Interleukin-4 enhances the survival of severe combined immunodeficient mice engrafted with human B-cell precursor leukemia

Human interleukin-4 (huIL-4) has been shown to inhibit the growth in vitro of cells from patients with acute lymphoblastic leukemia (ALL). With the aim of determining whether this cytokine might be useful in the treatment of patients with ALL, the effects of huIL-4 on human B- cell precursor ALL engrafted in severe combined immunodeficient (SCID) mice were examined. The inhibition of [3H] thymidine uptake of primary ALL cells by huIL-4 was maintained following engraftment and passage of leukemia in SCID mice. Five of seven xenograft leukemias showed significant inhibition in vitro by huIL-4 at concentrations as low as 0.5 ng/mL; furthermore, huIL-4 counteracted the proliferative effects of IL-7. When used to treat two human leukemias engrafted in SCID mice, huIL-4 200 microgram/kg/d, as a continuous 14-day subcutaneous infusion, suppressed the appearance of circulating lymphoblasts and extended survival of mice by 39% and 108%, respectively, the first demonstration of IL-4 activity against human leukemia in vivo. The mean steady-state huIL-4 level in mouse plasma during the infusion was 1.46 ng/mL (SEM +/- 0.14 ng/mL), which was similar to concentrations found to be effective in vitro. ALL cells obtained from mice relapsing after huIL-4 treatment continued to show inhibition by the cytokine in vitro. These data suggest that IL-4 may be useful in the treatment of patients with ALL.     

Genetic epidemiology of Charcot–Marie–Tooth in the general population

Background and purpose:  The frequency of different Charcot–Marie–Tooth (CMT) genotypes has been estimated in clinic populations, but prevalence data from the general population are lacking. Methods:  Our population‐based genetic epidemiological survey included persons with CMT residing in eastern Akershus County, Norway. The participants were interviewed and examined by one geneticist/neurologist and classified clinically, neurophysiologically and genetically. Results:  Two hundred and forty‐five persons from 116 families had CMT. This corresponds to 1 per 1214 persons (95% CI 1062–1366) have CMT in the general population. CMT1 (motor conduction velocity (MCV) <38 m/s), CMT2 (MCV >38 m/s) and CMT intermediate (MCV 25–45 m/s) were found in 48.2%, 49.4% and 2.4% of the families. A total of 27.2% of the families and 28.6% of the affected had a mutation in the investigated CMT genes. The prevalence of the peripheral myelin protein 22 (PMP22) duplication and point mutation in the connexin32 (Cx32), myelin protein zero (MPZ) and mitofusin2 (MFN2) genes was found in 13.6%, 6.2%, 1.2%, 6.2% of the families, and in 19.6%, 4.8%, 1.1%, 3.2% of the affected, respectively. None of the families had point mutations in the early growth response 2 (EGR2), PMP22 or small integral membrane protein of lysosome/late endosome (SIMPLE) genes. Conclusions:  CMT is the most common inherited neuropathy. At present, 43 CMT genes are known, and an examination of all known genes would probably only identify mutations in approximately 50% of those with CMT. Thus, it is probable that at least 30–50 CMT genes are yet to be identified.     

Occupational health legislation and practices related to seafarers on passenger ships focused on communicable diseases: results from a European cross-sectional study (EU SHIPSAN PROJECT)

Background  

Seafarers play an important role in the transmission of communicable diseases. The aim of the present study is to draw information and identify possible gaps on occupational health practices related to seafarers sailing on ships within the European Union Member States (EU MS) with focus on communicable diseases.     

European guidelines for topical photodynamic therapy part 2: emerging indications – field cancerization,photorejuvenation and inflammatory/infective dermatoses

In addition to established indications in non‐melanoma skin cancer in immunocompetent patients, photodynamic therapy (PDT) has been studied for the treatment, and possible prevention, of superficial skin cancers in immunosuppressed patients. As a topical photosensitizer can be applied over large areas, PDT is also increasingly used for field cancerization in photodamaged skin, with evidence of potential to delay the development of actinic keratoses and basal cell carcinoma, although direct evidence of prevention of invasive squamous cell carcinoma remains limited. PDT has been studied in patch/plaque‐stage cutaneous T‐cell lymphoma, with efficacy more likely in unilesional disease. Accumulating evidence supports the use of PDT in acne and several other inflammatory/infective dermatoses including cutaneous leishmaniasis, although protocols are still to be refined. Despite proven efficacy, PDT is not widely used in viral/genital warts, where pain during treatment can be intense. PDT is a therapeutic option for photorejuvenation, with improvement in fine wrinkles, mottled hyperpigmentation, roughness and sallowness reported.     

Antigen-presenting cells and keratinocytes express interleukin-12 in allergic contact dermatitis

Interleukin‐12 (IL‐12) has previously been suggested as playing a major rôle in the activation of cytotoxic lymphocytes. Recent reports indicate that cytotoxic CD8+ cells are critically involved in the elicitation phase of contact hypersensitivity reactions. In this study, the in situ expression of IL‐12 was investigated in normal human skin and in allergic contact dermatitis by immunohistochemistry. Skin biopsy specimens were obtained from allergic patch test reactions after 3 days, and from normal skin in 8 subjects. In contrast to normal skin, a strong enhancement of IL‐12 immunoreactivity was observed in the mononuclear cell infiltrate of allergic contact dermatitis. IL‐12 immunoreactivity was mainly located in the cytoplasm of dermal dendritic cells and macrophages as well as of some Langerhans cells. IL‐12‐positive cells were often found in close apposition to lymphocytes. Furthermore, positive immunostaining was also detected in keratinocytes at sites of marked exocytosis and spongiosis in the epidermis. In conclusion, the enhanced in situ expression of IL‐12 may contribute to the activation of cytotoxic lymphocytes and thereby represent an important factor in the pathogenesis of contact hypersensitivity reactions in humans.     

Transitorische akantholytische Dermatose (M. Grover) Eine Analyse des klinischen Spektrums anhand von 21 histologisch erfassten F?llen Eine Analyse des klinischen Spektrums anhand von 21 histologisch erfassten F?llen

Hintergrund und Fragestellung. Bei der 1970 von Grover erstmals beschriebenen transitorischen akantholytischen Dermatose finden sich klinisch meist juckende, ?demat?se oder hyperkeratotische Papeln oder Papulovesikel vorwiegend am Rumpf, die nach Wochen bis Monaten spontan abheilen. Histologisch typisch ist eine Akantholyse. Bei bis heute unklarer ?tiologie werden als Provokationsfaktoren Licht, Schwitzen und Hitze diskutiert. In unserer Arbeit soll das klinische Spektrum anhand eigener F?lle überprüft werden.     

Dermatitis herpetiformis: lymphocytes, immunoglobulins and complement factors in peripheral blood.

Peripheral blood lymphocytes from patients with dermatitis herpetiformis and healthy controls were investigated in order to determine the percentages of B-lymphocytes, T-lymphocytes and cells with receptors for the Fc part of human IgG (EA-RFC). Furthermore, the serum concentrations of IgG, IgA, IgM, IgD and IgE and the complement factors C3 and C4 were also measured. An increase in the mean percentages of lymphocytes with membrane-bound IgA and IgD, as well as an increase in the mean percentage of cells with receptors for the Fc part of human IgG (EA-RFC) were found in the patient group as compared with the control group. No differences between patient group and control group were found concerning the mean percentage of B-lymphocytes or T-lymphocytes. The mean serum concentrations of the various immunoglobulins and the complement factors investigated did not differ significantly between the two groups.     

Daylight photodynamic therapy for actinic keratosis: an international consensus: International Society for Photodynamic Therapy in Dermatology

Photodynamic therapy (PDT) is an attractive therapy for non-melanoma skin cancers including actinic keratoses (AKs) because it allows treatment of large areas; it has a high response rate and results in an excellent cosmesis. However, conventional PDT for AKs is associated with inconveniently long clinic visits and discomfort during therapy. In this article, we critically review daylight-mediated PDT, which is a simpler and more tolerable treatment procedure for PDT. We review the effective light dose, efficacy and safety, the need for prior application of sunscreen, and potential clinical scope of daylight-PDT. Three randomized controlled studies have shown that daylight-mediated PDT is an effective treatment of thin AKs. Daylight-mediated PDT is nearly pain-free and more convenient for both the clinics and patients. Daylight-mediated PDT is especially suited for patients with large field-cancerized areas, which can easily be exposed to daylight. Further investigations are necessary to determine at which time of the year and in which weather conditions daylight-mediated PDT will be possible in different geographical locations.     

美国卫生组织体系20年的变革和经验

1背景与资料上世纪80和90年代,美国的医院和医生组织投入大量时间和资源进行机构重组,以实现提高组织效率、改善财务绩效水平、机构长期生存、承担社区责任和救治病人的目的。而机构重组的主要趋势是建立“有组织的服务提供体系”,包括建立横向的医院联合体,横向的医生联合体,以及纵向的医院与医生联合体等。到目前为止,在美国开展的大量研究对上述机构重组效果的认识莫衷一是。