Psoriasis confined strictly to vitiligo areas – a Koebner‐like phenomenon?

Vitiligo and psoriasis are both common skin disorders. However, psoriasis strictly confined to pre-existing vitiligo areas is rare and suggests a causal relationship. We report here on two patients with a strict anatomical colocalization of vitiligo and psoriasis. The histopathological examinations showed typical changes for both diseases together with a dense infiltrate of CD4+ and CD8+ T cells. By immunohistochemistry, intracytoplasmatic granzyme B and tumour necrosis factor alpha (TNF-alpha) were detected within the T-cell population, suggesting the functional activity of these cells and the creation of a local T helper 1 (Th1)-cytokine milieu. Additionally, in one patient we could identify anti-melanocytic T cells by tetramer staining and enzyme-linked immunospot (ELISPOT) analysis. These skin-infiltrating lymphocytes might trigger, by the local production of Th-1 cytokines such as TNF-alpha and interferon-gamma (IFN-gamma), the eruption of psoriatic plaques in patients with a genetic predisposition for psoriasis.     

The dynamics of oral contraceptive use in the Netherlands 1990–1993

Data from an ongoing series of surveys on contraceptive use in the Netherlands were analyzed with respect to the percentages of oral contraceptive (OC) users who annually started use, discontinued use or switched to another OC type. The surveys had been conducted between 1990 and 1993 among samples of women aged 15–49 who belonged to a survey panel. Response rates of the surveys were 89–90% and the sample sizes ranged from 4560 to 4621 women. The assessed OC use rates reflected those of the Dutch population reasonably well. Of all respondents who had used OCs during the 12 months prior to the surveys, 12–15% discontinued use within this period, mainly in order to get pregnant, 12–16% were starters and 9–14% switchers. Of all starters 37% switched to another OC type within the first 12 months after starting. Switching was mainly related to the experience of perceived side-effects and wishes for better cycle control. The results highlighted the relevance of closely monitoring the individual woman's satisfaction with her OC. Since OC use appeared in many cases to be characterized by an active seeking for the most acceptable OC type, a wide range of OC types available and the development and introduction of new types is highly relevant for tailoring contraceptive use to individual needs.

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Resumen Se analizaron los datos de una serie de estudios que se están efectuando con respecto al uso de anticonceptivos en los Países Bajos a fin de determinar los porcentajes de usuarias de anticonceptivos orales (AO) que habían comenzado a utilizar, dejado de utilizar o pasado a otro tipo de AO, anualmente. Los estudios se habían efectuado entre 1990 y 1993 con muestras de mujeres de 15 a 49 años que formaban parte de un panel de estudio. Las tasas de respuesta de los estudios fueron del 89–90% y los tamaños de las muestras estuvieron comprendidos entre 4.560 y 4.621 mujeres. Las tasas de uso de AO evaluadas reflejaron las de la población holandesa razonablemente bien. De todas las encuestadas que habían utilizado AO durante los 12 meses anteriores a los estudios, el 12–15% dejó de utilizarlos dentro de este período, principalmente a fin de quedar embarazada, el 12–16% recién comenzaba a utilizarlos y el 9–14% había cambiado a otro tipo de AO. De todas las que recién comenzaban a utilizarlos, el 37% pasó a otro tipo de AO dentro de los 12 meses de iniciado su uso. El cambio se relacionaba principalmente con la experiencia de los efectos secundarios percibidos y el deseo de un mejor control del ciclo. Los resultados destacaron la importancia de una monitorización estrecha de la satisfacción individual de la usuaria con respecto a su AO. Dado que la utilización de AO pareció en muchos casos caracterizarse por la búsqueda activa del tipo más aceptable de AO, una amplia gama disponible de tipos de AO y el desarrollo y la introducción de nuevos tipos son aspectos que revisten gran importancia en la adaptación del uso de anticonceptivos a las necesidades individuales.

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Resumé Les données provenant d'une série en cours d'enquêtes sur l'utilisation des contraceptifs aux Pays-Bas ont été analysées du point de vue des pourcentages des utilisatrices de contraceptifs oraux (CO) qui ont, pendant chaque année, commencé à les utiliser, les ont abandonnés ou sont passées à un autre type de CO. Les enquêtes ont été menées entre 1990 et 1993 parmi des échantillons de femmes âgées de 15 à 49 ans qui constituaient la population étudiée. Les pourcentages de réponses aux enquêtes se sont élevés à 89–90% pour un échantillonnage allant de 4560 à 4621 femmes. Les pourcentages d'utilisation de CO évalués reflétaient assez bien ceux de la population néerlandaise en général. Parmi toutes ces femmes qui avaient utilisé les CO durant les 12 mois précédant l'enquête, 12–15% avaient cessé au cours de cette même période, en général pour avoir un enfant, 12–16% avaient commencé à les utiliser et 9–14% avaient changé de type de CO. Parmi toutes celles qui avaient commencé, 37% ont changé de produit au cours des 12 premiers mois. Le choix d'un autre type de CO étail essentiellement lié à des effets secondaires ressentis et au désir de mieux régler le cycle menstruel. Les résultats mettent en évidence combien il est important de suivre de près dans quelle mesure les femmes sont individuellement satisfaites du CO qu'elles adoptent. Etand donné que l'utilisation des Co semble, dans beaucoup ce cas, être caractérisée par une recherche active du type de CO le plus acceptable, le choix possible dans toute une gamme de CO, ainsi que la mise au point et l'introduction de nouveaux types, permettent remarquablement bien d'adapter l'utilisation des contraceptifs aux besoins individuels.

     

Circannual variation in lymphocyte subsets, revisited

BACKGROUND: Circadian and circannual variations in lymphocyte subsets, especially CD8+ T-lymphocytes, have been reported. This study focuses on CD4+ T-lymphocyte seasonal variation over a 6-year 8-month period. STUDY DESIGN AND METHODS: Lymphocyte subsets were quantitated monthly for four healthy individuals from 1986 through 1992 as part of a flow cytometry quality-control program. RESULTS: In general, there were no significant seasonal changes in the total number of white cells or in total lymphocyte counts. The absolute numbers of CD4+ T-lymphocytes were lowest in summer when the CD8+ T-lymphocytes were highest. Mean CD4+ T-lymphocyte counts were 846, 967, 618, and 695 per microL for Subjects 1 through 4, respectively, in winter and 432, 670, 355, and 766 per microL, respectively, in summer. Two healthy subjects had CD4+ T-lymphocyte counts lower than 300 per microL on one or more occasions during the study period. In three of the four subjects, the percentage of B-lymphocytes in winter was almost double that in summer. In one of the four subjects, no circannual rhythm was observed in these lymphocyte subpopulations. CONCLUSION: The seasonal variation in CD4+ T- lymphocyte counts demonstrated in three healthy individuals over almost 7 years is again of interest in light of renewed consideration of using surrogate tests, such as CD4+ T-lymphocyte counts, to screen for AIDS- like diseases that may be in the blood supply.     

Segmental duplications and gene conversion: Human luteinizing hormone/chorionic gonadotropin beta gene cluster

Segmental duplicons (>1 kb) of high sequence similarity (>90%) covering >5% of the human genome are characterized by complex sequence variation. Apart from a few well-characterized regions (MHC, β-globin), the diversity and linkage disequilibrium (LD) patterns of duplicons and the role of gene conversion in shaping them have been poorly studied. To shed light on these issues, we have re-sequenced the human Luteinizing Hormone/Chorionic Gonadotropin β (LHB/CGB) cluster (19q13.32) of three population samples (Estonians, Mandenka, and Han). The LHB/CGB cluster consists of seven duplicated genes critical in human reproduction. In the LHB/CGB region, high sequence diversity, concentration of gene-conversion acceptor sites, and strong LD colocalize with peripheral genes, whereas central loci are characterized by lower variation, gene-conversion donor activity, and breakdown of LD between close markers. The data highlight an important role of gene conversion in spreading polymorphisms among duplicon copies and generating LD around them. The directionality of gene-conversion events seems to be determined by the localization of a predicted recombination “hotspot” and “warm spot” in the vicinity of the most active acceptor genes at the periphery of the cluster. The data suggest that enriched crossover activity in direct and inverted segmental repeats is in accordance with the formation of palindromic secondary structures promoting double-strand breaks rather than fixed DNA sequence motifs. Also, this first detailed coverage of sequence diversity and structure of the LHB/CGB gene cluster will pave the way for studying the identified polymorphisms as well as potential genomic rearrangements in association with an individual's reproductive success.     

A rapid microagglutination test for the diagnosis of Legionella pneumophila (serogroup 1) infection

A rapid microagglutination test has been developed which can be performed in 30 minutes. Ninety-seven percent of 96 patients diagnosed as having Legionella pneumophila (serogroup 1) infection by indirect immunofluorescence were also detected by the rapid microagglutination test.     

The transplantation of hematopoietic stem cells after non-myeloablative conditioning: a cellular therapeutic approach to hematologic and genetic diseases

Originally, allogeneic hematopoietic stem cell transplantation (HSCT) was viewed as a form of rescue from the marrow lethal effects of high doses of chemo-radiotherapy used to both eradicate malignancy and to provide sufficient immunosuppression to ensure allogeneic engraftment. Clear evience of a therapeutic graft-versus-tumor (GVT) effect mediated by allogeneic affector cells (T cells) has prompted the exploration of HSCT regimens that rely solely upon host immunosuppression (non-myeloblative) to facilitate allogenic donor engraftment. The engrafted donor effector cells are then used to accomplish the task of eradicating host malignant cells. The non-myeloblative regimen developed in Seattle uses 2 Gy total body irradiation (TBI) before transplant followed by postgrafting cyclosporine (CSP) and mycophenolate mofetil (MMF). This regimen resulted in initial mixed donor-host chimerism in all patients with hematologic malignancies and genetic disorders who received HLA-matched sibling allografts. The 17% incidence of graft rejection was reduced to 3% with the addition of fludarabine, 30 mg/m²/day on d-4,-3, and-2. The non-myeloblative combination of fludarabine/TBI has also been successful at achieving high engraftment rates in recipients of 10 of 10 HLA antigen matched unrelated donor HSCTs in patients with hematologic malignancies. By reducing acute toxicities relative to conventional HSCT, most patients have received their pre- and post-HSCT therapy almost exclusively as outpatients. Acute and chronic GVHD occur after non-myeloablative HSCT, but the incidence and severity appear less compared to conventional HSCT. As in conventional transplants, immune dysregulation from GVHD and its treatment and delayed reconstitution of immune function continue to present risks to patients who have otherwise undergone successful non-myeloablative HSCT. Cellular therapeutic effects have been nobserved after non-myeloblative HSCT such as correction of inherited genetic disorders, and eradication of hematologic malignant diseases and renal cell carcinoma via GVT responses.