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.     

Der ältere Rettungspatient in der Notfallaufnahme

The elderly account for an ever-increasing proportion of emergency department patients. Demographic data show that the population which is 80 years of age or older will be further increasing in coming years. Due to this fact we sought the reasons of using of the emergency department by elderly patients (≥80 years), admitted by ambulance service, and to analyse the general management of this collective according to a younger comparison group. We used the data from a prospective registry, in which all consecutive patients admitted to the emergency department by ambulance service were included, to process this retrospective analysis. In this registry, diagnosis (in the ICD-10 classification), age, sex, and inpatient/outpatient treatment were documented. In addition further management, intensive care treatment, and outcome during emergency department stay were registered. The patients were stratified by age into two groups (< 80 years; ≥80 years). The observation period lasted from January 1, 2005 to December 31, 2005. During the study 6590 patients were observed of whom 5670 patients (86.0%) were under 80 years (PG<80) and 920 (14.0%) were 80 years of age or older (PG≥80). Comparing inpatient treatment (PG<80: 40.1%; PG≥80: 39.8%) vs outpatient treatment (PG<80: 59.9%; PG≥80: 60.2%) no significant difference between both groups was registered. In comparing the ICD- 10 main diagnosis categories, no relevant difference could be ascertained. By contrast a significantly higher mortality (3.0% vs 1.6%; p≤0.01) in the emergency department was shown within the PG≥80, especially if the diagnosis was myocardial infarction or stroke. The most frequent discharge diagnosis in the PG≥80 was acute myocardial infarction (6.7%). A percutaneous coronary intervention and artificial respiration was less frequently used in the elderly group. Patients beyond 80 years of age nowadays constitute a remarkable proportion of emergency department patients admitted by ambulance service. This group does not differ substantially from younger patients, neither in questions of inpatient or outpatient treatment nor in types of diagnosis. Elderly patients in the emergency department showed a higher mortality. Invasive interventions were less frequently used in this collective in comparison to younger patients. In consideration of the fact that the proportion of elderly will further increase in our population, this analysis may give basis for development of new strategies for the treatment of old patients in emergency departments.     

Increased Radiosensitivity as an Indicator of Genes Conferring Breast Cancer Susceptibility

PURPOSE: This paper briefly summarizes the research on increased radiosensitivity in breast cancer patients measured by the micronucleus test (MNT) and its association to genetic variants in DNA repair genes. More preliminary data are presented on the distribution of chromosomes and chromosome fragments in micronuclei (MN) in order to gain more information on clastogenic and aneugenic effects and better understand the phenotype of increased radiosensitivity. MATERIAL AND METHODS: Reports of relevant studies obtained from a search of PubMed and studies referenced in those reports were reviewed. In four patients with high MN frequency (three cancer patients, one control) and four probands with low MN frequency, the presence of chromosome fragments or whole chromosomes in MN was determined by fluorescence in situ hybridization analysis for chromosomes 1, 7, and 17. RESULTS: An increased MN frequency in breast cancer patients compared to controls has consistently been reported with high significance. Higher MN frequencies were observed in 20-50% of breast cancer patients. Chromosomal fragments of chromosome 17, but not of chromosomes 1 and 7 were more frequent in the probands with high MN frequency than in those with low frequency (p = 0.045). CONCLUSION: The MNT detects a cellular phenotype common to a portion of sporadic breast cancer patients. This phenotype is very likely to be genetically determined. For the genetic dissection of breast cancer susceptibility this phenotype may turn out to be more efficient than breast cancer itself. Additional parameters which can be measured simultaneously with the MN frequency may be able to further enhance its usefulness.     

Ethyl-EPA in Huntington disease—Potentially relevant mechanism of action

The pathomechanisms involved in the neuronal dysfunction in Huntington disease (HD) are still unresolved and may be heterogeneous. One potential mechanism might be related to the induction of mitochondrial dysfunction in the CNS. This might lead firstly to neuronal dysfunction and finally to the activation of apoptotic pathways. Several compounds, which should alleviate mitochondrial dysfunction, have been tested in preclinical models as well as in clinical trials of different scale. Recently we reported the efficacy of Ethyl-eicosapentaenoic acid (Ethyl-EPA) in patients with HD. Ethyl-EPA is a polyunsaturated fatty acid from the n − 3 group, which is in clinical development for HD and melancholic depression. In our trial with Ethyl-EPA in HD responding patients could be characterized by either a lower CAG repeat number or a chorea-predominant clinical expression of the disease. Here we would like to describe some evidence on the potential mechanism of action of Ethyl-EPA in HD. We specifically focus on pathways, which are known to be influenced in HD and are modified by Ethyl-EPA and which points to an involvement of mitochondrial function as a common target. Some attention is given to the NF-kappa B pathway and the c-Jun amino-terminal kinases (JNK) pathway, which both may lead to an activation of the antiproliferative factor p53 and consequently mitochondrial dysfunction. Further the effects of EPA or Ethyl-EPA in preclinical models of HD are described. The evidence from these studies led to the design of phase III clinical trials, which are ongoing.     

Decrease of glucose in the human visual cortex during photic stimulation.

Localized proton NMR spectroscopy was used to study cerebral metabolism in the visual cortex of healthy adults during rest and photic stimulation. Basal lactate levels showed considerable interindividual differences ranging from below detectability (less than 0.3 mM) to about 1 mM without consistent alteration during photic stimulation. Local brain glucose levels were significantly reduced (approximately 50%) during the entire period of photic stimulation and recovered to resting levels (approximately 0.8 mM) within 10 min after the end of stimulation. This decrease reflects the establishment of a new equilibrium due to enhanced delivery (blood flow) and enhanced consumption. The absence of lactate accumulation supports the hypothesis of a rapid efflux of lactate from brain tissue under activated conditions.     

Lack of effect of recombinant human interferon-alpha 2b on expression of 17-1A antigen on human colon cancer cells.

The effects of recombinant human interferon alpha (rHuIFN-alpha 2b) on cell growth, expression of antigenic receptor sites (r) and the affinity constant (Ka) of monoclonal antibody CO 17-1A IgG were studied on two human colorectal cancer cell lines, CX-1 and SW 1116. Cells were incubated with varying concentrations of rHuIFN-alpha 2b prior to exposure to 125I-labeled 17-1A IgG at 37 degrees C following which r and Ka were determined by means of Scatchard plots. Varying concentrations of rHuIFN-alpha 2b had significant growth inhibitory effects on CX-1 and SW 1116 cells, which were time and concentration dependent, but no effects on expression of r and Ka compared to controls. Our data indicate that rHuIFN-alpha 2b does not invariably increase the expression of tumor-associated antigens and that this effect may be independent of its antiproliferative activity. The in vitro response or lack thereof of neoplastic cells to rHuIFN-alpha 2b may be useful to identify those patients who potentially might gain from a clinical course of rHuIFN-alpha 2b for either therapeutic or diagnostic purposes.     

Detection of local recurrence of soft-tissue sarcoma with positron emission tomography using [18F]fluorodeoxyglucose

Background: It is often difficult to detect a local recurrence of soft-tissue sarcomas due to disturbance of the normal anatomy by previous surgery and radiotherapy. The aim of this study was to assess the value of positron emission tomography (PET) with [¹⁸F]fluoro-2-deoxy-d-glucose (FDG) for detecting local recurrences. Methods: In the period 1992–1995, 17 patients with proven or suspected local recurrence of soft-tissue sarcoma were examined using FDG-PET. Fifteen of these patients were ultimately proven to have a recurrence. Results: Recurrence was visualized in 14 patients (93%). Small tumors (maximum diameter 0.5 cm) were as easily visible as large lesions (maximum diameter 20 cm). In one patient the PET scan was positive, but the recurrence could not be proven histologically. Recurrence was proven 1 year later. A recurrent low-grade liposarcoma was not visualized. The two patients with benign lesions had a negative PET scan. The mean glucose metabolic rate was calculated to be 13.2 μmol/100 g/min (range 1.9–28.4). A correlation was found between the histological malignancy grade and the metabolic rate (p<0.05; Kruskal-Wallis). Conclusion: PET with FDG is a useful addition to the diagnostic armamentarium for detecting local recurrence of soft-tissue sarcomas and provides an indication of the malignancy grade of the recurrent lesion. Presented at the 47th Annual Meeting of The Society for Surgical Oncology, Houston, Texas, March 17–20, 1994.     

A method to remove artifacts in attenuation-corrected myocardial perfusion SPECT Introduced by misalignment between emission scan and CT-derived attenuation maps.

Nonuniform soft-tissue attenuation affects the diagnostic accuracy of SPECT in myocardial perfusion imaging. The attenuation map required for attenuation correction can be acquired using x-ray tomography (CT). Frequent findings in attenuation-corrected images are defects in the apical and anterior myocardial wall. We assume that these are artifacts produced by misalignment of SPECT images and the attenuation map. METHODS: One hundred forty patients underwent myocardial perfusion imaging with 99mTc-methoxyisobutylisonitrile. Twenty-seven of 140 showed pronounced defects in the apical or anterior wall only after CT-based attenuation correction. SPECT and corresponding CT slices were examined for misalignment in the ventrodorsal direction (y-direction) visually and by threshold-based delineation of the body surface. Mismatched studies were realigned and image reconstruction and analysis were redone. The effect of the correction was assessed visually and by semiquantitative analysis based on a 20-segment model using 4D-MSPECT. RESULTS: In 15 of 27 patients, the improved coregistration led to smaller and less-pronounced defects in the regions mentioned. In 6 of 27 patients, former defects were judged as normal. No improvement was seen in only 4 patients. In these 4 subjects, the mismatch in the y-direction was <1 pixel (7 mm), and visual inspection suggested a coincident mismatch in the craniocaudal direction. In 2 cases, coregistration was not possible because the body outline extended beyond the CT field of view. Semiquantitative analysis revealed a significant increase of the relative uptake in the apex; in the apical segments of the anterior, septal, and inferior wall; and in the mid-anterior and mid-anteroseptal segment. Basal segments of the anterolateral, lateral, and inferolateral wall and the middle inferolateral segment showed a significant decrease of relative uptake. CONCLUSION: Misalignment in the y-direction between SPECT and the attenuation map can lead to artifacts in the apical, septal, and anterior wall, which will appear as defects. It also can cause overcorrection in the basal inferior and lateral segments. There is evidence that mismatches along the other directions may have a similar effect. The coregistration of SPECT and the attenuation map needs to be verified for every patient, even when using integrated dual-modality imaging devices.