SummaryA method for biological equilibration (BE) of allergen reference preparations using the skin‐prick test (SPT) method and histamine HCl 10 mg/ml as reference substance (reference method), was evaluated. The precision was low for weals less than 10 mm2. The slope (log weal area/log concentration) of allergen and histamine did not vary significantly between investigators and allergens. The median slopes were 0.39 (n= 384) and 0.34 (n= 397), for allergen and histamine, respectively (P < 0.01). The concentration of allergen eliciting a weal of the same size as that of histamine HCl 1 mg/ml (Chl) in the median sensitive patient, 1000 Biological Units/ml (BU/ml), did not vary significantly between clinics/geographical regions (grasses, mites and moulds). As BE is repeatable between regions. BUs estimated by this method are generally valid. A high correlation (r= 0.91, P < 0.001) was found between the median Chl as estimated with histamine 1 and 10 mg/ml as reference substance, respectively. Thus, this reference method for BE is valid. The precision of the SPT method with histamine HCl 1 mg/ml is not as good as with 10 mg/ml, which is therefore recommended as the reference concentration.

The selective D2-dopamine receptor antagonist raclopride and its pharmacologically inactive (R)-enantiomer FLB472 were labelled with 11C and used in a study with positron emission tomography to examine the stereoselectivity of 11C-raclopride binding to central D2-dopamine receptors in three healthy men. After the injection of 11C-raclopride, there was a high accumulation of radioactivity in the dopamine-rich basal ganglia, whereas after the injection of 11C-FLB472 there was no such accumulation of radioactivity. Thus, the binding of 11C-raclopride is stereoselective. Distribution ratios [radioactivity in a brain region/"free" (not protein-bound) radioactivity in plasma] were calculated for the two enantiomers to study regional differences in the accumulation of radioactivity. The distribution ratios in white matter were similar for the two enantiomers. In the putamen, a three to four-fold higher distribution ratio was found for 11C-raclopride than for 11C-FLB472, reflecting the presence of specific binding of 11C-raclopride binding to D2-dopamine receptors in the basal ganglia. In the temporal and frontal cortices the distribution ratios were, however, only a few per cent higher for 11C-raclopride than for 11C-FLB472, indicating that if D2-dopamine receptors are present in the human neocortex, then their density is indeed very low.

The aim of biological standardization (BS) is to equilibrate the activity (potency) of allergen extracts from different source materials. This was done by performing skin prick tests (SPT) on patients who were sensitive to one of the following 10 allergens: Birch, alder, hazel, timothy, rye grass, velvet grass, cultivated rye, mugwort, D. farinae and Cladosporium herbarum. Patient sensitivity varied within a range of three to four powers of ten for each allergen investigated. The weal size in each patient corresponding to that elicited by histamine 1 mg/ml was calculated using the model log (mean weal diameter) = a + b log (concentration). The correlation coefficients of the regression lines of the allergen dose response relationship were found to be greater than 0.85 in most cases. The median slope for all extracts was 0.24. The slope for Cladosporium was significantly steeper than that for pollens. The amount of material in microgram dry weight (d.w./ml) equal to 1000 biological units/ml (BU/ml) varied within a factor of three between species for all tested purified allergen preparations but Cladosporium. For Cladosporium, about 30 times more material was needed than for D. farinae. When using crude rather than purified material, it was necessary to use five to ten times more to elicit a reaction corresponding to 1000 BU/ml, but the difference was significant only for Cladosporium. The narrow range of allergen concentrations used by us as well as other investigators does not assure positive skin prick test results in all patients with clinical symptoms due to the allergen in question. Skin prick testing should therefore be done over a wide range of concentrations to improve the methods for BS.

Four patients were found to react to occupational exposure to grinding of hard metal (tungsten carbide). Three of the patients had symptoms and signs compatible with an allergic alveolitis, the symptoms disappearing and the chest radiograph clearing when they were absent from work for a few months. Re-exposure to the offending agent led to new signs and symptoms. The first patient was re-exposed twice and each time reacted a little more seriously. After the last episode her chest radiograph has not cleared completely, in contrast to the first two times. The fourth patient had more typical occupational asthma. All the cases occurred in the part of the factory where air concentrations of cobalt were the lowest. The cobalt there is dissolved in the coolant necessary for grinding the hard metal. It occurs mainly in the ionised form, which is known to react with proteins and therefore presumably acts as a hapten. Protective measures, including choosing a coolant with minimal ability to dissolve cobalt and an effective exhaust system, should minimise the risk of this occupational disease in the future.Hard metal lung disease has been described since 1940 as a cause of death in respiratory failure because of fibrosis of the lungs. Hard metal is an alloy consisting of mainly (tungsten) wolfram carbide (70-95%) and cobalt (5-25%). Various amounts of other metals, such as titanium, tantalum and so on are often added. Because of its hardness, hard metal plays an important and increasing role in the industrialised world. It was

Regional brain glucose metabolism was investigated in healthy volunteers (n = 10) and in drug free schizophrenic patients (n = 20). The metabolism was determined by positron emission tomography (PET) with 11C-glucose as the tracer. Diagnosis of schizophrenia was made according to RDC and DSM III. Eight patients had their first psychotic episode, four patients had a subchronic course and eight patients had a chronic course with an exacerbation of their illness. Computed tomography (CT) of the brain were made in all the subjects. Regions of interest (n = 35) were drawn on displayed CT images and the marked regions were transferred to the corresponding slice of the PET examination. The PET investigation was made in a dimly lit, quiet room with the eyes of the subject covered. The time course of the 11C-glucose uptake was measured by a four ring PET scanner (PC-384-7B). Metabolic rates of glucose varied greatly among the schizophrenic patients investigated. The variance was significantly greater than that of the controls in most regions. Decreases in mean levels of metabolic rates were related to patients with subchronic or chronic courses. Changes in metabolism were not related to previous duration of neuroleptic treatment of the patients. Left-right asymmetries were found in the temporal lobe (area 22) and the basal frontal cortex (area 11), the metabolic rates of the patients being lower on the left side compared to the controls. Asymmetry of the metabolic rate of the amygdala in hebephrenic patients was the opposite of that found in paranoid patients and controls. Negative correlations between regional metabolic rates and autistic or negative symptoms were found. Thus, the lower the metabolic rate was, the more autistic the patient. Metabolic rates were not correlated to atrophic changes of the brain. No basis for a specific alteration in frontal cortical metabolism of schizophrenics was obtained. Changes in regional metabolic rates in schizophrenia are suggested to reflect disturbances in more general mechanisms which are of importance in neuronal function.