bluuebunny/crossref_metadata_2025 huggingface dataset:
Rhodotorula rubra fungaemia in an immunosuppressed patient
Authors: Papadogeorgakis H. , Frangoulis E. , Papaefstathiou C. , Katsambas A.
Published: September 2006

We report the case of a patient who, following surgical removal of an extensive tumour of the bowel, developed fungaemia. The yeast was isolated from repeated blood and urine cultures and identified as Rhodotorula rubra on the basis of macroscopic and microscopic features. Following treatment with amphotericin B, the patient's condition improved and the cultures became sterile.
Notalgia paresthetica: clinical, physiopathological and therapeutic aspects. A study of 12 cases
Authors: Raison‐Peyron N. , Meunier L. , Acevedo M. , Meynadier J.
Published: September 2006

Notalgia paresthetica (NP) is a common but often unrecognized neurocutaneous condition, with very few cases reported to date. It is characterized by pruritus localized in an area between D2 and D6 dermatomes, sometimes accompanied by sensory neuropathies and/or electrical conductivity disorders. Cutaneous pigmented patches and friction amyloidosis can arise with irritation. Some hereditary cases have been noted mainly in young patients, associated with multiple endocrine neoplasia type 2A. However, NP mainly occurs in older patients and most are sporadic pathologies linked with musculoskeletal compression of spinal nerves. Only capsaicin has shown some (but unfortunately only transient) efficacy in relieving NP symptoms. We present observations on 12 sporadic cases of NP. Spinal X‐rays revealed dorsal arthrosis or spinal static disequilibrium in nine of these patients. Six patients underwent spinal and paraspinal ultrasound or radiation (better) physiotherapy, and the symptoms subsided in four of these cases. These results highlighted that spinal disorders could be a determining factor in NP, indicating that patients could benefit from physiotherapy.
Past and current understanding of the pathophysiology of muscle cramps: why treatment of varicose veins does not relieve leg cramps
Authors: Jansen P.H.P. , Lecluse R.G.M. , Verbeek A.L.M.
Published: September 2006

Historically relevant hypotheses on the pathophysiology of muscle cramps are reviewed. Psychosomatic, static, vascular, myogenic and neural theories are highlighted from a clinician's point of view. Modern neurophysiologic research leaves little doubt that muscle cramp is caused by excitation of spinal motor neurones mediated by changes in presynaptic input. Nevertheless, obsolete theories and relative treatments stubbornly persist in clinical practice.
Multiple perifollicular fibromas
Authors: McKenna D.B. , Barry‐Walsh C. , Leader M. , Murphy G.M.
Published: September 2006

Perifollicular fibroma is a benign mesodermal tumour of the hair follicle. It can occur as a solitary papule or as multiple lesions that are clinically indistinguishable from other tumours of the pilar apparatus. Multiple perifollicular fibromas may be inherited although the pattern remains unclear. Adnexal tumours can be associated with internal malignancy and perifollicular fibromas have been linked with adenomatous colonic polyps. This report describes a patient with multiple perifollicular fibromas with no associated malignancy to date and a family pedigree suggestive of an autosomal dominant pattern of inheritance.
Hydroxyurea‐induced leg ulcers: is macroerythrocytosis a pathogenic factor?
Authors: Vélez Antonio , García‐Aranda José‐María , Moreno José‐Carlos
Published: September 2006

Hydroxyurea is a common cancer chemotherapy agent that inhibits ribonucleotide reductase, an enzyme essential to DNA synthesis. It is considered the drug of choice in the treatment of chronic myelogenous leukemia and essential thrombocythemia. The occurrence of leg ulcers have been described in 8.5% of patients receiving continuous treatment with hydroxyurea, but the cause of this complication is unknown. We report two additional patients and suggest that macroerythrocytosis, which occurs in almost all the patients taking hydroxyurea, may be a pathogenic factor. Macroerythrocytosis can be considered as an ‘acquired’ blood dyscrasia, and similar leg ulcers have long been known to occur with certain hereditary blood dyscrasias, such as sickle cell anemia, thalasemia, and spherocytosis.
Mid‐dermal elastolysis associated with Hashimoto's thyroiditis
Authors: Gambichler Thilo , Linhart Carola , Wolter Manfred
Published: September 2006

We report the case of a 38‐year‐old Caucasian female presenting asymptomatic plaques of fine wrinkling and perifollicular papular protrusions especially on the trunk. Histological examination evidenced loss of elastic fibers in the mid‐dermis due to elastophagocytosis, with giant cells and granuloma formation. Moreover, elevated titers of thyroid autoantibodies were detected and thyroid ultrasound revealed echo‐poor tissue. These findings met the diagnoses of mid‐dermal elastolysis and Hashimoto's thyroiditis. This association has not been reported before. We present a comprehensive overview of the literature and discuss the pathogenetic aspects of mid‐dermal elastolysis and the significance of the association with Hashimoto's thyroiditis.
Primary cutaneous mucormycosis: a diagnosis to consider
Authors: García‐Bustínduy Marta , Guimerá‐Martín‐Neda Francisco , Noda Antonio , Lecuona María , Sánchez‐González Rosalba , de Mesa María José González , Sáez‐Rodriguez Miguel , Martín‐Malagón Antonio , García‐Montelongo Rafael
Published: September 2006

Primary cutaneous mucormycosis is a deep fungal infection, mainly seen in diabetics and immunocompromised subjects. Rapid diagnosis and therapy are necessary to avoid fatal outcome. We describe the complete histopathological and microbiological studies of primary cutaneous mucormycosis in a 74‐year‐old man with several risk factors, such as chronic obstructive pulmonary disease, respiratory acidosis, hemolytic anemia, myelodysplastic syndrome and iatrogenic diabetes, due to corticosteroid therapy. He developed two cutaneous necrotic scars on his left leg. Mucormycosis was suspected and specimens from surgical debridement were histopathologically and microbiologically studied confirming the clinical diagnosis. Amphotericin B was given topically and intravenously resulting in complete healing of the ulcer. Risk factors and microbiological studies are compared with those in the current literature. It is necessary in certain cases to suspect mucormycosis infections in diabetics, immunocompromised subjects and even in healthy individuals. Rapid diagnosis and treatment are important, but they should be based on complete histopatholgical and microbiological studies, to establish the genus of the causal agent.
Fifth toenail clinical response to systemic antifungal therapy is not a marker of successful therapy for other toenails with onychomycosis
Authors: Avner S , Nir N , Henri T
Published: September 2006

Background  Onychodystrophy is a major manifestation of onychomycosis. However, nail trauma may also result in onychodystrophy. The fifth toenail, due to its location, suffers repeated friction/pressure trauma from shoes.

Objective  To test the hypothesis that treatment failure of fifth toenail onychomycosis is not a marker of treatment failure of other toenails with onychomycosis.

Methods  Fifty patients who had fifth toenail deformity (with or without onychomycosis) and onychomycosis of the other toenails were treated with oral terbinafine, 250 mg/day, for 4 months.

Results  Forty‐three patients completed the study. Before the study, 26/43 (61%) had callus lateral to the fifth toe (suggesting mechanical pressure in that area). Twenty‐one/43 (49%) of the fifth toenails had onychomycosis. At the end of the treatment period, only 4/21 (19%) of the fifth toenails (with initial onychomycosis), compared with 12/21 (57%) of the other toenails, were completely cured (CC). Out of the whole group (n = 43), the clinical cure rate of the fifth toenail was 4/43 (9%) and for the other toenails, 20/43 (47%) (P < 0.05). The mycological cure rates were 11/21 (52%) for the fifth toenail and 25/43 (58%) for the other toenails. Callus lateral to the fifth toe was associated with a poor clinical result (P < 0.01).

Conclusions  Clinical improvement of the fifth toenail after systemic antifungal therapy is less favourable and does not correspond with the clinical cure of the other toenails, mostly because of mechanical factors. Therefore, patients should be told to adjust their expectations as to the visual results of their antifungal treatment.
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

Background 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

Background  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.
Building an idea: the material construction of an ideal childhood
Authors: Kraftl Peter
Published: September 2006

This paper explores how ideas and ideals are constructed. More specifically, it follows how ideas and ideals of ‘childhood’ are constructed. Still more specifically, it attends to the ways in which idea(l)s of childhood are literally and materially constructed, in, through and as part of practices such as the building and maintenance of architectural forms. I argue that most studies of childhood largely ignore the importance of local, banal, ephemeral, mundane, material practices – often involved in the very constitution and performance of spaces – which are hugely significant to the construction of idea(l)s like childhood. By adopting a ‘critical geographical’ approach to the daily life of an alternative school in Pembrokeshire, in the United Kingdom, I demonstrate how particular arrays of usually un‐noticed practices are involved in the construction, constitution and evocation of idea(l)s like childhood.
Nefazodone: A Review of Its Neurochemical Mechanisms, Pharmacokinetics, and Therapeutic Use in Major Depressive Disorder
Authors: He Handan , Richardson J. Steven
Published: September 2006

Nefazodone, 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

Zaleplon (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

Keratinocytes 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

Cyclooxygenase‐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

If 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

Pressure 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

This 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.
Strategies to enhance transductional efficiency of adenoviral‐based gene transfer to primary human fibroblasts and keratinocytes as a platform in dermal wounds
Authors: Stoff Alexander , Rivera Angel A. , Banerjee N. S. , Michael Mathis J. , Espinosa‐de‐los‐Monteros Antonio , Le Long P. , De la Torre Jorge I. , Vasconez Luis O. , Broker Thomas R. , Richter Dirk F. , Stoff‐Khalili Mariam A. , Curiel David T.
Published: September 2006

Genetically modified keratinocytes and fibroblasts are suitable for delivery of therapeutic genes capable of modifying the wound healing process. However, efficient gene delivery is a prerequisite for successful gene therapy of wounds. Whereas adenoviral vectors (Ads) exhibit superior levels of in vivo gene transfer, their transductional efficiency to cells resident within wounds may nonetheless be suboptimal, due to deficiency of the primary adenovirus receptor, coxsackie‐adenovirus receptor (CAR). We explored CAR‐independent transduction to fibroblasts and keratinocytes using a panel of CAR‐independent fiber‐modified Ads to determine enhancement of infectivity. These fiber‐modified adenoviral vectors included Ad 3 knob (Ad5/3), canine Ad serotype 2 knob (Ad5CAV‐2), RGD (Ad5.RGD), polylysine (Ad5.pK7), or both RGD and polylysine (Ad5.RGD.pK7). To evaluate whether transduction efficiencies of the fiber‐modified adenoviral vectors correlated with the expression of their putative receptors on keratinocytes and fibroblasts, we analyzed the mRNA levels of CAR, αυ integrin, syndecan‐1, and glypican‐1 using quantitative polymerase chain reaction. Analysis of luciferase and green fluorescent protein transgene expression showed superior transduction efficiency of Ad5.pK7 in keratinocytes and Ad5.RGD.pK7 in fibroblasts. mRNA expression of αυ integrin, syndecan‐1 and glypican‐1 was significantly higher in primary fibroblasts than CAR. In keratinocytes, syndecan‐1 expression was significantly higher than all the other receptors tested. Significant infectivity enhancement was achieved in keratinocytes and fibroblasts using fiber‐modified adenoviral vectors. These strategies to enhance infectivity may help to achieve higher clinical efficacy of wound gene therapy.
Afghan Women: Recovering, Rebuilding
Authors: Wali Sima
Published: September 2006

The United States' foreign policy in Afghanistan has a long history of misguided plans and misplaced trust—a fact that has contributed to the destruction of the social and physical infrastructure of Afghan society. Afghans contend that after having fought as U.S. allies against the Soviet Union—with the price of more than two million dead—the United States swiftly walked away at the end of that bloody, twenty-three-year conflict. The toll of the war on Afghan society reflected in current statistics is so staggering as to be practically unimaginable: 12 million women living in abject poverty, 1 million people handicapped from land mine explosions, an average life expectancy of forty years (lower for women), a mortality rate of 25.7 percent for children under five years old, and an illiteracy rate of 64 percent. These horrific indicators place Afghanistan among the most destitute countries in the world in terms of human development.
New Priorities for Philanthropy
Authors: Bach Robert L.
Published: September 2006

The events of September 11 have forced institutions to reexamine their priorities and practices. Yet the first world war of the twenty-first century has left many wondering if there truly is a war, and what, if anything, different is demanded of them. The philanthropic sector in particular has not changed significantly, and it continues to struggle with fundamental concerns about its directions. If September 11 and its aftermath are to mean anything to philanthropy other than emergency relief, it must be a recognition that now is the time to tackle the problems and tensions that were ignored before the attacks. For nearly a year, philanthropy as a sector has not rallied behind this call for longer-term reform. Philanthropy should take up these tasks, no matter how daunting they may be, for if foundations do not lead the effort, it may be left to the governments and the militaries of the world to respond on their own.
Public Health or Clinical Ethics: Thinking beyond Borders
Authors: O'Neill Onora
Published: September 2006

Most work in medical ethics across the last twenty-five years has centered on the ethics of clinical medicine. Even work on health and justice has, in the main, been concerned with the just distribution of (access to) clinical care for individual patients. By contrast, the ethics of public health has been widely neglected. This neglect is surprising, given that public health interventions are often the most effective (and most cost-effective) means of improving health in rich and poor societies alike.

In this essay I explore two sources of contemporary neglect of public health ethics. One source of neglect is that contemporary medical ethics has been preoccupied—in my view damagingly preoccupied—with the autonomy of individual patients. Yet individual autonomy can hardly be a guiding ethical principle for public health measures, since many of them must be uniform and compulsory if they are to be effective. A second source of neglect is that contemporary political philosophy has been preoccupied—in my view damagingly preoccupied—with the requirements for justice within states or societies, and (until very recently) has hardly discussed justice across borders. Yet public health problems often cross borders, and public health interventions have to measure up to the problems they address.
Striking First: A History of Thankfully Lost Opportunities
Authors: Betts Richard K.
Published: September 2006

It is unlikely that George W. Bush feels constrained by international law when deciding whether to use military force abroad. Nevertheless, many of the United States' allies are reluctant to cooperate with and participate in military actions that cannot reasonably be justified under international law. And supportive allies, while perhaps not strictly necessary to the United States in its recent and foreseeable military campaigns, do make the military option easier to pursue. A war against Iraq would be difficult without access to bases and airspace in countries as diverse as Turkey, Saudi Arabia, Germany, and Canada. For this reason, at least, it would seem to be worth the president's while to adhere to international law where possible and, where this is not possible, to seek to change the rules.
The Slippery Slope to Preventive War
Authors: Crawford Neta C.
Published: September 2006

The Bush administration's arguments in favor of a preemptive doctrine rest on the view that warfare has been transformed. As Colin Powell argues, “It's a different world … it's a new kind of threat.” And in several important respects, war has changed along the lines the administration suggests, although that transformation has been under way for at least the last ten to fifteen years. Unconventional adversaries prepared to wage unconventional war can conceal their movements, weapons, and immediate intentions and conduct devastating surprise attacks. Nuclear, chemical, and biological weapons, though not widely dispersed, are more readily available than they were in the recent past. And the everyday infrastructure of the United States can be turned against it as were the planes the terrorists hijacked on September 11, 2001. Further, the administration argues that we face enemies who “reject basic human values and hate the United States and everything for which it stands.” Although vulnerability could certainly be reduced in many ways, it is impossible to achieve complete invulnerability.
Assistance with Fewer Strings Attached
Authors: Collingwood Vivien
Published: September 2006

International organizations and bilateral donors often tie financial assistance to the undertaking of political and economic reforms–a practice known as conditionality. In recent years, the use of good governance conditionality has provoked controversy in the academic and policy worlds. So far, the issue of whether conditionality is effective in achieving compliance with good governance norms has occupied center stage in the debate. However, whether it is morally defensible to attach political conditions to financial assistance has largely been taken for granted.

This article explores the extent to which it is morally defensible to attach good governance conditions to aid and loans in international society. It argues that the use of conditionality should be limited for two reasons. First, there is an unavoidable tension between conditionality and rights to self-determination. Second, focusing on conditionality can obscure the fact that the rules of the international economy are no less contestable than the governance of individual states, and, in turn, are in just as great a need of reform. This leads to two main conclusions. First, the use of conditionality should now be rooted in a conception of basic rights and complemented by more equitable rules in the global economy. Second, the attempt to make good governance within states an issue of global concern must be accompanied by greater democratization of the international financial institutions.
Who Should Get in? The Ethics of Immigration Admissions
Authors: Carens Joseph H
Published: September 2006

This article explores normative questions about what legal rights settled immigrants should have in liberal democratic states. It argues that liberal democratic justice, properly understood, greatly constrains the distinctions that can be made between citizens and residents. The longer people stay in a society, the stronger their moral claims become, and after a while they pass a threshold that entitles them to virtually the same legal status as citizens and eventually easy access to citizenship itself.
Israel's Policy of Targeted Killing
Authors: David Steven R.
Published: September 2006

Since the beginning of the second intifada in the fall of 2000, Israel has pursued a policy in which alleged Palestinian terrorists have been hunted down and killed by government order. The policy is not one of assassination and is consistent with international law because Israel is engaged in armed conflict with terrorists, those targeted are usually killed by conventional military means, not through deception, and the targets of the attacks are not civilians but combatants or are part of a military chain of command. Targeted killing has also been affirmed by Israel's High Court.

Although targeted killing has been pursued by Israel throughout its history, the scale of the present effort and the use of sophisticated military assets such as helicopter gunships and jet fighters set it apart from earlier practices. The effectiveness of the policy is called into doubt because it has not prevented–and may have contributed to–record numbers of Israeli civilians being killed. The policy has also resulted in informers being revealed, intelligence resources diverted, potential negotiating partners eliminated. It has also produced murderous retaliation and international condemnation of Israel. Benefits of the policy include impeding the effectiveness of terrorist operations, keeping terrorists on the run, and deterring some attacks. In addition, it affords the Israeli public a sense of revenge and retribution.

Because it targets the actual perpetrators of terrorism, targeted killing provides a proportionate and discriminate response to the threat Israel faces. Improving the policy will require better civilian oversight, greater care to eliminate harm to innocent bystanders, and refraining from killing political leaders. Despite its many shortcomings, Israel is justified in pursuing this policy so long as it faces a terrorist threat that the Palestinian Authority will not or cannot control.
Debating the Use of Racial and Ethnic Categories in Research
Authors: Wolf Susan M.
Published: September 2006

Debate over the proper use of racial and ethnic categories in biomedical research has raged in recent years. With the Human Genome Project showing that human beings are overwhelmingly alike genetically, exhibiting more genetic variation within supposed “races” than between them, many have come to doubt the scientific utility of such categories. Yet federal authorities use Directive 15 from the Office of Management and Budget (OMB) to mandate the continued use of such categories in research. Moreover, researchers studying health disparities argue that data collection using racial and ethnic categories is necessary to determine whether conditions and care vary by race and ethnicity. Epidemiologists also defend the use of racial and ethnic categories to understand contributors to disease such as the stress of experiencing racial prejudice and reduced access to care because of bias.
Racial and Ethnic Categories in Biomedical Research: There is No Baby in the Bathwater
Authors: Cho Mildred K.
Published: September 2006

There are deep divides over the use of racial and ethnic categories in biomedical research and its application in both medical and non-medical contexts. On one side of a roughly described dividing line are practitioners who need to use every piece of information at their disposal to solve pressing, realworld problems in real time, such as making clinical diagnoses or identifying perpetrators of crime. On the other side are scientists and policy makers committed to meeting a scientific and social need for accuracy and thus trying to avoid miscategorization.

As Jay Cohn describes in this issue, medical practitioners in particular have used racial and ethnic categories to “enhance diagnostic and therapeutic precision.” He argues for retaining this practice. The plea, motivated by genuine concern for patients, is to avoid “throwing the baby out with the bathwater.” However, Cohn and others mischaracterize the nature of the debate. The argument is not about whether differences among populations exist, or even whether differences among “races” exist.
Thinking Critically about Race and Genetics
Authors: Brewer Rose M.
Published: September 2006

The issue of how race and genetics should interrelate goes to the heart of an unfinished discussion about race and racism in both the United States and around the world. The category of race is still powerful and dangerous, especially in scientific work. Addressing this issue is all the more important given the fact that race is still frequently essentialized and treated as biologically real. This tendency continues even as social and natural scientists such as Troy Duster and Charles Mills largely agree that race is a social construction. Mills sees this racial construction as deeply rooted in the legal and constitutional orders of American society. Race is a modern category invented by white male scientists in the “era of modernity” and instantiated globally in the consciousness, social practices, and institutional interstices of Western European cultures, among countless others worldwide. Indeed, the pseudoscience of the period was highly informed by tales of difference brought back by explorers.
Legal Constraints on the Use of Race in Biomedical Research: Toward a Social Justice Framework
Authors: Roberts Dorothy E.
Published: September 2006

The scientific validity of racial categories has been the subject of debate among population geneticists, evolutionary biologists, and physical anthropologists for several decades. After World War II, the rejection of eugenics, which had supported sterilization laws and other destructive programs in the United States, generated a compelling critique of the biological basis of race. The classification of human beings into distinct biological “races” is a relatively recent invention propped up by deeply flawed evidence and historically providing the foundation of racist ideology and inequities of power. Social scientists’ conclusion that race is socially constructed was confirmed by genomic studies of human variation, including the Human Genome Project, showing high levels of genetic similarity within the human species. Some scholars came to believe that the science of human genetic diversity would replace race as the preeminent means of grouping people for scientific purposes.