Toxic epidermal necrolysis and Stevens-Johnson syndrome: a review

The aims of this review are to summarize the definitions, causes, and clinical course as well as the current understanding of the genetic background, mechanism of disease, and therapy of toxic epidermal necrolysis and Stevens-Johnson syndrome.

[Mason vertical gastroplasty in treatment of morbid obesity. Results of a prospective clinical study]

Morbid obesity (body mass index > 40 kg/m2) is a risk factor for cardiovascular, pulmonary, metabolic, neoplastic, and psychologic sequelae. In the present prospective clinical study 65 patients (11 men, 54 women) underwent vertical banded gastroplasty (Mason procedure) from June 1994 to October 1997. The median age was 41 +/- 5.3 years (range 18-69; n = 65). Preoperative body weight was 135 +/- 23 kg (96-229; n = 65), excess body weight in kg was 75 +/- 6.9 (44-155; n = 65) or in % 126 +/- 10 (78-223; n = 65) and BMI was 49 +/- 7.4 kg/m2 (39-69; n = 65). Mean hospital stay was 9.7 +/- 2.4 days (6-18; n = 65). Hospital mortality was 0% (0/65). Early complications were vomiting (30%) and problems in wound healing (15%; n = 65). Late complications (> 30 days) were incisional hernias (13.8%) and staple-line disruptions (12.3%; n = 65) with a reoperation rate of 23% (15/65). Median follow-up was 15.0 +/- 5.2 months (2-42) with a follow up rate of 100%. Mean weight loss after 12 months was 38.5 +/- 17 kg (30-98; n = 34) (P < 0.0001) and loss of excessive body weight 65 +/- 10% (57-86; n = 34), respectively (P < 0.0001). Cardiovascular risk factors (hypertension, diabetes, hyperlipidemia) were significantly improved within 12 months (n = 34). Vertical banded gastroplasty (Mason procedure)--well established for 20 years--is a good, safe therapy for morbid obesity if strict indications for operation are observed and if there is multidisciplinary long-term follow-up. Comorbid risk factors are considerably reduced and a long-term weight loss of more than 50% can be achieved without the risk of pathological metabolic changes.

Holocene climatic change and the development of the lake-effect snowbelt in Michigan, USA

Lake-effect snow is an important constraint on ecological and socio-economic systems near the North American Great Lakes. Little is known about the Holocene history of lake-effect snowbelts, and it is difficult to decipher how lake-effect snowfall abundance affected ecosystem development. We conducted oxygen-isotope analysis of calcite in lake-sediment cores from northern Lower Michigan to infer Holocene climatic variation and assess snowbelt development. The two lakes experience the same synoptic-scale climatic systems, but only one of them (Huffman Lake) receives a significant amount of lake-effect snow. A 177-cm difference in annual snowfall causes groundwater inflow at Huffman Lake to be 18O-depleted by 2.3��� relative to O'Brien Lake. To assess when the lake-effect snowbelt became established, we compared calcite-��18O profiles of the last 11,500 years from these two sites. The chronologies are based on accelerator-mass-spectrometry 14C ages of 11 and 17 terrestrial-plant samples from Huffman and O'Brien lakes, respectively. The values of ��18O are low at both sites from 11,500 to 9500 cal yr BP when the Laurentide Ice Sheet (LIS) exerted a dominant control over the regional climate and provided periodic pulses of meltwater to the Great Lakes basin. Carbonate ��18O increases by 2.6��� at O'Brien Lake and by 1.4��� at Huffman Lake between 9500 and 7000 cal yr BP, suggesting a regional decline in the proportion of runoff derived from winter precipitation. The Great Lakes snowbelt probably developed between 9500 and 5500 cal yr BP as inferred from the progressive 18O-depletion at Huffman Lake relative to O'Brien Lake, with the largest increase of lake-effect snow around 7000 cal yr BP. Lake-effect snow became possible at this time because of increasing contact between the Great Lakes and frigid arctic air. These changes resulted from enhanced westerly flow over the Great Lakes as the LIS collapsed, and from rapidly rising Great Lakes levels during the Nipissing Transgression. The ��18O difference between Huffman and O'Brien lakes declines after 5500 cal yr BP, probably because of a northward shift of the polar vortex that brought increasing winter precipitation to the entire region. However, ��18O remains depleted at Huffman Lake relative to O'Brien Lake because of the continued production of lake-effect snow.

Footprint of recycled water subsidies downwind of Lake Michigan

Continental evaporation is a significant and dynamic flux within the atmospheric water budget, but few methods provide robust observational constraints on the large-scale hydroclimatological and hydroecological impacts of this ���recycled-water' flux. We demonstrate a geospatial analysis that provides such information, using stable isotope data to map the distribution of recycled water in shallow aquifers downwind from Lake Michigan. The ��2H and ��18O values of groundwater in the study region decrease from south to north, as expected based on meridional gradients in climate and precipitation isotope ratios. In contrast, deuterium excess (d = ��2H ��� 8 �� ��18O) values exhibit a significant zonal gradient and finer-scale spatially patterned variation. Local d maxima occur in the northwest and southwest corners of the Lower Peninsula of Michigan, where ���lake-effect' precipitation events are abundant. We apply a published model that describes the effect of recycling from lakes on atmospheric vapor d values to estimate that up to 32% of recharge into individual aquifers may be derived from recycled Lake Michigan water. Applying the model to geostatistical surfaces representing mean d values, we estimate that between 10% and 18% of the vapor evaporated from Lake Michigan is re-precipitated within downwind areas of the Lake Michigan drainage basin. Our approach provides previously unavailable observational constraints on regional land-atmosphere water fluxes in the Great Lakes Basin and elucidates patterns in recycled-water fluxes that may influence the biogeography of the region. As new instruments and networks facilitate enhanced spatial monitoring of environmental water isotopes, similar analyses can be widely applied to calibrate and validate water cycle models and improve projections of regional hydroecological change involving the coupled lake-atmosphere-land system. Read More: http://www.esajournals.org/doi/abs/10.1890/ES12-00062.1

In vitro drug causality assessment in Stevens-Johnson syndrome - alternatives for lymphocyte transformation test

BACKGROUND Patients with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) are often exposed simultaneously to a few potentially culprit drugs. However, both the standard lymphocyte transformation tests (LTT) with proliferation as the assay end-point as well as skin tests, if done, are often negative. OBJECTIVE As provocation tests are considered too dangerous, there is an urgent need to identify the relevant drug in SJS/TEN and to improve sensitivity of tests able to identify the causative drug. METHODS Fifteen patients with SJS/TEN with the ALDEN score ��� 6 and 18 drug-exposed controls were included. Peripheral blood mononuclear cells (PBMC) were isolated and cultured under defined conditions with drugs. LTT was compared to the following end-points: cytokine levels in cell culture supernatant, number of granzyme B secreting cells by ELISpot and intracellular staining for granulysin and IFN�� in CD3(+) CD4(+), CD3(+) CD8(+) and NKp46(+) cells. To further enhance sensitivity, the effect of IL-7/IL-15 pre-incubation of PBMC was evaluated. RESULTS Lymphocyte transformation tests was positive in only 4/15 patients (sensitivity 27%, CI: 8-55%). Similarly, with granzyme B-ELISpot culprit drugs were positive in 5/15 patients (sensitivity 33%, CI: 12-62%). The expression of granulysin was significantly induced in NKp46(+) and CD3(+) CD4(+) cells (sensitivity 40%, CI: 16-68% and 53%, CI: 27-79% respectively). Cytokine production could be demonstrated in 38%, CI: 14-68% and 43%, CI: 18-71% of patients for IL-2 and IL-5, respectively, and in 55%, CI: 23-83% for IFN��. Pre-incubation with IL-7/IL-15 enhanced drug-specific response only in a few patients. Specificities of tested assays were in the range of 95 (CI: 80-99%)-100% (CI: 90-100%). CONCLUSIONS AND CLINICAL RELEVANCE Granulysin expression in CD3(+) CD4(+) , Granzyme B-ELISpot and IFN�� production considered together provided a sensitivity of 80% (CI: 52-96%) and specificity of 95% (80-99%). Thus, this study demonstrated that combining different assays may be a feasible approach to identify the causative drug of SJS/TEN reactions; however, confirmation on another group of patients is necessary.

[Drug-induced Stevens-Johnson syndrome in a patient with AIDS]

The Stevens-Johnson syndrome is a severe potentially life-threatening form of the erythema multiforme, affecting both skin and mucous membranes. We present a case of a 49-year-old male patient with AIDS who developed a Stevens-Johnson syndrome while being treated with pyrimethamine, sulfadiazine and phenytoin for cerebral toxoplasmosis. Further diagnostic evaluation of this dangerous cutaneous affection may prove difficult for several reasons. In particular, in patients with AIDS who are more susceptible for adverse drug reactions and who are simultaneously receiving a variety of drugs with a considerable potential of cutaneous side effects, therapy cannot be withhold for lack of therapeutic alternatives. Moreover, the low lymphocyte count in this case may have made reliable testing with lymphocyte transformation studies impossible. The evaluation and the differential diagnosis of the drug-induced Stevens-Johnson syndrome are discussed. Especially long- and moderately long-acting sulfonamides belong to the most important agents that can cause a drug-induced Stevens-Johnson syndrome. The pathogenesis and the risk factors for cutaneous hypersensitivity reactions in HIV-infected patients are only poorly understood. These kind of reactions, however, seem to occur more often in patients with a more advanced immunodeficiency.