Double-blind placebo-controlled house dust mite control measures in adult patients with atopic dermatitis.

BACKGROUND: Avoidance of allergens has been shown to be of benefit in patients with atopic asthma sensitized to indoor allergens. In atopic dermatitis, there is so far little information about the effect of house dust mite elimination strategies. OBJECTIVES: We therefore performed a randomized controlled study of house dust mite control in patients with this disease. METHODS: Twenty adult patients with moderate to severe atopic dermatitis were included. Inclusion criteria were a positive RAST to house dust mite antigen (CAP class > 3) and a concentration of > 2 microg g(-1) of the house dust mite antigen Der p1 in the patient's mattress dust. Patients were randomized to either the active treatment group (allergen-impermeable mattress encasing, acaricide spray containing tannic acid and benzylbenzoate) or a control group (allergen-permeable encasing, spray containing water and traces of ethanol). Severity of disease was estimated every 2 months by an established score (SCORAD), and eosinophil cationic protein (ECP) in the serum was determined by enzyme-linked immunosorbent assay. Furthermore, the use of topical steroids was quantified. Patients assessed daytime pruritus and pruritus-induced sleeplessness weekly on a visual analogue scale. The study lasted 1 year. RESULTS: At the end of the study, the active treatment group showed a statistically significant reduction in Der p1 exposure as compared with the control group. However, when comparing the change from the start to the end of the study, there was no statistically significant difference between active treatment and control groups as measured by the SCORAD score and by ECP levels in the serum. Some patients in the active treatment group reported less pruritus-induced sleeplessness, but there was no statistically significant difference between the two treatment groups. CONCLUSIONS: For adult patients with atopic dermatitis it was shown that 1 year of house dust mite avoidance reduced the allergen exposure, but an improvement of overall disease activity was not demonstrated.

Mathematical modeling of marker influx and efflux in cells.

The tumor promoter, phorbol 12-myristate 13-acetate (PMA), affects the processing of fluid that enters a cell from the ambient medium. Previous work showed that marker accumulates to a higher level in PMA-treated than in untreated cells. Since PMA also affects the physical activity of the membrane and stimulates the normal process of taking up extracellular fluid, called endocytosis, it is important to learn whether the perturbations in fluid processing can be attributed entirely to a change in the cell's limiting membrane. To this end, a model for fluid uptake and processing was developed and applied to experiments in which a marker for extracellular fluid was added to cells. From previous work on marker accumulation, it was deduced that there were at least two functional compartments involved in fluid movement. Compartment I is a rapidly filling and rapidly recycling compartment. Compartment II is a slowly filling and emptying compartment. Three routes of vesicle traffic must be considered, one mediating influx from the ambient medium into compartment I, a second, efflux from compartment I to the medium, and a third efflux from compartment I into compartment II. Using earlier models for processing, workers found it difficult to estimate rates of movement through either of the latter routes, as well as the volume of compartment I. The difficulty arises from the fact that only one kinetic constant can be estimated directly from data, namely the instantaneous uptake rate. The remaining data depend on measuring the total mass of marker in the cells. Since the concentration of marker in the cell changes continuously, it is advantageous to employ differential equations to simulate the tracer movement. By applying the model to experimental values, we found estimates for all three rates of fluid movement and the volume of compartment I. It is thought that the model will enable us to determine whether apparent alterations in the time course of uptake arise solely from altered properties of the limiting membrane.

Natural rubber latex allergy is not a cause of sudden infant death.

BACKGROUND: The causes for sudden infant death (SID) remain unclear. As infants can become sensitized to NRL allergens by pacifiers and latex mattresses, we tried to establish whether there is a relationship between SID and natural rubber latex (NRL) allergy. METHODS: We determined NRL-specific IgE concentrations in 112 unselected cases of SID by the CAP-FEIA method. RESULTS: NRL-specific IgE could be detected only in 1 sample (0.64 kU/l; CAP class 1). CONCLUSIONS: We conclude that NRL allergy is not a cause of SID.

2,2',4,4',5,5'-hexabromobiphenyl: its toxicokinetics, biotransformation and porphyrinogenic action in rats.

The porphyrinogenic action of 2,2',4,4',5,5'-hexabromobiphenyl and its toxicokinetics were studied in female Wistar rats that were treated every other day for 6 wk with oral doses of 112 mg/kg body weight. Subsequently, the animals were kept for a further period of 22.5 months but without supply of the brominated biphenyl. 10.5 months after cessation of treatment the compound reached a maximum concentration in the adipose tissue followed by a gradual decline of its content. In the liver the concentration of the substance started to decrease 3 months after cessation of treatment. In the excreta, hexabromobiphenylol and two pentabromobiphenyls were detected as metabolites. The rate of biotransformation amounted to about 5%. At the end of the dosing period no alterations in the content and profile of the hepatic porphyrins were observed. Urinary porphyrins and their precursors delta-aminolaevulinic acid and porphobilinogen were slightly elevated. The urinary porphyrin pattern and faecal porphyrin content and pattern did not differ from those of the controls. 15 and 18 months after cessation of treatment (16.5 and 19.5 months after the start of treatment) two animals were found to have marked alterations in the content and profile of hepatic porphyrins with uro- and heptacarboxyporphyrin predominating. It was concluded that there is an extreme delayed individual porphyric response to 2,2',4,4',5,5'-hexabromobiphenyl in female rats.

2,2',3',4,4'5,5'-Hepatachlorobiphenyl (PCB 180)--on its toxicokinetics, biotransformation and porphyrinogenic action in female rats.

The toxicokinetics and biotransformation of 2,2',3',4,4',5,5'-heptachlorobiphenyl, as well as its influence on the activity of microsomal and cytosolic enzymes and on the porphyrin pathway in the liver were studied in female rats following oral treatment with 7 mg/kg every other day for 3 months. One day after cessation of treatment the concentration of the compound in liver, spleen, CNS and blood was 100-500 times and in the trachea it was only 5 times less than in the adipose tissue. The daily excretion with the feces and urine amounted to 35 and 1.5 micrograms, respectively. In both excreta, heptachlorobiphenylol was identified as a metabolite. The biotransformation rate was estimated to be about 5%. Investigations of the liver revealed increases in the relative liver weight, total cytochrome P-450 content, O-deethylation of 7-ethoxycoumarin and in the activity of glutathione S-transferases. Disturbances of the hepatic porphyrin pathway were not detected. Only at the end of a post-dosing period of 12 months did the hepatic uroporphyrinogen decarboxylase show diminished activity. Only one of these animals with diminished enzyme activity showed drastically elevated porphyrins. In these animals, the fecal and urinary porphyrins did not differ from controls. At no time did heptachlorobiphenyl influence the urinary excretion of delta-aminolevulinic acid and porphobilinogen. The results indicate 1) that this congener shows expected toxicokinetics with the exception of being accumulated in the trachea and 2) that this congener induces disturbances of the hepatic porphyrin pathway several months after cessation of treatment.

[Data processing the the RAST laboratory]. / Datenverarbeitung im RAST-Labor.

We describe a clinical laboratory information system for the RAST laboratory based on personal computers. In developing this system, we paid special attention to easy handling which does not require any computer experience on the user's side. Data storage and retrieval are managed by a relational database system with fast data access. Aside from the usual functions of a laboratory information system, the laboratory work is facilitated by a clear distribution of samples, the possible on-line connection to various analyzers, as well as the provision of cumulative results and a fast access to archive data.

[Results of treatment of porphyria cutanea tarda with bloodletting and chloroquine]. / Ergebnisse bei der Behandlung der Porphyria cutanea tarda mit Aderlass und Resochin.

In 59 patients showing clear clinical and biochemical signs of porphyria cutanea tarda (PCT), we tested 3 different modes of therapy: 20 patients received combined treatment with repeated bleeding and chloroquine, 24 patients were exclusively treated with oral chloroquine in low doses, and 15 patients underwent repeated phlebotomy only. On an average, the time necessary for remission amounted to 3.5, 10.2, and 12.5 months, respectively. So the combined therapy proved the quickest. In patients with the acquired form of PCT, the pattern of urinary porphyrin normalized; those suffering from hereditary PCT retained the typically high uro/copro ratio. The values of the plasma porphyrin count and the plasma porphyrin index (PPI), which had been greatly enhanced before, went down to normal after therapy.

Studies on uroporphyrinogen decarboxylase of etiolated Euglena gracilis Z.

1. A 423-fold purified fraction of uroporphyrinogen decarboxylase (EC 4.1.1.37) showing a specific activity of 770 units/mg protein has been employed in order to study some properties in etiolated Euglena gracilis Z. 2. Uroporphyrinogen decarboxylase has a relative molecular mass of 54,000, an optimum pH of 7.2 and exhibits Michaelis-Menten kinetics, employing both uroporphyrinogen I and uroporphyrinogen III as substrates. 3. Anaerobic conditions seem not to be necessary for uroporphyrinogen decarboxylase activity. Neither EDTA nor cysteine affected enzyme activity, whereas dithiothreitol produced a remarkable activation of coproporphyrinogen formation. 4. Kinetic data employing both substrates showed an accumulation of porphyrinogen (i.e. hexa- and hepta-porphyrin) containing six or seven COOH groups, depending on the uroporphyrinogen concentration used. 5. An unusual elution profile of the intermediates on Sephacryl S-200 was found.

Elimination of porphyrins and their precursors in rats pretreated with hexabromobenzene.

The elimination times of porphyrins and their precursors and of hexabromobenzene (HBB) itself were studied in female rats given 15 mg HBB by stomach tube every other day for 4 months. The concentrations of HBB in the blood, liver and adipose tissue were in the ratio 1:1.5:25, 24 hr after the last dose. Two weeks after the end of treatment, HBB was no longer detectable in the tissues. In animals given a single oral dose of 16.6 mg HBB/kg body weight, HBB was no longer detectable in adipose tissue 12 days after dosing. The half-life of HBB in adipose tissue was about 2.5 days in the animals given HBB for 4 months, and at the end of the treatment the concentrations of porphyrin in the liver, urine and faeces were increased to about 1000, 600-700 and 60-70 times the control values. The amounts of delta-aminolaevulinic acid and porphobilinogen in the urine of treated animals were 6-7 times those in controls. After the end of HBB treatment, it took almost 1.5 yr for delta-aminolaevulinic acid and porphobilinogen excretion to return to normal. Nearly 2 yr were needed for complete elimination of the accumulated liver porphyrins.

Quincke's edema in a dialysis patient after administration of acrylic bone cement: possible role of ethylene oxide allergy.

A 33-year-old female dialysis patient suffered from osteomyelitis and luxation of the dens axis with cervical myelopathy. In the past she had had three attacks of anaphylaxis after treatment with dialyzers that had been sterilized with ethylene oxide. IgE-type antibodies directed against human serum albumin-ethylene oxide complexes could be demonstrated in the patient's serum by radioallergosorbent techniques. Immediately after an operation in which acrylic bone cement (Palacos-R) sterilized with ethylene oxide was implanted for stabilization of the cervical spine, the patient developed massive edema of the larynx, pharynx, and tongue, suggesting Quincke's edema. It is concluded that ethylene oxide present in acrylic bone cement may induce acute allergic reactions in sensitized patients. Dialysis patients may be at special risk, since the incidence of ethylene oxide allergy in this patient population is about 10%.

Association of ethylene-oxide-induced IgE antibodies with symptoms in dialysis patients.

IgE-type antibodies to human serum albumin/ethylene oxide conjugates were determined in 153 patients (140 unselected, 13 selected for presence of eosinophilia) on regular dialysis treatment by radioallergosorbent test (RAST) techniques. In 10.7% of unselected patients and 30.8% of selected patients, RAST values suggested ethylene oxide sensitisation. High RAST values were commonly associated with anaphylactoid reactions during dialysis and with chronic asthma. Ethylene oxide antibodies should be sought routinely in patients presenting with these symptoms and the necessity of ethylene oxide sterilisation of disposable dialysis equipment should be re-evaluated.

[Hypersensitivity phenomena in dialysis patients. Incidence of eosinophilia, raised IgE and ethyleneoxide-induced antibodies]. / Hypersensitivitätsphänomene bei Dialysepatienten. Häufigkeit von Eosinophilie, IgE-Erhöhung und Ethylenoxid-induzierten Antikörpern.

The hypersensitivity parameters eosinophil count, serum IgE and IgE-type antibodies to ethylene oxide-albumin conjugates (ETO-antibodies), were determined in 182 dialysis patients. Eosinophilia was seen in 21.7% of patients, IgE elevation in 21.4% and ETO-antibodies in 12.4%. A pathological change in at least one of the measured parameters was present in 33.1%. The appearance of ETO-antibodies was frequently associated with severe clinical symptoms, especially asthma and anaphylactic shock. Sensitisation is apparently common in dialysis patients. Since ETO-antibodies are often associated with severe clinical symptoms, their presence should be sought in those dialysis patients showing incompatibility reactions or asthma.

A porphyria cutanea tarda-like distribution pattern of porphyrins in plasma, hemodialysate, hemofiltrate, and urine of patients on chronic hemodialysis.

The porphyrin investigations of plasma, dialysate, hemofiltrate, and urine in 50 chronic renal patients without bullae undergoing hemodialysis imply that a hyperporphyria exists. All 50 dialysis patients without blisters had significantly elevated plasma porphyrins with a mean of 27.4 micrograms/liter (SD: 10.0). Normal values were established in 51 nonporphyric ambulatory patients with normal renal function. The mean plasma porphyrin content in this group was 10.6 micrograms/liter (SD: 1.7). Porphyrin values in dialysates of 41 patients with chronic renal failure ranged from 2.6-6.3 micrograms/liter (mean, 3.9 micrograms/liter) and were much lower than the porphyrin content in hemofiltrates of 9 patients which ranged from 10-27 micrograms/liter with a mean of 20 micrograms/liter. In addition, plasma, hemofiltrate, and urine of 5 dialysis patients with blisters and porphyria cutanea tarda (PCT) were investigated. The plasma values were extremely elevated and exceeded those of PCT patients with normal renal function. Whether the dermatologic manifestations of chronic hemodialysis can be interpreted as a "forme fruste" of PCT should be subjected to further investigations.

[Penetration of benzoyl peroxide in the skin]. / Untersuchung zur Penetration von Benzoylperoxid in die Haut.

Benzoyl peroxide preparations have proven to be effective agents in the treatment of acne. In comparison to the numerous clinical communications, very few reports exist concerning the pharmacokinetics of benzoyl peroxide. The benzoyl peroxide content of abraded horny layers and its metabolite benzoic acid were investigated by high-pressure liquid chromatography after application (1-2 min) of emulsion containing benzoyl peroxide. It was found that benzoyl peroxide penetrates the stratum corneum very quickly where it is rapidly degraded to benzoic acid. No benzoyl peroxide depot in the stratum corneum could be demonstrated.