Efficacy and safety of nivolumab for patients with pre-treated type B3 thymoma and thymic carcinoma: results from the EORTC-ETOP NIVOTHYM phase II trial.

BACKGROUND: Thymic malignancies are rare intrathoracic tumors, which may be aggressive and difficult to treat. They represent a therapeutic challenge in the advanced/metastatic setting, with limited treatment options after the failure of first-line platinum-based chemotherapy. They are frequently associated with autoimmune disorders that also impact oncological management. MATERIALS AND METHODS: NIVOTHYM is an international, multicenter, phase II, two-cohort, single-arm trial evaluating the activity and safety of nivolumab [240 mg intravenously (i.v.) q2 weeks] alone or with ipilimumab (1 mg /kg i.v. q6 weeks) in patients with advanced/relapsed type B3 thymoma or thymic carcinoma, after exposure to platinum-based chemotherapy. The primary endpoint is progression-free survival rate at 6 months (PFSR-6) based on RECIST 1.1 as per independent radiological review. RESULTS: From April 2018 to February 2020, 55 patients were enrolled in 15 centers from 5 countries. Ten patients (18%) had type B3 thymoma and 43 (78%) had thymic carcinoma. The majority were male (64%), and the median age was 58 years. Among the 49 eligible patients who started treatment, PFSR-6 by central review was 35% [95% confidence interval (CI) 22% to 50%]. The overall response rate and disease control rate were 12% (95% CI 5% to 25%) and 63% (95% CI 48% to 77%), respectively. Using the Kaplan-Meier method, median progression-free survival and overall survival by local assessment were 6.0 (95% CI 3.1-10.4) months and 21.3 (95% CI 11.6-not estimable) months, respectively. In the safety population of 54 patients, adverse events (AEs) of grade 1/2 were observed in 22 (41%) patients and grade 3/4 in 31 (57%) patients. Treatment-related AEs of grade 4 included one case of neutropenia, one case of immune-mediated transaminitis, and two cases of myocarditis. CONCLUSIONS: Nivolumab monotherapy demonstrated an acceptable safety profile and objective activity, although it has been insufficient to meet its primary objective. The second cohort of NIVOTHYM is currently ongoing to assess the combination of nivolumab plus ipilimumab.

DNA hypermethylation analysis in sputum for the diagnosis of lung cancer: training validation set approach.

BACKGROUND: Lung cancer has the highest mortality of all cancers. The aim of this study was to examine DNA hypermethylation in sputum and validate its diagnostic accuracy for lung cancer. METHODS: DNA hypermethylation of RASSF1A, APC, cytoglobin, 3OST2, PRDM14, FAM19A4 and PHACTR3 was analysed in sputum samples from symptomatic lung cancer patients and controls (learning set: 73 cases, 86 controls; validation set: 159 cases, 154 controls) by quantitative methylation-specific PCR. Three statistical models were used: (i) cutoff based on Youden's J index, (ii) cutoff based on fixed specificity per marker of 96% and (iii) risk classification of post-test probabilities. RESULTS: In the learning set, approach (i) showed that RASSF1A was best able to distinguish cases from controls (sensitivity 42.5%, specificity 96.5%). RASSF1A, 3OST2 and PRDM14 combined demonstrated a sensitivity of 82.2% with a specificity of 66.3%. Approach (ii) yielded a combination rule of RASSF1A, 3OST2 and PHACTR3 (sensitivity 67.1%, specificity 89.5%). The risk model (approach iii) distributed the cases over all risk categories. All methods displayed similar and consistent results in the validation set. CONCLUSIONS: Our findings underscore the impact of DNA methylation markers in symptomatic lung cancer diagnosis. RASSF1A is validated as diagnostic marker in lung cancer.

A randomized phase II study comparing erlotinib versus erlotinib with alternating chemotherapy in relapsed non-small-cell lung cancer patients: the NVALT-10 study.

BACKGROUND: Epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) administered concurrently with chemotherapy did not improve outcome in non-small-cell lung cancer (NSCLC). However, in preclinical models and early phase noncomparative studies, pharmacodynamic separation of chemotherapy and TKIs did show a synergistic effect. PATIENTS AND METHODS: A randomized phase II study was carried out in patients with advanced NSCLC who had progressed on or following first-line chemotherapy. Erlotinib 150 mg daily (monotherapy) or erlotinib 150 mg during 15 days intercalated with four 21-day cycles docetaxel for squamous (SQ) or pemetrexed for nonsquamous (NSQ) patients was administered (combination therapy). After completion of chemotherapy, erlotinib was continued daily. Primary end point was progression-free survival (PFS). RESULTS: Two hundred and thirty-one patients were randomized, 115 in the monotherapy arm and 116 in the combination arm. The adjusted hazard ratio for PFS was 0.76 [95% confidence interval (CI) 0.58-1.02; P = 0.06], for overall survival (OS) 0.67 (95% CI 0.49-0.91; P = 0.01) favoring the combination arm. This improvement was primarily observed in NSQ subgroup. Common Toxicity Criteria grade 3+ toxic effect occurred in 20% versus 56%, rash in 7% versus 15% and febrile neutropenia in 0% versus 6% in monotherapy and combination therapy, respectively. CONCLUSIONS: PFS was not significantly different between the arms. OS was significantly improved in the combination arm, an effect restricted to NSQ histology. STUDY REGISTRATION NUMBER: NCT00835471.

Propagation of uncertainties in soil and pesticide properties to pesticide leaching.

In the new Dutch decision tree for the evaluation of pesticide leaching to groundwater, spatially distributed soil data are used by the GeoPEARL model to calculate the 90th percentile of the spatial cumulative distribution function of the leaching concentration in the area of potential usage (SP90). Until now it was not known to what extent uncertainties in soil and pesticide properties propagate to spatially aggregated parameters like the SP90. A study was performed to quantify the uncertainties in soil and pesticide properties and to analyze their contribution to the uncertainty in SP90. First, uncertainties in the soil and pesticide properties were quantified. Next, a regular grid sample of points covering the whole of the agricultural area in the Netherlands was randomly selected. At the grid nodes, realizations from the probability distributions of the uncertain inputs were generated and used as input to a Monte Carlo uncertainty propagation analysis. The analysis showed that the uncertainty concerning the SP90 is 10 times smaller than the uncertainty about the leaching concentration at individual point locations. The parameters that contribute most to the uncertainty about the SP90 are, however, the same as the parameters that contribute most to uncertainty about the leaching concentration at individual point locations (e.g., the transformation half-life in soil and the coefficient of sorption on organic matter). Taking uncertainties in soil and pesticide properties into account further leads to a systematic increase of the predicted SP90. The important implication for pesticide regulation is that the leaching concentration is systematically underestimated when these uncertainties are ignored.

Farm factors associated with the use of antibiotics in pig production.

The aim of this study was to investigate farm-level economic and technical factors that are associated with the use of antibiotics on pig farms. Identification of such factors, like farm size and net farm result, may help to increase epidemiological knowledge and to specify farm advice and policy making to reduce inappropriate use of antibiotics. The study used over 300 farm-year records collected during 2004 to 2007 from pig farms in the Netherlands. Data included economic and technical factors as well as antibiotic administration. Data were statistically analyzed for factors associated with antibiotic use, both for fattening pig and sow farms (piglets only), separately. The response variable was the average number of daily dosages per average pig year. Statistical analysis was performed on 16 and 19 potential explanatory factors for the fattening pig and sow farms, respectively. The results showed that, both on the fattening pig and sow farms, the average use of antibiotics increased from 2004 to 2006, but decreased during 2007, but the effect of year was not significant (P > 0.05). Use of antibiotics varied between individual farms. Large farm repeatability for the use of antibiotics in the different years was found. Factors associated (P < 0.05) with the use of antibiotics included: farm system, number of pigs, and population density in the region of the farm (for sow farms only). As these factors are easy to collect and to register, they can be used to specify farm advice and investigation, as well as for policy making. The majority of the technical and economic factors were not significantly (P > 0.05) related to the on-farm use of antibiotics. Therefore, it is recommended to focus future research on the potential role of socioeconomic factors associated with antibiotic use on pig farms.

Resection of secondary pulmonary malignancies in head and neck cancer patients.

BACKGROUND: This study aimed to evaluate a single institute's experience with resection of metachronous pulmonary malignancy in patients treated for squamous cell carcinoma of the head and neck. METHODS: Sixty-three consecutive patients treated curatively for head and neck squamous cell carcinoma underwent surgical resection of malignant lung lesions. Survival was estimated and potential prognostic factors investigated. RESULTS: The median overall survival for the total group was 22.2 months. Fifty-one patients (81 per cent) had one lung lesion, while the remainder had multiple lesions (range, two to seven). In the 63 patients, 35 lobectomies, 4 pneumonectomies and 24 wedge resections were performed. For patients with pulmonary squamous cell carcinoma (n = 52), the three-year survival rate was 35 per cent (95 per cent confidence interval, 22-48); for patients with resected adenocarcinoma (n = 10), it was 50 per cent (95 per cent confidence interval, 18-75). The overall five-year survival rate was 30 per cent (95 per cent confidence interval, 19-42). CONCLUSION: In patients treated curatively for head and neck squamous cell carcinoma, resection of secondary pulmonary cancer is associated with favourable long term overall survival, especially for patients with adenocarcinoma lesions.

Descriptive modelling to predict deoxynivalenol in winter wheat in the Netherlands.

Predictions of deoxynivalenol (DON) content in wheat at harvest can be useful for decision-making by stakeholders of the wheat feed and food supply chain. The objective of the current research was to develop quantitative predictive models for DON in mature winter wheat in the Netherlands for two specific groups of end-users. One model was developed for use by farmers in underpinning Fusarium spp. disease management, specifically the application of fungicides around wheat flowering (model A). The second model was developed for industry and food safety authorities, and considered the entire wheat cultivation period (model B). Model development was based on observational data collected from 425 fields throughout the Netherlands between 2001 and 2008. For each field, agronomical information, climatic data and DON levels in mature wheat were collected. Using multiple regression analyses, the set of biological relevant variables that provided the highest statistical performance was selected. The two final models include the following variables: region, wheat resistance level, spraying, flowering date, several climatic variables in the different stages of wheat growing, and length of the period between flowering and harvesting (model B only). The percentages of variance accounted for were 64.4% and 65.6% for models A and B, respectively. Model validation showed high correlation between the predicted and observed DON levels. The two models may be applied by various groups of end-users to reduce DON contamination in wheat-derived feed and food products and, ultimately, reduce animal and consumer health risks.

Phase I/II study of a 3 weekly oral taxane (DJ-927) in patients with recurrent, advanced non-small cell lung cancer.

INTRODUCTION: A phase I/II study was performed to assess the efficacy and toxicity of a new oral taxane in patients with recurrent, advanced Non-small Cell Lung Cancer. PATIENTS AND METHODS: Patients who were treated with one prior, taxane free chemotherapy regimen, were eligible for this study. A single oral dose of DJ-927 (27 mg/m) was given every 3 weeks. In case of good tolerance, one dose escalation to 35 mg/m was allowed. Response and toxicity were measured and plasma pharmacokinetic analysis was performed during the first course. RESULTS: From October 2004 to September 2005, 36 patients gave informed consent and 34 received medication. The mean age was 58 years (range, 33-75 years). The majority of patients were pretreated with a combination of cisplatin and gemcitabine. Median interval between end of first treatment and the registration of this study was 7 months (range, 0.8-22 months). Twelve patients died on study of which eight due to disease progression. In four patients with preexisting cardiac disease, toxicity led to cardiac worsening and subsequent death. Grade 3 and 4 toxicities according to the National Cancer Institute Common Toxicity Criteria were neutropenia in 18 patients (53%), anemia in six patients (18%), nausea and fatigue in two patients (6%), febrile neutropenia and neurotoxicity in one patient (3%). The overall response rate for all patients was 5.6% (Confidence Interval [CI] 0.7-18.7%). The percentage of patients with stabilization for >6 weeks was 47%. The median time to progression was 97 days (CI: 47-167 days) and the median survival time was 120 days (CI: 68-222 days) for the ITT group. Since only a minority of patients (3) tolerated the higher drug dose we omitted this dose level because of hematological toxicity. Pharmacokinetic analysis showed that the median area under the curve (t = 0-168 hours) was 1752 +/- 1355 ngr/ml/h and the half-life was 167 +/- 77 hours. CONCLUSION: When administered once every 3 weeks, this oral taxane formulation of DJ-927 was well-absorbed with a long terminal half-life of 167 +/- 77 hour. DJ-927 has antitumor activity against Non-small Cell Lung Cancer when given as second-line monotherapy (overall response rate in 5.6%; CI 0.7-18.7%). Ten patients experienced SD for more than 8 weeks. Different types of dose administration (metronomic dosing) or combination with other cytotoxic agents should be considered in future studies.

EGFR and KRAS mutations as criteria for treatment with tyrosine kinase inhibitors: retro- and prospective observations in non-small-cell lung cancer.

Results of individualized therapy guided by mutational tumor profile of patients with non-small-cell lung cancer are presented. After confirming the importance of epidermal growth factor receptor (EGFR) and KRAS mutations for (non)response on gefitinib in a retrospective series of patients, EGFR mutations were looked for before--and were a condition for--treatment with gefitinib or erlotinib. To increase the chance to find such a mutation, we selected patients on the basis of smoking status, gender and histopathology. Out of 41 patients selected, 13 (32%) were found to harbor an EGFR mutation. In nine of them it concerned deletions in exon 19 and in none of them KRAS mutations were detected. All nine patients with an exon 19 deletion had a favorable and continuing response to tyrosine kinase inhibitors (TKIs), while four other patients with point mutations responded less favorably: stable disease or a response of short duration. These observations confirm the potential role of EGFR and KRAS mutations in predicting (non)response to TKIs. Exon 19 deletions that are associated with the best responses might be used for first-line treatment selection, while KRAS mutations could play a role in excluding patients from treatment with TKIs.

Population Dynamics of Fusarium spp. and Microdochium nivale in Crops and Crop Residues of Winter Wheat.

ABSTRACT Naturally occurring populations of Fusarium avenaceum, F. culmorum, F. graminearum, F. poae, and Microdochium nivale were studied in two field experiments from anthesis in June 2003 until harvest in crops of winter wheat, and subsequently during 10 months after harvest until June 2004 on their residues exposed on the soil surface under field conditions. The dynamics of the different pathogens were estimated by quantifying the amount of DNA present in wheat tissues using TaqMan-polymerase chain reaction. While colonization of grain by Fusarium spp. and M. nivale was low, high amounts of DNA of F. avenaceum, F. graminearum, and F. culmorum were found in ear residues, internodes, and nodes of the mature crop. Amounts of DNA of pathogens decreased significantly during the following 10 months in residues of internodes and nodes, but not in residues of stem bases. Knowledge on population dynamics of pathogens will help to develop preventive measures aimed at reduction of inoculum sources of head blight pathogens.

Residual inorganic soil nitrogen in grass and maize on sandy soil.

Nitrogen (N) remaining as inorganic ('mineral') soil N at crop harvest (N(minH)) contributes to nitrate leaching. N(minH) data from 20 (grass) and 78 (maize) experiments were examined to identify main determinants of N(minH). N-rate (A) explained 51% (grass) and 34% (maize) of the variance in N(minH). Best models included in addition crop N-offtake (U), offtake in unfertilised plots (U(0)), and N(minH) in unfertilised plots (N(minH,0)) and then explained up to 75% of variance. At low N-rates where apparent N recovery rho keeps to its initial value rho(ini), N(minH) keeps to its base level N(minH,0). At N-rates that exceed the value A(crit) where rho drops below rho(ini), N(minH) rises above N(minH,0) by an amount proportional to (rho(ini)-rho)A. About 80% of (rho(ini)-rho)A was found as N(minH,) in grass as well as in maize. The fraction (1-rho(ini))A does not appear to contribute to N(minH) at low N-rates (A< or =A(crit)) or at high N-rates (A>A(crit)).

Intraoperative photodynamic therapy after pleuropneumonectomy in patients with malignant pleural mesothelioma: dose finding and toxicity results.

OBJECTIVE: To determine the optimal administered dose of meta-tetrahydroxyphenylchlorin (mTHPC) for intraoperative photodynamic therapy (IPDT) in resected malignant pleural mesothelioma (MPM). The primary objective of this combination treatment was to improve local tumor control. DESIGN: Phase I/II dose escalation study. SETTING: Two Dutch cancer centers. PATIENTS: The study included 28 patients (2 women, 26 men), with pathologically confirmed MPM. The mean age was 57 years (age range, 37 to 68 years), and the World Health Organization performance score was 0 to 1. Epithelial mesotheliomas were found in 17 patients, a sarcomatous mesothelioma was found in 1 patient, and mixed epithelial sarcomatous mesotheliomas were found in 10 patients. METHODS: Patients were injected with 0.075 mg/kg (4 patients), 0.10 mg/kg (19 patients), or 0.15 mg/kg (5 patients) mTHPC 4 or 6 days before undergoing surgery and IPDT. Complete surgical resection (i.e., pleuropneumonectomy) was followed by integral illumination with monochromatic light of 652 nm (10 J/cm(2)). The real-time fluence rate measurements were performed using four isotropic detectors in the chest cavity to calculate the total light dose. RESULTS: Dose-limiting toxicity was reached at the level of 0.15 mg/kg mTHPC. Three patients died in the perioperative period, and one death was directly related to photodynamic therapy. Real-time dosimetry identified 12 patients in whom additional illumination had to be given to the diaphragmatic sinuses, which were unavoidably shielded during integral illumination. In two patients, illumination was cancelled due to the insufficient resectability of the tumor. The median survival time for all 28 patients was 10 months. Local tumor control, 9 months after treatment, was achieved in 13 of the 26 patients treated with IPDT. CONCLUSION: IPDT using mTHPC, combined with a pleuropneumonectomy, resulted in local control of disease in 50% of the treated cases. The considerable toxicity associated with the procedure, however, precludes its recommendation for widespread use. Stricter patient selection and improvements of the IPDT technique may reduce the toxicity.

Caelyx in malignant mesothelioma: a phase II EORTC study.

BACKGROUND: The use of doxorubicin has shown some activity in malignant mesothelioma but prolonged administration is hampered by cardiotoxicity. Caelyx, a new liposomal and pegylated form of doxorubicin has shown a better pharmacokinetic and toxic profile then doxorubicin. In a phase II study, the efficacy and toxicity of Caelyx was tested in previously untreated patients with malignant pleural mesothelioma. PATIENTS AND METHODS: Thirty-three patients who had measurable or evaluable histologically confirmed malignant pleural mesothelioma were included in the study. Caelyx (45 mg/m2) was given i.v. on outpatient base every four weeks for nine cycles or till progression or unacceptable toxicity occurred. RESULTS: Of the 33 patients, 32 were evaluable for toxicity and 31 for response. Two patients had a partial response (6%, 95% confidence interval: 0.2%-20.2%). The median survival was 13 months. Forty percent of the patients received >6 cycles. Toxicity was mild with palmar plantar erythrodysesthesia being most pronounced (62% grade 1-2, 6% grade 3) and of limited duration. Ten percent of patients had grade 3 anemia and 3% grade 3 thrombocytopenia. Two patients (6%) had grade 3 or 4 cardiac toxicity, which was not drug related. CONCLUSION: At the prescribed dose, single agent Caelyx is well tolerated but its activity in chemotherapy-naive mesothelioma patients does not warrant further investigation as a single agent.

A CT-assisted method of dosimetry in brachytherapy of lung cancer. Rotterdam Oncological Thoracic Study Group.

BACKGROUND: The toxicity of endobronchial brachytherapy (EB), in particular fatal haemoptysis and bronchial wall necrosis, has been correlated with the total dose, fraction size, volume encompassed by the 100% isodose, and a proximal tumor location. We describe a CT-based planning method which, by improving target volume definition and volumetric dose information, can improve the therapeutic ratio of EB. MATERIALS AND METHODS: Sixteen CT-assisted EB procedures were performed in patients who were treated with palliative high-dose rate EB. The CT data were used to analyze applicator position in relation to anatomy. An example of a three-dimensional optimized treatment plan was generated and analyzed using different types of dose-volume histograms. RESULTS: The procedure was well tolerated by patients and no post-procedure complications were observed. The bronchial applicator was eccentrically positioned at the level of the carina/mainstem bronchus in 12 (of 14) CT scans. A planning CT prior to EB was not found to be useful as the final target volume and/or the final applicator position were not reliably predicted before the therapeutic bronchoscopy. CT-scans performed with the applicator in situ allowed the bronchial segments in the target volume to be identified and enabled dose prescription to the bronchial mucosa. CONCLUSIONS: CT-assisted EB is feasible and underlines the need for using centered applicators for proximally located tumors. By enabling accurate mucosal dose prescription, CT-assisted EB may reduce the toxicity of fractionated EB in the curative setting. However, faster on-line EB treatment planning is needed for the routine clinical application of this technique.

[Findings in children with psoriasis]. / Bevindingen bij kinderen met psoriasis.

OBJECTIVE: To describe the clinical characteristics and treatments of children with psoriasis. DESIGN: Retrospective, descriptive. METHODS: The medical records were studied of all 38 children with psoriasis who visited the outpatient clinic for Dermatology of the University Hospital/Wilhelmina Children's Hospital Utrecht, the Netherlands, for the first time between 1 January 1995 and 31 December 1997. RESULTS: The 38 children accounted for 3.6% of all children in whom a diagnosis was made. There were 19 boys and 19 girls. 79% had psoriasis vulgaris and 11% psoriasis guttata. Average age of onset was 6.8 years for girls and 9.3 years for boys. Family history was positive in 42%. The limbs were affected most. Nail changes were seen in 11%. Provoking factors were stress, infections, summertime and injuries of the skin. In almost all patients in the outpatient department local mono- and/or combination therapy of corticosteroids in cream or ointment with salicylic acid and tar was given.

Effects of granulocyte colony-stimulating factor (G-CSF) treatment on granulocyte function and receptor expression in patients with ventilator-dependent pneumonia.

Considerable experimental evidence in animals suggests that treatment with G-CSF may have a beneficial effect in the management of severe infections in non-neutropenic hosts. This beneficial effect is attributed to an enhancement of granulopoiesis and neutrophil function, the latter possibly involving up-regulation of receptors on neutrophils that are involved in antibody-mediated cytotoxicity and killing of microorganisms. We compared neutrophil function and phenotype in blood and bronchoalveolar lavage fluid (BALF) of 10 patients with severe ventilator-dependent pneumonia, at baseline and following initiation of G-CSF treatment as adjunct to standard therapy. G-CSF treatment was associated with three-fold increased blood neutrophil counts at day 3 of treatment compared with baseline counts. Mean serum G-CSF concentration increased from 313 to 2007 pg/ml. After correction for lavage dilution effects, BALF G-CSF levels did not differ significantly from baseline, nor did neutrophil receptor expression (FcgammaRI, FcgammaRII, FcgammaRIII, CR3, and L-selectin) or indicators of neutrophil function such as respiratory burst activity, phagocytosis and killing of Candida albicans in BALF or blood. The mortality in this group of patients was 30% and compared favourably to the APACHE II-derived predicted mortality of 60%. We conclude that the possible therapeutic benefit of G-CSF administration in the early phase of severe bacterial pneumonia is not readily explained by its effect on baseline indicators of neutrophil function or receptor expression.

Prostate symptoms in general practice: seriousness and inconvenience.

OBJECTIVE: To estimate the seriousness and inconvenience of prostatism in a general practice population and to assess the consultation with the general practitioner (GP) in relation to seriousness of prostatism. DESIGN: A questionnaire was sent to a random sample of 979 men aged 50 years and over from two general practices in a village, and two in a city in the western part of The Netherlands. MAIN OUTCOME MEASURE: Seriousness and inconvenience of prostatism according to the Symptom Index for Benign Prostatic Hyperplasia. Consultation with the GP for urinary symptoms. RESULTS: The prevalence of prostatism with moderate to severe symptoms was 20%. The majority (60%) of the men with prostatism did not consult their GP with these symptoms, and one fifth (19%) felt "mostly dissatisfied" to "terrible" due to their symptoms. Of this last group, a few (1.4% of the total population) nevertheless did not consult their GP. CONCLUSIONS: Prostatism is a symptom complex caused not only by benign prostate hyperplasia. Prostatism is under-reported in general practice. Men with micturition problems should be encouraged to consult their practitioner.

Hymenoptera sting challenge of 348 patients: relation to subsequent field stings.

BACKGROUND: Patients with a history of a serious anaphylactic reaction after a Hymenoptera sting are usually given venom immunotherapy. Because the natural history of Hymenoptera sting anaphylaxis is often of a declining severity, there is a chance of overtreatment. OBJECTIVE: Identification of patients at risk for a future anaphylactic reaction may reduce the number of patients who need venom immunotherapy. METHODS: We investigated the relation between the grade of hypersensitivity to an in-hospital sting challenge and the reaction to a subsequent accidental field sting. From 1982 through 1992, 348 patients with mild or no symptoms after a sting challenge were not given venom immunotherapy. All patients were asked by letter whether they had experienced a subsequent field sting. In case of a sting, the severity of the reaction was further evaluated. RESULTS: Information could be obtained from 327 patients: 129 had been re-stung, and 110 of them had only had a local reaction. Thirteen patients had experienced mild systemic symptoms, and six patients had experienced serious manifestations. In two of the latter group hypotension was observed. CONCLUSION: In 95% of patients with a previous anaphylactic reaction, the result of the in-hospital sting challenge provided a good prediction of tolerance to a subsequent Hymenoptera field sting.

Metabolic activity and population dynamics of rhizobia introduced into unamended and bentonite-amended loamy sand.

Respiration measurements showed that the cumulative amount of CO(2) respired by rhizobia introduced into sterile bentonite-amended loamy sand was significantly higher than it was in unamended loamy sand. The maintenance respiration of rhizobial cells was not influenced by the presence of bentonite clay. Carbon was used more efficiently during growth in bentonite-amended than in unamended loamy sand. The presence of bentonite clay increased the growth rate of rhizobia introduced into sterile soil. Survival studies performed in nonsterile bentonite-amended loamy sand showed that the use of high (10 cells per g of dry soil) rather than lower (10 to 10 cells per g of dry soil) inoculum densities increased the final survival levels of introduced rhizobia. In unamended loamy sand, the application of 10 or 10 cells per g of dry soil resulted in similar final survival levels. Pore shape and the continuity of the water-filled pore system were suggested to largely determine the colonization rate of protective microhabitats.

Mushroom worker's lung. Detection of antibodies against Shii-take (Lentinus edodes) spore antigens in Shii-take workers.

Indoor cultivation of the edible mushroom Shii-take (Lentinus edodes) regularly leads to symptoms of mushroom worker's lung (MWL) in workers. An immunologic test is described allowing detection of IgG type antibodies against Shii-take spore antigens. It was found that MWL patients employed in Shii-take picking (n = 5) have significantly increased antibody titres against Shii-take spore antigens. Different control groups, viz, MWL patients employed in the cultivation of the white button mushroom Agaricus bisporus (n = 14) and of the oyster mushroom Pleurotus spp (n = 3), patients with Bechterew's syndrome (n = 7), sarcoidosis (n = 7), rheumatoid arthritis (n = 9), and healthy controls were found in the same range of low titres. The use of protective masks during picking reduced complaints of the workers (n = 14). However, their antibody titres increased with duration of employment despite the protection.