Exposure–response relationships of occupational inhalative allergens

Only a few threshold limit values exist at present for allergens in the workplace known to cause bronchial asthma. This contrasts with the great number of occupational asthma cases observed in industrialized countries. Recently published studies provide clear evidence for exposure intensity response relationships of occupational allergens of plant, microbiological, animal or man-made origin. If allergen exposure levels fall short of determined limit values, they are not associated with an increased risk of occupational asthma. Corresponding data are available for wheat flour (1–2.4 mg/m³), fungal α-amylase (0.25 ng/m³), natural rubber latex (0.6 ng/m³), western red cedar (0.4 mg/m³) and rat allergens (0.7 μg/m³). It is suggested to stipulate legally binding threshold limit values (TLV/TWA) on this basis in order to induce more effective primary preventive measures. If no reliable data on the health risk of an occupational airborne noxa exist, the lowest reasonably practicable exposure level has to be achieved. Appropriate secondary preventive measures have to be initiated in all workplaces contaminated with airborne allergens. Verified exposure–response relationships provide the basis for risk assessment and for targeted interventions to reduce the incidence of occupational asthma also in consideration of cost benefit aspects. ‘Occupational asthma is a disease characterized by variable airflow limitation and/or airway hyperresponsiveness due to causes in a working environment. These causes can give rise to asthma through immunological or non-immunological mechanisms [ 1 ]. Up to 15% of all asthma cases are of occupational origin or have at least a significant causal occupational factor [ 1 2 3 4 5 6 7 8 9 10 ]. According to the New Zealand part of the European Respiratory Health Survey, an increased risk of asthma prevalence was found for several occupations such as laboratory technicians, food producers, chemical workers, plastic and rubber workers [ 11 ]. The Spain part of this study comprising 2646 Spanish subjects showed an asthma risk to be attributed to occupational exposures between 5 and 6.7% [ 12 ]. Main asthma-inducing agents in the workplace are flour, grain and feed dust, animal dander/urinary proteins and isocyanates. Further, several inhalative irritants such as chlorine, acid or alkaline aerosols play a pivotal role. Many low molecular weight chemicals have irritative as well as allergenic effects on the airways, e. g. isocyanates and acid anhydrides. In addition to chronic or repetitive exposures, also singular accidental exposure to high concentrations of irritative or toxic airborne substances can cause occupational asthma. This condition is frequently called reactive airways dysfunction [ 13 ].     

Baker''s asthma due to the enzyme xylanase — a new occupational allergen

The asthmatic baker showed IgE-mediated sensitization to xylanase of Aspergillus niger used as a baking additive. Inhalative challenge with approximately 0.5 microg of the enzyme resulted in an immediate-type asthmatic reaction. This case, as well as a preliminary screening of symptomatic bakers, shows that xylanase is a further relevant type I-sensitizer in the baking industry.     

MRT-gesteuerte regionale Tiefenhyperthermie

Zusammenfassung Fragestellung: Die regionale Tiefenhyperthermie in Kombination mit Chemotherapie und/oder Radiotherapie ist ein vielversprechendes Behandlungskonzept für lokal fortgeschrittene, tiefliegende Tumoren. Ziel dieses Projektes ist die nichtinvasive, dreidimensionale Darstellung der Gewebsver?nderungen und der Temperaturverteilungen w?hrend der regionalen Tiefenhyperthermie. Methodik: Die Magnetresonanztomographie bietet prinzipiell geeignete Methoden für die Gewebecharakterisierung und für die MR-Thermometrie. Auf der Basis eines innovativen Hyperthermieapplikators und eines offenen MR-Tomographen wurde ein neues MRT-Hyperthermie-Hybridsystem entwickelt und erprobt. Ergebnisse: Nach der erfolgreichen Erprobung des neuen MRT-Hyperthermie-Hybridsystems an Phantomen und Probanden konnte erstmals am Patienten eine simultane MR-Bildgebung und Tiefenhyperthermie durchgeführt werden. Die T1-Relaxationszeit erscheint nach unseren derzeitigen Forschungsergebnissen ein vielversprechender Ansatz für die MR-Thermometrie bei 0,2 T zu sein. Schlu?folgerung: Der erstmalige klinische Einsatz des MRT-Hyperthermie-Hybridsystems kann als wichtiger Meilenstein für die Gesamtentwicklung der regionalen Tiefenhyperthermie bezeichnet werden. Das neue Ger?t und die unterschiedlichen MRT-Verfahren, insbesondere die der MR-Thermometrie, müssen nun in klinischen Studien untersucht werden.      

Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor

Immune mechanisms and the renin-angiotensin system are implicated in preeclampsia. We investigated 25 preeclamptic patients and compared them with 12 normotensive pregnant women and 10 pregnant patients with essential hypertension. Antibodies were detected by the chronotropic responses to AT1 receptor-mediated stimulation of cultured neonatal rat cardiomyocytes coupled with receptor-specific antagonists. Immunoglobulin from all preeclamptic patients stimulated the AT1 receptor, whereas immunoglobulin from controls had no effect. The increased autoimmune activity decreased after delivery. Affinity-column purification and anti-human IgG and IgM antibody exposure implicated an IgG antibody directed at the AT1 receptor. Peptides corresponding to sites on the AT1 receptor's second extracellular loop abolished the stimulatory effect. Western blotting with purified patient IgG and a commercially obtained AT1 receptor antibody produced bands of identical molecular weight. Furthermore, confocal microscopy of vascular smooth muscle cells showed colocalization of purified patient IgG and AT1 receptor antibody. The protein kinase C (PKC) inhibitor calphostin C prevented the stimulatory effect. Our results suggest that preeclamptic patients develop stimulatory autoantibodies against the second extracellular AT1 receptor loop. The effect appears to be PKC-mediated. These novel autoantibodies may participate in the angiotensin II-induced vascular lesions in these patients.     

Plasma clearance of cortisol as a function of plasma cortisol levels in normal and obese persons and in patients with uraemia or cirrhosis of the liver.

Plasma cortisol levels in 2 normal persons, 2 obese persons, 2 uraemic patients, and 2 patients with cirrhosis of the liver were raised in 4 steps by a combination of iv priming doses and continuous infusions of cortisol. Plasma cortisol levels and transcortin binding were measured as well as plasma clearance rates of labelled and unlabelled cortisol during each of the 5 experimental periods. Plasma cortisol levels increased less and plasma clearance rates of labelled and unlabelled cortisol increased more in obese persons than in normal persons; in patients with disturbed metabolism of cortisol (uraemia, cirrhosis of the liver) the reverse is true. Plasma clearance rates of free cortisol were calculated and differed from an estimated hepatic plasma flow of 0.7 1/min under certain conditions. Since free cortisol is metabolized faster than transcortin-bound cortisol, increasing plasma clearance rates of cortisol are probably due to increasing ratios free/bound cortisol when total plasma cortisol levels are raised. Low plasma clearance rates of cortisol in uraemia and cirrhosis of the liver are thought to be due to endproduct inhibition, respectively reduced liver cell mass.