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The unified neutral theory of biodiversity: do the numbers add up?

Hubbell's unified neutral theory is a zero-sum ecological drift model in which population sizes change at random in a process resembling genetic drift, eventually leading to extinction. Diversity is maintained within the community by speciation. Hubbell's model makes predictions about the distribution of species abundances within communities and the turnover of species from place to place (beta diversity). However, ecological drift cannot be tested adequately against these predictions without independent estimates of speciation rates, population sizes, and dispersal distances. A more practical prediction from ecological drift is that time to extinction of a population of size N is approximately 2N generations. I test this prediction here using data for passerine birds (Passeriformes). Waiting times to speciation and extinction were estimated from genetic divergence between sister populations and a lineage-through-time plot for endemic South American suboscine passerines. Population sizes were estimated from local counts of birds in two large forest plots extrapolated to the area of wet tropical forest in South America and from atlas data on European passerines. Waiting times to extinction (ca. 2 Ma) are much less than twice the product of average population size (4.0 and 14.4 x 10(6) individuals in South America and Europe) and generation length (five and three years) for songbirds, that is, 40 and 86 Ma, respectively. Thus, drift is too slow to account for turnover in regional avifaunas. Presumably, other processes, involving external drivers, such as climate and physiographic change, and internal drivers, such as evolutionary change in antagonistic interactions, predominate. Hubbell's model is historical and geographic, and his perspective importantly links local and regional process and pattern. Ecological reality can be added to the mix while retaining Hubbell's concept of continuity of communities in space and time.

Biodiversity↗

Mineralization and bone formation on microcarrier beads with isolated rat calvaria cell population.

Using enzymatically isolated rat bone cells in the presence of cytodex microcarrier beads, osteoblastic cell differentiation and bone nodule formation were studied at the optical and electron microscopic level. Cytochemical method showed an intense alkaline phosphatase activity mainly around the microcarriers where the cells have formed multilayers on day 4 of cultures. On day 7 of experiment cultures, Von Kossa method stained positively only the cytodex microcarriers. During the following days, bone nodule formation was closely associated with cytodex microcarriers. In contrast, in control cultures with negatively charged glass beads, cells failed to pile up around the glass beads, and bone nodule formation occurred randomly in the culture dishes with 24 hour delay. Light microscopy observations of experiment cultures revealed the formation of nodular structures, with active osteoblastic cells forming a mineralized matrix in which osteocytes were present. Transmission electron microscopy revealed first, a mineralization process of the surface of the cytodex microcarriers which appeared like a granular electron-dense, collagen-free layer followed by the deposit of a collagenous matrix. These results indicated that cytodex microcarriers provided an excellent matrix for bone cell differentiation and mineralization.

Animals↗

Landscape changes in the Mullica River basin of the Pinelands National Reserve, New Jersey, USA.

In 1979, the Pinelands Commission was established as a regional land-use planning and regulatory agency charged with the implementation of a Comprehensive Management Plan (CMP) for the Pinelands National Reserve (New Jersey, USA). The CMP was created to balance land preservation and development interests in the Reserve. Because water-quality degradation from developed and agricultural landscapes is associated with changes in the composition of biological communities, monitoring landscape changes provides one of the most direct measures of the impact of land-use policies on the Pinelands ecosystem. In this study, we prepared detailed, land-cover maps within randomly selected aerial-photograph plots for a major watershed in the Reserve. We used these land-cover maps to quantify changes in landscape composition and structure (i.e., patch size, patch area, and number of patches) and characterize land-cover transitions in the basin between 1979 and 1991. Because the study period represented the first 12 years of the regional-planning effort in the Reserve, we evaluated the relationship between land-cover transitions and Commission management-area designations which permit different land-use intensities. Although the landscape composition was similar in 1979 and 1991, we found an increase in the total area and number of developed-land, managed-grassland, and barren-land patches. An increase in the number of patches and a decrease in the total area and median and third-quartile patch sizes for forest land and for all patches regardless of cover type indicated that fragmentation of forest land and the landscape as a whole occurred during the study period. The major land-cover transitions that occurred during the period were the loss of forest land to development and associated cover types and the conversion of one agricultural type to another. Overall, land-cover transitions during the period were found to be consistent with the Commission management-area designations, which indicated that the regional-planning effort has been successful in directing human activities to appropriate areas of the basin.

Agriculture↗

Molecular identification of chromosomal forms of Anopheles gambiae sensu stricto.

The Afrotropical malaria vectors Anopheles gambiae sensu stricto and An. arabiensis, responsible for more than 3/4 of the world Plasmodium falciparum inoculations, are members of the Anopheles gambiae complex, a group consisting of six sibling species. The nominal species (An. gambiae s.s.) is by far the most anthropophilic vector and its adaptation to man and his environment involves further ongoing speciation processes. This fact is shown by the existence of a number of incipient taxonomic units characterised by different chromosomal arrangements derived from the presence of polymorphic paracentric inversions. This speciation process is centered in West Africa, where five so-called 'chromosomal forms' have been described, designated with a non-Linnean nomenclature: Forest, Bissau, Savanna, Bamako, and Mopti. Studies on the distribution and the ecology of these incipient species have highlighted specific adaptations to eco-ethological parameters, which might reflect on their relative efficiency as malaria vectors. Cytogenetic analysis, in spite of some inherent difficulties, has proved to be a powerful tool for the identification of An. gambiae sibling species and the individual chromosomal forms. Yet, modern molecular tools are now available, providing alternative faster low-cost technologies, and we discuss here their relative merits.

Animals↗

Cognitive-behavioural interventions for children who have been sexually abused.

BACKGROUND: Despite differences in perceptions of what constitutes child sexual abuse there is a general consensus amongst clinicians and researchers that this is a substantial social problem which affects large numbers of children and young people worldwide. The effects of sexual abuse manifest themselves in a wide range of symptoms, including fear, anxiety, post-traumatic stress disorder and behaviour problems such as externalising or internalising, or inappropriate sexual behaviours. Child sexual abuse is associated with increased risk of psychological problems in adulthood. Knowing what is most likely to benefit children already traumatised by these events is important. OBJECTIVES: The aim of this review was to assess the efficacy of cognitive-behavioural approaches (CBT) in addressing the immediate and longer-term sequelae on children who have been sexually abused. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 5, 2005), MEDLINE (1966-November 2005); EMBASE (1980-November 2005); CINAHL (1982-November 2005), PsycINFO (1897-November 2005); LILACS (1982-November 2005); SIGLE (1980 to November 2005) and the register of the Cochrane Developmental, Psychosocial and Learning Problems Group (November 2005) were searched. SELECTION CRITERIA: Included studies were randomised or quasi-randomised controlled trials investigating the efficacy of cognitive behavioural therapy on children and adolescents up to age 18 years who had experienced sexual abuse. DATA COLLECTION AND ANALYSIS: Titles and abstracts identified in the search were independently assessed for eligibility by two reviewers (GM and PR). Data were extracted and entered into REVMAN (JH and GM), and synthesised and presented in both written and graphical form (forest plots). MAIN RESULTS: Ten trials, including 847 participants, were included in this review. Data suggest that CBT may have a positive impact on the sequelae of child sexual abuse, but most results were statistically non-significant. AUTHORS' CONCLUSIONS: The review confirms CBT's potential as a means of addressing the adverse consequences of child sexual abuse, but highlights the tenuousness of the evidence base and the need for more carefully conducted and better reported trials.

Adolescent↗

Effect of disturbances on the genetic diversity of an old-forest associated lichen.

Lichens associated with old forest are commonly assumed to be negatively affected by tree logging or natural disturbances. However, in this study performed in a spruce-dominated sylvopastoral landscape in the Swiss Jura Mountains, we found that genetic diversity of the epiphytic old-forest lichen Lobaria pulmonaria depends on the type of disturbance. We collected 923 thalli from 41 sampling plots of 1 ha corresponding to the categories stand-replacing disturbance (burnt), intensive logging (logged) and uneven-aged forestry (uneven-aged), and analysed the thalli at six mycobiont-specific microsatellite loci. We found evidence for multiple independent immigrations into demes located in burnt and logged areas. Using spatial autocorrelation methods, the spatial scale of the genetic structure caused by the clonal and recombinant component of genetic variation was determined. Spatial autocorrelation of genotype diversity was strong at short distances up to 50 m in logged demes, up to 100 m in uneven-aged demes, with the strongest autocorrelation up to 150 m for burnt demes. The spatial autocorrelation was predominantly attributed to clonal dispersal of vegetative propagules. After accounting for the clonal component, we did not find significant spatial autocorrelation in gene diversity. This pattern may indicate low dispersal ranges of clonal propagules, but random dispersal of sexual ascospores. Genetic diversity was highest in logged demes, and lowest in burnt demes. Our results suggest that genetic diversity of epiphytic lichen demes may not necessarily be impacted by stand-level disturbances for extended time periods.

Ascomycota↗

Mosaic microecological differential stress causes adaptive microsatellite divergence in wild barley, Hordeum spontaneum, at Neve Yaar, Israel.

Genetic diversity at 38 microsatellite (short sequence repeats (SSRs)) loci was studied in a sample of 54 plants representing a natural population of wild barley, Hordeum spontaneum, at the Neve Yaar microsite in Israel. Wild barley at the microsite was organized in a mosaic pattern over an area of 3180 m2 in the open Tabor oak forest, which was subdivided into four microniches: (i) sun-rock (11 genotypes), (ii) sun-soil (18 genotypes), (iii) shade-soil (11 genotypes), and (iv) shade-rock (14 genotypes). Fifty-four genotypes were tested for ecological-genetic microniche correlates. Analysis of 36 loci showed that allele distributions at SSR loci were nonrandom but structured by ecological stresses (climatic and edaphic). Sixteen (45.7%) of 35 polymorphic loci varied significantly (p < 0.05) in allele frequencies among the microniches. Significant genetic divergence and diversity were found among the four subpopulations. The soil and shade subpopulations showed higher genetic diversities at SSR loci than the rock and sun subpopulations, and the lowest genetic diversity was observed in the sun-rock subpopulation, in contrast with the previous allozyme and RAPD studies. On average, of 36 loci, 88.75% of the total genetic diversity exists within the four microniches, while 11.25% exists between the microniches. In a permutation test, G(ST) was lower for 4999 out of 5000 randomized data sets (p < 0.001) when compared with real data (0.1125). The highest genetic distance was between shade-soil and sun-rock (D = 0.222). Our results suggest that diversifying natural selection may act upon some regulatory regions, resulting in adaptive SSR divergence. Fixation of some loci (GMS61, GMS1, and EBMAC824) at a specific microniche seems to suggest directional selection. The pattern of other SSR loci suggests the operation of balancing selection. SSRs may be either direct targets of selection or markers of selected haplotypes (selective sweep).

Alleles↗

Cytogenetic analysis of the bipotential murine pre-B cell lymphoma, P388, and its derivative macrophage-like tumor, P388D1, using SKY and CGH.

Spectral karyotyping (SKY) and comparative genomic hybridization (CGH) were used to elucidate the divergent cytogenetic make-up of the prototypical bilineage lymphoblastic pre-B lymphoma, P388, and its progenitor macrophage-like tumor, P388D1. P388 was found to be diploid and genomically stable. P388D1 was triploid, highly unstable and characterized by numerous marker chromosomes (Chrs) and composite rearrangements. The karyotype of P388D1 was so complex that its clonal relatedness to P388 would have remained questionable without confirmation by molecular analysis of the clonotypic immunoglobulin heavy-chain and light-chain gene recombinations that coexisted in both tumors. The intrinsic instability of the P388D1 genome was indicated by the observation that only four out of 42 aberrations uncovered by SKY (in a total of 27 metaphases) occurred consistently (100% incidence), whereas 27 changes occurred non-randomly (27 to 96% incidence) and 11 alterations randomly (4 to 11% incidence). Persistent cytogenetic instability was also observed in P388 'macrophages' after phorbol ester- and ionomycin-induced conversion in vitro of P388 lymphoma cells. The 'cytogenetic noise' in these cells was manifested by a multiplicity of sporadic chromosomal aberrations; ie 25 distinct changes were identified by SKY in 40 metaphases. The results in P388D1 and P388 'macrophages' were interpreted to indicate that the myeloid differentiation program in the bipotential pre-B cell lymphoma P388 is invariably characterized by karyotypic instability. The study presented here demonstrates the power of the combined SKY and CGH approach to resolve complicated karyotypes of important and widely used mouse tumors.

Animals↗

Borrelia burgdorferi infection prevalences in questing Ixodes ricinus ticks (Acari: Ixodidae) in urban and suburban Bonn, western Germany.

From March to October 2003, a total of 2,518 host-seeking Ixodes ricinus ticks (1,944 nymphs, 264 females, 310 males) were collected by blanket dragging at 45 sites all over the city area of Bonn, western Germany, to be checked for Borrelia burgdorferi infection. The collection sites included 20 private gardens, nine public recreational parks, the boundaries of 14 sylvatic suburban areas and two footpaths between suburban farmed fields. Generally, numbers of specimens collected along sylvatic suburban areas and at urban sites with dense tree populations were significantly higher than at the other collection sites. Out of 1,394 specimens (865 nymphs, 241 females, 288 males) that were randomly chosen for Borrelia analysis by a simple PCR, 250 (17.9 %) were found to be infected with B. burgdorferi sensu lato. While the infection prevalences varied significantly between females (26.6%), males (12.5%) and nymphs (17.3%), there were no striking differences between sylvatic and unwooded sites. A total of 92.8% of the ticks Borrelia-positive by the simple PCR were also positive in a diagnostic nested PCR. Using genospecies-specific oligonucleotide probes, single Borrelia genospecies infections (91.4%) could be assigned to B. afzelii (39.5%), B. garinii (27.9%), B. burgdorferi sensu stricto (15.6%) and B. valaisiana (8.6%) by DNA hybridization. Various combinations of double infections were observed in 4.3% of the infected ticks. Another 4.3% of the Borrelia infections were untypeable. The B. burgdorferi genospecies distribution in the city area was shown to be variable from site to site and, even more, it was distinct from rural collection sites near Bonn. This is ascribed to a different spectrum of reservoir hosts. Taking into account the infection prevalences of host-seeking ticks in the forested surroundings of Bonn, our study demonstrates that the risk of acquiring Lyme disease after a tick bite in urban/suburban areas is comparably as high as in woodlands outside of the city.

Animals↗

Molecular evidence of natural hybridization between abies veitchii and A. homolepis (Pinaceae) revealed by chloroplast, mitochondrial and nuclear DNA markers.

Sub-alpine Abies veitchii and A. homolepis are distributed in the central part of Honshu Island, Japan, and their habitats are segregated vertically. These species sometimes form a mixed forest in the overlapping area of the two species, that is, in the upper limit of the A. homolepis habitat and the lower limit of A. veitchii. These species have been considered to be distantly related because they were classified into different sections by most conventional classifications. No natural hybridization has been reported between the two species. The aim of this study was to demonstrate, through the use of molecular markers, whether natural hybridization takes place between these two species at two experimental sites on Mt. Fuji, where the species occur naturally. DNA markers from paternally inherited chloroplast DNA (cpDNA), maternally inherited mitochondrial DNA (mtDNA) and biparentally inherited nuclear DNA (nDNA), were used for this study. As organelle DNA markers, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) markers were developed to determine the maternal and paternal species for each individual. Two of 334 individuals possessed a cpDNA haplotype derived from A. homolepis and a mtDNA haplotype from A. veitchii. Furthermore, the nDNA of these two individuals was analysed using the random amplified polymorphic DNA (RAPD) assay to investigate their genomic composition. RAPD analysis indicated that the nuclear genomes of the two individuals were derived from both species. We conclude that A. veitchii and A. homolepis produce natural hybrids, and that their systematic relationship should be re-evaluated.

Base Sequence↗

Genetics of Euglossini bees (Hymenoptera) in fragments of the Atlantic Forest in the region of Viçosa, MG.

With uncontrolled deforestation, forest fragments remain, which in most cases are in different stages of regeneration and present isolated populations. In the present study we analyzed the genetic patterns of Eulaema nigrita populations in seven Atlantic Forest fragments of different sizes and successional stages in the region of Viçosa, MG. This was done by RAPD molecular markers. We observed that the area of the fragments had no effect on the genetic variability of E. nigrita in the direction predicted by meta-population models. Medium-sized well-preserved woods presented the lowest variability, whereas large and small woods were statistically identical. The evidence supports the notion that rural areas present greater dispersal among fragments, implying greater similarity between the populations of fragments located in rural areas when compared to fragments in urban areas.

Animals↗

Species richness and ecological characterization of myxomycetes and myxomycete-like organisms in the canopy of a temperate deciduous forest.

The ecological community of myxomycetes and myxomycete-like organisms (MMLO) in the canopy of living deciduous trees was studied in a riparian deciduous forest at Leipzig, Germany. A systematic survey carried out with a total of 146 moist chamber cultures resulted in 386 records of 37 taxa, with 32 myxomycetes, two myxobacteria, two protostelids and the fruit body forming ciliate Sorogena stoianovitchae, the latter recorded for the first time for Europe. With 94% of all cultures positive for MMLO, these organisms are present consistently in the investigated sections of white-rotten twigs attached to living trees at 10-30 m above the ground. Our sampling recovered a majority of the likely species, with 37 out of the 42-45 predicted according to a species-accumulation curve and two other estimators of species richness. Nonmetric multidimensional scaling revealed pH, water-holding capacity and stage of decay to explain most of the variation in species distribution. Arcyria cinerea and Perichaena depressa as the most common species occurred in 32% and 29% of all samples, respectively. Viewing the sampled twigs as habitat islands and a single spore as sufficient to establish a population, a simulation program assuming a random spore rain estimated an average of 0.4 and 0.35 spore hits per twig as necessary to explain the observed frequencies. This is matched by the potential productivity of the substrate. All fruit bodies from the cultured twigs would be able to create a spore rain of 86 (A. cinerea) or 40 (P. depressa) spore hits per twig when dispersed evenly over the plot. The terminal fall velocity of spores was measured, revealing that it took about 5 h for a spore to land (30 m) in still air and indicating high dispersal ability for canopy-inhabiting MMLO.

Animals↗

Mitochondrial phylogeny of pine cone beetles (Scolytinae, Conophthorus) and their affiliation with geographic area and host.

Pine cone beetles (Conophthorus spp.) feed and kill immature cones of Pinus species, thereby reducing seed production and seriously impairing reforestation of forest ecosystems. Population variation of Conophthorus reproductive behavior has hampered the development of semiochemical control of these pests. This difficulty is compounded by a lack of taxonomic knowledge and species diagnostic characters. Researchers and managers rely, in part, on host associations and geographic locality for species identifications and these have arguable taxonomic utility. However, host use and/or geographic separation may influence Conophthorus lineage diversification. To improve Conophthorus taxonomy and understand the association of host and geography with lineage diversification, a phylogeny of 43 individuals, including all valid species and a robust sample of C. ponderosae from different hosts, is reconstructed using 785 nucleotides of the 3'-end of the mitochondrial cytochrome oxidase I gene. Thirty trees were recovered in a parsimony analysis and the strict consensus was well resolved and supported by branch support measures. Conophthorus was monophyletic but mitochondrial polyphyly was uncovered for several species. The data also suggested an underestimation of species diversity. Phylogenetically related Conophthorus lineages were significantly associated with geographic proximity but not with host, as indicated by comparisons of character optimized geographic distributions and host associations against randomized distributions of these attributes on the parsimony tree. These results suggest that geographic separation better explains the mode of Conophthorus lineage diversification than does host specialization. Based on these results, researchers and managers of Conophthorus should consider populations as potentially different evolutionary entities until species boundaries are delineated via a robust phylogenetic revision of Conophthorus.

Amino Acids↗

Foliar temperature-respiration response functions for broad-leaved tree species in the southern Appalachians.

We measured leaf respiration in 18 eastern deciduous forest tree species to determine if there were differences in temperature-respiration response functions among species or among canopy positions. Leaf respiration rates were measured in situ and on detached branches for Acer pensylvanicum L., A. rubrum L., Betula spp. (B. alleghaniensis Britt. and B. lenta L.), Carya glabra (Mill.) Sweet, Cornus florida L., Fraxinus spp. (primarily F. americana L.), Liriodendron tulipifera L., Magnolia fraseri Walt., Nyssa sylvatica Marsh., Oxydendrum arboreum L., Platanus occidentalis L., Quercus alba L., Q. coccinea Muenchh., Q. prinus L., Q. rubra L., Rhododendron maximum L., Robinia psuedoacacia L., and Tilia americana L. in the southern Appalachian Mountains, USA. Dark respiration was measured on fully expanded leaves at 10, 15, 20, 25, and 30 degrees C with an infrared gas analyzer equipped with a temperature-controlled cuvette. Temperature-respiration response functions were fit for each leaf. There were significant differences in response functions among species and by canopy position within species. These differences were observed when respiration was expressed on a mass, nitrogen, or area basis. Cumulative nighttime leaf respiration was calculated and averaged over ten randomly selected nights for each leaf. Differences in mean cumulative nighttime respiration were statistically significant among canopy positions and species. We conclude that effects of canopy position and species on temperature-respiration response functions may need to be considered when making estimates of whole-tree or canopy respiration.

Journal Article↗

[Progress in vaccination against AIDS].

Two vaccination trials against AIDS viruses are reported. The first trial was a prophylactic vaccination carried out in the pig-tailed macaque (Macacca nemestrina) against simian immunodeficiency virus (SIV) variant PBj14. The immunogen was a Semliki forest virus (SFV) recombinant expressing SFV - PBj14 envelope protein. Vaccination did not prevent infection but protected the animals against the disease (a fulminant form of AIDS that kills the animal within 12-15 days). The second trial was a therapeutic vaccination carried out with HIV-I-infected hemophilic patients. The immunogen was a toxoïd of alpha interferons. (A toxoïd of alpha interferons is an inactivated and immunogenic preparation of alpha interferons). Vaccination induced the production of neutralizing anti alpha interferon antibody. As a result, circulating alpha interferon concentrations were drastically lowered and the clinical status of patients significantly improved.

AIDS Vaccines↗

Short-latency vergence eye movements induced by radial optic flow in humans: dependence on ambient vergence level.

Radial patterns of optic flow, such as those experienced by moving observers who look in the direction of heading, evoke vergence eye movements at short latency. We have investigated the dependence of these responses on the ambient vergence level. Human subjects faced a large tangent screen onto which two identical random-dot patterns were back-projected. A system of crossed polarizers ensured that each eye saw only one of the patterns, with mirror galvanometers to control the horizontal positions of the images and hence the vergence angle between the two eyes. After converging the subject's eyes at one of several distances ranging from 16.7 cm to infinity, both patterns were replaced with new ones (using a system of shutters and two additional projectors) so as to simulate the radial flow associated with a sudden 4% change in viewing distance with the focus of expansion/contraction imaged in or very near both foveas. Radial-flow steps induced transient vergence at latencies of 80-100 ms, expansions causing increases in convergence and contractions the converse. Based on the change in vergence 90-140 ms after the onset of the steps, responses were proportional to the preexisting vergence angle (and hence would be expected to be inversely proportional to viewing distance under normal conditions). We suggest that this property assists the observer who wants to fixate ahead while passing through a visually cluttered area (e.g., a forest) and so wants to avoid making vergence responses to the optic flow created by the nearby objects in the periphery.

Adult↗

Two new coccidian parasites from the slate-colored grosbeak (Pitylus grossus) of South America.

In July and August 1990, fecal samples from 2 slate-colored grosbeaks were collected from the rain forest of Ecuador. Upon examination, 2 new species of coccidia were discovered. Oocysts of Isospora pityli n. sp. are spheroid or subspheroid, 20.1 x 18.8 (20-20.5 x 17-20) microns, with a shape index of 1.07 (1.0-1.18) but lacking a micropyle, oocyst residuum, and polar granules. Sporocysts are ovoid, 14.7 x 9.4 (12-17 x 8-11) microns, with small nipplelike Stieda bodies, no substieda bodies, and residua composed of an amorphous cluster of coarse, nonuniform granules. Sporozoites each possess a large refractile body at 1 end and appear to be enclosed in a thin membrane within the sporocyst along with the residuum. Oocysts of L. formarum n. sp. are spheroid or subspheroid, 24.6 x 23.5 (21-27 x 20-25) microns, with a shape index of 1.05 (1.0-1.09) but with no micropyle, oocyst residuum, or polar granules. Sporocysts are ovoid, 15.7 x 11.3 (14-17 x 10-13) microns, with small, nipplelike Stieda bodies and large triangular or conical-shaped substieda bodies with irregular lower edges. Sporozoites each possess an oblong refractile body at 1 end and appear packed together randomly and enclosed in a membrane along with a spheroid residuum composed of fine, uniform granules.

Animals↗

Low-dose thalidomide therapy for refractory cutaneous lesions of lupus erythematosus.

BACKGROUND: Thalidomide is an anti-inflammatory agent and an immunomodulator that inhibits the production of tumor necrosis factor alpha. It has shown promise as a treatment option for the cutaneous manifestations of lupus erythematosus (LE). OBJECTIVE: To assess the degree of clinical response per subtype of cutaneous lupus, the duration of therapy before documented clinical improvement, and the incidence of adverse effects, including peripheral neuropathy, with low-dose thalidomide therapy at 100 mg daily in the treatment of refractory cutaneous lesions of LE. METHODS: This retrospective medical record review of patients with refractory cutaneous manifestations of LE is one of the largest modern series in the literature. There were 29 patients seen at the Department of Dermatology, Wake Forest University School of Medicine (Winston-Salem, NC), who were unresponsive to conventional agents including antimalarial agents, and who started treatment between 1998 and 2000. Twenty-three patients who took the drug for 1 month or more were included in the analysis. Clinical responses were assessed by the investigators based on statements of improvement listed in the clinic notes and were categorized as "no response," "partial response," and "complete response." Partial response was classified as either 75% or greater or less than 75% improvement. The incidence of adverse effects including peripheral neuropathy was determined. RESULTS: Of the 23 patients, 17 (74%) demonstrated complete resolution of the cutaneous manifestations of LE, whereas 3 patients (13%) demonstrated 75% or greater partial improvement; 3 patients (13%) had less than 75% partial clinical improvement; and 21 patients (91%) who demonstrated a complete or partial response did so within 8 weeks of initiating thalidomide therapy. CONCLUSIONS: Based on the results of this case series, we believe that thalidomide should be given prime consideration as a treatment for antimalarial drug-resistant interface lesions of LE. The design of prospective, randomized, double-blind, placebo-controlled trials for this indication is warranted.

Adult↗