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Background The ACURATE neo™ is a novel, second-generation self-expanding supra-annular transcatheter heart valve (THV). The objective of this multi-centre registry is to assess the safety, clinical utility, and impact of 'learning-curve-experience' (LCE) on transcatheter aortic valve replacement outcomes in the United Kingdom (UK) and Ireland. Methods We prospectively collected data from seven ACURATE neo™ THV implanting centres (n = 484) between February 2016 and November 2020. We compared mortality rates and outcomes in the LCE group (n = 120) compared to next successive 120 cases. Results The mean age of the cohort was 81.9(SD: 6.1) years and the majority were in the moderate risk category (EuroSCORE-II):3.3(SD: 3). The 97.5% of cases were performed under local anesthetic. The valve was successfully deployed in 98.8% of cases. The survival rate at 30 days was 97.9%. The incidence of stroke was 2.5%. Life threatening bleeding occurred in 0.6% of cases and vascular access complications occurred in 21 (4.3%) patients. Implantation-related conduction abnormalities occurred in 8.3% but only 5.6% required a PPM. The successful valve deployment occurred in 96% of the patients in the LCE group compared to 100% in the other group (p = 0.04; OR-2[CI 1.7-2.3]). The mortality rates at 30 days (1.7% vs. 1.7%) and 1 year (1.9% vs. 2.7%) were comparable between the two groups. Conclusions This study represents the largest published UK and Ireland real-world experience of the ACURATE neo™ valve. The procedural success rates and safety outcomes were excellent and endorse its utility in clinical practice. The LCE appears to have an impact on the successful valve deployment but without translating into short-term or long-term outcomes.

Ancient shoreline–shelf depositional systems are influenced by an unusually wide array of geological, biological and hydrodynamic processes, with sediment transport and deposition primarily determined by the interaction of river, wave (including storm) and tidal processes, and changes in relative sea level. Understanding the impact of these processes on shoreline–shelf morphodynamics and stratigraphic preservation remains challenging. Numerical modelling integrated with traditional facies analysis provides an increasingly viable approach, with the potential to quantify, and thereby improve understanding of, the impact of these complex coastal sedimentary processes. An integrated approach is presented here that focuses on palaeotidal modelling to investigate the controls on ancient tides and their influence on sedimentary deposition and preservation – one of the three cornerstones of the ternary process classification scheme of shoreline-shelf systems. Numerical tidal modelling methodology is reviewed and illustrated in three palaeotidal model case studies of different scales and focus. The results are synthesised in the context of shoreline–shelf processes, including a critique and modification of the process-based classification scheme. The emphasis on tidal processes reflects their global importance throughout Earth’s history. Ancient palaeotidal models are able to highlight and quantify the following four controls on tidal processes: (1) the physiography (shape and depth) of oceans (1000s km scale) determines the degree of tidal resonance; (2) the physiography of ocean connections to partly enclosed water bodies (100–1000s km scale) determines the regional-scale flux of tidal energy (inflow versus outflow); (3) the physiography of continental shelves influences shelf tidal resonance potential; and (4) tides in relatively local-scale embayments (typically 1–10s km scale) are influenced by the balance of tidal amplification due to funnelling, shoaling and resonance effects versus frictional damping. In deep time, palaeogeographic and palaeobathymetric uncertainty can be accounted for in palaeotidal models by performing sensitivity analyses to different scenarios, across this range of spatial scales. These tidal process controls are incorporated into an updated predictive decision tree for determining shoreline–shelf process regime in terms of the relative interaction of wave, fluvial and tidal processes. The predictive decision tree considers the effects of basin physiography, shelf width and shoreline morphology on wave, fluvial and tidal processes separately. Uncertainty and ambiguity in applying the widely used three-tier process classification scheme are reduced by using the decision tree in conjunction with a proposed two-tier classification of process regime that is limited to primary and secondary processes. This two-tier classification scheme is illustrated in the three case studies, showing how integration of numerical modelling with facies analysis of the preserved stratigraphic record improves confidence in prediction of tide-influenced shoreline-shelf process regimes. Wider application of this approach will further improve process-based classifications and predictions of modern and ancient shoreline–shelf systems.

Pneumococcal meningitis is a highly lethal form of bacterial meningitis that occurs following brain infection by the Gram-positive cocci Streptococcus pneumoniae. Not only does it cause acute mortality, but pneumococcal meningitis also accounts for the highest proportion of survivors living with neurological sequelae, including behavioral disorders, cognitive deficits, hearing loss, motor impairment and epilepsy. More than 90 distinct pneumococcal serotypes have been identified worldwide based on their capsular compositions and serological responses. Serotype replacement continually poses great challenge to costly vaccination programs in developed countries (Koelman et al., 2020), this has therefore emphasized the need to develop new treatment strategies in addition to improving vaccine coverage. Various immunomodulatory agents, such as complement system inhibitors and matrix metalloproteinase inhibitors, have been shown to improve disease severity and mortality when tested in animal models (Bewersdorf et al., 2018). Nevertheless, given the evidence of long-term cognitive deficits and behavioral problems in patients who were clinically well recovered from pneumococcal meningitis, it remains unclear how the protection at the early inflammatory stage may translate into long-term functional recovery. With this in mind, we have established an integrated approach to investigate the interplay between acute host inflammatory response and ensuing neurological deficits in a mouse model of pneumococcal meningitis in animals that survive the lethal disease due to antibiotic ceftriaxone treatment. This has enabled the identification of a nexus between the toll-like receptors (TLRs) 2 and 4, interferon-gamma (IFN-γ) and the enzyme indoleamine 2,3-dioxygenase-1 (IDO-1) that contributes to enduring neurological impairments. Here, we will highlight the findings of our systematic studies in the hope of opening avenues for future research relevant to both meningitis as well as other neurological diseases.

German Romanticism is a thinking of life as exposed. Philosophical conceptions of botanical life are paradigmatic of this. Goethe, Schelling, and Hegel each address the plant in their respective philosophies of nature. This article traces the connections and divergences in their thinking of plants, focusing on the role of love (Goethe), lack (Hegel), and exposure (Schelling) in order to present the plant as a peculiarly apt figure for considerations of life as exposed.

During pneumococcal meningitis, clearance of bacteria by recruited neutrophils is crucial for host protection. However, these innate immune mechanisms are often insufficient and treatment with antibiotics is necessary to prevent death. Despite this antibiotic treatment, approximately half of all survivors suffer lifelong neurological problems. There is growing evidence indicating the harmful effects of neutrophils on CNS integrity. Therefore, the present study investigated the roles of neutrophils in the acute inflammatory response and the resulting long-term neuropsychological effects in murine pneumococcal meningitis. Long-term behavioural and cognitive functions in mice were measured using an automated IntelliCage system. Neutrophil depletion with antibody 1A8 as adjunctive therapy was shown to remarkably impair survival in meningitic C57BL/6J mice despite antibiotic (ceftriaxone) treatment. This was accompanied by increased bacterial load in the cerebrospinal fluid (CSF) and an increase in IL-1β, but decrease in TNF, within the CSF at 20h after bacterial inoculation. In the longer term, the surviving neutrophil-depleted post-meningitic (PM) mice displayed reduced diurnal hypolocomotion compared to PM mice treated with an isotype antibody. However, they showed nocturnal hyperactivity, and greater learning impairment in a patrolling task that is believed to depend upon an intact hippocampus. The data thus demonstrate two important mechanisms: 1. Neutrophil extravasation into the CNS during pneumococcal meningitis influences the pro-inflammatory response and is central to control of the bacterial load, an increase in which may lead to death. 2. Neutrophil-mediated changes in the acute inflammatory response modulate the neuropsychological sequelae in mice that survive pneumococcal meningitis.

Synthetic cannabinoids (SCs) have rapidly proliferated as recreational drugs, and may present a substantial health risk to vulnerable populations. However, information on possible effects of long-term use is sparse. This study compared acute and residual effects of the popular indazole carboxamide SC compounds AB-PINACA and AB-FUBINACA in adolescent rats with ∆9-tetrahydrocannabinol (THC) and control treatments. Albino Wistar rats were injected (i.p.) with AB-PINACA or AB-FUBINACA every second day (beginning post-natal day (PND) 31), first at a low dose (0.2 mg/kg on 6 days) followed by a higher dose (1 mg/kg on a further 6 days). THC-treated rats received equivalent doses of 6 × 1 mg/kg and 6 × 5 mg/kg. During drug treatment, THC, AB-PINACA, and AB-FUBINACA decreased locomotor activity at high and low doses, increased anxiety-like behaviours and audible vocalisations, and reduced weight gain. Two weeks after dosing was completed, all cannabinoid pre-treated rats exhibited object recognition memory deficits. These were notably more severe in rats pre-treated with AB-FUBINACA. However, social interaction was reduced in the THC pre-treated group only. Six weeks post-dosing, plasma levels of cytokines interleukin (IL)-1α and IL-12 were reduced by AB-FUBINACA pre-treatment, while cerebellar endocannabinoids were reduced by THC and AB-PINACA pre-treatment. The acute effects of AB-PINACA and AB-FUBINACA were broadly similar to those of THC, suggesting that acute SC toxicity in humans may be modulated by dose factors, including inadvertent overdose and product contamination. However, some lasting residual effects of these different cannabinoid receptor agonists were subtly different, hinting at recruitment of different mechanisms of neuroadaptation.

Cerebral malaria (CM) is a severe complication of and a leading cause of death due toPlasmodium falciparuminfection. CM is likely the result of interrelated events, including mechanical obstruction due to parasite sequestration in the microvasculature, and upregulation of Th1 immune responses. In parallel, blood-brain-barrier (BBB) breakdown and damage or death of microglia, astrocytes, and neurons occurs. We found that a novel formulation of a liposome-encapsulated glucocorticosteroid,β-methasone hemisuccinate (nSSL-BMS), prevents experimental cerebral malaria (ECM) in a murine model and creates a survival time-window, enabling administration of an antiplasmodial drug before severe anemia develops. nSSL-BMS treatment leads to lower levels of cerebral inflammation, expressed by altered levels of corresponding cytokines and chemokines. The results indicate the role of integrated immune responses in ECM induction and show that the new steroidal nanodrug nSSL-BMS reverses the balance between the Th1 and Th2 responses in malaria-infected mice so that the proinflammatory processes leading to ECM are prevented. Overall, because of the immunopathological nature of CM, combined immunomodulator/antiplasmodial treatment should be considered for prevention/treatment of human CM and long-term cognitive damage.

Concurrent ectoparasite infections on fishes are commonly encountered in the wild and in aquaculture (Rohde 1984; Hoffman 1999), for example, infections of both Ichthyophthirius multifiliis Fouquet, 1876 (Hymenostomatida: Ichthyopththiriidae; Colorni 2008) and gill‐infecting monogenoids (Platyhelminthes: Monogenoidea; Whittington and Chisholm 2008). The decision to aggressively treat infections of either of these parasites can be prudent in aquaculture systems. Both taxa have direct life cycles and short generation times, which may result in high infection intensities that can debilitate or kill the fish host (Noga 2010). Various chemical therapies have been evaluated to prevent, reduce, or eliminate such infections. Typical treatments for killing monogenoids include: freshwater or saltwater baths, formalin, copper sulfate (CuSO4), hydrogen peroxide, mebendazole, trichlorphon, and praziquantel (Whittington and Chisholm 2008). Treatments for infections of I. multifiliis (Ich) include: temporary exposure to high temperature, formalin, malachite green, CuSO4, potassium permanganate, and sodium chloride (Colorni 2008). Despite the common occurrence of these parasites on fish, little species‐specific information exists for the vast majority of fish–parasite combinations across the diversity of culture systems and captive settings. Formalin is approved by the US Food and Drug Administration (US FDA) for use as a treatment for external monogenetic trematodes in fish at up to 250 mg/L for up to 1 h (US FWS/AFS 2008). The ambiguity of this recommendation suggests a wide therapeutic range with no interpretation of repeated applications. Likewise, little information exists on the safety or efficacy of repeated formalin treatments on fish, and CuSO4 has an indeterminate approval status but is widely accepted as having high efficacy. In October 2009, white bass, Morone chrysops (Rafinesque, 1820; Perciformes: Moronidae), in a flow‐through culture system were diagnosed with concurrent infections of the gill‐infecting monogenoid Onchocleidus mimus (Mueller, 1936; Monogenoidea: Ancyrocephalidae) and Ich. O. mimus has a direct life cycle with no intermediate host required and as the intensity of infection increases can become problematic to a population. This study reports an opportunistic evaluation of the efficacy of repeated applications of formalin and CuSO4 to reduce, control, or eradicate these infections in cultured white bass.

Peracetic acid (PAA) is a relatively new compound suggested for use to treat pathogens in aquaculture. It is approved for use in Europe, but not in the United States. This study determined the effectiveness of PAA for fungus control on channel catfish, Ictalurus punctatus (Rafinesque), eggs. The study consisted of five PAA concentrations (2.5, 5, 10, 15 and 20 mg L)1) and an untreated control in a flowthrough system. A single spawn was used for each replication (N = 4). Eggs were treated twice daily until the embryos developed eyes. When hatching was complete for all viable eggs, fry were counted to determine the percent survival in each treatment. Fungal growth was severe in the untreated controls resulting in 11% survival. Treatments of 2.5, 5 and 10 mg L)1 PAA were significantly different from the controls (P < 0.05). The highest percent survival of hatched fry was with 5 mg L)1 PAA administered twice daily; the 2.5 mg L)1 PAA treatment had slightly less survival, but gives a higher margin of safety in case of treatment error. Very little fungus was present in treatments receiving 2.5 mg L)1 PAA or higher, and concentrations of 15 and 20 mg L)1 PAA were toxic to the eggs. The mean survivals in the 0, 2.5, 5, 10, 15 and 20 mg L)1 PAA treatments were 11%, 60%, 63%, 62%, 32% and 0%, respectively. Therefore, PAA may be a compound that merits further investigations regarding its use in U.S. aquaculture.

Aquaflor (florfenicol, 50% type A medicated article) is a relatively new antibiotic used in U.S. aquaculture and has been widely accepted as a safe and effective therapeutant. Some peer-reviewed studies have suggested that 15 mg florfenicol (FFC)·kg−1 body weight (BW)·d−1 for 10 d controls mortality to a greater extent than 10 mg FFC·kg−1 BW·d−1 for 10 d. This study evaluated the safety of Aquaflor to sunshine bass (female white bass Morone chrysops × male striped bass M. saxatilis) when administered in feed at 15 (1× the maximum proposed therapeutic dose), 45 (3×), and 75 (5×) mg FFC·kg−1 BW·d−1 for 20 d (2× the currently approved 10-d treatment duration). The medicated feed was top-coated with Aquaflor and fed at 2% BW·d−1 divided equally between the morning and afternoon feedings. Juvenile sunshine bass (13.6 ± 1.6 g [mean ± SD]) were stocked into 100-L flow-through tanks at 20 fish per tank. Diets were randomly assigned to three replicate tanks per treatment; fish in three additional nonstudy...

We model tides and associated bed shear stress in the Early Jurassic Laurasian Seaway of northwest Europe. Sensitivity tests with different water depths highlight those regions that are least affected by paleobathymetric uncertainty. Results show that although the vast seaway was largely microtidal, the tides were still capable of affecting sediment transport more than 2000 km from the open ocean. Flow constriction associated with shallow platforms and straits produced elevated bed shear stresses (a direct proxy for the entrainment and transport of sediment) that were decoupled from tidal range and were capable of transporting sand. Areas of increased bed shear stress broadly correlate with published geological data. Varying the water depth in the basin provides an insight into the effects of an idealized transgression. Increasing the water level leads to a net reduction in the bed shear stress at the shelf edge, but promotes further penetration of tidal energy into the basin interior, although it is still focused into areas of flow constriction. Further drowning of the seaway eventually widens the straits to the point that they fail to constrict the flow and bed shear stress is reduced. Increasing water level counterintuitively leads to an increase in bed shear stress in a small number of locations.

In a text where “[m]istakes are everywhere and errors abound,” 1 no error or mistake is so important in Finnegans Wake as humanity’s fall. The profundity of this error, a seemingly indelible stroke, is matched by the difficulty of its erasure, for nothing less than the death of a God could wipe it clean. The celebration of such a bestowal of divine grace upon an undeserving humanity is sung in the “Exultet” hymn of Holy Saturday in the Catholic Church, and the phrase “O felix culpa,” taken from it, forms an “energetic non-centre” of Finnegans Wake, according to Fritz Senn (164). More than just a phrase from the Mass or even a representation of the fall of humanity itself, “O felix culpa” also marks the influence of John Milton’s Paradise Lost upon the Wake and points to the murders of Chief Secretary Lord Frederick Cavendish and Under-Secretary Thomas Henry Burke in Phoenix Park, as well as to the exposure of Richard Pigott as a forger. After a brief survey of these references, I will show that the full importance of the felix culpa for Joyce is only encountered when the fall is understood as a fall into text (becoming a word of the flesh), that the fortuity of the fall is found in the act of writing itself, and that “felix culpa” marks the inter-penetration of divine and human creation in writing. I. In the Mass The “Exultet” hymn is the Praeconium to the Mass of Holy Saturday, Easter Eve. Holy Saturday forms the exact middle of the Easter vigil, between Christ’s crucifixion on Good Friday and his Easter resurrection. As such, it is a liminal moment between death and rebirth, not only in the life of Christ but in the life of the Christian congregation as well. Ildefonso Schuster’s annotation of the Sacramentary describes an ancient Easter tradition maintaining that the second coming of Christ was to occur on the anniversary of the night in which he rose from the tomb: “The faithful, therefore, assembled in the Church and kept watch in expectation of the parousia; but, when midnight had come and gone, and no one had appeared from heaven, they

Heidegger’s reflections on grace culminate in the years 1949-54 where grace names a figure for the ineluctable exposure of existence. Heidegger rethinks the relationship between what exists and the world in which it is found as one that is always open to grace. For Heidegger, this world is what he terms the “dimension” between earth and sky. The relationship is only possible where existence is no longer construed as a self-contained presence but instead is thought as something between presence and absence. In this essay, Heidegger’s references to grace in five contexts are considered: the 1949 Bremen lectures, the 1951 essay “... Poetically Dwells Man...,” the 1953 “Dialogue on Language,” the 1951 lecture on “Language,” and the 1954 speech at his nephew’s ordination.

Trematode parasites can cause massive infections in commercially raised fish. The most promising approach for the control of these infections is the reduction or elimination of snails that serve as vectors for the trematodes. A recent approach, the application of high concentrations of slurried hydrated lime (SHL) or copper sulfate pentahydrate (CSP) along pond margins (shoreline treatment), has shown promise in reducing populations of the marsh rams-horn snail Planorbella trivolvis (the snail vector of Bolbophorus damnificus and Clinostomum marginatum) in experimental ponds. While CSP has been shown to effectively reduce snail numbers, treatment efficacy and application methods using SHL have not been well defined. Four SHL treatments were evaluated for their ability to kill marsh rams-horn snails in experimental units designed to mimic commercial aquaculture ponds. The treatments were applied at water temperatures of 75–79°F (24–26°C), total alkalinity of 137–257 mg CaCO3/L of water, and total ...

The proinflammatory cytokine interferon-gamma (IFNγ) recently was shown to play a crucial role in experimental pneumococcal meningitis (PM) pathogenesis, and we aimed in this study to investigate IFNγ-driven nitric oxide synthase-2 (NOS2)-mediated pathogenesis of murine PM. We demonstrate that costimulation of toll-like receptors and IFNγ receptors was synergistic for NOS2 expression in cultured murine microglia. Using an experimental PM model, wild-type mice treated with anti-IFNγ antibody, as well as IFNγ and NOS2 gene knockout (GKO) mice, were inoculated intracerebroventricularly with 10(3) colony-forming units of Streptococcus pneumoniae (WU2 strain). Mice were monitored daily during a 200-h disease course to assess survival rate and blood-brain barrier (BBB) permeability measured at 48 h. IFNγ deficiency was protective in PM, with an approximate 3-fold increase in survival rates in both antibody-treated and IFNγ GKO mice compared to controls (P

On 16 November 1963, the U. S. Fish and Wildlife Service Fish Farming Experimental Station at Stuttgart, Arkansas, became the first institution to import grass carp (Ctenopharyngodon idella) into the United States. This introduction was the result of at least seven years of effort to find an effective biological control for problematic aquatic weeds. The introduction was in keeping with a strong environmental and political mandate of that day to replace the broad use of chemicals with biological controls. For about 10 years, federal and state agencies and university systems strongly promoted introductions, spawning, and nationwide stocking of the grass carp. In 1966, the USFWS laboratory at Stuttgart, Arkansas, was apparently responsible for the first accidental release of grass carp to the environment. By 1972, grass carp were stocked in open water systems, documented in 16 states, and established in the Mississippi River system. All this occurred before the first private-sector commercial produ...

The importance of fish health studies prior to the 1970s is largely ignored by US fish health investigators. This is because today's literature searches rarely obtain research information prior to 1970. The absence of this earlier literature can result in the duplication of research efforts and missing data that could change the course of a scientific investigation. This is particularly true for studies in fish parasitology. Much of the descriptive literature done between 1900 and 1950 is still valid today and may be the only work available for reference. Older data is also important to understanding disease origin and disease etiology. Information on diseased fish from the geographic region, now known as the United States of America, was first recorded in about 1609 when Captain John Smith described a fish kill. In the 19th century, more than 250 pieces of literature written by US investigators were retrieved that described diseases and parasites of fish. After 1899, only the studies of more prominent fish health specialists, as determined by publication records, have been highlighted. In general, this review documents the development of fish health studies in the US. It serves as a historical document, but more importantly as a resource of older works important to today's scientific studies.

Pneumococcal meningitis often results in death or neurological sequelae, but the underlying pathogenetic mechanisms remain poorly understood. In C57BL/6J mice subjected to intracerebroventricular (icv) challenge with Streptococcus pneumoniae, the chemokine CCL2 and cytokines interferon-γ, interleukin (IL)-1β, IL-6 and tumour necrosis factor were prominently expressed in the brain during the acute phase of the disease. The upregulation of these immune mediators was markedly diminished in IL-18-deficient mice. Uninfected IL-18(-/-) mice exhibited decreases in anxiety phenotype and licking behaviour, and an increase in behavioural habituation, in an automated monitoring system (the IntelliCage). Without antibiotic intervention, a majority of IL-18(+/+) mice developed irreversible disease after icv S. pneumoniae but this was significantly improved by deleting IL-18 gene function. IL-18(+/+) mice cured of pneumococcal meningitis with four doses of ceftriaxone, initiated at 20 h post-inoculation, showed enduring sequelae. These included abnormal behavioural phenotypes featuring diurnal hypoactivity and nocturnal hyperactivity, light phobia and disrupted cognitive function. While the hyperactive phenotype was absent in the corresponding IL-18(-/-) survivors, cognitive impairments and behavioural deficits were still present. Overall, the results suggest that the high levels of cytokines and/or chemokines released after pneumococcal challenge provoked a series of pathological events, ultimately causing acute death. Furthermore, since only a subset of behavioural phenotypes were ameliorated in the pneumococcus-infected IL-18(-/-) mice, the pathological pathways causing mortality may be, at least in part, distinct from those leading to long-term neurological sequelae.

N/A NHMRC

1 Harry K. Dupree Stuttgart National Aquaculture Research Center, U. S. Department of Agriculture, AgriculturalResearch Service, Stuttgart, AR, USA2 The University of Southern Mississippi, Department of Costal Sciences, Gulf Coast Research Laboratory, OceanSprings, MS, USA3 Aquaculture/Fisheries Center, Department of Aquaculture/Fisheries, University of Arkansas at Pine Bluff, AR, USA

Although its etiology remains unknown, evidence has accumulated to support an autoimmune pathogenesis for alopecia areata. Our review summarizes the immunologic data and also examines the role of genetics, atopy, and psychologic stress in this disorder. Until etiology is better understood, treatments for alopecia areata are likely to remain palliative. Nevertheless, newer therapies such as photochemotherapy, topical immunotherapy, and perhaps systemic immunotherapy (e.g., inosiplex) offer new hope for patients with extensive disease.

It has been shown previously that alopecia areata can be treated with dinitrochlorobenzene (DNCB) and other contact allergens. Whether these agents work by inducing immunologic stimulation or simply a nonspecific inflammatory reaction has not been definitively demonstrated. To test the relative importance of these two mechanisms, we have randomly studied 22 patients with alopecia areata to whom either DNCB or croton oil was applied topically. Sixty-three percent of patients without spontaneous regrowth of hair regrew hair after DNCB application. None of those treated with croton oil regrew hair when treated later with DNCB. Therefore, a proved contact allergen was shown to be required for therapeutic success. Patient acceptance of the induced contact dermatitis was excellent. In light of recent data on the mutagenicity of DNCB to bacteria, other contact allergens for topical immunotherapy are being sought.

Twenty-two patients with alopecia areata were treated with a combination of topical 0.1% 8-methoxypsoralen and UVA (PUVA). Eight of the twenty-two patients (36.3%) responded with excellent regrowth (terminal hair in at least 75% of the treated scalp), and two patients (9.1%) showed good regrowth (terminal hair in 50% to 75% of the treated scalp). The mean total UVA exposure and the mean total number of treatments for the entire treatment course for these responders was 171.7 joules/cm2 and 47.4 treatments, respectively. Eight of the nine responders available for follow-up experienced some degree of relapse when PUVA treatments were tapered or during a follow-up period (mean, 8.3 months) after treatment was discontinued. Despite the failure of topical PUVA to change the long-term course of alopecia, the combination of PUVA with other therapeutic modalities may result in the prolongation of the beneficial effect in selected patients. The mechanism of action of PUVA in alopecia areata might involve an immunomodulatory effect.

An 8-year-old girl initially manifested clinical and histopathologic findings of circumscribed scleroderma. She had both linear and plaque lesions. Although she was free of constitutional symptoms, laboratory evaluation revealed substantial evidence of systemic lupus erythematosus (SLE). This included a positive anti-nuclear antibody test (rim pattern), positive LE cell preparation test, elevated anti-double-stranded DNA activity, positive lupus band test (IgM and C3) in involved and uninvolved skin, and renal biopsy findings consistent with SLE. Sclerodermatous change as an initial sign of SLE is rare. We review previous reports of an association of circumscribed scleroderma, especially the linear form, with serologic evidence of systemic autoimmune disease.

Forty-five children with alopecia areata were prospectively studied by means of both clinical and laboratory evaluation for evidence of endocrine diseases and autoantibodies. Twenty-four percent had an abnormality as determined by one or more thyroid function studies (thyroxine, triiodothyronine, and thyroid-stimulating hormone) and/or elevation of microsomal antibody levels. In 16%, smooth muscle antibody was present, and in 4%, parietal cell antibody was present. Routine thyroid function testing is recommended for all children with alopecia areata.

A patient presented with a solitary plaque initially interpreted on light microscopy as benign lymphoplasia. Monoclonal antibody studies were used to define the B cell origin of the infiltrate and to characterize its probable malignant potential. Monoclonal antibody typing is a useful technique to evaluate lymphocytic infiltrates that may be difficult to categorize on the basis of routine light microscopy.

Confluent and reticulated papillomatosis of Cougerot and Carteaud (CRP) is a distinctive clinicopathologic entity, of unknown etiology, which shows some resemblance to pityriasis versicolor. A case of CRP that showed a signific ant therapeutic response to topical selenium sulfide is reported. In previously described cases, response to this agent and to other medications, both antifungal and keratolytic, has been variable. A review of these cases reveals conflicting evidence regarding the questionable role of Malassezia furfur in CRP.

• Epidermodysplasia verruciformis is a rare, often hereditary disease characterized by a generalized cutaneous infection with human papillomavirus (HPV), depressed cell-mediated immunity, and a propensity for transformation of the warty lesions to squamous cell carcinoma on primarily sun-exposed areas of the skin. A 37-year-old man with congenital lymphatic dysplasia and a history of squamous cell carcinoma of the groin and foot was observed by us to have edema of all four extremities, numerous flat warts, and pityriasis versicolor-like papules over the trunk and arms. Condylomatous lesions were noted in the groin and a periungual verrucous nodule on the thumb. Biopsies showed the trunk and arm lesions to be verrucae and the thumb lesion to be Bowen's disease. Results of molecular hybridization studies from four lesions of the arms showed the presence of only HPV 3 DNA; HPV 16-related DNA was detected in the intraepidermal carcinoma on the thumb. Immunologic evaluation revealed anergy to routine skin testing, depressed mitogen-stimulated lymphocyte transformation, decreased B-lymphocyte count, and a severe reversal of the T-lymphocyte helper:suppressor ratio. (Arch Dermatol1987;123:1511-1516)

A 27-year-old woman developed a chronic, recurrent eruption of the face and upper extremities with the clinical and histopathologic features of recurrent granulomatous dermatitis with eosinophilia (Wells'syndrome). As described in 15 previously reported cases, this disorder is characterized by two clinical phases (ensinophilic cellulitis and granuloniatou plaque phase) and three histopathologic stages. The latter are particularly remarkable for a diffuse dermal and subcutaneous eosinophilia in acute lesions and scattered flame figures in chronic lesions. Distinctive findings in this case were the predominance of facial involvement and the symptomatic response to topical corticosteroids. Although etiology and pathogenesis are unknown, we feel that Wells'syndrome is a unique yet rarely recognized clinicopathologic entity.

The efficacy of the topical allergen squaric acid dibutylester (SADBE) was investigated in the treatment of twenty-six patients with alopecia areata or alopecia totalis. The patients had their disease for a mean duration of 8.3 years (range, 3 months to 27 years). Sensitization was attempted with 2% SADBE in acetone. Five individuals could not be sensitized. The twenty-one sensitized patients were treated with topical applications of 0.001% to 1.0% SADBE in acetone adjusted to produce and maintain dermatitis for an average of 21 weeks. Eleven (52%) had excellent responses consisting of complete regrowth in six and cosmetically acceptable regrowth in five. The average treatment time for regrowth was 11 weeks (range, 5-20 weeks). Ten (48%) had no clinical response after an average of 19 weeks of therapy (range, 4-42 weeks). Topical SADBE is an effective therapy for some patients with long-standing alopecia areata.

Tar gels are currently promoted as effective substitutes for crude coal tar preparations in responsive dermatoses. The gel vehicles contain approximately one-third alcohol. We report a case of a disulfiram (Antabuse) reaction in a patient using tar gel. Report of a Case A 29-year-old man was admitted for inpatient therapy of extensive psoriasis with tar gel (Estar) and ultraviolet B energy. He had a history of psychiatric difficulties and alcohol abuse; however, he denied alcohol use for 48 hours prior to hospitalization. Otherwise, results of further history and review of symptoms were normal. Physical examination showed guttate and plaque forms of psoriasis covering approximately 20% of the body surface area. The results of the remainder of the examination were within normal limits. Nightly tar gel therapy was initiated. Six days later, after consultation with a psychiatrist, the patient agreed to institution of disulfiram therapy, 125 mg orally every morning.

• An 8-year-old girl initially manifested clinical and histopathologic findings of circumscribed scleroderma. She had both linear and plaque lesions. Although she was free of constitutional symptoms, laboratory evaluation revealed substantial evidence of systemic lupus erythematosus (SLE). This included a positive antinuclear antibody test (rim pattern), positive LE cell preparation test, elevated antidouble-stranded DNA activity, positive lupus band test (IgM and C3) in involved and uninvolved skin, and renal biopsy findings consistent with SLE. Sclerodermatous change as an initial sign of SLE is rare. We review previous reports of an association of circumscribed scleroderma, especially the linear form, with serologic evidence of systemic autoimmune disease. ( Arch Dermatol 116:69-73, 1980)

Address: 1Molecular Immunopathology Unit, Bosch Institute and School of Medical Sciences, University of Sydney, Sydney, NSW 2006, Australia, 2Malaria Research Group, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford University, Oxford OX3 9DU, UK and 3Anatomy and Histology, Bosch Institute and School of Medical Sciences, University of Sydney, Sydney, NSW 2006, Australia