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Special methodological problems in antibiotic susceptibility testing of fermentative actinomycetes.

Knowledge on the antibiotic suceptibility of pathogenic fermentative actinomycetes is still fragmentary and contradictory, which is one reason why even today the chemotherapy of human actinomycosis may still present problems. Complete and reliable data on the in vitro sensitivity of these pathogens can be obtained, however, when standardized and specially adapted methods of susceptibility testing are employed. Special adaptation should cover the general technique of in vitro testing, as well as the choice of test media, the preparation of inocula, incubation methods and method of reading results. Provided that all factors are taken into account which might cause difficulties in test reproducibility and therapeutic relevance of the results, in vitro tests appear to contribute to the revision and updating of treatment regimes for actinomycosis. Our findings indicate that, apart from ampicillin the clinical efficacy of which has already often been proved, mezlocillin, cefoxitin, clindamycin, tetracyclines, rifampicin and erythromycin may be recommended as alternative drugs which would seem to offer good chances of success.

Actinomycetaceae↗

Microsurgery of the hypothalamus with special reference to craniopharyngioma.

After a short survey of microanatomy, microtopography, neurophysiology and neuropathophysiology of the hypothalamus the surgical approaches to the hypothalamus with special reference to the craniopharyngiomas are described in detail. Based on 100 personal cases (1954-1979) the special procedure, depending on the site and extent of the tumour and its involvement of the hypothalamus, is discussed. Primary radical excision (19 cases) with a mortality rate of 10.5% seems to be the method of choice, as late mortality recurrences and secondary operations are frequent after non-radical procedures. Modern microsurgical technique promises to achieve primary radical excision more frequently and with less risk.

Cerebral Angiography↗

Membrane structural specialization of the toad urinary bladder revealed by the freeze-fracture technique. I. The granular cell.

Examination of the toad urinary bladder by freeze-fracture electron-microscopy demonstrates structural specialization of the granular cell's luminal membrane compared to its basal membrane. Although both membranes appear to possess about 1,700 intramembranous particles per mum2, those of the luminal membrane tend to be significantly larger in size. In addition, the fracturing properties of the two membranes are markedly different: the majority of particles are found on fracture face B (outer membrane face), in the case of the luminal membrane, and the majority are found on fracture face A (inner membrane face), in the case of the basal membrane. While the two fracture faces of the basal membrane possess a similar distribution of particle sizes, in the case of the luminal membrane the B face was found to possess particles generally larger than those found on the A face. It was established that the probability of luminal membrane particles adhering to face B instead of face A is closely correlated with the size of the particle. The structural specialization of the granular cell's luminal membrane may have an important relationship to the characteristic permeability properties of this membrane and the capacity of this cell type to respond physiologically to the hormone vasopressin.

Animals↗

The role of the liver in clearance of glycoproteins from the general circulation, with special reference to intestinal alkaline phosphatase.

Glycoproteins represent a wide variety of macromolecules with important physiological functions. Characteristic variations in carbohydrate composition and plasma concentration of these proteins may occur during pathological conditions. Steady-state plasma concentrations are determined by release from normal or diseased tissues and simultaneous clearance from the general circulation. The liver occupies a central position in the production but also clearance and catabolism of such glycoproteins. A number of specialized receptor-mediated transport processes for different types of glycoproteins in this organ is reviewed. Membrane recognition is generally followed by absorptive endocytosis and vesicle transport to lysosomes, Golgi system and/or bile canaliculis. The charge of the protein, the nature of the terminal sugar residue or complex formation with other glycoproteins may determine the extent of uptake in the various cell types of the liver. By means of these transport processes the liver is able to remove potentially dangerous macromolecules such as denatured proteins, aggressive enzymes and immunocomplexes from the general circulation. Drugs can bind to some of these proteins or may interact with the hepatic transport or catabolism processes. Special attention is paid to the hepatic clearance of asialoglycoproteins with terminal galactose groups. Intestinal alkaline phosphatase is used as a model compound to characterize the pharmacokinetic profiles of hepatic uptake and biliary excretion in the rat in vivo and isolated perfused rat livers. Histochemical and electron-microscopic studies demonstrated a galactose-specific, receptor-mediated endocytotic process, mainly but not exclusively localized in centrolobular hepatocytes. Drug interactions with these processes will be the subject of further investigations.

Alkaline Phosphatase↗

Initial evaluation of children with heart murmurs by the non-specialized paediatrician.

UNLABELLED: To analyse the ability of the non-specialized paediatrician to evaluate children with a heart murmur and the consequences of this evaluation for the need of further investigations, we undertook a prospective and consecutive study of 100 children, referred for initial evaluation of a heart murmur. Except for 1 child with a slight peripheral pulmonary artery stenosis, 53% of the children were correctly diagnosed as having no heart disease. In a project design where 47% of the children were referred for an echocardiographic study, no clinically significant heart disease was missed. CONCLUSION: Clinical evaluation without laboratory tests performed by paediatricians without any special training in cardiology could correctly acquit 50% of the children of heart disease, with no need for further investigation.

Adolescent↗

Special Escherichia coli serotypes among enterotoxigenic strains from diarrhoea in adults and children.

106 enterotoxigenic Escherichia coli strains from children and adults from many parts of the world were serotyped for O and H antigens. Some O:H types, i.e. O6:H16, 08:H9, O15:H11, O25:H42, O78:H11 and O78:H12, were found repeatedly from different geographical locations. Some of these O:H serotypes were only found rarely among more than 20000 E. coli strains collected over many years from different locations and sources. It is suggested that these special O:H serotypes represent clones which have been selected to the special conditions in the small intestine and selected to carry the plasmids necessary to provoke diarrhoea.

Adult↗

Wilms tumor presenting with abdominal pain: a special subgroup of patients.

BACKGROUND: Although significant progress has been made in the management of children with Wilms tumor, two major controversies still exist: the extent of radiographic evaluation necessary before surgery and the role of preoperative chemotherapy. This study sought to determine whether patients with Wilms tumor who presented with abdominal pain defined a special subset of patients who might require a more extensive preoperative work-up and neoadjuvant chemotherapy. METHODS: From 1970 to 1995, 250 children were treated for Wilms tumor at a single pediatric institution. A retrospective chart review determined presenting signs and symptoms for each patient. RESULTS: Thirty-four (14%) patients (mean age 5.5 years) sought medical attention with a chief complaint of abdominal pain. The stage distribution for these patients tended to be higher and was significantly different (P <.001, chi(2)-analysis) from those presenting without pain. Four (14%) of 29 patients with tumor available for analysis were found to have anaplastic histology. CONCLUSION: These data suggest that patients with Wilms tumor who present with abdominal pain represent a special subgroup that tends to be older and has an increased incidence of tumor rupture, anaplasia, and higher stage. These patients may benefit from a more extensive preoperative evaluation and consideration of neoadjuvant chemotherapy.

Abdominal Pain↗

[Special osteosynthesis-techniques for use on traumatic bone fractures in the region of hip and knee endoprostheses (author's transl)].

Special problems are associated with fractures of bones with implanted endoprostheses. These problems are a result of unusual fracture-types often combined with damage and loosening of parts of the prosthesis, the limited applicability of standard osteosynthesis-procedures and the impaired blood supply of the bone caused by the destruction of the medullary vessels after filling the medullary canal with bone cement. Special operative techniques for the treatment of those problem-fractures are demonstrated such as the extension of the prosthesis by an elastic shaft and the concentric osteosynthesis of an unstable acetabulum by a newly developed implant.

Acetabulum↗

Thymic stromal cell specialization and the T-cell receptor repertoire.

Ten years ago, we proposed a model for thymus function in which thymic epithelial cells are primarily responsible for imprinting major histocompatibility complex (MHC)-restricted specificity, and bone marrow-derived macrophages or dendritic cells are responsible for the induction of self-tolerance. Since then, transgenic and knockout models have allowed for a dissection of thymic stromal components in vivo, leading to a new understanding of their specialized functions. We have determined that with regard to class II-restricted CD4 T-cell development, two distinct subsets of thymic epithelium help shape the repertoire: Cortical epithelium appears solely responsible for positive selection, whereas a fucose-bearing subset of medullary epithelium is specialized for negative selection. This absolute separation of positive and negative selection into two distinct spatial and temporal compartments leads to a much simpler view of the process of repertoire selection. Finally, a novel view of the function of the thymic medulla is discussed.

Animals↗

Acid metabolite of progabide pharmacokinetics following single administration in the rabbit with special references to HPLC and (3H) muscimol radioreceptor assay.

The aim of the present study was to monitor plasma levels of progabide and its metabolites in the rabbit following single oral administration of 20 mg.kg-1. The plasma levels were determined selectively using high performance liquid chromatography (HPLC) and then correlated with a global estimation by a (3H) muscimol radioreceptor assay (RRA). In our "in vitro" binding conditions progabide itself was virtually ineffective (IC50 greater than 100 microM) so only RRA active materiel plasma concentrations were studied. A good enough correlation (r = 0.71) has been established between HPLC and RRA plasma concentrations from 0 to 3 hours following oral administration specially considering the absorption phase. But with closed regards to the elimination pharmacokinetic parameters specially the elimination half-life values (t1/2el (RRA) = 1.67 h and t1/2el (HPLC) = 0.70 h) that correlation should be weaker than the former instead metabolites including GABAmide and GABA itself are probably present in amounts likely to affect the displacement of specific binding in the (3H) muscimol radioreceptor assay.

Animals↗

Transposase and cointegrase: specialized transposition proteins of the bacterial insertion sequence IS21 and related elements.

The bacterial insertion sequence IS21 shares with many insertion sequences a two-step, reactive junction transposition pathway, for which a model is presented in this review: a reactive junction with abutted inverted repeats is first formed and subsequently integrated into the target DNA. The reactive junction occurs in IS21-IS21 tandems and IS21 minicircles. In addition, IS21 shows a unique specialization of transposition functions. By alternative translation initiation, the transposase gene codes for two products: the transposase, capable of promoting both steps of the reactive junction pathway, and the cointegrase, which only promotes the integration of reactive junctions but with higher efficiency. This review also includes a survey of the IS21 family and speculates on the possibility that other members present a similar transpositional specialization.

Amino Acid Sequence↗

Safety of ProHance in special populations.

The safety profile of ProHance in special populations was evaluated by analyzing data extracted from the database of phase I-III studies which included data on 2,656 ProHance injections of which 119 in pediatric patients, 814 in elderly patients and 30 in patients with varying degrees of renal impairment (moderate, severe or end stage requiring hemodialysis). ProHance was administered at doses ranging from 0.1 mmol/kg to 0.3 mmol/kg and was found to be safe in all patient populations irrespective of age and of pre-existing renal impairment. There appeared to be no correlation between incidence of adverse events and dose level in these special populations and the higher dose level of 0.3 mmol/kg could be safely administered also to patients with end stage renal disease requiring hemodialysis, from whom the contrast medium was rapidly and efficiently dialysed.

Adult↗

[Special features of the skin in newborns and young infants].

Detailed knowledge of the special features of neonatal and infant skin is a prerequisite for adequate skin care in this age group. Immediately postpartum, the newborn baby's skin assumes vital functions regarding water and electrolyte homeostasis and thermoregulation, as well as innate and adaptive host defense. Due to its functional and structural immaturity, premature skin requires special care. Mature neonates demonstrate benign, transient skin lesions that do not require specific therapy but have to be distinguished from serious and potentially life-threatening illnesses.

Humans↗

Novel mechanistic concepts for the control of leukocyte transmigration: specialization of integrins, chemokines, and junctional molecules.

The emigration of leukocytes from the circulation is a critical step during immune surveillance and inflammatory reactions and is governed by a coordinated interplay involving a spectrum of adhesion and signal molecules. As the original multistep model of leukocyte trafficking undergoes continuous revision and refinement, the identification of additional molecules and the emergence of novel concepts for their intricately overlapping functions indicate that this process is still not completely understood. Early studies defining the multistep model described the rapid transition of selectin-mediated leukocyte rolling into integrin-dependent arrest followed by transendothelial diapedesis. It has become apparent that highly specialized chemoattractive cytokines termed chemokines and their heptahelical receptors are involved in the emigration of leukocytes not only by inducing chemotaxis but also by regulating integrins to trigger cell arrest in shear flow. In light of the enormously pleiotropic role of integrins and chemokines in vertebrate biology, this review summarizes and highlights selected aspects of currently evolving concepts refining the multistep model: (a) the differential activation of integrin avidity by chemokines and its implications, (b) the functional specialization of chemokines and their receptors in leukocyte recruitment, and (c) the multilayered molecular "zipper" controlling the completion of diapedesis at interendothelial junctions.

Animals↗

Transient division of labor and behavioral specialization in the ant Formica schaufussi.

Cooperative prey retrieval in the monomorphic ant Formica schaufussi is carried out by workers that perform functionally distinct roles which persist only for the duration of a single retrieval event. A forager (scout) that locates prey too large to retrieve individually organizes cooperative prey transport by recruiting nestmates (recruits) to assist in retrieval. The scout and recruit roles appear to be determined by whether a worker activates recruitment or is recruited from the nest. Scouts organize recruitment and play a key role in maintaining the cohesion of the retrieval group. If a scout that has initiated group transport is experimentally removed, the recruited workers composing the retrieval group typically abandon the prey and cooperative foraging is terminated. In this context, recruits are unable to function as scouts and reorganize group transport. Individuals marked as recruits in one prey retrieval, however, can switch and act as scouts in subsequent retrievals. Because the roles of individuals persist within but not between retrieval events, the specialization involved in cooperative prey retrieval cannot easily be explained as a response associated with age-related or genetic predispositions. This transient division-of-labor, in which individual roles may persist only for the duration of a single group action, represents a novel type of short-term individual specialization.

Animals↗

Areal specialization of pyramidal cell structure in the visual cortex of the tree shrew: a new twist revealed in the evolution of cortical circuitry.

Cortical pyramidal cells, while having a characteristic morphology, show marked phenotypic variation in primates. Differences have been reported in their size, branching structure and spine density between cortical areas. In particular, there is a systematic increase in the complexity of the structure of pyramidal cells with anterior progression through occipito-temporal cortical visual areas. These differences reflect area-specific specializations in cortical circuitry, which are believed to be important for visual processing. However, it remains unknown as to whether these regional specializations in pyramidal cell structure are restricted to primates. Here we investigated pyramidal cell structure in the visual cortex of the tree shrew, including the primary (V1), second (V2) and temporal dorsal (TD) areas. As in primates, there was a trend for more complex branching structure with anterior progression through visual areas in the tree shrew. However, contrary to the trend reported in primates, cells in the tree shrew tended to become smaller with anterior progression through V1, V2 and TD. In addition, pyramidal cells in V1 of the tree shrew are more than twice as spinous as those in primates. These data suggest that variables that shape the structure of adult cortical pyramidal cells differ among species.

Animals↗

Specialized basement membrane of monkey maturation stage ameloblasts mediates firm ameloblast-enamel association by its partial calcification.

A basement membrane-like structure associated with the maturation stage ameloblasts of the monkey (Macaca fuscata) tooth germ was examined with high resolution electron microscopy. The tissue was prepared either with or without demineralization. This structure was composed of a lamina lucida-like (lamina lucida) and lamina densa-like (lamina densa) structure. The latter was made up of a fine "cord" network, the major constituent of the basement membrane. It was closely associated with the third layer of a 200 nm wide looser cord network. In specimens without demineralization the third layer and a part of the lamina densa were calcified, and it formed the edge of the enamel. This particular area had a higher electron density, and the size, shape, and arrangement of mineral crystals were different from those of the rest of the enamel. Also, mineralization appeared to be proceeding along the cords. These observations indicate that this dense layer is a highly specialized basement membrane which mediates the firm association of maturation stage ameloblasts with the enamel by means of the mineralization of a part of this basement membrane itself which becomes integrated as a part of the enamel. Also, this highly specialized manner of association is favorable with the reported control of the loss of organic substances in the maturing enamel by maturation stage ameloblasts.

Ameloblasts↗

Company observational post-marketing studies: drug risk assessment and drug research in special populations--a study-based analysis.

OBJECTIVES: Company observational post-marketing studies (COPS) claim to provide essential data about drug risks and effectiveness in special populations not admitted to pre-approval clinical trials. Since COPS are often mainly regarded as a marketing activity, this study-based analysis tries to evaluate the scientific contributions of COPS. MATERIAL AND METHODS: Thirty-five COPS were identified by hand-searching through medical journals, writing to pharmaceutical manufacturers and using MEDLINE. Fourteen COPS evaluated cardiovascular drugs, 9 evaluated NSAIDs and 12 evaluated various other indications. RESULTS: Thirty-five COPS listed effectiveness, 31 listed safety and 8 listed patient compliance as principal objectives. Not a single COPS included a control group. Seventeen of 21 evaluable COPS mentioned extensive exclusion criteria similar to those in clinical trials. Median observation time was 8 weeks, too short for chronic diseases and for adverse drug reactions with longer latency periods. One new adverse event was regarded. Global assessments of the outcomes by physicians dominated and were not based on objective clinical findings. None of the studies specified any details concerning the standardisation of observations or quality-control procedures. DISCUSSION AND CONCLUSION: The current COPS scheme does not contribute significantly to our knowledge of drug safety and the effects in special populations. Despite serious criticism over the past 20 years, the poor quality of COPS compared with dramatic improvements of pre-approval trials - implies a need for detailed guidelines for non-experimental phase IV research, similar to the Good Clinical Practice-Guideline of the European Community.

Anti-Inflammatory Agents, Non-Steroidal↗