Search Results - (Author, Cooperation:R. Stahlmann)
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1Latest Papers from Table of Contents or Articles in PressL. H. Fraser ; J. Pither ; A. Jentsch ; M. Sternberg ; M. Zobel ; D. Askarizadeh ; S. Bartha ; C. Beierkuhnlein ; J. A. Bennett ; A. Bittel ; B. Boldgiv ; Boldrini, II ; E. Bork ; L. Brown ; M. Cabido ; J. Cahill ; C. N. Carlyle ; G. Campetella ; S. Chelli ; O. Cohen ; A. M. Csergo ; S. Diaz ; L. Enrico ; D. Ensing ; A. Fidelis ; J. D. Fridley ; B. Foster ; H. Garris ; J. R. Goheen ; H. A. Henry ; M. Hohn ; M. H. Jouri ; J. Klironomos ; K. Koorem ; R. Lawrence-Lodge ; R. Long ; P. Manning ; R. Mitchell ; M. Moora ; S. C. Muller ; C. Nabinger ; K. Naseri ; G. E. Overbeck ; T. M. Palmer ; S. Parsons ; M. Pesek ; V. D. Pillar ; R. M. Pringle ; K. Roccaforte ; A. Schmidt ; Z. Shang ; R. Stahlmann ; G. C. Stotz ; S. Sugiyama ; S. Szentes ; D. Thompson ; R. Tungalag ; S. Undrakhbold ; M. van Rooyen ; C. Wellstein ; J. B. Wilson ; T. Zupo
American Association for the Advancement of Science (AAAS)
Published 2015Staff ViewPublication Date: 2015-07-18Publisher: American Association for the Advancement of Science (AAAS)Print ISSN: 0036-8075Electronic ISSN: 1095-9203Topics: BiologyChemistry and PharmacologyComputer ScienceMedicineNatural Sciences in GeneralPhysicsKeywords: *Biodiversity ; Biomass ; *Grassland ; *Plant Development ; Stress, PhysiologicalPublished by: -
2Articles: DFG German National LicensesVormann, J. ; Förster, C. ; Zippel, U. ; Lozo, E. ; Günther, T. ; Merker, H.-J. ; Stahlmann, R.
Springer
Published 1997Staff ViewISSN: 1432-0827Keywords: Key words:Magnesium — Calcium — Bone — Cartilage — QuinolonesSource: Springer Online Journal Archives 1860-2000Topics: BiologyMedicinePhysicsNotes: Abstract. Quinolone-induced arthropathy has been described in juvenile rats between 3 and 6 weeks of age, but not in adult rats. The mechanism of this chondrotoxic effect is probably related to the Mg2+-chelating properties of the drugs, since identical cartilage lesions were observed in magnesium-deficient juvenile rats without quinolone treatment. However, the reasons for the phase-specificity of the effect are unknown. In the present study, we fed a magnesium-deficient diet to Wistar rats at different postnatal developmental stages. Cartilage lesions were only observed in magnesium-deficient rats between 3 and 5 weeks of age, but not in rats receiving the magnesium-deficient diet during weeks 5 to 8, weeks 8 to 11, or months 15 to 16. The formation of cartilage lesions was not related to the magnesium concentration in plasma, since magnesium concentrations in plasma were similarly reduced in rats with and without cartilage lesions. However, chondrotoxicity correlated with magnesium content in articular cartilage. In articular cartilage (articular and epiphyseal cartilage in immature rats) and bone, magnesium content was more reduced in rats receiving the magnesium-deficient diet between 3 and 5 weeks of age as compared with rats receiving the magnesium-deficient diet during weeks 8 to 11 postnatally. It was not possible to reduce the magnesium content in bone tissue of 15-month-old Wistar rats, which suggests a lower magnesium turnover in aged rats. Magnesium content in epiphyseal cartilage of 2-week-old rats (total femoral head) was 41.9 ± 16.9 mmol/kg dry weight. The magnesium content in joint hyaline cartilage was significantly lower in 4-week-old rats (19.5 ± 3.6 mmol/kg dry weight) and increased subsequently again to 48.5 ± 9.2 mmol/kg dry weight (mean ± SD; n= 8 to 16). Increase of the magnesium content in femoral bone between weeks 4 and 6 postnatally was less pronounced (139 ± 10 and 175 ± 15 mmol/kg dry weight, respectively). Taken together, these data show that in 4-week-old rats, magnesium concentration in joint hyaline cartilage is significantly lower than at other times during postnatal development. Only at this developmental stage can cartilage lesions be induced by feeding rats a magnesium-deficient diet. This period correlates well with the sensitive phase of immature rats toward the chondrotoxic action of quinolones.Type of Medium: Electronic ResourceURL: -
3Articles: DFG German National LicensesGraf, R. ; Gossrau, R. ; Merker, H. -J. ; Schwabe, R. ; Stahlmann, R. ; Nau, H.
Springer
Published 1985Staff ViewISSN: 1432-119XSource: Springer Online Journal Archives 1860-2000Topics: BiologyMedicineNotes: Summary A number of organs from adult female mice were investigated after continuous application of the anticonvulsant drug valproic acid (VPA) by enzyme cytochemistry, light and electron microscopy, pharmacokinetics and clinical chemistry. VPA plasma levels were maintained between 55 μg/ml and 67 μg/ml for three days following subcutaneous implantation of drug reservoirs. Effects detectable by enzyme cytochemical or electron microscopical means were mainly observed in liver, kidney, thymus and spleen. A strict concentration-dependency of drug effects could not be found. In the liver, the activities of some surface-membrane hydrolases were increased at the biliary pole; the activities of other hydrolases were decreased or unchanged. Electron microscopically, number and lenghth of microvilli of hepatocytes were increased and many of them showed fat inclusions, mitochondrial swellings and autophagic vacuoles. In some of the proximal convoluted tubules of the kidney, the reaction product originating from microvillous and lysosomal hydrolases was diffusely distributed and its amount lowered. This was paralleled by tubular cells with an increased number of fat droplets and swollen mitochondria or destroyed tubular cells, as demonstrated by electron microscopy. Additionally, peritubular endothelial cells were arranged in a garland-like pattern. Alkaline phosphatase was activated in the straight portion of the proximal tubules. Increased glucose, creatinine and total protein concentrations and increased γ-glutamyl transpeptidase and alkaline phosphatase activities in the urine reflected well the damage of the proximal renal tubules. Cortical and medullary morphology varied considerably in the thymus. In extreme cases, the cortical zone was either reduced in size or the medulla showed a cortex-like structure or vice versa (inverted type of thymus). The thymic cortical reticular cells showed increased aminopeptidase A activity accompanied by a generalized aminopeptidase M and alkaline phosphatase reaction. Our data indicate that — in addition to the liver — also the kidney, thymus and spleen are target organs of VPA-induced toxicity in the mouse.Type of Medium: Electronic ResourceURL: -
4Articles: DFG German National LicensesStahlmann, R. ; Kühner, S. ; Shakibaei, M. ; Schwabe, R. ; Flores, J. ; Evander, S. A. ; van Sickle, D. C.
Springer
Published 2000Staff ViewISSN: 1432-0738Source: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract The systemic effects of ciprofloxacin in immature Beagles were studied. Dogs of 10–11 weeks were dosed orally for 5 days with 0 (n=3), 30 (n=5) and 200 (n=5) mg ciprofloxacin/kg body wt. Plasma concentrations were measured by high-performance liquid chromatography (HPLC) 1 h after dosing (assuming to be peak concentrations). In view of the high doses used, the plasma concentrations were rather low and declined during the study period. For example, plasma concentrations in the high dose group were 6.6 ± 0.9 mg/l (day 1), 3.9 ± 1.4 mg/l (day 3), and 2.6 ± 1.6 mg/l (day 5). In control dogs and in dogs treated with the low dose of ciprofloxacin no pathological changes were seen by light microscopy. However, cleft formation and erosions were observed in joint cartilage from two of five dogs treated with 200 mg/kg. It is noteworthy that despite the high dose used cartilage lesions were not detectable in all five dogs of this group by light microscopy. Using antibodies against cell membrane receptors (e.g. the α5β1-integrin) or matrix components (fibronectin, collagen II) the articular cartilage effects were studied in detail by immunohistochemistry. The most sensitive alteration was an increase in fibronectin which was detectable in the vicinity of the lesions in cartilage samples from the group of dogs administered the high dose. No clear-cut changes were seen with the use of antibodies against other matrix components. Electron microscopy revealed typical alterations in chondrocytes from dogs treated with ciprofloxacin: e.g., swollen mitochondria and enlarged rough endoplasmic reticulum. These changes were much more pronounced in dogs from the high dose group than in dogs from the low dose group. Our main conclusion is that after oral administration ciprofloxacin exhibits rather low chondrotoxicity, even in the most sensitive species known to date. This correlates with the findings in humans that ciprofloxacin seems to be less chondrotoxic than pefloxacin or other quinolones.Type of Medium: Electronic ResourceURL: -
5Articles: DFG German National LicensesStahlmann, R. ; Merker, H. J. ; Hinz, N. ; Chahoud, I. ; Webb, J. ; Heger, W. ; Neubert, D.
Springer
Published 1990Staff ViewISSN: 1432-0738Keywords: Ofloxacin ; Quinolones ; Marmosets ; Rats ; ArthropathiaSource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract Arthropathia in juvenile animals is the most important toxic effect induced by quinolones. We conducted pharmacokinetic and morphological studies with ofloxacin on non-human primates (Callithrix jacchus, Marmosets) and rats. In the marmoset, electron microscopy and the application of immuno-morphological methods proved to be suitable for the detection of specific alterations in cartilage (e. g. loss of proteoglycanes and altered chondrocytes). Subsequently performed electron microscopic examinations in rats showed similar specific alterations of the femur cartilage surface after multiple oral applications of 600 mg ofloxacin/kg body wt. These results were correlated with pharmacokinetic data obtained for the same species. After single oral application of 100, 300 or 600 mg ofloxacin/kg body wt to 5 week-old rats peak plasma levels were achieved 15–45 min after administration indicating a rapid absorption of the drug. The following peak concentrations were measured for the three doses applied (mean±SD): 8.9±2.1, 22.6±7.5 mg/l and 33.5±9.8 mg/l, respectively. After 360 min the concentrations were 1.1±0.4, 5.9±2.5 and 15.9±5.1 mg/l, respectively. After subcutaneous injection of 100 mg ofloxacin/kg body wt the mean peak concentration was 27.7±2.6 mg/l after 45 min (0.5±0.2 mg/l after 360 min). In the marmoset higher plasma concentrations were measured with comparable doses. One, 3, and 6 h after the last of nine administrations of 200 mg ofloxacin/kg body wt, the mean (±SD) plasma concentrations were: 42.7±16.7, 40.6±9.5, and 26.5±3.6 mg ofloxacin/l plasma. Typical alterations of the joint cartilage of juvenile rats (e. g. opened chondrocyte cavities, swelling of rough endoplasmic reticulum and mitochondrial swelling in the chondrocytes) were induced by oral administration of ofloxacin at doses that were approximately 100 times higher than therapeutic ones, but led to peak plasma concentrations which were only approximately 10 times above the therapeutic level. Since we found corresponding cartilage alterations in marmosets and rats, this species provides a convenient model for additional studies on chondrotoxic effects of quinolones.Type of Medium: Electronic ResourceURL: -
6Articles: DFG German National LicensesStahlmann, R. ; Kühner, S. ; Shakibaei, M. ; Flores, J. ; Vormann, J. ; van Sickle, D. C.
Springer
Published 2000Staff ViewISSN: 1432-0738Source: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract Quinolone-induced chondrotoxicity is possibly associated with the magnesium-chelating properties of quinolones. This toxic effect seems to be restricted to a rather short time period during postnatal development as shown in rats and dogs. We studied developmental changes of the integrin pattern on canine chondrocytes (e.g. the αvβ3- or α5β1-integrin), because integrin function depends on divalent cations, as well as the matrix composition (e.g., collagen type II, fibronectin), in 11-, 18-, and 55-week-old Beagles (n=8) by immunohistochemistry. We also analyzed the magnesium and calcium content by atomic absorption spectroscopy in cartilage and bone and studied the effects of a magnesium-deficient diet on joint cartilage in four immature Beagles (18 weeks old at necropsy). The dogs were fed the magnesium-deficient diet for 40 to 46 days. All dogs exhibited gait alterations (`limping') after 4 weeks on the magnesium-deficient diet. Male, magnesium-deficient dogs exhibited pronounced weakness in their front legs; in one of these dogs the front legs were hyperextended to a 90° angle. We observed no significant differences in the integrin pattern in samples from dogs at different developmental stages or in magnesium-deficient dogs in comparison to age-matched controls. Localization of fibronectin in the joint cartilage was found to vary with the age of the dogs as well as with the site of collection. In the middle zone of immature joint cartilage, corresponding to the predilective site of quinolone-induced cartilage lesions, we observed a slight increase in staining with the fibronectin antibody in some samples from magnesium-deficient dogs. Electron microscopy revealed alterations in chondrocytes from the magnesium-deficient dogs (e.g., swollen mitochondria and enlarged endoplasmic reticulum) which are also seen after treatment with quinolones. In summary, we found no significant differences of the integrin pattern on chondrocytes from joint cartilage of dogs at various developmental stages. However, magnesium deficiency in immature dogs induced similar clinical symptoms as quinolone treatment as well as distinct alterations in chondrocytic fibronectin staining and their ultrastructure. This corroborates our findings in rats where magnesium chelation is an important event in quinolone-induced chondrotoxicity.Type of Medium: Electronic ResourceURL: -
7Articles: DFG German National LicensesFörster, C. ; Kociok, K. ; Shakibaei, M. ; Merker, H.-J. ; Vormann, J. ; Günther, T. ; Stahlmann, R.
Springer
Published 1996Staff ViewISSN: 1432-0738Keywords: Key words Quinolone-induced arthropathy ; Magnesium deficiency ; Joint cartilage ; Integrin expression ; ImmunohistochemistrySource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract Recently, we showed that magnesium deficiency induces lesions in knee joint cartilage from 5-week-old rats that are very similar to ofloxacin-induced cartilage defects. We concluded that quinolone-induced arthropathy is probably due to chelation of magnesium and thus a deficit in functionally available magnesium in joint cartilage (Stahlmann et al. 1995). As magnesium deficiency in joint cartilage could impair chondrocyte-matrix interaction which is mediated by cation-dependent integrin receptors of the β1-subfamily, we investigated integrin expression in joint cartilage from untreated, ofloxacin-treated and magnesium-deficient Wistar rats. With immunohistochemical methods using monoclonal and polyclonal antibodies, we showed that the integrin pattern in joint cartilage from rats corresponded largely to integrin expression described for human cartilage tissue: β1, α1, α3 and αν subunits and the α5β1 and ανβ3 heterodimers were consistently expressed. Joint cartilage lesions were detected in ofloxacin-treated and magnesium-deficient rats. Lesions were more pronounced in the quinolone-treated group. Expression of several integrins was reduced in the vicinity of lesions after oral treatment with 2 × 600 mg ofloxacin/kg for 1 day. Gross-structural lesions (e. g., cleft formation, unmasked collagen fibres) in magnesium-deficient rats were very similar but changes in integrin expression were less pronounced. On the other hand, changes in cartilage matrix composition showed similar alterations in ofloxacin-treated and magnesium-deficient rats: fibronectin deposition in the cartilage matrix increased in both groups while glycosaminoglycan content decreased. In summary, similar defects occur in ofloxacin-treated and magnesium-deficient rats and with immunohistochemical methods subtle differences are demonstrable.Type of Medium: Electronic ResourceURL: -
8Articles: DFG German National LicensesFörster, C. ; Schwabe, R. ; Lozo, E. ; Zippel, U. ; Vormann, J. ; Günther, T. ; Merker, H. J. ; Stahlmann, R.
Springer
Published 1997Staff ViewISSN: 1432-0738Keywords: Key words Quinolones ; Magnesium ; Arthropathy ; Rats ; OfloxacinSource: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract Quinolone treatment or magnesium deficiency induce identical cartilage lesions in juvenile rats and show additive arthropathogenic effects. It has been shown previously that neither condition is arthropathogenic in 8-week-old rats. Joint cartilage from aged individuals is rather prone to pathological alterations but information on prolonged quinolone treatment and/or dietarily induced magnesium deficiency in aged animals is not available. We treated magnesium-deficient (n = 9) aged Wistar rats (age 15 months) and age-matched controls with daily doses of 600 mg ofloxacin/kg body wt. by gastric intubation for 28 days. Further groups of magnesium-deficient and control rats (n = 9 and n = 10, respectively) received the vehicle only. Peak plasma concentrations of ofloxacin in adult rats were 20.5 ± 5.6 mg/l (mean ± SD) following treatment with a single dose of 600 mg/kg body wt. At the end of the experiment the degree of magnesium deficiency was most pronounced in plasma (Mg2+-def., 0.33 ± 0.12 mmol/l; control, 0.97 ± 0.08 mmol/l) and less pronounced in sternal cartilage (Mg2+-def., 10.8 ± 3.6 mmol/kg dry wt; control, 13.3 ± 2.8 mmol/kg dry wt), whereas the magnesium concentration in femoral bone remained unchanged (Mg2+-def., 201 ± 13 mmol/kg dry wt; control, 204 ± 11 mmol/kg dry wt). Histological investigation of the knee joints revealed no cartilage lesions following ofloxacin treatment, magnesium deficiency or a combination of both conditions. By contrast, cartilage lesions such as scars and erosions of the joint surface, chondrocyte clusters within acellular areas of the cartilage matrix and persisting clefts were detectable in knee joints from 7 of 10 adult rats (age 9 months) which had been treated with 4 × 600 mg fleroxacin/kg body wt. at 5 weeks of age. Mean plasma concentration of fleroxacin in juvenile rats was approx. 50 mg/l between 1.5 and 6 h after dosing and the drug was still detectable in plasma 48 h after dosing (0.4 ± 0.1 mg/l). Our data indicate that joint cartilage in aged rats is not altered by a 4-week quinolone treatment, even during magnesium deficiency. Cartilage lesions in adult rats were only detectable if the animals had been treated during the sensitive phase at 5 weeks postnatally.Type of Medium: Electronic ResourceURL: -
9Articles: DFG German National LicensesStaff View
ISSN: 1439-0973Source: Springer Online Journal Archives 1860-2000Topics: MedicineDescription / Table of Contents: Summary The cartilage damaging effect of quinolones on juvenile experimental animals represents an unusual effect which is unknown, in this form, for other classes of substances. Since the damage is manifested at quite low doses the manufacturers and regulatory agencies have taken the consequence of declaring these preparations counter-indicated for children and adolescents up to the end of the growing period. Motor disturbances were observed only rarely, and only in individual cases, seen after therapeutic use of these drugs for the treatment of bacterial infections. In spite of long-term and sometimes high dose treatment with nalidixic acid during the 1960s and 1970s (the arthropathogenic effect on dogs was first described in 1977) no joint alterations could be demonstrated clinically or by x-ray. From this the conclusion can be drawn that the effects seen in animal experiments under therapeutic conditions do not occur with the same intensity in humans. But, since many questions concerning this unusual toxic potential are still unanswered, quinolones continue to be counter-indicated for patients who are in the growing phase. Further experimental data and clinical observations are necessary to exclude with certainty the possible danger of joint damage to young patients. Even today it is still unclear whether the generally favourable clinical observations made with nalidixic acid also hold true for the other quinolones and whether differences in the possible risks exist. It will only become possible to define, with the necessary amount of certainty, indications for the use of quinolones in pediatrics when further information is available.Notes: Zusammenfassung Die knorpelschädigende Wirkung der Chinolone bei juvenilen Versuchstieren stellt einen ungewöhnlichen toxischen Effekt dar, der in dieser Form von anderen Substanzklassen nicht bekannt ist. Da sich die Schäden zum Teil bereits bei recht niedriger Dosierung manifestieren, haben Hersteller und Zulassungsbehörden die Konsequenz gezogen, diese Präparate als kontraindiziert bei Kindern und Jugendlichen bis zum Abschluß des Wachstums einzustufen. Bei der klinischen Anwendung der Präparate zur Behandlung diverser bakterieller Infektionen wurden nur selten in Einzelfällen Störungen von seiten des Bewegungsapparates gesehen. Überwiegend zeigen die klinischen Erfahrungen aus den sechziger und siebziger Jahren (die arthropathogene Wirkung beim Hund wurde erst 1977 beschrieben), daß trotz langfristiger und zum Teil hochdosierter Behandlung mit Nalidixinsäure keine Gelenkveränderungen aufgefallen sind, die sich klinisch oder röntgenologisch nachweisen ließen. Daraus kann zumindest der Schluß gezogen werden, daß die tierexperimentell beobachteten Wirkungen unter therapeutischen Bedingungen nicht in gleicher Ausprägung auftreten. Da jedoch noch einige Fragen offen sind hinsichtlich dieses ungewöhnlichen toxischen Potentials, gilt nach wie vor die Kontraindikation für Chinolone bei Patienten im Wachstumsalter. Weitere experimentelle Daten und klinische Erfahrungen sind notwendig, um mit größerer Sicherheit eine mögliche Gefährdung jugendlicher Patienten hinsichtlich eventueller Gelenkschäden durch Chinolone ausschließen zu können. Bis heute ist zum Beispiel unklar, ob die insgesamt günstigen klinischen Erfahrungen mit Nalidixinsäure auch für andere Chinolone gelten und ob es Unterschiede hinsichtlich einer möglichen Gefährdung gibt. Erst wenn weitere Informationen vorliegen, könnte es möglich sein, mit der erforderlichen Sicherheit auch in der Pädiatrie mögliche Indikationen für die Chinolone zu definieren.Type of Medium: Electronic ResourceURL: -
10Articles: DFG German National LicensesStaff View
ISSN: 1439-0973Source: Springer Online Journal Archives 1860-2000Topics: MedicineDescription / Table of Contents: Summary Twelve normal volunteers in the fasting state were given 1000 mg cefaclor, and the serum and urine concentrations over 8 h and 24 h respectively were measured. The average peak serum concentration was 34.6 ± 7.8 mg/l, this value being reached after 65.2 ± 11.1 min; the half-life was 42.5 ± 8.3 min. In another six volunteers the absorption of 500 mg of cefaclor following administration in the fasting state and after a test breakfast was studied. The peak serum concentrations after administration in the fasting state were 16.1 ± 3.2 mg/l, and after a meal 12.5 ± 1.9 mg/l; the areas under the curve did not differ. The low recovery rate of cefaclor in urine observed in this series of investigations could be partly explained by the inactivation of the substance in urine. Cefaclor was administered therapeutically to 23 patients, most of whom were suffering from bronchopulmonary infections and chronic pyelonephritis. The results of therapy were good in four patients, satisfactory in 13 patients and unsatisfactory in three patients. Intolerance was rare.Notes: Zusammenfassung 1000 mg Cefaclor wurden 12 Normalprobanden nüchtern verabreicht und die Serumkonzentrationen über 8 h sowie die Urinkonzentrationen über 24 h bestimmt. Die Serummaximalkonzentration lag im Mittel bei 34,6 ± 7,8 mg/l, die Zeit bis zum Erreichen dieses Spiegels betrug 65,2 ± 11,1 min, die Halbwertzeit konnte mit 42,5 ± 8,3 min bestimmt werden. Bei sechs weiteren Probanden wurde die Resorption von 500 mg Cefaclor nach nüchterner Gabe und nach Verabreichung während eines Testfrühstücks untersucht. Die Serummaximalkonzentrationen lagen nach nüchterner Gabe bei 16,1 ± 3,2 mg/l, nach nichtnüchterner Gabe bei 12,5 ± 1,9 mg/l, die Flächen unter der Kurve unterschieden sich nicht. Die in den Untersuchungsreihen gefundenen niedrigen Cefaclor-Urinrecoveryraten können teilweise durch eine Inaktivierung der Substanz im Urin erklärt werden. Therapeutisch wurde Cefaclor bisher bei 23 Patienten mit vorwiegend bronchopulmonalen Infektionen und chronischen Pyelonephritiden eingesetzt. Die Therapieresultate waren in 4 Fällen gut, 13mal zufriedenstellend und 3mal unzureichend. Unverträglichkeitsreaktionen waren selten.Type of Medium: Electronic ResourceURL: -
11Articles: DFG German National LicensesStaff View
ISSN: 1439-0973Source: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Conclusions SDD in ventilated ICU patients continues to be a controversial issue. This form of prophylaxis significantly reduces infection-related morbidity in ICU patients, but, despite the large number of trials assessed, no definite conclusions can be drawn about the effect of this type of prophylaxis on mortality. There is evidence to support the use of SDD in some patient populations, including ventilated polytrauma patients, patients who have undergone surgery for oesophageal tumours and liver transplant patients. The use of SDD in patients receiving long-term ventilation, must, however, be questioned.Type of Medium: Electronic ResourceURL: -
12Articles: DFG German National LicensesStahlmann, R. ; Klug, S. ; Lewandowski, C. ; Chahoud, I. ; Bochert, G. ; Merker, H. -J. ; Neubert, D.
Springer
Published 1987Staff ViewISSN: 1439-0973Source: Springer Online Journal Archives 1860-2000Topics: MedicineType of Medium: Electronic ResourceURL: -
13Articles: DFG German National LicensesStaff View
ISSN: 1439-0973Source: Springer Online Journal Archives 1860-2000Topics: MedicineDescription / Table of Contents: Summary In a randomized crossover study, the pharmacokinetics of two new cephalosporin antibiotics, cefaclor (CCL), and cefadroxil (CDX), were determined after oral administration of 1000 mg (capsules) on an empty stomach in 12 normal subjects in comparison to cephalexin (CEX). Serum concentrations were measured during a period of 8 h and urine recovery during 24 h. The significant parameters of bioavailability of an orally administered substance were determined. The maximum serum concentrations (ymax) were 38.8 ± 8.1 mg/l (CEX), 34.6 ± 7.8 mg/l (CCL), 33.0 ± 5.4 mg/l (CDX); the areas under the curves were 93.0 ± 14.8 h · mg/l (CEX), 74.5 ± 9.9 h · mg/l (CCL), and 108.5 ± 18.4 h · mg/l (CDX). In a further crossover study with 6 subjects, 1000 mg CEX and CDX were given during a standard breakfast. The ymax of CEX decreased to 23.1 ± 6.6 mg/l in contrast to CDX with an unchanged ymax of 32.7 ± 3.4 mg/l.Notes: Zusammenfassung In einer randomisierten Überkreuzstudie wurden die pharmakokinetischen Parameter zweier neuer Cephalosporin-Antibiotika, Cefaclor (CCL) und Cefadroxil (CDX), im Vergleich zu Cephalexin (CEX) bestimmt. Die 12 Probanden erhielten jeweils 1000 mg in Kapselform nüchtern oral verabreicht. Die Serumkonzentrationen wurden über einen Zeitraum von 8 h und die Urinausscheidung über 24 h gemessen. Die aussagekräftigen Parameter der biologischen Verfügbarkeit von oral applizierten Substanzen wurden ermittelt. Die maximalen Serumkonzentrationen (ymax) waren 38,8 ± 8,1 mg/l (CEX), 34,6 ± 7,8 mg/l (CCL), 33,0 ± 5,4 mg/l (CDX). Die Flächen unter den Kurven wurden mit 93,0 ± 14,8 h · mg/l (CEX), 74,5 ± 9,9 h · mg/l (CCL) sowie 108,5 ± 18,4 h · mg/l (CDX) berechnet. In einer weiteren Überkreuzstudie bei 6 Testpersonen wurden jeweils 1000 mg Cephalexin bzw. Cefadroxil während eines Standardfrühstücks gegeben. Die maximalen Serumkonzentrationen des Cephalexin fielen auf 23,1 ± 6,6 mg/l ab im Gegensatz zu Cefadroxil mit einem unveränderten ymax von 32,7 ± 3,4 mg/l.Type of Medium: Electronic ResourceURL: -
14Articles: DFG German National LicensesStaff View
ISSN: 1435-4373Source: Springer Online Journal Archives 1860-2000Topics: MedicineNotes: Abstract In this review the general and specific difficulties encountered in the evaluation of safety and tolerance of antimicrobial agents in clinical trials are discussed. In addition to the usual pharmacological and toxicological effects (adverse drug reactions) occurring in individual patients, microbiologically induced side-effects also have to be considered. The different methods for registration of side-effects and their limitations are discussed. A system is proposed for evaluation of the cause/effect relationships of adverse drug reactions. A system is also discussed for the evaluation of the severity of adverse drug reactions, and different classifications are presented.Type of Medium: Electronic ResourceURL: