Adsorption of anionic and cationic surfactants on anionic colloids: supercharging and destabilization.

We present herein a study on the adsorption of anionic (SDS), cationic (CTAB), and nonionic (C(12)E(5)) surfactants onto anionic silica nanoparticles. The effects of this adsorption are studied by means of the static structure factor, S(q), and the collective diffusion coefficient, D(c), obtained from small-angle X-ray scattering and dynamic light scattering measurements, respectively. The effective charge on the particles was determined also from classical electrophoresis and electroacoustic sonic-amplitude measurements. The surface tension of the sample was also investigated. Of particular note is the adsorption of SDS onto the silica nanoparticles, which leads to supercharging of the interface. This has interesting repercussions for structures obtained by the layer-by-layer (LbL) technique, because emulsions stabilized with supercharged and hydrophobized silica are perfect candidates for use in a multilayer system.

Absorption pattern of trospium chloride along the human gastrointestinal tract assessed using local enteral administration.

BACKGROUND AND OBJECTIVES: The antimuscarinic drug trospium chloride is hydrophilic and therefore does not enter the CNS when used for the treatment of overactive bladder disturbances. However, the same property is the main reason for low and variable oral bioavailability. The present study was performed to assess the influence of intestinal site on absorption of the drug as the basis for the development of modified release preparations. METHODS: In a change-over pilot study, 8 healthy male volunteers received single 20 mg doses oftrospium chloride orally as a tablet (reference), as Eudragit-coated tablets dissolving at pH 6.0 (local administration into the small intestine), and rectally via a mini enema (corresponding to local administration into the large intestine). Plasma concentrations of trospium chloride were determined up to 36 hours after administration using GC/MS. RESULTS: Extent and rate of trospium chloride absorption declined rapidly upon administration into more distal regions of the gastrointestinal tract. C(max) (median: 6.42 ng/ml) and AUC(0.tlast) (42.28 ng/ml x h) were highest and t(max) (3.5 h) was shortest after administration of the reference tablet. AUC(0-tlast) reached 78% (90% CI 43 - 139%) after small intestine administration and 2% (90% CI 1 - 9%) following rectal administration, respectively, relative to the values for the oral tablet. CONCLUSION: Trospium chloride is absorbed primarily in the upper gastrointestinal tract. Development of modified release preparations must balance prolonged apparent absorption rates of the drug against a decrease in bioavailability.

[Selection, problems and perspective of quality indicators]. / Auswahl, Probleme und Perspektiven von Qualitätsindikatoren.

The advances in information technology offer new possibilities to gather and analyse health-related information in order to get an inside view into the quality of medical care. Applied medical interventions and the related outcome for the patient can be evaluated if information of a certain degree of complexity is available. Performance measures are based on collection and aggregation of data. They try to abstract medical performances in order to get objective and comparable variables. These variables are useful in evaluating and monitoring the different dimensions of patient care. Performance measurement can inform people about the outcomes they can expect from certain treatments. Beside formal criteria such as validity and reliability, the specific objectives determine the selection of a relevant performance measure. This article describes actual problems and solutions in the data collection and the analysis of performance measures for the domain of oncology. This way, we want to encourage the meaningful, but critical use of performance measures in medicine. The provision of such information can build the basis for the process of medical decision making by physicians, the selection of a suitable medical institution by patients, and the allocation of resources by providers.

[Patient-oriented, treatment-accompanying documentation as a basis for evaluation with medical oncology as an example]. / Patientenorientierte, behandlungsbegleitende Dokumentation als Basis der Versorgungsforschung am Beispiel der Onkologie.

The documentation of patient characteristics, procedures of care and follow-up of the disease plays an important role in monitoring quality of care and support of clinical research. In order to evaluate the use of Clinical Practice Guidelines and their positive implications towards quality of care (especially patient's outcome), some closer reflections are needed to meet the special requirements. Our intention is to optimise content and extent of the collected information to characterise the different dimensions of the quality of medical care best possible. During the past two decades a comprehensive infrastructure concerning tumour documentation has evolved in Germany. To ensure the possibility to compare and evaluate diagnostic and therapeutic approaches in different medical institutions or health care systems, the systematic, patient-oriented treatment accompanying tumour documentation is a compelling requirement. It is a difficult task to describe pattern of care and measure both performance and outcome objectively. The paradigm of a patient-oriented treatment accompanying documentation includes the collection of clinical relevant process and outcome data in order to reflect the intention and way of thinking of the treating physicians and to get an impression of the "real world effectiveness" of the applied interventions.

Structured clinical documentation for the assessment of medical care.

The developing infrastructure for tumour documentation in Germany offers the unique opportunity to provide the physicians with useful clinical information, to evaluate standards of care, and get an impression about the "real-world-effectiveness" of cancer care. In order to compare and evaluate diagnostic and therapeutic approaches in different medical institutions or health care systems, the systematic, patient-oriented, treatment accompanying tumour documentation is a compelling requirement. Our intention is to optimise content and extent of the collected information to characterise the different dimensions of the quality of medical care the best possible. We found that most of the problems are deriving from the contextually and timely correct documentation of medical procedures which includes diagnostic as well as therapeutic interventions. The content of the documentation together with standards of care, such as Clinical Practice Guidelines, should be parallel developed in interdisciplinary co-operation. This way, the fundamental domains of performance, such as appropriateness, availability, continuity, safety, effectiveness, and timeliness of medical care can described and evaluated objectively.

Development of an oncology data network in Germany.

In the 1990ies, an oncology data network has been set up mainly in the New States of Germany. Although not formally planned and established as a whole, it consists of a number of initiatives, that co-operate well and gain added value from this co-operation. From the technological view, the centre of the network is the Giessener Tumordokumentationssystem (GTDS), that was developed at Giessen University. We present important basic conditions in which this development took place, show some results and describe future directions of the development.

[Standards in information technology-assisted tumor documentation]. / Standards in der IT-unterstützten Tumordokumentation.

Data standards are a irrevocable pre-condition for a variety of applications in information technology, e.g. documentation, communication, and analysis. For this purpose, contents as well as rules for the representation of contents have to be defined. Tumour documentation has a long standing tradition. This contribution shows, which standards exist, how they are related to each other, what they are used for, and which tools exist.

Combining dictionary techniques with extensible markup language (XML)--requirements to a new approach towards flexible and standardized documentation.

In oncology various international and national standards exist for the documentation of different aspects of a disease. Since elements of these standards are repeated in different contexts, a common data dictionary could support consistent representation in any context. For the construction of such a dictionary existing documents have to be worked up in a complex procedure, that considers aspects of hierarchical decomposition of documents and of domain control as well as aspects of user presentation and models of the underlying model of patient data. In contrast to other thesauri, text chunks like definitions or explanations are very important and have to be preserved, since oncologic documentation often means coding and classification on an aggregate level and the safe use of coding systems is an important precondition for comparability of data. This paper discusses the potentials of the use of XML in combination with a dictionary for the promotion and development of standard conformable applications for tumor documentation.

Integrated knowledge-based functions in a hospital cancer registry--specific requirements for routine applicability.

The background of the presented work is the design, realization, and routine use of integrated knowledge-based functions in the context of a hospital cancer registry. The first field of application was supporting registrars to detect data inconsistencies and incompleteness timely during the documentation process. Especially, we focused on the acceptance of the administrator of the underlying information system and on the phenomenon of duplicate and outdated messages. These aspects are specific for integrated knowledge based functions and a precondition for obtaining a routine applicability and acceptance.

Data warehousing as a tool for quality management in oncology.

At present, physicians are constrained by their limited skills to integrate and understand the growing amount of electronic medical information. To handle, extract, integrate, analyse and take advantage of the gathered information regarding the quality of patient care, the concept of a data warehouse seems to be especially interesting in medicine. Medical data warehousing allows the physicians to take advantage of all the operational data they have been collecting over the years. Our purpose is to build a data warehouse in order to use all available information about cancer patients. We think that with the sensible use of this tool, there are economic benefits for the Society and an improvement of quality of medical care for patients.

A model for integration and continuous development of standards for tumour documentation using relational database techniques and extensible markup language.

In oncology various international and national standards exist for different aspects of a disease. These standards, maintained by different organisations, have multiple relationships with each other. A common data dictionary like UMLS would facilitate the reorganisation of such relationships when a new version of a standard is published. While the modelling of relationships usually is restricted to types having a relevant frequency, there are often relationships which are expressed in texts like definitions or explanations. Such texts are a very important supplement for the acceptance and the safe use of coding systems, but often are neglected when implementing coding systems in computerised systems, because they are costly to implement. This paper discusses potentials when integrating various sources in a common, database based dictionary enhanced by XML (Extensible Markup Language) techniques.

[Urologic tumors in Germany. Initial data of 56,013 cases from clinical cancer registers]. / Urologische Tumoren in Deutschland. Ersterhebungen an 56013 Fällen aus klinischen Krebsregistern.

Since 1985 a special work group involved in the coordination of hospital cancer registries in Germany (AKKK) has been collecting, storing and analysing data on tumour patients, received from cancer centres, oncological departments and specialised practices. The documentation of tumour patients is based, among other things, on information concerning localisation, histological findings and tumour spread. The data are stored in a central database administered by the work group. At present it contains data on approximately 500,000 oncological patients. In the period from 1987 to 1992, 56,013 initial entries were made concerning patients with urological tumours. Of these cases, tumours of the kidney (n = 11,424) constituted 20.4%. In 94.6% of the cases, histological investigation revealed a renal cell carcinoma-pT1: 5.8%; pT2: 53.6%, pT3: 37.2% and pT4: 3.4%. Tumours of the urinary bladder (n = 16,246) constituted 29.0% of all urological tumours. In 93.8% of the cases a transitional cell carcinoma was detected-pTis: 1.0%; pTa: 36.9%; pT1: 29.6%; pT2: 16.9%; pT3: 11.4%; pT4: 4.4%. Transitional cell carcinomas of the ureter or of the collecting system (n = 1,846) constituted 3.3% of the cases. The proportion of testicular tumours (n = 6,594) amounted to 11.8%; 53.6% of these germ-cell tumours (n = 6,281) were seminomas and 46.6% were non-seminomas. In all, 66.3% of the cases were lymph-node negative. Tumours of the prostate (n = 19,903) constituted 35.5% of the cases. In the period from 1987 to 1992, the proportion of lymph-node-positive prostate carcinomas decreased from 39.8% to 16.2%. The detailed analysis of these data shows how the hospital cancer registries can support the discussion regarding diagnosis and therapy of urological tumours.

[The solubility and bioequivalence of silymarin preparations]. / Untersuchungen zum Freisetzungsverhalten und zur Bioäquivalenz von Silymarin-Präparaten.

Seven silymarin products (pharmacies only), two of them with two batches each, were analysed for their ingredients, in particular silibinin (CAS 22888-70-6) and tested in vitro for their liberation of active agents. Founded on the results of these tests three products were checked for bioequivalence. Therefore, a typical phase I 3 fold crossover study was performed showing one product (Legalon) to be qualified by an approx. 2 fold higher silibinin availability compared to the two other preparations.

[A new inclusion complex of silibinin and beta-cyclodextrins: in vitro dissolution kinetics and in vivo absorption in comparison with traditional formulations]. / Nuovo complesso di inclusione tra la silibina e la beta-ciclodestrina: velocità di dissoluzione in vitro e assorbimento in vivo in confronto a formulazioni tradizionali.

The very low bioavailability of silybinin, the main constituent of silymarin, so far prevented the development of an oral pharmaceutical specialty based on this active ingredient. To overcome this difficulty, an inclusion complex between Silybinin and beta-Cyclodextrin was prepared. The new complex was compared in vitro tests (dissolution rate) and in a in vivo test (rat bile elimination) with silybinin, silymarin and one traditional formulation based on silybinin. The results show a dramatic increase in the dissolution rate of the complex (> 90% within 5 min) respect to the silybinin that confirm to be practically insoluble (< 5%). The in vivo results agree with the dissolution rates; after administration of the silybinin complex p.o., the silybinin concentration in the rat bile was near 20 times more than after administration of silybinin as is or in a traditional formulation. In the last two cases, the silybinin concentration was even 6 times less than after administration of the same amount of silymarin. These data show that the beta-CD complex solved the problem of the bioavailability of silybinin which, in the traditional formulation utilised as reference, proved to be not bioavailable.

[The value of ultrasound-controlled fine-needle biopsy in the diagnosis of possible neck tumors]. / Stellenwert der ultraschallgesteuerten Feinnadelbiopsie in der Diagnostik unklarer Halstumoren.

From October 1985 to July 1988 we performed a study to examine 106 patients with head and neck tumours, by using ultrasound as a guiding system for fine-needle aspiration biopsy. It could be shown that this method has a high diagnostic significance at the neck with a low rate of risks. In a first step puncture was effected to obtain material for cytology, if necessary also for a bacteriological examination. Normally, in a second step a fine-needle cutting biopsy was done to obtain histological material. The combined use of aspiration and cutting needle biopsy achieved correct tumour status in 91.5%, whereas in 73.6% the correct type of lesion was diagnosed. A false status assessment and errors in identifying the lesions occurred in 2 of 106 cases; there of was one false negative status assessment. In cases of benign neck cysts, neck abscesses and non-specific lymphadenopathy, a cutting neck biopsy is not required, provided the clinical diagnosis is in accordance with the result of aspiration cytology and the further clinical progress. The advantage of the ultrasound-guided puncture compared with palpation-guided puncture is the certainty of locating the region of interest even in deep lesions without an appreciable risk of complications. In our opinion, ultrasound-guided fine needle aspiration biopsy is indicated in all cases of unclear head and neck tumours which could be treated conservatively if the result of the puncture is non-malignant.

[Ultrasonic diagnosis of the salivary glands]. / Ultraschalldiagnostik der Speicheldrüsen.

Sonography of the salivary glands is a valuable diagnostic tool in acute and chronic sialadenitis, sialadenoses, lymphadenopathies and tumours lesions. A new examination technique is presented: ultrasound-guided fine needle biopsy. We report on our experience in 308 patients with parotid and in 47 patients with submaxillary gland diseases examined between 1982 and 1987. The diagnostic accuracy and limitations of sonography are discussed compared with sialography, computed tomography and magnetic resonance imaging.

Prevalence of goitre and hypothyroidism in Southern Tanzania: effect of iodised oil on thyroid hormone deficiency.

In the Southern Highlands of Tanzania the prevalence of endemic goitre due to iodine deficiency is in the range of 90% and hypothyroidism in the range of 50% of schoolchildren. The present study confirms these data and documents the beneficial effect of Lipiodol injections on thyroid function in children around the age of puberty compared with untreated children from the same villages. On the other hand, a decrease in the prevalence of goitre could not be shown. A beneficial effect is shown for infants of mothers who received iodine during pregnancy. It seems that this form of supplementation is sufficient for breast fed children for more than three years, even when a second child has been delivered in the meantime. In contrast, older siblings of these babies may become hypothyroid when breast feeding is stopped. The determination of thyroid autoantibodies in iodine treated and untreated children and in young adults showed no increasing prevalence of positive findings thus excluding iodine induced chronic thyroiditis at least in the young target population.

Iodine deficiency, hypothyroidism, and endemic goitre in southern Tanzania. A survey showing the positive effects of iodised oil injections by TSH determination in dried blood spots.

UNLABELLED: The Ukinga and Uwanji regions, located in the southern highlands of Tanzania, were studied for the degree of iodine deficiency and the incidence of goitre and hypothyroidism, respectively. A urinary iodine excretion as low as 17.6 +/- 9.3 micrograms/g creatinine was observed in Wangama village. The mean goitre prevalence in 27 villages in Uwanji ranged between 65 and 96% (n = 3031 schoolchildren). Of 681 pregnant women from Ukinga 79.6% had goitre. The prevalence of cretinism as estimated on clinical criteria was 3% in Magoye (Uwanji). A normal serum TSH (below 2.1 mU/l) was observed in only 12 out of 66 school children before iodine prophylaxis, whereas the T4/TBG ratio was decreased in 36 of 63 cases. Blood spot TSH levels in newborn infants (n = 219) from mothers without iodine supplementation were above 12 mU/l in 45%. In contrast, only 20.3% of the newborn (n = 118) had elevated blood spot TSH (p less than 0.002) when the mothers had received an iodised oil injection during pregnancy. Most of the newborn (n = 18; 75%) of the latter group with elevated TSH (n = 24) came from mothers who had received the iodine injection only 1-25 days before delivery. Maternal iodine prophylaxis in late pregnancy does not increase the rate of neonatal hypothyroidism. CONCLUSIONS: It has been confirmed that severe iodine deficiency resulting in endemic goitre, cretinism, and hypothyroidism is prevalent in the regions studied. Dried blood spot TSH determinations may serve as an index for the efficiency of iodine prophylaxis programmes. Such a programme was carried out with relatively little expenditure and effort on a large scale basis.

[Goiter epidemiology. IV. Thyroid volumes in German and Swedish school children]. / Strumaepidemiologie. IV. Schilddrüsenvolumina bei deutschen und schwedischen Schulkindern.

Thyroid volume was determined by ultrasound in 13-year-old school-children (n = 2244) from 23 places in the Federal Republic of Germany and in 224 school-children from Stockholm (where there is adequate iodine supply). The results show that thyroid size gradually increases from north to south. There are clear endemic nests in the central region of the Federal Republic of Germany. Mean thyroid volume in Swedish children was 4.2 ml, in German children 9.3 ml. More than one third of German children have a larger thyroid volume than the largest volume measured in Swedish children. The results support the need for iodine-salt prophylaxis for the entire German Federal Republic.