Hydrolysis of lactitol, maltitol and Palatinit by human intestinal biopsies

1. The hydrolysis of sugar alcohols of the disaccharide type such as lactitol, maltitol and Palatinit (the latter an equimolar mixture of 6-O-alpha-D-glucopyranoside-D-mannitol and 6-O-alpha-D-glucopyranoside-D-sorbitol) by homogenates of human intestinal biopsies were compared with corresponding natural disaccharides such as lactose, maltose and isomaltose. Seven of the human biopsies were normal with regard to their disaccharidase activities, while twelve biopsies showed decreased levels of disaccharidase activities. 2. All biopsies, normal as well as abnormal, showed essentially the same capacity to hydrolyse the sugar alcohols. Activities towards lactitol (0.34 IE/g protein (where IE = mumol disaccharide hydrolysed/min at 37 degrees)) and Palatinit (2.50 IE/g protein) were only 1.3% of those towards lactose and isomaltose. The activity towards maltitol was much higher (19.1 IE/g protein), approximately 10% of that towards maltose and about as high as the activity towards trehalose. This finding indicates that despite the fact that lactitol and Palatinit were poor substrates, significant amounts of ingested maltitol might be digested and utilized by man. 3. Glucose release was reduced by approximately 25% when maltitol or Palatinit were present at concentrations equal to those of maltose. Palatinit decreased the hydrolysis of sucrose by 12%. Lactitol had no inhibitory effect on the hydrolysis of disaccharides.     

Operative versus non-operative treatment of recent injuries to the ligaments of the knee. A prospective randomized study

Two hundred consecutively seen patients who had an injury to either the anterior cruciate ligament or the medial collateral ligament, or both, were randomly allocated to treatment by either conservative or a surgical regimen. Injuries to the medial collateral ligament could not be demonstrated to benefit from surgical treatment in any respect--with or without surgery the results were excellent. With injuries to the anterior cruciate ligament, recovery was more rapid without surgery but otherwise the results differed between the groups in only one respect: the pivot-shift test was more often positive after conservative treatment. The results were good in both treatment groups even though most of the patients who had an injury of the anterior cruciate ligament were somewhat less pleased with the outcome after a period of time.     

Occurrence and Distribution of Bone Tumors in Beagle Dogs Exposed to 90Sr

Radiation-induced bone tumors in beagle dogs exposed to ⁹⁰Sr have been evaluated in terms of their incidence, time of appearance, occurrence as multiple tumors, anatomic distribution, and the influence of sex on their development. Among dogs fed ⁹⁰Sr during skeletal development, the incidence of bone tumors was dose dependent. Tumors thus appeared in 10 of 19 dogs receiving average skeletal doses of 130 Gy, 15 of 60 receiving 97 Gy, 5 of 61 receiving 61 Gy, 2 of 65 receiving 26 Gy, and 1 of 40 receiving 1.3 Gy. No tumors appeared among 66 dogs who received 8 Gy, 78 who received 0.3 Gy, and 80 non-irradiated controls, all of which have been observed for life. Among dogs given a single intravenous injection of ⁹⁰Sr in early adulthood, tumor production was somewhat higher than among ⁹⁰Sr-fed dogs at the same radiation dose: bone tumors were present in 6 of 25 dogs who received 62 Gy and 1 of 20 dogs who received 7.5 Gy. Bone tumors appeared sooner and were more often multiple in animals receiving the higher doses. Long bones were the sites of most of the tumors appearing after the highest dose level. Bones of the head, particularly the mandible, were the predominant site of tumors in the next highest dose level group.     

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.     

Comparative in vivo evaluation of technetium and iodine labels on an anti-HER2 affibody for single-photon imaging of HER2 expression in tumors.

In vivo diagnosis with cancer-specific targeting agents that have optimal characteristics for imaging is an important development in treatment planning for cancer patients. Overexpression of the HER2 antigen is high in several types of carcinomas and has predictive and prognostic value, especially for breast cancer. A new type of targeting agent, the Affibody molecule, was described recently. An Affibody dimer, His6-(ZHER2:4)2 (15.4 kDa), binds to HER2 with an affinity of 3 nmol/L and might be used for the imaging of HER2 expression. The use of 99mTc might improve the availability of the labeled conjugate, and Tc(I)-carbonyl chemistry enables the site-specific labeling of the histidine tag on the Affibody molecule. The goals of the present study were to prepare 99mTc-labeled His6-(ZHER2:4)2 and to evaluate its targeting properties compared with the targeting properties of 125I-4-iodobenzoate-His6-(ZHER2:4)2 [125I-His6-(ZHER2:4)2]. METHODS: The labeling of His6-(ZHER2:4)2 with 99mTc was performed with an IsoLink kit. The specificity of 99mTc-His6-(ZHER2:4)2 binding to HER2 was evaluated in vitro with SK-OV-3 ovarian carcinoma cells. The comparative biodistributions of 99mTc-His6-(ZHER2:4)2 and 125I-His6-(ZHER2:4)2 in tumor-bearing BALB/c nu/nu mice were determined. RESULTS: The labeling yield for 99mTc-His6-(ZHER2:4)2 was approximately 60% (50 degrees C), and the radiochemical purity was greater than 97%. The conjugate was stable during storage and under histidine and cysteine challenges and demonstrated receptor-specific binding. The biodistribution study demonstrated tumor-specific uptake levels (percentage injected activity per gram of tissue [%IA/g]) of 2.6 %IA/g for 99mTc-His6-(ZHER2:4)2 and 2.3 %IA/g for 125I-His6-(ZHER2:4)2 at 4 h after injection. Both conjugates provided clear imaging of SK-OV-3 xenografts at 6 h after injection. The tumor-to-nontumor ratios were much more favorable for the radioiodinated Affibody. CONCLUSION: The use of Tc(I)-carbonyl chemistry enabled us to prepare a stable, site-specifically labeled 99mTc-His6-(ZHER2:4)2 conjugate that was able to bind to HER2-expressing cells in vitro and in vivo. The indirectly radioiodinated conjugate provided better tumor-to-liver ratios. The labeling of Affibody molecules with 99mTc should be investigated further.     

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.