controls (N=17,821) were matched on gender, rank, and marital and HRA status.Results: We found 3 different patterns of association between alcohol use and domestic violence depending upon both the race/ethnicity of the perpetrator and whether or not alcohol was involved in the spouse abuse event. First, after adjusting for demographic and psychosocial factors, weekly heavy drinking (>14 drinks per week) and alcohol‐related problems (yes to 2 or more of 6 alcohol‐related problem questions, including the CAGE) were significant predictors of domestic violence among whites and Hispanics only. Also for the white soldiers, the presence of family problems mediated the effect of alcohol‐related problems on spouse abuse. Second, alcohol‐related problems predicted drinking during a spouse abuse incident for all 3 race groups, but this relation was moderated by typical alcohol consumption patterns in Hispanics and whites only. Finally, alcohol‐related problems predicted drinking during a spouse abuse incident, but this was a complex association moderated by different psychosocial or behavioral variables within each race/ethnic group.Conclusion: These findings suggest important cultural/social influences that interact with drinking patterns.
Arrhythmogenesis in the Developing Heart During Anoxia‐Reoxygenation and Hypothermia‐Rewarming: An In Vitro Model
Authors: SARRE ALEXANDRE , MAURY PHILIPPE , KUCERA PAVEL , KAPPENBERGER LUKAS , RADDATZ ERIC 
Published: September 2006

Introduction: The spatio‐temporal pattern of arrhythmias in the embryonic/fetal heart subjected to a transient hypoxic or hypothermic stress remains to be established. Methods and Results: Spontaneously beating hearts or isolated atria, ventricles, and conotruncus from 4‐day‐old chick embryos were subjected in vitro to 30‐minute anoxia and 60‐minute reoxygenation. Hearts were also submitted to 30‐minute hypothermia (0–4°C) and 60‐minute rewarming. ECG disturbances and alterations of atrial and ventricular electromechanical delay (EMD) were systematically investigated. Baseline functional parameters were stable during at least 2 hours. Anoxia induced tachycardia, followed by bradycardia, atrial ectopy, first‐, second‐, and third‐degree atrio‐ventricular blocks and, finally, transient electromechanical arrest after 6.8 minutes, interquartile ranges (IQR) 3.1–16.2 (n = 8). Reoxygenation triggered also Wenckebach phenomenon and ventricular escape beats. At the onset of reoxygenation QT, PR, and ventricular EMD increased by 68%, 70%, and 250%, respectively, whereas atrial EMD was not altered. No fibrillations, no ventricular ectopic beats, and no electromechanical dissociation were observed. Arrhythmic activity of the isolated atria persisted throughout anoxia and upon reoxygenation, whereas activity of the isolated ventricles abruptly ceased after 5 minutes of anoxia and resumed after 5 minutes of reoxygenation. During hypothermia‐rewarming, cardiac activity stopped at 17.9°C, IQR 16.2–20.6 (n = 4) and resumed at the same temperature with no arrhythmias. All preparations fully recovered after 40 minutes of reoxygenation or rewarming. Conclusion: In the embryonic heart, arrhythmias mainly originated in the sinoatrial tissue and resembled those observed in the adult heart. Furthermore, oxygen readmission was by far more arrhythmogenic than rewarming and the chronotropic, dromotropic, and inotropic effects were fully reversible.
Weight development in patients treated with risperidone: a 5‐year naturalistic study
Authors: Neovius M. , Eberhard J. , Lindström E. , Levander S. 
Published: September 2006

Objective:  To examine annual weight‐development in a sample of 215 psychotic patients treated with risperidone over 5 years.Method:  Naturalistic longitudinal study.Results:  The sample was more obese than the general population at baseline, but also increased much more in mean body mass index over approximately the same time period, while patients off medication seemed to remain weight stable. Excessive weight gain (>7%) was experienced by 40.2% and was weakly associated with weight at baseline (β = −0.2%; P = 0.02), while independent of gender, symptoms, years of illness, prolactin levels and nicotine consumption. In patients with complete weight data (n = 87), approximately 72% (3.4 ± 8.3 kg) of the observed 5 years weight gain (4.7 ± 11.6 kg) had been accumulated after 2 years.Conclusion:  Antipsychotic drug treatment resulted in significant weight gain, which levelled off over time. Unfortunately, few significant predictors of adverse weight development could be identified, leaving little guidance for clinical decision making regarding this specific side‐effect.
Chemokines, cytokines, and growth factors in keratinocytes and dermal endothelial cells in the margin of chronic diabetic foot ulcers
Authors: Galkowska Hanna , Wojewodzka Urszula , Olszewski Waldemar L. 
Published: September 2006

ABSTRACTKeratinocytes and dermal endothelial cells, excluding leukocytes that infiltrate wounds, are the main source of soluble factors regulating healing of skin ulcers. We used immunohistochemistry to analyze the expression of various chemotactic and growth factors and their receptors in the margin of diabetic foot ulcers and in normal nondiabetic foot skin. Our study found significantly elevated expression of transforming growth factor‐β1 (TGF‐β1) and type I TGF‐β receptors (TGFβR1), granulocyte macrophage colony‐stimulating factor (GM‐CSF), and epidermal growth factor (EGF) in keratinocytes in the ulcer margin (p<0.05). Significantly increased expression of monocyte chemotactic protein‐1, GM‐CSF, CXCR1, and TGFβRI and decreased expression of interleukin (IL)‐10, IL‐15, and TGF‐β1 were observed in ulcer dermal endothelial cells (p<0.05). There was a lack of up‐regulation of IL‐8, CCR2A, IL‐10 receptor, GM‐CSF receptor, platelet‐derived growth factors and their receptors, vascular endothelial growth factor and its type II receptor, EGF receptor, insulin‐like growth factor‐1, and nitric oxide synthase‐2 in both KCs and endothelial cells in the ulcer. Finally, there was a lack of up‐regulation of IL‐10 and IL‐15 in keratinocytes and of EGF, basic fibroblast growth factor, and nitric oxide synthase‐3 in endothelial cells in the ulcer margins. The enhanced expression of some factors responsible for KC behavior could suggest an unimpaired capacity of keratinocytes to reepithelialize the margin of diabetic foot ulcers. However, lack of up‐regulation of some angiogenic and leukocyte chemotactic factors, associated with the reduced influx of immune cells, may account for a poor formation of granulation tissue and chronicity of ulcer epithelialization.
Prostaglandin E2 differentially modulates human fetal and adult dermal fibroblast migration and contraction: implication for wound healing
Authors: Sandulache Vlad C. , Parekh Aron , Li‐Korotky Ha‐Sheng , Dohar Joseph E. , Hebda Patricia A. 
Published: September 2006

ABSTRACTCyclooxygenase‐2 is up‐regulated shortly after dermal injury and it has been shown to have important activity during the repair process. Its main product in the skin, prostaglandin E2 (PGE2), modulates both inflammatory and fibrotic processes during wound healing and partially dictates the overall outcome of wound healing. PGE2 signaling has been shown to be altered during fetal wound healing. This study was designed to examine the mechanism(s) by which PGE2 regulates fibroblast migration and contraction and to determine whether these mechanisms are conserved in fetal‐derived dermal fibroblasts. Fetal and adult dermal fibroblasts express all four PGE2 receptors. PGE2 inhibits fetal and adult fibroblast migration in a dose‐dependent manner through the EP2/EP4–cAMP–protein kinase A pathway. However, fetal fibroblasts appear to be refractory to this effect, requiring a 10‐fold higher concentration of PGE2 to achieve a similar degree of inhibition as adult fibroblasts. Inhibition of adult fibroblast migration correlated with disruption of the actin cytoskeleton. In contrast, PGE2 or a cAMP analog did not disrupt the actin cytoskeleton of fetal dermal fibroblasts. These findings were extended using a modified free‐floating, fibroblast‐populated collagen lattice (FPCL) contraction assay designed to measure fibroblast contraction. PGE2‐inhibited FPCL contraction by adult fibroblasts, but fetal fibroblasts exhibited higher rates of FPCL contraction and a blunted response to exogenous modulation by PGE2 or a cyclase activator (forskolin). These findings indicate that fetal dermal fibroblasts are partially refractory to the effects of PGE2, a major inflammatory mediator associated with dermal wound healing. This effect may have significant and specific relevance to the scarless fetal wound‐healing phenotype.
Antibacterial properties of EMLA® and lidocaine in wound tissue biopsies for culturing
Authors: Berg Jais O. , Mössner Belinda K. , Skov Marianne N. , Lauridsen Jorgen , Gottrup Finn , Kolmos Hans J. 
Published: September 2006

ABSTRACTIf a tissue biopsy from a chronic wound is sampled for culture, the antibacterial properties of local anesthetics may pose a problem in producing false‐negative results. The purpose of this study was to investigate the effects of EMLA® (AstraZeneca) and lidocaine on common wound pathogenic bacteria. An in vitro study of a total of 25 clinical isolates and ATCC reference strains of Staphylococcus aureus (including methicillin‐resistant S. aureus), Escherichia coli, Pseudomonas aeruginosa, and Streptococcus pyogenes was conducted. The isolates were exposed to the local anesthetic drugs (and some of their contents separately) at 35°C over a 24‐hour period and time–kill curves were recorded. No culture media were used and saline was used for controls. EMLA® was found to have a rapid acting and powerful antibacterial effect and should not be used before culturing tissue samples. Lidocaine 1% was found not to inhibit the bacterial strains when exposure time was held below 2 hours. We conclude that culturing tissue from a wound biopsy is safe within 2 hours when a pure, preservative‐free lidocaine 1% solution is used.
Long‐term invasive measurement of subcutaneous oxygen partial pressure above the sacrum on lying healthy volunteers
Authors: Völker Hans‐Ullrich , Röper Gerhard , Sterk Jürgen , Willy Christian 
Published: September 2006

ABSTRACTPressure ulcers are frequently seen dermal lesions, but little is known about their pathophysiology. It is generally assumed that prolonged tissue pressure impairs blood circulation thus causing ischemic damage to tissue. Therefore, subcutaneous oxygen partial pressure was measured to confirm this hypothesis. In the past, various authors have conducted tests on healthy subjects to determine oxygen partial pressure transcutaneously during periods not exceeding 20 minutes. All found a decrease at susceptible sites, e.g., the sacrum. The present study was the first one to measure oxygen partial pressure subcutaneously above the sacrums of four test subjects during a period of 5 hours. In all cases, the values first decreased to a minimum of 37% of baseline before they returned to the initial values. This observation is in contradiction to former studies, which start from the assumption of critical ischemia due to interface pressure, measured on healthy volunteers too.
Diagnostic validity of three swab techniques for identifying chronic wound infection
Authors: Gardner Sue E. , Frantz Rita A. , Saltzman Charles L. , Hillis Stephen L. , Park Heeok , Scherubel Melody 
Published: September 2006

ABSTRACTThis study examined the diagnostic validity of three different swab techniques in identifying chronic wound infection. Concurrent swab specimens of chronic wounds were obtained using wound exudate, theZ‐technique, and the Levine technique, along with a specimen of viable wound tissue. Swab and tissue specimens were cultured using quantitative and qualitative laboratory procedures. Infected wounds were defined as those containing 1 × 106or more organisms per gram of tissue. Accuracy was determined by associating the quantitative cultures of swab specimens with the cultures from tissue specimens using receiver operating characteristic curves. Of the 83 study wounds, 30 (36%) were infected. Accuracy was the highest for swab specimens obtained using Levine's technique at 0.80. Based on Levine's technique, a critical threshold of 37,000 organisms per swab provided a sensitivity of 90% and a specificity of 57%. The mean concordance between swab specimens obtained using Levine's technique and tissue specimens was 78%. The findings suggest that swab specimens collected using Levine's technique provide a reasonably accurate measure of wound bioburden, given that they are more widely applicable than tissue cultures. The diagnostic validity of Levine's technique needs further study using an alternative reference standard, such as the development of infection‐related complications.