Incomplete digestion of codfish represents a risk factor for anaphylaxis in patients with allergy

BACKGROUND: Fish represents one of the most important allergenic foods causing severe allergic reactions. Nevertheless, it has been shown that gastric digestion significantly reduces its allergenic capacity. OBJECTIVE: In this study, we assessed the absorption kinetics of fish proteins and investigated the clinical reactivity of patients with fish allergy to codfish digested at physiological or elevated gastric pH. METHODS: Healthy individuals were openly challenged with codfish and blood samples were evaluated by histamine release for absorbed fish allergens. Patients with allergy were recruited on the basis of previously diagnosed codfish allergy. Fish extracts were digested with gastric enzymes at pH 2.0 and 3.0 and used for histamine release, skin prick tests, and titrated double-blind placebo-controlled food challenges. RESULTS: Ingestion experiments in subjects without allergy revealed absorption of biologically active fish allergens only 10 minutes after ingestion with maximal serum levels after 1 to 2 hours. Incubation of fish proteins with digestive enzymes at pH 2.0 resulted in a fragmentation of the proteins leading to a reduced biological activity evidenced by a significantly smaller wheal reaction and reduced histamine release. Fish digested at pH 3.0 revealed comparable reactivity patterns as undigested extracts. Moreover, these test materials triggered reactions at 10-fold to 30-fold lower cumulated challenge doses in patients with allergy. CONCLUSION: Our data indicate the paramount importance of gastric digestion for fish allergens because the quantitatively significant absorption and elicitation of symptoms seemed to take place in the intestine. CLINICAL IMPLICATIONS: Hindered digestion puts patients with fish allergy at risk to develop severe allergic reactions at minute amounts of allergens.     

The Perceived Adjustment to Chronic Illness Scale (PACIS): a global indicator of coping for operable breast cancer patients in clinical trials

Subjective well-being is a major aspect of quality of life and is therefore increasingly used as an endpoint in clinical trials. It is influenced to a great extent by the complex process of coping with the disease and its treatment. Assessment of coping is methodologically demanding, especially in large clinical trials. We therefore developed a single-item measure, the Perceived Adjustment to Chronic Illness Scale (PACIS), as an indicator of coping, complementary to other scales related to quality of life. We sought to validate this instrument in a subgroup of 121 Swiss patients participating in the International Breast Cancer Study Group (IBCSG) adjuvant trials. At months 3 and 6 of adjuvant treatment PACIS showed a distinct pattern of highly significant rank correlations with several disease-and treatment-related problem areas from the Herschbach coping inventory (FBBK); 42% of the variance of PACIS at month 3 was explained by the FBBK (P=0.0001). The portion of explained variance was considerably higher for the Italian-(70%) than for the German-speaking (30%) subgroups. Patients who rated more effort to cope with their disease on PACIS indicated more frequent use of 3 of 15 coping strategies in relation to psychological distress. These were crying and becoming desperate, taking tranquillizers and alcohol and other people are far worse off. These three coping strategies may define a high-risk group for poor psychosocial outcome. Patients whose PACIS scores showed that it required less effort to cope tended to use the strategy seeing a positive side of the problem. We conclude that PACIS can be used as a global indicator of the coping process in large multicultural clinical trials of adjuvant therapy for breast cancer.Some of these data were presented at the postgraduate course: Current Concepts in Psycho-oncology IV, Memorial Sloan-Kettering Cancer Center New York, October 1991 [11]     

Sound level dependence of the primary auditory cortex: Simultaneous measurement with 61-channel EEG and fMRI

Sound level dependence has been investigated for years with event-related potentials (ERP). A serotonergic modulation of the sound level dependence only of the primary auditory cortex but not of the auditory association cortex has been suggested by a number of clinical and preclinical studies. Therefore, a precise covering of the activity of the primary auditory cortex seems necessary if sound level dependence is used as an indicator of the central serotonergic system. Recent fMRI studies described a pronounced sound level dependence only in the Heschl gyrus/primary auditory cortex but not in auditory association areas. In the present simultaneous 61-channel EEG and fMRI study investigating fourteen healthy subjects, we found a high correlation between the loudness-dependent change of the extent of fMRI activation (number of activated voxels) and the corresponding changes of the mean current source density within the same region of interest covering the primary auditory cortex (r = 0.84, P < 0.001). Our findings suggest a close relationship between the fMRI signal and event-related potential activity. In addition, the correspondence of the ERP-based data and the fMRI results further supports the validity of the ERP localization approach.     

The European Competence Network on Mastocytosis

The European Competence Network on Mastocytosis (ECNM) is a Europe-wide, multinational cooperative approach attempting to improve recognition, diagnosis, and therapy of mastocytosis. The network is composed of local centers, physicians, and scientists who have dedicated their work to patients with mastocytosis. However, because of the rarity and complexity of the disease, each single component in the network alone would fail to meet important demands and to reach solid conclusions in this field of applied medicine. The ECNM represents an attempt to overcome this restriction as a cooperative multicenter platform that should serve as an important basis for the development of new therapeutic strategies and diagnostic concepts, and for the standardization of techniques used to determine diagnostic and prognostic parameters. Moreover, using future central databases and registries, a suitable infrastructure for the development of co-operative multicenter clinical trials will be established. In addition, the ECNM is dedicated to provide the best available information about the disease to patients and physicians.     

Ventilator-associated pneumonia in a surgical intensive care unit: epidemiology, etiology and comparison of three bronchoscopic methods for microbiological specimen sampling

Background  

Ventilator-associated bacterial pneumonia (VAP) is a important intensive care unit (ICU)-acquired infection in mechanically ventilated patients. Early and correct diagnosis of VAP is difficult but is an urgent challenge for an optimal antibiotic treatment. The aim of the study was to evaluate the incidence and microbiology of ventilator-associated pneumonia and to compare three quantitative bronchoscopic methods for diagnosis.     

Tissue Doppler echocardiography: a new method of evaluating perfusion-dependent myocardial function during PTCA

The increasing demand for insight into the relationship between coronary perfusion and myocardial function stimulated the development of tissue Doppler echocardiography. This new technique was applied simultaneously with PTCA of a subtotal LAD lesion (single vessel disease, no collaterals) in a 68-year-old patient suffering from unstable angina pectoris. Prior to the conventional signs of ischaemia a decrease in myocardial tissue velocities and a loss of color-coded heart cycle intervals was observed. A myocardial velocity gradient calculated from the higher subendocardial and lower subepicardial velocity decreased from 3.3 to 1.3. This decrease was prevented by an active autohaemoperfusion device which supplied blood distally to an insufflated balloon (60 ml/min). Thus, contractility and viability might be maintained by preserving myocardial velocity gradients.     

Feasibility of 18F-fluoromethylcholine PET/CT for imaging of vessel wall alterations in humans—first results

Purpose Recently published data indicated ¹⁸F-fluorocholine to be feasible for imaging vulnerable atherosclerotic plaques in an animal model. Methods Five patients undergoing whole-body ¹⁸F-fluoromethylcholine-(¹⁸F-FMCH-) PET/CT for imaging of prostate cancer disease were retrospectively evaluated. Whole-body PET scans were started immediately after i.v. injection of ¹⁸F-FMCH. About 5–15 min after tracer injection, acquisition of scans of the pelvis and abdomen was performed. PET, CT, and PET/CT slices were generated for review and visual analyses of the abdominal aorta and the common iliac arteries were performed. Vascular findings in examined arteries and surrounding structures due to artifacts were excluded from further analysis. The lower threshold of ¹⁸F-FMCH uptake was set above the background activity within the examined vessels. Morphological classification of vessel wall alterations (WA) included structural wall alterations without additional calcification (SWA), structural wall alterations associated with calcifications (SWC), and solely calcified lesions (CL). They were correlated with ¹⁸F-FMCH uptake qualified as present and vice versa. Results A total of 31 WA were identified. Positive ¹⁸F-FMCH uptake was found in 14 lesions (SWA: n = 5; SWC: n = 9). Sixteen of 17 ¹⁸F-FMCH negative lesions were identified as CL without additional structural vessel wall alteration. One SWA did not show any ¹⁸F-FMCH accumulation. None of the CLs as well as unaltered parts of the vessel wall showed ¹⁸F-FMCH uptake. Conclusions Our initial data in five patients with a total of 31 vessel wall alterations show promising results indicating for the first time the feasibility of ¹⁸F-FMCH for in vivo imaging of structural WA in humans.     

Establishment, characterization and drug sensitivity testing in primary cultures of human thymoma and thymic carcinoma

Thymomas and thymic carcinomas are peculiar epithelial tumors of the anterior mediastinum. They may show aggressive clinical behavior and are a paradigm for the interaction between the tumor and the immune system. So far, adequate functional studies enabling a better understanding of this malignancy have not been performed, since human thymoma/thymic carcinoma cell lines have not been available. Here, the authors describe the establishment, characterization and functional analyses of epithelial cell lines from a Type B1-thymoma and a poorly differentiated thymic carcinoma. By Fluorescence-activated cell sorting (FACS) analyses, both cell lines were aneuploid. The aneuploid cell fraction of the thymic carcinoma cell line was characterized by a high proliferation index of 55.9%, in contrast to a lower proliferation rate of the aneuploid cell fraction of the thymoma (19.7%). Array-based comparative genomic hybridization (aCGH) and conventional cytogenetic analysis of the thymoma revealed only minor imbalances whereas the thymic carcinoma was characterized by a complex karyotype in the hyperdiploid range that was readily defined with multicolor FISH (mFISH). Application of a selective COX-2 inhibitor reduced cell viability in both cell lines in a dose-dependent manner. In conclusion, these first cell lines of a thymoma and a CD5-positive thymic carcinoma are useful tools for further in vitro studies of cellular, molecular and genetic aspects of the disease and for functional tests to evaluate new therapeutic targets.     

Stereotactic, high single-dose irradiation of stage I non-small cell lung cancer (NSCLC) using four-dimensional CT scans for treatment planning

We reviewed response rates, local control, survival and side effects after non-fractionated stereotactic high single-dose body radiation therapy for lung tumors.

Forty patients with stage I non-small cell lung cancer (NSCLC) underwent radiosurgery involving single-dose irradiation. The standard dose prescribed to the isocenter was 30 Gy with an axial safety margin of 10 mm and a longitudinal safety margin of 15 mm. The planning target volume (PTV) was defined using three CT scans with reference to the phases of respiration so that the movement span of the clinical target volume (CTV) was enclosed.

The volume of the bronchial carcinomas varied from 4.2 to 130 cm³ (median: 19.5 cm³), and the PTV derived from four-dimensional CT (4D-CT) scans using image fusion ranged from 15.6 to 390.5 cm³ (median: 101 cm³). Tumor size ranged from 1.7 to 10 cm at largest focuses. Follow-up periods varied from 6.0 to 61.5 months (median: 20 months). We observed three local tumor recurrences, resulting in an actuarial local tumor control of 81% at 3 years. With the exception of two rib fractures, no serious late toxicity was observed. The overall survival probability rates were: 2 years: 66%, 3 years: 53% (median overall survival: 37 months). Cancer-specific survival probability was: 2 years: 71%, 3 years: 57%.

Non-fractionated high single-dose SBRT for NSCLC is more convenient for the patient and less time-consuming than hypofractionated SBRT, but data dealing with this method are still scanty. This alternative treatment results in favourable local control and acceptable toxicity.