Thermographic analysis of skin test reaction using AGA thermovision

The course of infrared thermography including isothermograms on the skin surface was investigated considering blood flow, redness of the skin and permeability of blood vessel, in the following skin reactions: 1. Intracutaneous injection of histamine and histamine liberator compound 48/80 increased the heat radiation. Local application of antihistamine externa which decreased the development of the urticarial histamine reaction, increased the infrared radiation of the skin surface. Combined injection of histamine or histamine liberators with antihistamines in a sufficient dosis (1:1 respectively 4:1) diminished also the heat radiation in addition to the urticarial reaction. 2. The Pyrexal reaction of the skin with early erythema and later papule development shows an equivalent picture in the AGA Thermovision. The pretreatment shows an equivalent picture in the AGA Thermovision. The pretreatment of the skin with corticosteroid ointments shows a corresponding lowering of the erythema, of papule development as well as of heat radiation. The blanching of corticosteroids after occlusive dressing is difficult to recognize by the isotherms of AGA Thermovision. 3. Allergic reactions of the immediate type show, corresponding to the wheal eruption, a marked increased of heat radiation combined with a projection of the enlarged veins on the skin surface. 4. Allergic reactions of the delayed type are combined with a definite elevation of heat radiation of the skin. The area of a positive skin test with allergic eczematous reaction shows a distinct elevation of ann infrared radiation. Although the allergic skin area which was substantiated by a positive skin test was no longer visible, a distinct infrared radiation could be detected. Preventive treatment of the test area of skin patch-testing with corticosteroids inhibits the heat radiation even if the allergic eczematous reaction occurs faintly. The thermographic analysis of the different skin test reactions complied with the morphological aspects of the reaction.     

Genetic variation of the HNA-3a encoding gene

BACKGROUND: Antibodies against the human neutrophil alloantigen‐3a (HNA‐3a) play an important role in transfusion‐related acute lung injury. The HNA‐3a and ‐3b alloantigens result from a single‐nucleotide exchange in the choline transporter‐like protein 2 gene (CTL2). We sought for additional polymorphisms that might impair antibody binding to or genotyping of the HNA‐3a or ‐3b antigens. STUDY DESIGN AND METHODS: CTL2‐specific complementary DNA (cDNA) fragments were generated from 67 unrelated blood donors followed by DNA sequencing. Polymerase chain reaction with sequence‐specific primers (PCR‐SSP) was used to test a higher number of donors for relevant new single‐nucleotide polymorphisms (SNPs). The granulocyte agglutination test recommended for HNA‐3a antibody detection was performed to check HNA‐3a antibody binding to the products of the CTL‐2 gene variants. RESULTS: Two new missense mutations were demonstrated in the CTL2 cDNA: a 537C>T * exchange leading to a Leu153Phe amino acid substitution and 988C>T variation predicting Thr301Met change. The inherited 537T variant is located in HNA‐3a allele results impaired granulocyte agglutination by four of 14 antibodies tested while 988T remains nearly unaffected. CONCLUSIONS: The Leu153Phe exchange next to the HNA‐3a/b defining amino acid position can impede the binding of HNA‐3a alloantibodies. The HNA‐3a genotyping by PCR‐SSP might produce misleading results in HNA‐3ab heterozygous individuals with the additional CTL2‐537T variation of the HNA‐3a antigen. These findings must account for the development of new screening assays.     

Association of pre‐diagnosis physical activity with recurrence and mortality among women with breast cancer

Evidence is emerging that physical activity (PA) may improve overall survival after breast cancer diagnosis. However, the effect of PA on breast cancer recurrence and on cause‐specific mortality is less investigated. We assessed the association of pre‐diagnosis PA with recurrence, overall and cause‐specific survival in a prospective cohort study in Germany including 3,393 non‐metastatic breast cancer patients aged 50–74 years. Cox proportional hazards models were calculated adjusted for relevant prognostic factors. During a median follow‐up of 5.6 years, 367 patients deceased. Overall mortality was significantly inversely associated with pre‐diagnosis recreational PA. However, this effect was mainly attributed to deaths due to causes other than breast cancer. Multiple fractional polynomial analyses yielded a nonlinear association with markedly increased non‐breast cancer mortality for women who did not engage in any sports or cycling in the years before the breast cancer diagnosis with a hazard ratio (HR, none vs. any) of 1.71, 95% confidence interval (1.16, 2.52). There were no further risk reductions with increasing activity levels. The association with breast cancer‐specific mortality showed a similar dose‐response but was far less pronounced with HR (none vs. any) = 1.22 (0.91, 1.64). In contrast, regarding cancer recurrence the dose‐response was linear. However, this association was restricted to estrogen/progesterone receptor‐negative (ER?/PR?) cases (p_interaction = 0.033) with HR (highest vs. no recreational PA) = 0.53 (0.24, 1.16), p_trend = 0.0045. Thus, breast cancer patients with a physically inactive lifestyle pre‐diagnosis may decease prematurely irrespective of their cancer prognosis. Higher levels of exercise may reduce the risk of recurrence of ER?/PR? breast tumors.     

IMMUNOHEMATOLOGY: Rapid screening of granulocyte antibodies with a novel assay: flow cytometric granulocyte immunofluorescence test

BACKGROUND: White blood cell (WBC)‐associated antibodies can lead to severe pulmonary transfusion reactions (transfusion‐related acute lung injury [TRALI]). Investigation of a large number of blood donor samples using the standard granulocyte immunofluorescence test (GIFT) and granulocyte agglutination test (GAT) proved to be difficult to perform due to the time‐consuming process and the large quantity of test cells required. This study describes the novel flow cytometric GIFT (Flow‐GIFT) method for a rapid detection of granulocyte antibodies by flow cytometric analysis. STUDY DESIGN AND METHODS: A total of 141 sera were analyzed for the presence of granulocyte antibodies that were previously associated with suspected TRALI. As test cells whole blood samples from human neutrophil antigen (HNA)‐typed donors were isolated using cell sedimentation in a ficoll density gradient. WBCs were incubated with the respective serum and binding of antibodies to the test cells was detected using fluorescein isothiocyanate–conjugated anti‐human antibody. Standard GIFT and GAT were performed as reference methods. RESULTS: Seven sera containing anti‐HNA‐3a, CD16, and HLA Class I were negative in the standard GIFT and eight sera containing anti‐HNA‐2a, anti‐CD16, and anti‐HLA Class I were not detected in the GAT. The novel Flow‐GIFT was able to detect all granulocyte antibodies, which were only detectable in a combination of standard GIFT and GAT. In serial dilution tests, the Flow‐GIFT detected the antibodies at higher dilutions than the reference methods GIFT and GAT. CONCLUSION: The Flow‐GIFT method permits rapid detection of granulocyte antibodies requiring fewer donor test cells. This method is ideal for automation and will potentially open the way for screening of granulocyte antibodies in a large donor population.     

Objective Estimates Improve Risk Stratification for Primary Graft Dysfunction after Lung Transplantation

Primary graft dysfunction (PGD) is a major cause of early mortality after lung transplant. We aimed to define objective estimates of PGD risk based on readily available clinical variables, using a prospective study of 11 centers in the Lung Transplant Outcomes Group (LTOG). Derivation included 1255 subjects from 2002 to 2010; with separate validation in 382 subjects accrued from 2011 to 2012. We used logistic regression to identify predictors of grade 3 PGD at 48/72 h, and decision curve methods to assess impact on clinical decisions. 211/1255 subjects in the derivation and 56/382 subjects in the validation developed PGD. We developed three prediction models, where low‐risk recipients had a normal BMI (18.5–25 kg/m²), chronic obstructive pulmonary disease/cystic fibrosis, and absent or mild pulmonary hypertension (mPAP<40 mmHg). All others were considered higher‐risk. Low‐risk recipients had a predicted PGD risk of 4–7%, and high‐risk a predicted PGD risk of 15–18%. Adding a donor‐smoking lung to a higher‐risk recipient significantly increased PGD risk, although risk did not change in low‐risk recipients. Validation demonstrated that probability estimates were generally accurate and that models worked best at baseline PGD incidences between 5% and 25%. We conclude that valid estimates of PGD risk can be produced using readily available clinical variables.     

Oxcarbazepine placebo-controlled, dose-ranging trial in refractory partial epilepsy

PURPOSE: The goal of the study was to evaluate the safety and efficacy of a broad oxcarbazepine (OXC) dosage range (600, 1200, and 2400 mg/d) as adjunctive therapy for uncontrolled partial seizures and to determine the relationship between trough plasma 10-monohydroxy derivative concentrations and OXC safety and efficacy. METHODS: This multinational, multicenter, randomized, 28-week, double-blind, placebo-controlled, four-arm, parallel-group trial enrolled 694 patients aged 15-65 years with uncontrolled partial seizures with or without secondarily generalized seizures. The primary efficacy variable was percentage change in seizure frequency per 28 days relative to baseline. RESULTS: The median reduction in seizure frequency was 26%, 40%, 50%, or 8% for patients receiving 600, 1200, or 2400 mg/d OXC or placebo, respectively (all p < or = 0.0001). Of patients in the 600, 1200, or 2400 mg/d OXC groups, 27%, 42%, and 50% respectively, had more than 50% reduction in seizure frequency compared with 13% for placebo (all p < 0.001). Higher plasma 10-monohydroxy derivative concentrations were associated with larger decreases in seizure frequency (p = 0.0001). During the double-blind treatment phase, 84%, 90%, 98%, and 76% of patients receiving 600, 1200, or 2400 mg/d OXC or placebo, respectively, reported one or more adverse events. The most common adverse events were related to the nervous and digestive systems. CONCLUSIONS: OXC is safe and effective as adjunctive therapy in patients with uncontrolled partial seizures. OXC 600 mg/d was the minimum effective dosage; effectiveness of OXC increased with dose. The rapid and fixed titration to high doses was associated with an increased risk of adverse events, which could potentially be reduced by adjusting concomitant antiepileptic medication and by using a slower, flexible OXC titration schedule.     

Therapeutic effect of argon plasma coagulation on small malignant gastrointestinal tumors

In endoscopy, argon plasma coagulation (APC) is a new principle of non-contact electrocoagulation and has proved to be a sufficient tool for palliative endoscopic treatment of gastrointestinal neoplasms, predominantly of the oesophagus and colorectum. In a study of 67 patients suffering from histologically confirmed and endosonographic T1-staged tumours of the gastrointestinum, 10 patients were selected for endoscopic APC treatment because of the impossibility of surgical therapy. Although the application was primarily of a palliative nature, in 9 of 10 cases of minor neoplasms, no further tumour could be detected in biopsies during the observation period (9.45±2.8 months). One patient was not cured locally. In none of the patients was any serious complication noticed during the outpatient follow-up. The effective results and lack of severe complications suggest this technique as an alternative therapy in selected patients with smaller gastrointestinal tumours.Abbreviation APC argon plasma coagulation