Safety and efficacy of pimecrolimus cream 1% in the daily practice: Results of a patient self‐observation study in patients with atopic dermatitis

Background: Pimecrolimus cream 1% has proven to be well‐tolerated and effective in controlled clinical studies in patients with atopic dermatitis (AD). In a 15‐week patient self‐observation study, safety and efficacy was investigated in the daily practice. Patients and methods: 3502 patients with AD (mean age 26.2 ± 18 years, 62% female) received pimecrolimus cream 1% from 810 physicians in the German Federal Republic.The severity of the disease was assessed at baseline, two times during the 15‐week observation period and at the end of treatment.Patients recorded daily the degree of erythema and pruritus. At the end of treatment, safety and efficacy were assessed by the physician based on patient's daily records and by the patient. Results: The percentage of patients with severe or massive AD decreased from 25% to 7%, whereas the percentage of patients without or with mild symptoms increased from 9% to 55%.The efficacy of treatment was rated by physicians as good or very good in 83.5% of cases and by 79% of patients.At baseline 35% of the patients were free of flares as compared to 75% at the end of therapy. Disease control was better in patients who followed the recommended treatment algorithm for pimecrolimus cream.Tolerability was mostly rated as good or very good. Conclusion: Treatment with pimecrolimus cream 1% for patients with AD is well‐tolerated and effective in daily practice.     

Clozapine-induced cholestatic jaundice: a case report

We report on a patient who became jaundiced during treatment with clozapine (Leponex). Histologically, cholestatic hepatitis with single-cell necroses of hepatocytes and infiltration of the portal zones with eosinophilic granulocytes were found. The patient recovered after discontinuation of clozapine, and liver function tests returned to normal within 4 weeks. This adverse effect of clozapine suggests that this "atypical" tricyclic neuroleptic resembles the phenothiazines both with regard to therapeutic spectrum and side effects.     

Strain dependency of the transfer of experimental immune insulitis in mice.

Multiple treatment with low doses of streptozotocin induces hyperglycaemia with concomitant lymphocytic infiltrations into pancreatic islets (insulitis) in several mouse strains. The transfer of cellular immune reactions against islet cells by means of spleen cells was tested in two congeneic and five allogeneic strain combinations. Donor mice were treated on 5 consecutive days with 40 mg streptozotocin per kg body weight. Three weeks later, 5 x 10(7) live spleen cells were transferred into thymusless recipient mice. Insulitis which had developed in about 70% of the donors was only transferable from C57B1/6J to congeneic thymusless mice. In a second congeneic and in all allogeneic strain combinations, cellular immune reactions against pancreatic islets could not be transferred. In none of the recipients of spleen cells from diabetic donors was hyperglycaemia observed. As streptozotocin-induced cellular immune reactions against pancreatic islet cells were only transferable in one congeneic and in no allogeneic strain combinations, it is concluded that there is a genetic restriction both on the levels of donor and recipient mice.     

An immunohistochemical study of the breast using antibodies to basal and luminal keratins,alpha-smooth muscle actin,vimentin, collagen IV and laminin

Summary The distribution of simple epithelial (K8/18/ 19) and basal (myoepithelial) (K5/14) keratins, -smooth-muscle actin, vimentin, collagen IV and laminin in normal mammary glands and in benign proliferative lesions was studied using monoclonal antibodies (mAbs). These antibodies (Abs) identified myoepithelial cells and luminal cells specifically. In lesions with adenosis and papillomas, the two-layered formation resembled that of normal glands with a purely myoepithelial-epithelial differentiation. In scleradenotic lesions, the main cell was of myoepithelial immunophenotype with intermixed trabecular-tubular proliferations of simple-type epithelium. The sclerosis seems to be the result of an irregular basal lamina synthesis by the myoepithelial cells. In contrast to these lesions, epitheliosis represents a purely intraluminal cell proliferation of clearly simple epithelial immunophenotype and of cells with a basal keratin phenotype, lacking myoepithelial differentiation antigen actin. The basal keratin type epithelium may represent post-stem or intermediate cells developing into luminal epithelium. Epitheliosis appears to be a purely epithelial hyperplasia with striking similarity to the regeneration of normal breast epithelium. The different proliferative patterns may give an explanation for differences in potential cancer risks of patients with these lesions.Dedicated to Prof. Dr. G. Seifert on the occasion of his 70th birthday     

Triple fluorescence labelling of neuronal,glial and vascular markers revealing pathological alterations in various animal models

The simultaneous detection of glia, vessels and neurons facilitates insights into the complex chemoarchitecture of the central nervous system. Here, we present a simple, robust and versatile approach for the carbocyanine triple fluorescence labelling of neuronal, vascular and glial markers.The usefulness of this procedure is shown for rat brain tissue under physiological conditions, after traumatic brain injury caused by controlled cortical impact injury, and after stroke following middle cerebral artery occlusion. Moreover, the versatility of the method is verified by its application to sections from old triple transgenic mice with age-dependent β-amyloidosis and tau hyperphosphorylation in the hippocampus, modelling neuropathological alterations in Alzheimer‘s disease. To exemplify the usefulness of the approach for analysis of the enteric nervous system, it was applied to whole mounts from the horse intestine.The biotinylated lectin from potato (Solanum tuberosum) is presented as an excellent tool to detect both vessels and microglia. Furthermore, this lectin revealed macrophages after experimental insults, and senile plaques in aged triple transgenic mice. A large portion of astroglia was demonstrated by immunolabelling of glial fibrillary acidic protein. Neurons were detected by monoclonal antibodies directed against neuronal nuclei and, in horse tissues, mouse-anti-HuC/D recognizing a conserved nuclear protein. Confocal laser-scanning microscopy elucidated spatial relationships of the relevant markers and their pathological alterations after experimental insults and in transgenic mice with Alzheimer-like lesions.     

Long-term exposure to telmisartan as monotherapy or combination therapy: efficacy and safety

This multicentre, open-label extension study to four controlled trials involved 888 patients with mild-to-moderate primary hypertension. Patients received telmisartan 40-80 mg once daily with add-on hydrochlorothiazide (HCTZ; 12.5-25 mg) if necessary and/or other antihypertensives to achieve diastolic blood pressure (DBP) control (<90 mmHg). Treatment continued for up to 4 years. At treatment end, 578 (65.1%) patients were on telmisartan monotherapy, 106 (11.9%) were on telmisartan + HCTZ 12.5 mg, 101 (11.4%) were on telmisartan + HCTZ 25 mg, and 103 (11.6%) were on telmisartan + another antihypertensive + HCTZ. Overall, 84.4% (746/884) patients achieved DBP control. The highest proportion of responders was in the telmisartan monotherapy (40 or 80 mg) treatment category (89.0% 1,511/574 patients]). The mean change in systolic blood pressure (SBP)/DBP from the previous trial baseline to last available trough was -21.2/-17.3 mmHg with telmisartan alone, -24.6/-16.7 mmHg with telmisartan + HCTZ, and - 18.7/-14.9 mmHg with telmisartan + another antihypertensive +/- HCTZ. Most adverse events were of mild-to-moderate intensity and unrelated to treatment. The proportions of patients discontinuing the study due to adverse events, by treatment at onset, were 7.3% (65/888) with telmisartan monotherapy, 6.6% (20/304) with telmisartan + HCTZ and 2.9% (3/103) with telmisartan + another antihypertensive +/- HCTZ. There were 15 deaths during the study, but none was considered drug related. Thus, telmisartan alone or in combination with other antihypertensives achieved and maintained clinically relevant reductions in DBP and SBP. This long-term analysis supports the favourable efficacy and safety profile of telmisartan both as monotherapy and in combination with other antihypertensive drugs.     

Ungewöhnliche Verläufe traumatischer Epiduralhämatome

Within one year in 71 cases of skull injury trepanations were done. There were 36 epidural hematomas among these, 10 of them presented an atypical course or peculiar symptoms. The analysis of our cases shows that in skull and brain injury with fractures and atypical neurological signs an active diagnosis is needed. The computerized tomography makes it possible to demonstrate the position and the extent of intracranial hemorrhages. The method is non-invasive and reliable. If in patients with a skull injury the computerized tomography is used consequently, epidural hematomas will be recognized more frequently. It will be possible to reduce the number of cases with a fatal outcome.