Budesonide for the treatment of collagenous colitis: first results of a pilot trial.

OBJECTIVE: Collagenous colitis is a chronic watery diarrhea disorder characterized by a subepithelial collagen layer and a lymphoplasmacytic infiltration within the lamina propria. However, no standard treatment has been introduced by controlled clinical trials. Aim of the present pilot trial was to investigate the clinical effects of orally administered budesonide (3 mg t.i.d.) in 7 patients with collagenous colitis. In addition, the histomorphological changes after budesonide treatment were described in a group of 3 patients. METHODS: The study was performed as an open label pilot trial. Study end point was the clinical remission of collagenous colitis defined by stool frequency and stool consistency. RESULTS: The results indicate a rapid and sustained clinical response in all patients. Stool frequency significantly decreased (p < 0.001) from 10.43 +/- 5.56 per day (4-20 per day) to 3.3 +/- 1.2 (1-5 per day) after 10 days and to 1.86 +/- 0.69 per day (1-3 per day) after 10 wk. Moreover stool consistency changed from watery (6 patients) or soft (1 patient) to soft (1 patient) or solid (6 patients). Clinical improvement was achieved within the first 10 days in all patients and maintained after dose reduction. In 3 patients no diarrhea recurred within 7, 12, or 15 months after treatment with budesonide was terminated. In these patients control biopsies were taken and showed a marked regression of both characteristics, the collagen band and the lymphoplasmacytic infiltration. CONCLUSIONS: With respect to the preliminary data from this pilot trial, budesonide with its high topical and low systemic effects seems to be of therapeutic clinical benefit in collagenous colitis. A therapeutic effect could be demonstrated for both therapeutic goals, the clinical response and morphological changes. Further studies on the effects of budesonide on mucosal collagen metabolism and long-term follow-up are warranted.

A selective HPLC/RIA for the determination of budesonide.

A combined HPLC/RIA procedure is described for the selective determination of budesonide (BUD) in plasma. The assay involves the extraction of plasma or serum samples with ethylacetate, consequent HPLC separation of intact budesonide from cross-reacting metabolites on a C8 reversed phase column, collection of the budesonide containing fraction and determination of budesonide immunoreactivity with the budesonide antiserum. The method was accurate, sensitive (IC50 value of 0.9 ng ml-1) and reproducible (intra- and inter-day less than 15%) with a limit of quantification of 0.133 ng ml-1 (RSD < 25%). The evaluation of a limited number of clinical samples after oral administration of budesonide by both the HPLC/RIA procedure and a direct RIA using the same antiserum differed in average by a factor of 2, with the ratio of HPLC/RIA-RIA results declining as a function of time. Thus, this ratio might be a suitable indicator for probing for the ratio of budesonide and overall metabolites on a semi-quantitative level.

Studies on the pharmacokinetics and metabolism of prednicarbate after cutaneous and oral administration.

Prednicarbate (PC) is a nonhalogenated derivative of prednisolone which is used for the local treatment of corticoid-sensitive skin diseases. In this study, the pharmacokinetics and the metabolism of PC in humans are investigated after cutaneous ointment application (75 mg PC) and after systemic oral administration (40 mg PC) in 8 healthy volunteers. In addition, the possible suppression of endogenous cortisol secretion by both application forms was monitored. After oral administration no intact PC, but significant levels of the first metabolite prednisolone-17-ethylcarbonate (PRED-17-EC) were determined. PRED-17-EC was further metabolized with a half life of 1.6 h to prednisolone. After percutaneous administration neither PC nor other known metabolites could be detected systemically. The low systemic bioavailability after dermal application was also reflected in an unchanged cortisol secretion pattern. According to animal studies our metabolic studies in humans suggest that the prednisolone-17-ester PRED-17-EC, which has a receptor binding affinity comparable to that of dexamethasone is the pharmacologically active compound. As PRED-17-EC subsequently undergoes an inactivation step to the low active prednisolone this may be the reason for the dissociation of good local efficacy and low systemic side effects.

[Prognostic significance of macroscopic and microscopic findings in acute inhalation damage in the most severely burned patients]. / Prognostische Bedeutung makroskopischer und mikroskopischer Befunde bei der akuten Inhalationsschädigung schwerstbrandverletzter Patienten.

The bronchoscopic examination of the upper respiratory tract is thought to be of major value recognizing and determining the severity of an inhalation injury in burn patients. From clinical observation however it can be questioned if the initial bronchoscopic aspect has indeed any prognostic significance concerning soon or later developing pulmonary complications in those patients. In 15 burn patients with inhalation injury the endoscopically evident lesions of the respiratory tract were classified and documented by photography. Additionally bronchus biopsies for histological examination were taken from different levels of the bronchus tree and a bronchoalveolar lavage (BAL) was performed to gather lung cells of peripheral lung areas. Summarizing the results no firm relations between macroscopically classified degrees of respiratory damage and histopathological diagnosed destructions were found; patients, however, whose differentiation of BAL cells showed an extreme neutrophilia developed progressive lung insufficiency (ARDS) a few days later.

[IgG subclass distribution in the serum of patients with homozygous alpha1-antitrypsin deficiency]. / IgG-Subklassenverteilung im Serum von Patienten mit homozygotem alpha 1-Antitrypsinmangel.

In 12 patients with homozygotic ZZ-phenotype alpha 1 antitrypsin deficiency, the serum levels of the IgG subclasses IgG1-4 were studied. In four of these patients, isolated or combined disorders or defects in the distribution of the IgG subclasses were detected; in cases with low IgG2 and absent IgG3, the clinical course of the disease was complicated by bronchiectasis.

[Risk of contrast medium reactions in cardiac diagnosis. Pretreatment with glucocorticoids and antihistaminics in known cases of intolerance to contrast media]. / Risiko von Kontrastmittelreaktionen in der Herzdiagnostik. Vorbehandlung mit Glucocorticoiden und Antihistaminika bei bekannter Kontrastmittelunverträglichkeit.

Among 4178 patients who between 1980 and 1986 had undergone left-heart catheterization with left-heart injections and coronary angiography there were 76 (1.8%) with previous reactions to contrast media. These latter patients were given, three days before the planned investigation, 6 alpha-methylprednisolone, 24 mg daily by mouth, and phenhydramine hydrogenmaleinate, 150 mg daily, and two hours before the investigation 80 mg 6 alpha-methylprednisolone hemisuccinate intravenously. The effect of this prophylactic regimen was tested prospectively. Diatrizoate 76% was the contrast medium used. Of 4102 patients without known contrast-medium intolerance 137 (3.34%) had a reaction, 27 of them (0.66%) severe enough to require treatment. Among the 76 patients with known previous reactions, nine (11.8%) had reactions, one very severe requiring treatment, the others mild. The described pre-injection regimen thus allows indicated left-heart contrast-medium injection to be undertaken at a justifiable risk.

[Shock lung (ARDS): glucocorticoids?]. / Schocklunge (ARDS): Glukokortikoide?

Numerous experimental investigations have demonstrated the benefit of glucocorticoids in the initial phase of the shocklung syndrome (ARDS), showing an increasing pulmonary perfusion by blocking the formation of vasoactive substances and a stabilization of endothelial and lysosomal membranes; another effect is to be seen in the inhibition of neutrophilic chemotaxis and pulmonary leukostasis, leading to reduced inflammatory reaction and less severe pulmonary damage. Clinical studies of glucocorticoid therapy in ARDS indicate a higher rate of surviving patients, when they were treated early and with glucocorticoids in a high dosage. The ill-defined condition of ARDS, however, and the use of different dosages in most of the studies limit the comparison of success dependent on those regimes; e.g. the given dosage varies from a single dose of 250 mg. methylprednisolone to several infusions of 30 mg./kg. body weight. According to the pharmacokinetics of glucocorticoids, the desired effects cannot be expected by application of a single and small dosage. To verify the benefit of high-dosage glucocorticoids in ARDS a stronger definition is needed to mark the onset of the syndrome and the start of glucocorticoid treatment. Additionally the dosage regimen should be standardised.