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Background: Invasive mycoses are an important cause of illness and death in immunocompromised patients. Infections with molds other than aspergilli have been increasingly seen in patients with hematologic cancers, but epidemics of these infections have not yet been reported. Objective: To describe an outbreak of invasive mycoses with Paecilomyces lilacinus in severely neutropenic patients. Design: An outbreak investigation. Setting: The hematology-oncology isolation and bone marrow transplantation unit of the University Hospital, Basel, Switzerland. Patients: 25 consecutive patients admitted between :17 August t9S3 (the date of the first manifestation of P. lilacinus infection) and 31 October 1993 (when the unit was closed). Measurements: Clinical and microbiological data, including histologic findings; cultures from several patient sites; and environmental examinations of potential airborne, parenteral, enteric, and horizontal routes of transmission. Infections were defined by the isolation of P. lilacinus from clinically evident skin eruptions. Results: 12 of the 25 patients (48%) were infected or colonized. Nine patients (36%), including all bone marrow transplant recipients, had documented invasive P. lilacinus infections. All 9 infected patients had papular, pustular, or necrotic skin eruptions. Two patients with severe graftversus-host disease died with refractory fungal disease; 1 also had microbiologically documented endophthalmitis and kidney infiltrates. Seven affected patients no longer had P. lilacinus after recovery of bone marrow function. The organism was resistant in vitro to amphotericin B, itraconazole, and fluconazole. Patients did not respond clinically to these agents. The outbreak was ultimately traced to a contaminated, commercially available, pharmaceutically prepared skin lotion. The outbreak ended after the skin lotion was recalled and has not recurred after a follow-up period of 2 years. Conclusion: Contaminated skin lotion is a potential cause of opportunistic fungal infections in immunocompromised hosts. Paecilomyces lilacinus is a common saprophytic mold that can cause, by direct cutaneous inoculation, invasive infections associated with illness and death., Skin lotions may be a possible source for infections from the fungus Paecilomyces (P.) lilacinus that may be life-threatening among patients with compromised immune systems. P. lilacinus infections were identified in 12 of 25 patients admitted over a two-month period to an isolated hospital ward for patients undergoing bone marrow transplants and those with blood cancers. Two patients died. All nine of the bone marrow transplant patients developed P. lilacinus infection resulting in skin lesions. Researchers traced the source of the infection to a skin lotion that was subsequently recalled.

Thrombocythemia is a condition that involves an increase in the number of platelets (small blood cells involved in blood clotting). In patients with thrombocythemia, the bone marrow produces more megakaryocytes (cells that become platelets) than normal. The clinical manifestations of this disease include gastrointestinal tract bleeding, arterial or venous thrombosis (formation of blood clots), problems with blood circulation in the fingers and toes, stroke, and heart attack. Also, cases of gout and peptic ulcer have been reported in patients with thrombocythemia. This disease usually occurs in people in their thirties and forties. In an attempt to identify the clinical features and manifestations associated with thrombocythemia, the case records of 268 patients attending the Mayo Clinic between 1975 and 1989 were reviewed. Twenty-two percent of the patients had a related skin condition (cutaneous manifestation). The most common skin conditions involved the presence of a purplish discoloration of the skin caused by bleeding into the tissue or by blood clots, and erythromelalgia (reddening and burning pain in the feet or hands). Other types of skin lesions and manifestations that were associated with thrombocythemia included ulcers of the legs and toes, gangrene (tissue death), livedo reticularis (purple discoloration of the skin), thrombophlebitis (inflammation of a vein with blood clotting), itching, and Raynaud's phenomenon (white or blue discoloration of the fingers caused by blood vessel constriction in response to cold or emotion). These results indicate that thrombocythemia is related to a wide variety of skin disorders. In many cases, the presence of one of the skin disorders mentioned above provided the basis for a diagnosis of thrombocythemia. It is important to diagnose cases of thrombocythemia because of the dangerous vascular events, such as hemorrhage and stroke, that can result. (Consumer Summary produced by Reliance Medical Information, Inc.)

A review of published reports concerning trichothiodystrophy (sulfur-deficient brittle hair) is provided, with a discussion of findings often associated with this inherited disorder. Although abnormalities of the hair constitute the only sign necessary for a diagnosis of trichothiodystrophy, other parts of the body that share the same developmental origin (ectodermal or neuroectodermal cell layers of the early embryo) are almost always involved. Signs and symptoms in hair, nails, skin, the nervous system, eyes, genitals, lungs, bones, the immune system, and the cardiovascular system are listed. The hair of patients with this disorder is brittle, unruly, easily broken and dry, and it shows alternating light and dark bands when viewed with polarizing microscopy. Cuticles are defective or absent. Both hair and nails are composed of two types of proteins, filamentous (low-sulfur proteins) and matrix (proteins rich in sulfur and tyrosine, an amino acid). Patients with trichothiodystrophy have greatly decreased levels of high-sulfur proteins, while retaining apparently normal levels of low-sulfur proteins. Some patients with trichothiodystrophy manifest an ectodermal dysplasia, a developmental defect that affects hair, teeth, nails, and sweat glands. Diagnostic problems exist for these disorders and are discussed. The literature review comprises 95 reported cases of trichothiodystrophy, with detailed reports on 91 patients. Eight or more cases showed growth retardation and mental retardation, nail abnormalities, sparse axillary hair, defective DNA (genetic material) repair, and other signs. When diagnostic criteria for this disorder are fulfilled, the clinician should consider additional evaluation to determine whether other symptoms are present. When appropriate, the issue should also be brought up for genetic counseling, since the disorder is apparently inherited in an autosomal recessive manner. (Consumer Summary produced by Reliance Medical Information, Inc.)

Das juvenile Xanthogranulom (JXG) ist die häufigste Form der Non-Langerhans-Zell-Histiozytose. Es handelt sich um einen seltenen, angeborenen oder im späteren Alter auftretenden gutartigen Tumor. Die klassische Form des JXG ist durch rötlich-gelbe benigne Papeln oder Knötchen mit Prädilektion am Kopf, Hals und Rumpf gekennzeichnet, doch können auch den Extremitäten oder extrakutanen Stellen Läsionen auftreten. In den meisten Fällen findet sich nur eine solitäre Läsion, allerdings können auch multiple Papeln oder Knötchen vorliegen. Sonderformen sind unter anderem das gemischte, riesige, subkutane, eruptive, gruppierte und plaqueartige JXG, und das JXG wurde überdies mit systemischen Erkrankungen in Verbindung gebracht. Die Diagnose wird im Wesentlichen auf Grundlage des klinischen Erscheinungsbildes gestellt und in der Regel durch die histologische Untersuchung bestätigt. In der vorliegenden Arbeit berichten wir über einen sehr seltenen Fall eines symmetrischen juvenilen Riesenxanthogranuloms vom Plaque-Typ im Gesicht (symmetrical giant facial plaque-type juvenile xanthogranuloma, SGFP-JXG); außerdem nehmen wir einen Vergleich mit der klassischen Form des JXG sowie JXG-Varianten vor und diskutieren die Differentialdiagnosen. Vorgestellt wurde uns ein 4-jähriges Mädchen kaukasischer Abstammung mit plaqueartigen Läsionen auf beiden Wangen, die aus gelblichen konfluierenden Papeln bestanden. Die histologische Untersuchung zeigte eine histiozytäre Läsion mit Bildung von Touton-Riesenzellen, und die immunhistochemischen Ergebnisse bestätigten die Diagnose SGFP-JXG. Im Vergleich zum klassischen JXG tritt das SGFP-JXG in manchen Fällen später auf, und die spontane Abheilung kann länger dauern. Begleiterkrankungen und eine systemische Beteiligung wurden nicht festgestellt. Die histopathologische Untersuchung ist erforderlich, um diese Form des JXG von anderen Histiozytosen abzugrenzen. Unseres Wissens wurden bisher nur vier Fälle von SGFP-JXG in der Literatur beschrieben.

While solid-state nuclear magnetic resonance (ssNMR) has emerged as a powerful technique for studying viral capsids, current studies are limited to capsids formed from single proteins or single polyproteins. The ability to selectively label individual protein components within multiprotein viral capsids and the resulting spectral simplification will facilitate the extension of ssNMR techniques to complex viruses. In vitrocapsid assembly by combining individually purified, labeled, and unlabeled components in NMR quantities is not a viable option for most viruses. To overcome this barrier, we present a method that utilizes sequential protein expression and in cell assembly of component-specifically labeled viral capsids in amounts suitable for NMR studies. We apply this approach to purify capsids of bacteriophage ϕ6 isotopically labeled on only one of its four constituent protein components, the NTPase P4. Using P4-labeled ϕ6 capsids and the sensitivity enhancement provided by dynamic nuclear polarization, we illustrate the utility of this method to enable ssNMR studies of complex viruses.

ABSTRACTIntroduction: Sativex® spray is clinically utilized to deliver delta9-tetrahydrocannabinol and cannabidiol to oral mucosa for systemic absorption. We challenge the consensus that the mechanism of absorption following the oro-mucosal application occurs via the buccal tissue.Areas covered: Correctness of the consensus of this absorption pathway arose when reviewing publications regarding the influence fed versus fasting states have on pharmacokinetics of these cannabinoids administered to the oral mucosa. This finding is more suitable for peroral administration, where stomach content affects the absorption profile. We hypothesize that these cannabinoids are ingested and absorbed in the gastrointestinal tract.Expert opinion: Although clinical importance of Sativex® is not disputed, the wide acceptance of its being a successful example of drug delivery through oral mucosa is questionable. Sativex® acts as an example for other drugs delivered to oral mucosa for systemic absorption and unintentionally washed by the saliva flow into the gastrointestinal tract. Delivery of each medicine through oral mucosa should be validated in-vivoto ensure this route to be the predominant one. Revealing the underlying absorption mechanisms would enable predicting the impact of different physiological parameters such as saliva flow and fed/fasting states on the pharmacokinetics of the delivered medication.

The phase composition, structural parameters, and basic magnetic characteristics of BaFe12O19 hexaferrites prepared by the mechanochemical synthesis with subsequent annealing at a temperature of 1000°С and 1100°С for 1 h are investigated. The influence of the annealing temperature on the properties of synthesized materials is analyzed. Values of the saturation magnetization and the anisotropy field are determined. It is established that annealing temperature in the interval 1000 - 1100 °C does not significantly affect on the phase composition and the size of nanoparticles. The value of the anisotropy field increases substantially with increasing temperature.

Patients with epidermodysplasia verruciformis (EV) and biallelic null mutations of TMC6 (encoding EVER1) or TMC8 (EVER2) are selectively prone to disseminated skin lesions due to keratinocyte-tropic human β-papillomaviruses (β-HPVs), which lack E5 and E8. We describe EV patients homozygous for null mutations of the CIB1 gene encoding calcium- and integrin-binding protein-1 (CIB1). CIB1 is strongly expressed in the skin and cultured keratinocytes of controls but not in those of patients. CIB1 forms a complex with EVER1 and EVER2, and CIB1 proteins are not expressed in EVER1- or EVER2-deficient cells. The known functions of EVER1 and EVER2 in human keratinocytes are not dependent on CIB1, and CIB1 deficiency does not impair keratinocyte adhesion or migration. In keratinocytes, the CIB1 protein interacts with the HPV E5 and E8 proteins encoded by α-HPV16 and γ-HPV4, respectively, suggesting that this protein acts as a restriction factor against HPVs. Collectively, these findings suggest that the disruption of CIB1–EVER1–EVER2-dependent keratinocyte-intrinsic immunity underlies the selective susceptibility to β-HPVs of EV patients.

Elastic fibers, a major component of the extracellular matrix of the skin, are often exposed to ultraviolet (UV) radiation throughout mammalian life. We report on an in vitrostudy of the alterations in bovine nuchal ligament elastic fibers resulting from continuous UV-A exposure by the use of transmission electron microscopy (TEM), histology, mass spectrometry, and solid state 13C NMR methodologies. TEM images reveal distinct cracks in elastic fibers as a result of UV-A irradiation and histological measurements show a disruption in the regular array of elastic fibers present in unirradiated samples; elastic fibers appear shorter, highly fragmented, and thinner after UV-A treatment. Magic angle spinning 13C NMR was applied to investigate possible secondary structural changes or dynamics in the irradiated samples; our spectra reveal no differences between UV-A irradiated and non-irradiated samples. Lastly, MALDI mass spectrometry indicates that the concentration of desmosine, which forms cross-links in elastin, is observed to decrease by 11 %following 9 days of continuous UV-A irradiation, in comparison to unirradiated samples. These alterations presumably play a significant role in the loss of elasticity observed in UV exposed skin.

Lipid microdomains (‘lipid rafts’) are plasma membrane subregions, enriched in cholesterol and glycosphingolipids, which participate dynamically in cell signaling and molecular trafficking operations. One strategy for the study of the physicochemical properties of lipid rafts in model membrane systems has been the use of nuclear magnetic resonance (NMR), but until now this spectroscopic method has not been considered a clinically relevant tool. We performed a proof-of-concept study to test the feasibility of using NMR to study lipid rafts in human tissues. Platelets were selected as a cost-effective and minimally invasive model system in which lipid rafts have previously been studied using other approaches. Platelets were isolated from plasma of medication-free adult research participants (n=13) and lysed with homogenization and sonication. Lipid-enriched fractions were obtained using a discontinuous sucrose gradient. Association of lipid fractions with GM1 ganglioside was tested using HRP-conjugated cholera toxin B subunit dot blot assays. 1H high resolution magic-angle spinning nuclear magnetic resonance (HRMAS NMR) spectra obtained with single-pulse Bloch decay experiments yielded spectral linewidths and intensities as a function of temperature. Rates of lipid lateral diffusion that reported on raft size were measured with a two-dimensional stimulated echo longitudinal encode-decode NMR experiment. We found that lipid fractions at 10–35% sucrose density associated with GM1 ganglioside, a marker for lipid rafts. NMR spectra of the membrane phospholipids featured a prominent ‘centerband’ peak associated with the hydrocarbon chain methylene resonance at 1.3ppm; the linewidth (full width at half-maximum intensity) of this ‘centerband’ peak, together with the ratio of intensities between the centerband and ‘spinning sideband’ peaks, agreed well with values reported previously for lipid rafts in model membranes. Decreasing temperature produced decreases in the 1.3ppm peak intensity and a discontinuity at ~18°C, for which the simplest explanation is a phase transition from Ldto Lophases indicative of raft formation. Rates of lateral diffusion of the acyl chain lipid signal at 1.3ppm, a quantitative measure of microdomain size, were consistent with lipid molecules organized in rafts. These results show that HRMAS NMR can characterize lipid microdomains in human platelets, a methodological advance that could be extended to other tissues in which membrane biochemistry may have physiological and pathophysiological relevance.

Graphene nanoribbons (GNRs) with robust electronic band gaps are promising candidate materials for nanometer-scale electronic circuits. Realizing their full potential, however, will depend on the ability to access GNRs with prescribed widths and edge structures and an understanding of their fundamental electronic properties. We report field-effect devices exhibiting ambipolar transport in accumulation mode composed of solution-synthesized GNRs with straight armchair edges. Temperature-dependent electrical measurements specify thermally activated charge transport, which we attribute to inter-ribbon hopping. With access to structurally precise materials in practical quantities and by overcoming processing difficulties in making electrical contacts to these materials, we have demonstrated critical steps toward nanoelectric devices based on solution-synthesized GNRs.

Electromagnetic media with generic linear response provide a rich class of Lorentz violation models. In the framework of a general covariant metric-free approach, we study electromagnetic wave propagation in these media. We define the notion of an optic tensor and present its unique canonical irreducible decomposition into the principle and skewon parts. The skewon contribution to the Minkowski vacuum is a subject that does not arise in the ordinary models of Lorentz violation based on a modified Lagrangian. We derive the covector parametrization of the skewon optic tensor and discuss its i/(l)-gauge symmetry. We obtain several compact expressions for the contribution of the principle and skewon optic tensor to the dispersion relation. As an application of the technique proposed here, we consider the case of a generic skewon tensor contributed to a simple metric-type principle part. Our main result: Every solution of the skewon-modified Minkowski dispersion relation is necessarily spacelike or null. It provides an extreme violation of the Lorentz symmetry. The case of the antisymmetric skewon is studied in detail, and some new special cases (electric, magnetic, and degenerate) are discovered. In the case of a skewon represented by a symmetric matrix, we observe a parametric gap that has some similarity to the Higgs model. We worked out a set of specific examples that justify the generic properties of the skewon models and demonstrate the different types of Lorentz violation phenomena. [ABSTRACT FROM AUTHOR]

IMPORTANCE: Ichthyosis with confetti (IWC) is a genodermatosis caused by dominant negative mutations in the gene encoding keratin 10 (KRT10). We investigated clinical and genetic details of a substantial number of patients with IWC in order to define major and minor criteria for diagnosis of this rare disorder. OBSERVATIONS: Parallel clinical investigation of 6 patients with IWC revealed a novel spectrum of phenotypes. We found several features that qualify as major criteria for diagnosis, which are clearly and consistently associated with the condition. These included malformation of ears, hypoplasia of mammillae, and dorsal acral hypertrichosis. Genetic analysis of patients revealed several different frameshift mutations in intron 6 or exon 7 of KRT10. Analysis of this locus in 17 unrelated control individuals revealed 2 novel polymorphisms of KRT10. CONCLUSIONS AND RELEVANCE: We present for the first time to our knowledge the spectrum of clinical variability of IWC in 6 patients with confirmed mutations in KRT10. From this, we have extracted major and minor criteria to aid early and correct clinical diagnosis. Ectodermal malformations, present in all patients, suggest a novel classification of IWC as a syndrome. There is remarkable genetic variation at the IWC disease locus within control individuals from the general population.

Although skin is the largest organ of the human body, cutaneous drug metabolism is often overlooked, and existing experimental models are insufficiently validated. This proof-of-concept study investigated phase II biotransformation of 11 test substrates in fresh full-thickness human skin explants, a model containing all skin cell types. Results show that skin explants have significant capacity for glucuronidation, sulfation, N-acetylation, catechol methylation, and glutathione conjugation. Novel skin metabolites were identified, including acyl glucuronides of indomethacin and diclofenac, glucuronides of 17β-estradiol, N-acetylprocainamide, and methoxy derivatives of 4-nitrocatechol and 2,3-dihydroxynaphthalene. Measured activities for 10 μM substrate incubations spanned a 1000-fold: from the highest 4.758 pmol·mg skin–1·h–1for p-toluidine N-acetylation to the lowest 0.006 pmol·mg skin–1·h–1for 17β-estradiol 17-glucuronidation. Interindividual variability was 1.4- to 13.0-fold, the highest being 4-methylumbelliferone and diclofenac glucuronidation. Reaction rates were generally linear up to 4 hours, although 24-hour incubations enabled detection of metabolites in trace amounts. All reactions were unaffected by the inclusion of cosubstrates, and freezing of the fresh skin led to loss of glucuronidation activity. The predicted whole-skin intrinsic metabolic clearances were significantly lower compared with corresponding whole-liver intrinsic clearances, suggesting a relatively limited contribution of the skin to the body’s total systemic phase II enzyme-mediated metabolic clearance. Nevertheless, the fresh full-thickness skin explants represent a suitable model to study cutaneous phase II metabolism not only in drug elimination but also in toxicity, as formation of acyl glucuronides and sulfate conjugates could play a role in skin adverse reactions.

Finsler geometry is a natural generalization of pseudo-Riemannian geometry. It can be motivated e.g. by a modified version of the Ehlers-Pirani-Schild axiomatic approach to space-time theory. Also, some scenarios of quantum gravity suggest a modified dispersion relation which could be phrased in terms of Finsler geometry. On a Finslerian space-time, the universality of free fall is still satisfied but local Lorentz invariance is violated in a way not covered by standard Lorentz invariance violation schemes. In this paper we consider a Finslerian modification of Maxwell's equations. The corrections to the Coulomb potential and to the hydrogen energy levels are computed. We find that the Finsler metric corrections yield a splitting of the energy levels. Experimental data provide bounds for the Finsler parameters. [ABSTRACT FROM AUTHOR]

The axion modification of electrodynamics can be considered as produced by an irreducible part of the constitutive pseudotensor. In this paper, we study the modification of wave propagation produced by the second irreducible part, called the skewon. We introduce the notions of the skewon optic tensor and skewon optic covector. With these devices we prove that in a pseudo-Riemannian manifold endowed with an arbitrary skewon at least one solution of the dispersion relation is spacelike. This means that the skewon generates superluminal wave motion and is thus ruled out on the basis of special-relativistic principles. [ABSTRACT FROM AUTHOR]

We analyze the spectrum of the three-site Bose-Hubbard model with periodic boundary conditions using a semiclassical method. The Bohr-Sommerfeld quantization is applied to an effective classical Hamiltonian which we derive using resonance normal form theory. The derivation takes into account the 1:1 resonance between frequencies of a linearized classical system and brings nonlinear terms into a corresponding normal form. The obtained expressions reproduce the exact low-energy spectrum of the system remarkably well even for a small number of particles N corresponding to fillings of just two particles per site. Such small fillings are often used in current experiments, and it is inspiring to get insight into this quantum regime using essentially classical calculations. [ABSTRACT FROM AUTHOR]

Da Rocha and Rodigues RR claim i that in classical electrodynamics in vector calculusthe distinction between polar and axial vectors and in exterior calculusbetween twisted and untwisted forms is inappropriate and superfluous, and ii that they can derive the Lorentz force equation from Maxwells equations. As to i, we point out that the distinction of polaraxial and twisteduntwisted derives from the property of the electric charge of being a pure scalar, that is, not carrying any screw sense. Therefore, the mentioned distinctions are necessary ingredients in any fundamental theory of electrodynamics. If one restricted the allowed coordinate transformations to those with positive Jacobian determinants or prescribed an equivalent constraint, then the RR scheme could be accommodated; however, such a restriction is illegal since electrodynamics is, in fact, also covariant under transformations with negative Jacobians. As to ii, the “derivation” of the Lorentz force from Maxwells equations, we point out that RR forgot to give the symbol F the field strength in Maxwells equations an operational meaning in the first place. Thus, their proof is empty. Summing up: the approach of RR does not bring in any new insight into the structure of electrodynamics.

Ectodermal dysplasias are heterogeneous heritable conditions characterized by congenital defects of one or more ectodermal structures and their appendages. Of approximately 200 different ectodermal dysplasias, about 30 have been identified at molecular level with identification of the causative gene. Itin and Fistarol emphasized that rather commonly nonfully expressed phenotypes exist, which make a clinical diagnosis more difficult. FreireMaia and Pinheiro used the clinical aspects for their classification and Priolo integrated molecular genetic and clinical aspects for her scheme. Those two more historical classification schemes have the difficulty that when applied strictly, several additional groups of disorders should be integrated within the term of ectodermal dysplasias, for example, keratodermas with skin or hair alterations or the ichthyoses with associated abnormalities. Such consequent classification would lead to an endless list of conditions and would be useless for practical work. Recent evidence implicates a genetic defect in different pathways orchestrating ectodermal organogenesis. Modern molecular genetics will increasingly elucidate the basic defects of the different syndromes and yield more insight into the regulatory mechanisms of morphogenesis. In this way a reclassification of ectodermal dysplasias will be possible according to the function of their involved mutated genes. I will focus on the fact that with molecular methods it is possible to diagnose oligosymptomatic forms of ectodermal dysplasia. This is much more common than earlier anticipated and with the classification of ectodermal dysplasia on the basis of molecular diagnosis a new avenue is opened for symptom complexes which were impossible to classify in former times. © 2009 WileyLiss, Inc.

Abstract: This paper reports on the observation of the aging of cubic oxide ferrimagnet nanopowders prepared by mechanochemical synthesis, which manifests itself in a variation of the phase composition, structural parameters, and main magnetic properties.

Objective.To investigate a large outbreak of scabies in an intensive care unit of a university hospital and an affiliated rehabilitation center, and to establish effective control measures to prevent further transmission.Design.Outbreak investigation.Setting.The intensive care unit of a 750-bed university hospital and an affiliated 92-bed rehabilitation center.Methods.All exposed individuals were screened by a senior staff dermatologist. Scabies was diagnosed on the basis of (1) identification of mites by skin scraping, (2) identification of mites by dermoscopy, or (3) clinical examination of patients without history of prior treatment for typical burrows. During a follow-up period of 6 months, the attack rate was calculated as the number of symptomatic individuals divided by the total number of exposed individuals.Interventions.All exposed healthcare workers (HCWs) and their household members underwent preemptive treatment. Initially, the most effective registered drug in Switzerland (ie, topical lindane) was prescribed, but this prescribption was switched to topical permethrin or systemic ivermectin as a result of the progression of the outbreak. Individuals with any signs or symptoms of scabies underwent dermatological examination.Results.Within 7 months, 19 cases of scabies were diagnosed, 6 in children with a mean age of 3.1 years after exposure to the index patient with HIV and crusted scabies. A total of 1,640 exposed individuals underwent preemptive treatment. The highest attack rate of 26%–32% was observed among HCWs involved in the care of the index patient. A too-restricted definition of individuals at risk, non-compliance with treatment, and the limited effectiveness of lindane likely led to treatment failure, relapse, and reinfestation within families.Conclusions.Crusted scabies resulted in high attack rates among HCWs and household contacts. Timely institution of hygienic precautions with close monitoring and widespread, simultaneous scabicide treatment of all exposed individuals are essential for control of an outbreak.

Minkowski's concept of a four‐dimensional physical space is a central paradigm of modern physics. The three‐dimensional Maxwellian electrodynamics is uniquely generalized to the covariant four‐dimensional form. Is the (1+3) decomposition of the covariant four‐dimensional form unique? How do the different sign assumptions of electrodynamics emerge from this decomposition? Which of these assumptions are fundamental and which of them may be modified? How does the Minkowski space‐time metric emerge from this preliminary metric‐free construction? In this paper we are looking for answers to the problems mentioned. Our main result is the derivation of four different possible sets of electrodynamic equations which may occur in different types of isotropic electromagnetic media. The wave propagation in each of these media is described by the Minkowskian optical metrics. Moreover, the electric and magnetic energies are nonnegative in all cases. We also show that the correct directions of the Lorentz force (as a consequence of the Dufay and the Lenz rules) hold true for all these cases. However, the differences between these four types of media must have a physical meaning. In particular, the signs of the three electromagnetic invariants are different. Minkowski's concept of a four‐dimensional physical space is a central paradigm of modern physics. Is the (1+3) decomposition of the covariant four‐dimensional form unique? How do the different sign assumptions of electrodynamics emerge from this decomposition? Which of these assumptions are fundamental and which of them may be modified? How does theMinkowski space‐time metric emerge from this preliminary metric‐free construction? This paper looks for answers to the problems mentioned.

Minkowskis concept of a fourdimensional physical space is a central paradigm of modern physics. The threedimensional Maxwellian electrodynamics is uniquely generalized to the covariant fourdimensional form. Is the 1+3 decomposition of the covariant fourdimensional form unique? How do the different sign assumptions of electrodynamics emerge from this decomposition? Which of these assumptions are fundamental and which of them may be modified? How does the Minkowski spacetime metric emerge from this preliminary metricfree construction? In this paper we are looking for answers to the problems mentioned. Our main result is the derivation of four different possible sets of electrodynamic equations which may occur in different types of isotropic electromagnetic media. The wave propagation in each of these media is described by the Minkowskian optical metrics. Moreover, the electric and magnetic energies are nonnegative in all cases. We also show that the correct directions of the Lorentz force as a consequence of the Dufay and the Lenz rules hold true for all these cases. However, the differences between these four types of media must have a physical meaning. In particular, the signs of the three electromagnetic invariants are different.

The phase composition, the structural parameters, and the basic magnetic characteristics of a number of nanosized powders of simple spinel ferrites produced by the method of mechanochemical reactions from salt systems were studied. The influence of size and surface effects on the saturation magnetization and magnetic anisotropy was determined. The applicability of the shell model to the description of the magnetic properties of nanosized spinel ferrites is discussed.

The problem of derivation of the equations of motion from the field equations is considered. Einstein's field equations have a specific analytical form: They are linear in the second order derivatives and quadratic in the first order derivatives of the field variables. We utilize this particular form and propose a novel algorithm for the derivation of the equations of motion from the field equations. It is based on the condition of the balance between the singular terms of the field equation. We apply the algorithm to a non‐linear Lorentz invariant scalar field model. We show that it results in the Newton law of attraction between the singularities of the field moved on approximately geodesic curves. The algorithm is applicable to the N‐body problem of the Lorentz invariant field equations.

We study which geometric structure can be constructed from the vierbein (frame/coframe) variables and which field models can be related to this geometry. The coframe field models, alternative to GR, are known as viable models for gravity, since they have the Schwarzschild solution. Since the local Lorentz invariance is violated, a physical interpretation of additional six degrees of freedom is required. The geometry of such models is usually given by two different connections-the Levi-Civita symmetric and metric-compatible connection and the Weitzenböck flat connection. We construct a general family of linear connections of the same type, which includes two connections above as special limiting cases. We show that for dynamical propagation of six additional degrees of freedom it is necessary for the gauge field of infinitesimal transformations (antisymmetric tensor) to satisfy the system of two first-order differential equations. This system is similar to the vacuum Maxwell system and even coincides with it on a flat manifold. The corresponding 'Maxwell-compatible connections' are derived. Alternatively, we derive the same Maxwell-type system as a symmetry condition of the viable model Lagrangian. Consequently, we derive a nontrivial decomposition of the coframe field to the pure metric field plus a dynamical field of infinitesimal Lorentz rotations. An exact spherical-symmetric solution for our dynamical field is derived. It is bounded near the Schwarzschild radius. Further off, the solution is close to the Coulomb field.

GM-CSF (granulocyte-macrophage colony stimulating factor) plays a central role in inflammatory processes. Treatment with antibodies neutralizing murine GM-CSF showed significant therapeutic effects in mouse models of inflammatory diseases. We constructed by phage display technology a human scFv, which could potently neutralize human GM-CSF. At first, a human VL repertoire was combined with the VH domain of a parental GM-CSF-neutralizing rat antibody. One dominant rat/human scFv clone was selected, neutralizing human GM-CSF with an IC50 of 7.3 nM. The human VL of this clone was then combined with a human VH repertoire. The latter preserved the CDR 3 of the parental rat VH domain to retain binding specificity. Several human scFvs were selected, which neutralized human GM-CSF at low nanomolar concentrations (IC50 ≥ 2.6 nM). To increase serum half-life, a branched 40 kDa PEG-polymer was coupled to the most potent GM-CSF-neutralizing scFv (3077) via an additional C-terminal cysteine. PEG conjugation had a negligible effect on the in vitro neutralizing potential of the scFv, although it caused a significant drop in binding affinity owing to a reduced on-rate. It also significantly increased the stability of the scFv at elevated temperatures. In mouse experiments, the PEGylated scFv 3077 showed a significantly prolonged elimination half-life of 59 h as compared with 2 h for the unconjugated scFv version. PEGylated scFv 3077 is a potential candidate for development of a novel antibody therapy to treat pro-inflammatory human diseases.

Ectodermal dysplasias are a large group of heritable conditions characterized by congenital defects of one or more ectodermal structures and their appendages: hair (hypotrichosis, partial, or total alopecia), nails (dystrophic, hypertrophic, abnormally keratinized), teeth (enamel defect or absent), and sweat glands (hypoplastic or aplastic). The ectodermal dysplasias, as a rule, are not pure “one‐layer diseases.” Mesodermal and, rarely, endodermal dysplasias coexist. Embryogenesis exhibits distinct tissue organizational fields and specific interactions among the germ layers that may lead to a wide range of ectodermal dysplasias when genes important for development are mutated or otherwise altered in expression. Of the approximately 200 different ectodermal dysplasias, about 30 have been studied at the molecular level with identification of the causative gene. Freire‐Maia and Pinheiro used the clinical aspects for their classification, and Priolo integrated molecular genetic and clinical aspects for her scheme. Those two more historical classification schemes have the difficulty that, when applied strictly, several additional groups of diseases should be integrated within the term “ectodermal dysplasias,” e.g. keratodermas with skin or hair alterations or the ichthyoses with associated features. Such consequent classification would lead to an endless list of diseases and would be useless for the practical work. Recent evidence implicates a genetic defect in different pathways orchestrating ectodermal organogenesis. Modern molecular genetics will increasingly elucidate the basic defects of the different syndromes and yield more insight into the regulatory mechanisms of embryology. In this way, a reclassification of ectodermal dysplasias will be possible according to the function of their involved mutated genes. Lamartine recently proposed a helpful classification according to the functions of the genes discovered in different types of ectodermal dysplasias. Accordingly, the present overview categorizes the various ectodermal dysplasias into four major functional subgroups: cell–cell communication and signaling, adhesion, transcription regulation, and development. © 2004 Wiley‐Liss, Inc.

AbstractPlasmablastic lymphoma (PBL) is a rare and relatively new entity originally described in HIV-infected individuals. This subset of Epstein-Barr-virus (EBV)-related non-Hodgkin lymphomas is now regarded as a distinct clinicopathological category of AIDS-associated lymphomas occurring preferentially in the oral cavity and showing a poor prognosis. We describe for the first time an EBV-associated PBL with an isolated cutaneous distribution on the lower extremities in an HIV-infected heterosexual male and point to the unique clinical, morphological and immunophenotypic characteristics of this lymphoma. The patient presented with fast growing solid and livid nodules on both legs. The large, blastic tumor cells showed the following immunophenotype: CD138+, CD45+, CD20–, CD10–, CD3–, CD30–, bcl-2–, bcl-6–, LMP-1– and EMA–. The proliferation fraction (Mib-1) was >90%. EBV association was demonstrated by in situ hybridization (EBV-encoded RNAs 1/2). Polymerase-chain-reaction-based DNA analysis demonstrated a clonal IgH rearrangement in the absence of a bcl-2/IgH translocation. PBL in HIV patients may occur not only in the oral cavity, but can probably involve any other organs including the skin.Copyright © 2004 S. Karger AG, Basel

Background:Scarce data exist concerning dermatological consultations within departments of internal medicine. To date, no survey has been carried out in Switzerland to elucidate this issue. The aim of this study was to analyze the spectrum of skin diseases internists are confronted with and to study their diagnostic accuracy in cutaneous diseases. In addition, we wanted to evaluate the motivation for dermatologists to cooperate closely with internists. Patients and Methods:The study included patients with dermatological problems treated at the Department of Internal Medicine at the Kantonsspital Aarau, Switzerland. All patients had been referred to the Department of Dermatology for examination between 1999 and 2001. Patient data were analyzed demographically, by referral modus, diagnoses and therapy. To evaluate the knowledge of internists and dermatologists in cutaneous medicine, 15 clinical slides of common dermatoses with a patient history were shown and asked for diagnostic suggestions to 32 internists of the Kantonsspital Aarau and to 13 dermatologists of the University Hospital Basel, Switzerland. Results:1,290 patients were referred to the Department of Dermatology. 1,737 dermatological diagnoses were made including 348 different dermatoses. Eczema was the single most common diagnosis (12.6%), followed by actinic and bowenoid precancerosis (6.2%), drug eruption (4.2%), verrucae (4%) and mycosis (3.8%). The top ten diagnoses accounted for 41.7% of all skin-related diagnoses. Infection-related dermatoses were most common (20.5%) followed by different types of eczema (12.6%), malignant cutaneous tumors and malignant visceral conditions (11.2%). Local therapy was prescribed in 64.2% and systemic therapy in 22.6% of the patients. 15.9% did not receive specific therapy because the consultation request was only a diagnostic one. 146 skin biopsies were performed (11.3%). Systemic diseases with cutaneous manifestations accounted for 15.7%. In general, these conditions were not commonly seen by dermatologists in daily practice. The internists recognized 51.1% of the cutaneous manifestations during examination and 49% when presented with slides. Conclusions:Internists are confronted with a different spectrum of cutaneous diseases compared with dermatologists. Due to the broad spectrum of skin diseases, it is a challenging task for internists to recognize dermatoses. Our study elucidates that patients, internists and dermatologists may profit from a close cooperation.

Risikofaktoren für die Entwicklung maligner Melanome sind vielfältig. Sie sind sowohl durch genetische Faktoren als auch durch Umwelteinflüsse bedingt. Ein gut dokumentiertes genetisches Risiko für die Entwicklung eines Melanoms ist eine Mutation im CDKN2A-Gen, welches auf dem Chromosom 9 lokalisiert ist. Dieses Tumorsuppressor-Gen ist für die Regulation des Zellzyklus mitverantwortlich, und eine Mutation in diesem Gen führt auch gehäuft zu familiären Pankreaskarzinomen. Die Penetranz dieser Mutation wird durch UV-Energie mitbeeinflusst. Eine weitere Risikokonstellation ist eine Variante des atypischen familiären Nävussyndroms, welche auf dem Chromosom 1p36 codiert. Patienten mit Xeroderma pigmentosum weisen eine gestörte DNA-Reparaturfähigkeit auf, weshalb sich bereits in frühem Lebensalter bei dieser autosomal rezessiv vererbten Krankheit zahlreiche maligne Hauttumoren inklusive maligne Melanome entwickeln können. Neue Daten haben eine gestörte DNA-Reparaturfähigkeit auch bei Patienten mit sporadischen Melanomen dokumentiert. Konstitutionelle Risiken sind rotblonde Haare und blaue Augen. Der wichtigste Umweltfaktor, der besonders bei genetischer Prädisposition das Risiko einer Melanomentstehung weiter erhöht, ist die UV-Exposition. Wiederholte Sonnenbrände vor dem 15. Lebensalter, aber auch eine hohe kumulative UV-Belastung gehen mit einem erhöhten Melanomrisiko einher. Die wichtigsten präventiven Maßnahmen sind die regelmäßige Untersuchung des ganzen Integumentes bei Patienten mit familiärem dysplastischem Nävussyndrom. Alle Menschen sollen, unabhängig von ihrem Risikoprofil, einen konsequenten Sonnenschutz durchführen, der nicht nur das Auftragen von Sonnencreme, sondern auch das Tragen von Hut, Hemd, Hose und Sonnenbrille beinhaltet. Eine direkte Sonnenexposition ist während der Mittagsstunden zu vermeiden. In der heutigen Zeit ist es möglich geworden, im Rahmen von Studien DNA-Analysen bei Patienten mit familiären malignen Melanomen durchzuführen. Vor- und Nachteile der genetischen Beratung werden diskutiert.

Heritable disorders of cornification form a large, clinically and genetically heterogeneous group. Recent advances in molecular genetics provide for the first time the opportunity to reliably classify some of these disorders based on their underlying etiology. Many rare phenotypes, however, still remain unclassified and do not fit into established classification schemes. We report here a 12-year-old girl who developed an ichthyosis vulgaris-like skin disorder 6 months after birth. Several years later, the clinical features had changed considerably. The patient had developed streaks of hyperkeratotic, slightly scaling skin with underlying erythema distributed in a reticulate, occasionally annular pattern on the trunk and extremities. The lesions were stable and had not changed significantly in size or distribution over the ensuing years. Histopathologic and ultrastructural findings were nonspecific and there was no evidence for metabolic disorders. The partial clinical overlap with erythrokeratodermia variabilis prompted us to screen several connexin genes but no pathogenic mutations were identified. We believe that this disorder belongs to the group of erythrokeratodermas and represents a novel, previously unrecognized entity. © 2003 Wiley-Liss, Inc.

We consider an elliptic billiard whose shape slowly changes. During slow evolution of the billiard certain resonance conditions can be fulfilled. We study the phenomena of capture into a resonance and scattering on a resonance which lead to the destruction of the adiabatic invariance in the system.

In linear elasticity, we decompose the elasticity tensor into two irreducible pieces with 15 and 6 independent components, respectively. The vanishingof the piece with 6 independent components corresponds to the Cauchy relations. Thus, for the first time, we recognize the group-theoretical underpinning of the Cauchy relations.

The coframe (teleparallel) description of gravity is known as a viable alternative to GR. One of advantages of this model is the existence of a conserved energy–momentum current witch is covariant under all symmetries of the three-parameter Lagrangian. In this paper we study the relation between the covector valued current and the energy–momentum tensor. Algebraic properties of the conserved current for different values of parameters are derived. It is shown that the tensor corresponding to the coframe current is traceless and, in contrast to the electromagnetic field, has in general a non vanishing antisymmetric part. The symmetric part is also non zero for all values of the parameters. Consequently, the conserved current involves the energy–momentum as well as the rotational (spin) properties of the field.

Haarschaftanomalien sind klinisch gekennzeichnet durch vermehrte Brüchigkeit und schlechte Kämmbarkeit der Haare. Die Haare sind trocken und spröde mit fehlendem Glanz. Haarschafterkrankungen können lokalisiert oder diffus auftreten und sind entweder anlagebedingt oder erworben. Für die Praxis ist neben Anamnese und Klinik die lichtmikroskopische Betrachtung der Haarschäfte die diagnostisch wichtigste Untersuchungsmethode. Die Behandlung von Haarschafterkrankungen sollte möglichst die Ursache beeinflussen. Praktisch bedeutsam ist eine Vermeidung wiederholter Traumatisierung der Haare. Warmlufttrocknung, Frottieren der Haare, Dauerwellen und aggressive Färbeprozeduren sind bei bestehenden Haarschafterkrankungen ungeeignet. Kosmetisch sind kurze Frisuren günstiger als das Tragen von langen, schütteren Haaren.

The obstruction for the existence of an energy-momentum tensor for the gravitational field is connected with differential-geometric features of the Riemannian manifold. This must not be valid for alternative geometrical structures. A teleparallel manifold is defined as a parallelizable differentiable 4D-manifold endowed with a class of smooth coframe fields related by global Lorentz, i.e. SO(1, 3) transformations. In this paper a general free parametric class of teleparallel models is considered. It includes a 1-parameter subclass of viable models with the Schwarzschild coframe solution. A new form of the coframe field equation is derived from the general teleparallel Lagrangian by introducing the notion of a 3-parameter conjugate field strength &calF;^a. The field equation turns out to have a form completely similar to the Maxwell field equation d * &calF;^a &equal; &calT;^a. By applying the Noether procedure, the source 3-form &calT;^a is shown to be connected with the diffeomorphism invariance of the Lagrangian. Thus the source &calT;^a of the coframe field is interpreted as the total conserved energy–momentum current. The energy–momentum tensor for the coframe is defined. The total energy–momentum current of a system of a coframe and a material field is conserved. Thus a redistribution of the energy–momentum current between material and coframe (gravity) fields is possible in principle, unlike in the standard GR. For special values of parameters, when the GR is reinstated, the energy–momentum tensor gives up the invariant sense, i.e. becomes a pseudo-tensor. Thus even a small-parametric change of GR turns it into a well-defined Lagrangian theory.

AbstractFor the first time, we describe a case of type 2 segmental Darier disease with concomitant band-like areas of healthy skin. This clinical observation gives a further hint for the understanding of type 2 segmental manifestations in autosomal dominant diseases. We had observed a 17-year-old patient with Darier disease since the age of 13 years. On the frontal aspect of his body, the lesions were found to be diffusely and rather symmetrically disseminated. On the back, however, a band-like pattern of pronounced involvement with concomitant streaks of healthy skin, both following the lines of Blaschko, was noted. Type 2 segmental manifestation of autosomal dominant disorders can be explained by the assumption that the individual carries a germline mutation that gives rise to a diffuse, nonsegmental distribution of the disease. In addition, a postzygotic mutation occurring at an early developmental stage would result in loss of heterozygosity and give rise, in a segmental area, to a homozygous or hemizygous state of the mutation. This would explain the enhanced severity of the segmental lesions. Theoretically, an early event of mitotic recombination should give rise, simultaneously, to a clone of cells that are homozygous for the corresponding wild-type allele, and for this reason paired segmental areas of either excessive or absent involvement, in the form of twin spotting, should occur on the background of an ordinary, nonsegmental phenotype, as exemplified by Happle and König in a case of epidermolytic hyperkeratosis of Brocq. These authors stated that, in autosomal dominant skin disorders, segmental areas of healthy skin will usually be difficult to recognize. This may explain why such a twin spot phenomenon has so far not been encountered in Darier disease.Copyright © 2002 S. Karger AG, Basel

In 1996, English and McCollough described an unusual entity in 2 sisters characterized by a transient and recurrent keratoderma exclusively on the palms after water exposure. The condition developed 3–5 min after exposure to water and resolved within a short time after drying. This finding was associated with a tightening sensation. Yan et al. coined the term ‘aquagenic palmoplantar keratoderma’, and the designation ‘aquagenic syringeal acrokeratoderma’ was suggested by MacCormack et al. Until now, a total of 8 cases have been reported. We documented 2 new cases with acquired aquagenic syringeal acrokeratoderma. A 25-year-old female had observed within the last 3 months a burning sensation on the palms after some minutes of water contact. Physical examination revealed a perfectly normal skin on the palms. Three minutes after water immersion of 20°C, a whitish discoloration appeared on the palms and a thickening of the palmar skin was visible. In addition, the eccrine pores were much more prominent. Few minutes after drying the skin, the situation returned to a normal state. The second patient, a 33-year-old female noticed a painful whitish discoloration of the skin on the palms after a short period of water immersion. Sometimes the white skin could be peeled off. In the last year, hyperhidrosis developed, and a more reddish aspect of the palms appeared. In our office after rinsing the hands with water at room temperature, a whitish discoloration in the center of the palms appeared which was associated with a painful sensation. After drying, the whitish lesions disappeared almost completely within 30 min. Aquagenic palmar keratoderma describes an acquired and transient condition which occurs after brief exposure to water and disappears after drying within minutes to an hour. Only rarely may a slight hyperkeratosis remain for a longer time. The possible pathophysiology and treatment options are discussed.

Trichothiodystrophy (TTD) refers to a heterogeneous group of autosomal recessive disorders that share the distinctive features of short, brittle hair and an abnormally low sulfur content. Within the spectrum of the TTD syndromes are numerous interrelated neuroectodermal disorders. The TTD syndromes show defective synthesis of high-sulfur matrix proteins. Abnormalities in excision repair of ultraviolet (UV)-damaged DNA are recognized in about half of the patients. Three distinct autosomal recessive syndromes are associated with nucleotide excision repair (NER) defects: the photosensitive form of TTD, xeroderma pigmentosum, and Cockayne syndrome. The unifying feature of these conditions is exaggerated sensitivity to sunlight and UV radiation. In contrast to patients with xeroderma pigmentosum, no increase of skin cancers in patients with TTD has been observed. Genetically, 3 complementation groups have been characterized among photosensitive patients with TTD. Most patients exhibit mutations on the two alleles of the XPDgene. Rarely, mutated XPBgene or an unidentified TTD-Agene may result in TTD. In UV-sensitive TTD, the TFIIH transcription factor containing XPB and XPD helicase activities necessary for both transcription initiation and DNA repair is damaged. Beyond deficiency in the NER pathway, it is hypothesized that basal transcription may be altered leading to decreased transcription of specific genes. Depressed RNA synthesis may account for some clinical features, such as growth retardation, neurologic abnormalities, and brittle hair and nails. Therefore the attenuated expression of some proteins in differentiated cells is most likely explained by a mechanism distinct from DNA repair deficiency. The first transgenic mouse models for NER deficiencies have been generated. The TTD mouse as well as related cell models will provide important tools to understand the complex relationships between defects in DNA repair, low-sulfur hair shaft disorders, and the genotype-phenotype correlates for this constellation of inherited disorders, including the lack of predisposition to cancer in patients with TTD. (J Am Acad Dermatol 2001;44:891-920.) Learning objective:At the completion of this learning activity, participants will have a current understanding of the expanded and further defined clinical spectrum of the TTD syndromes. Participants will have gained new insight into the genetic and molecular characteristics and causes for the low-sulfur hair disorders.

This article explores the basic definition of adventure therapy, which leads to the critical questions of whether adventure therapy is a profession, and if there should be a certification system. In considering the definition of Adventure Therapy three basic areas are considered in the defining process. These basic areas are: (a) level of change, (b) degree held, and (c) population served. In considering whether adventure therapy is a profession or a set of tools and techniques, the place of adventure therapy in academic institutions is considered. The consideration of certification includes an exploration of who gets to define what is certified. The article concludes with a number of challenges raised for those who consider their practice to be adventure therapy.

The reaction of stomatological porcelain with titanium and titanium nickelide during sintering in the range 1050-1300°C was investigated. It was shown that when the sintering temperature is increased, silicides and other oxides are formed in place of the basic components (titanium and silicon oxides or titanium nickelide). Reactions in the porcelain ― titanium system take place in the solid state, but in the porcelain ― titanium nickelide system at temperatures above 1120°C they occur with the participation of liquid phases.

Normal cardiovascular development is exquisitely dependent on the correct dosage of the angiogenic growth factor and vascular morphogen vascular endothelial growth factor (VEGF). However, cardiac expression of VEGF is also robustly augmented during hypoxic insults, potentially mediating the well-established teratogenic effects of hypoxia on heart development. We report that during normal heart morphogenesis VEGF is specifically upregulated in the atrioventricular (AV) field of the heart tube soon after the onset of endocardial cushion formation (i.e. the endocardium-derived structures that build the heart septa and valves). To model hypoxia-dependent induction of VEGF in vivo, we conditionally induced VEGF expression in the myocardium using a tetracycline-regulated transgenic system. Premature induction of myocardial VEGF in E9.5 embryos to levels comparable with those induced by hypoxia prevented formation of endocardial cushions. When added to explanted embryonic AV tissue, VEGF fully inhibited endocardial-to-mesenchymal transformation. Transformation was also abrogated in AV explants subjected to experimental hypoxia but fully restored in the presence of an inhibitory soluble VEGF receptor 1 chimeric protein. Together, these results suggest a novel developmental role for VEGF as a negative regulator of endocardial-to-mesenchymal transformation that underlies the formation of endocardial cushions. Moreover, ischemia-induced VEGF may be the molecular link between hypoxia and congenital defects in heart septation.

Eccrine angiomatous hamartoma (EAH) is an exceedingly rare benign tumor-like lesion prevalent in childhood which may produce pain and marked sweating. Although an aggressive treatment is not generally indicated, surgery may be considered in severe cases. In this report we present novel morphological findings by immunophenotyping, document the first MRI findings in EAH and emphasize the importance of preoperative imaging of such lesions.

Considerable attention has been focused on developing a synthetic route to a carbon−nitrogen material with mechanical and thermal properties comparable or superior to those of diamond. To date, no substance with the desired C3N4 stoichiometry in a silicon-nitride crystal lattice has been reported. One of the principal difficulties in the pursuit of ultrahard carbon−nitrogen (CN) solids is the characterization of amorphous CN samples. We describe a solid-state NMR study of a paracyanogen-like solid utilizing ¹³C-¹⁵N adiabatic-passage Hartmann−Hahn cross-polarization (APHH-CP) to perform dipolar filtering and show that this method is well-suited for recoupling ¹³C-¹⁵N in network solids. In addition, high-frequency electron paramagnetic resonance (EPR) indicates a density of electron spins of approximately 1 × 10¹⁷ e^-/cm³. We conclude by discussing how NMR and EPR data may be useful for optimizing CN-polymer samples as potential precursors for ultrahard carbon nitrogen solids.

Darier disease is an autosomal dominant disorder which may occasionally become manifest in a segmental form. Two clinical phenotypes with a different genetic background have been elaborated in recent years. More than 50 patients with isolated linear disease expression have been documented. In this phenotype the skin outside the segmental affection is absolutely normal. Such a phenotype is explained by a postzygotic mutation with somatic mosaicism which was labeled as type 1 manifestation of segmental forms in autosomal skin disorders. A patient with classical type 1 segmental Darier disease is presented. On the other hand, only 3 patients with Darier disease showing a segmental manifestation in combination with a diffuse distribution have so far been observed. These cases correspond to the recently described type 2 manifestation of segmental forms of autosomal dominant disorders. We describe a fourth patient with type 2 segmental Darier disease. The genetic explanation of such a phenotype is possible with the assumption that a germline mutation for the disease exists but, in addition, a postzygotic mutation is needed resulting in loss of heterozygosity. Hence, in a circumscribed region a homozygous or hemizygous state of the mutation is apparent which can explain the enhanced severity of the segmental manifestation.