Comparison of tenocytes and mesenchymal stem cells seeded on biodegradable scaffolds in a full-size tendon defect model.

In order to investigate cell-based tendon regeneration, a tendon rupture was simulated by utilizing a critical full-size model in female rat achilles tendons. For bridging the defect, polyglycol acid (PGA) and collagen type I scaffolds were used and fixed with a frame suture to ensure postoperatively a functional continuity. Scaffolds were seeded with mesenchymal stem cells (MSC) or tenocytes derived from male animals, while control groups were left without cells. After a healing period of 16 weeks, biomechanical, PCR, histologic, and electron microscopic analyses of the regenerates were performed. Genomic PCR for male-specific gene was used to detect transplanted cells in the regenerates. After 16 weeks, central ossification and tendon-like tissue in the superficial tendon layers were observed in all study groups. Biomechanical test showed that samples loaded with tenocytes had significantly better failure strength/cross-section ratio (P < 0.01) compared to MSC and the control groups whereas maximum failure strength was similar in all groups. Thus, we concluded that the application of tenocytes improves the outcome in this model concerning the grade of ossification and the mechanical properties in comparison to the use of MSC or just scaffold materials.

Thyroid hormone-responsive genes mediate otolith growth and development during flatfish metamorphosis.

Flatfish begin life as up-right swimming, bilaterally symmetrical larvae that metamorphose into asymmetrically shaped juveniles that swim with a highly lateralized posture. We have previously shown that TH induces abrupt growth and mineralization of one component of the vestibular system, the otoliths, during early larval development and metamorphosis. Here we report that four of five vestibular-specific genes that we tested (alpha-tectorin, otogelin, otolith matrix protein, and otopetrins 1 and 2 that are known to be associated with otolith development in other vertebrates are up-regulated 1.5- to 7-fold in larval flatfish during spontaneous metamorphosis and/or following 72 h of TH treatment. These findings suggest that otolith growth and development are mediated by diverse TH-responsive genes during flatfish metamorphosis.

Thyroid hormone mediates otolith growth and development during flatfish metamorphosis.

Flatfish begin life as bilaterally symmetrical larvae that swim up-right, then abruptly metamorphose into asymmetrically shaped juveniles with lateralized swimming postures. Flatfish metamorphosis is mediated entirely by thyroid hormone (TH). Changes in flatfish swim posture are thought to be regulated via vestibular remodeling, although the influence of TH on teleost inner ear development remains unclear. This study addresses the role of TH on the development of the three otolith end-organs (sacculus, utricle, and lagena) during southern flounder (Paralichthys lethostigma) metamorphosis. Compared with pre-metamorphosis, growth rates of the sacculus and utricle otoliths increase dramatically during metamorphosis in a manner that is uncoupled from general somatic growth. Treatment of P. lethostigma larvae with methimazol (a pharmacological inhibitor of endogenous TH production) inhibits growth of the sacculus and utricle, whereas treatment with TH dramatically accelerates their growth. In contrast with the sacculus and utricle otoliths that begin to form and mineralize during embryogenesis, a non-mineralized lagena otolith is first visible 10-12 days after hatching. The lagena grows during pre- and pro-metamorphosis, then abruptly mineralizes during metamorphic climax. Mineralization of the lagena, but not growth, can be induced with TH treatment, whereas treatment with methimazol completely inhibits lagena mineralization without inhibiting its growth. These findings suggest that during southern flounder metamorphosis TH exerts differential effects on growth and development among the three types of otolith.

[Management of patients with lymphatic diseases and lipoedema during the COVID-19 pandemic. Recommendations of the Spanish Group of Lymphology]. / La atención al paciente con patología linfática y lipedema en la pandemia COVID-19. Recomendaciones del Grupo Español de Linfología (GEL).

The COVID-19 pandemic poses a challenge to the management of non-COVID pathologies such as lymphatic diseases and lipoedema. The use of telemedicine can prevent the spread of the disease. A system is needed to help determine the clinical priority and selection of face-to-face or telemedicine options for each patient and how to carry them out during the pandemic. The Spanish Lymphology Group has drafted a consensus document with recommendations based on the literature and clinical experience, as clinical practice guidelines for the management of lymphatic abnormalities and lipoedema during the COVID-19 pandemic. These recommendations must be adapted to the characteristics of each patient, the local conditions of the centres, and the decisions of health care professionals. The document contains minimum criteria, subject to modifications according to the evolution of the pandemic, scientific knowledge and instructions from health authorities.

Usefulness of transesophageal echocardiography in identifying small left ventricular apical thrombus.

OBJECTIVES: The aim of this study was to determine whether transesophageal echocardiography could clarify the nature of equivocal echodense structures in the left ventricular apical region frequently found on transthoracic echocardiography by directing the ultrasound beam from the left ventricular base to the apex and achieving better image quality. BACKGROUND: Transthoracic echocardiography often reveals an echogenic structure suggesting thrombus in the left ventricular apical region because of limited near-field resolution and echo vibration artifact in apical views. METHODS: Thirty-six patients with coronary artery disease or dilated cardiomyopathy who had apical wall motion abnormalities and equivocal transthoracic echodense structures were studied with transesophageal echocardiography using special manipulation of the transesophageal probe for adequate imaging of the apical region. Left ventricular thrombus was defined when echogenic structures with a clearly delineated margin adjacent to but distinct from the endocardium were observed in at least two different tomographic views in the four-chamber and left ventricular long-axis views during both systole and diastole. RESULTS: Left ventricular thrombus (mean size 1.3 +/- 0.7 cm2) was defined by transesophageal echocardiography in 19 (53%) of 36 patients with suspected thrombus on transthoracic echocardiography in the four-chamber or left ventricular long-axis view. Heavy trabeculation or extremely high echo reflection, or both, was observed in the apical region in 12 patients (33%). No extra structures in the apical region were found in five patients. In 19 patients with transesophageal echocardiographically defined thrombus, 6 patients (31%) experienced arterial embolic events before the transesophageal procedure. In contrast, none of 17 patients without transesophageal echocardiographically defined thrombi had systemic embolism (p < 0.03). CONCLUSIONS: 1) Transesophageal echocardiography is useful in identifying left ventricular apical thrombus in patients with unclear echogenic structures on transthoracic apical images; and 2) the high incidence of arterial embolism in patients with transesophageal echocardiographically detected left ventricular thrombus indicates the clinical importance of such thrombus.

Diadenosine-5-phosphate exerts A1-receptor-mediated proarrhythmic effects in rabbit atrial myocardium.

(1) Diadenosine polyphosphates have been described to be present in the myocardium and exert purinergic- and nonreceptor-mediated effects. Since the electrophysiological properties of atrial myocardium are effectively regulated by A(1) receptors, we investigated the effect of diadenosine pentaphosphate (Ap(5)A) in rabbit myocardium. (2) Parameters of supraventricular electrophysiology and atrial vulnerability were measured in Langendorff-perfused rabbit hearts. Muscarinic potassium current (I(K(ACh/Ado))) and ATP-sensitive potassium current (I(K(ATP))) were measured by using the whole-cell voltage clamp method. (3) Ap(5)A prolonged the cycle length of spontaneously beating Langendorff perfused hearts from 225+/-14 (control) to 1823+/-400 ms (Ap(5)A 50 micro M; n=6; P<0.05). This effect was paralleled by higher degree of atrio-ventricular block. Atrial effective refractory period (AERP) in control hearts was 84+/-14 ms (n=6). Ap(5)A>/=1 micro M reduced AERP (100 micro M, 58+/-11 ms; n=6). (4) Extrastimuli delivered to hearts perfused with Ap(5)A- or adenosine (>/= micro M)-induced atrial fibrillation, the incidence of which correlated to the concentration added to the perfusate. The selective A(1)-receptor antagonist CPX (20 micro M) inhibited the Ap(5)A- and adenosine-induced decrease of AERP. Atrial fibrillation was no longer observed in the presence of CPX. (5) The described Ap(5)A-induced effects in the multicellular preparation were enhanced by dipyridamole (10 micro M), which is a cellular adenosine uptake inhibitor. Dipyridamole-induced enhancement was inhibited by CPX. (6) Ap(5)A (

Comparative pharmacokinetics of new quinolones.

The pharmacokinetic properties of the new quinolones are characterised by a high volume of distribution, long biological half-life, low serum protein binding, elimination mainly by the kidneys, high total and renal clearances, limited biotransformation and a moderate to excellent bioavailability after oral administration. However, each quinolone derivative (ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin) possesses individual pharmacokinetic characteristics, which should be considered in the treatment of patients, especially when liver and/or renal dysfunction exists.

The anaerobic threshold in cystic fibrosis: comparison of V-slope method, lactate turn points, and Conconi test.

Physical exercise can improve sputum clearance in patients with cystic fibrosis (CF). To set up individual training protocols it is desirable to know the anaerobic threshold (AT). Established methods such as blood lactate measurements and ergometry can only be performed in specialized centers. Conconi showed that the heart rate threshold (HRT), i.e., the deflection point from the linear relationship between work load and heart rate, correlated significantly with the AT in healthy adults. To assess the reliability of the HRT in CF, we performed ergometry in 32 CF patients (mean age, 21.0 +/- 5.5 years; mean Shwachman score, 77.8 +/- 12.0) according to the Conconi protocol. The HRT was compared with the aerobic threshold (AeT) as determined by the V-slope method and with two turn points in the lactate performance curve (LTP1, LTP2). An HRT could be obtained in only 17 of the 32 patients (53%). In these 17 patients there was a significant correlation between HRT and the other thresholds, but the absolute values for the AT differed considerably: The mean HRT was 132% higher than the AeT according to Beaver, 107% higher than LTP1, and 19% higher than LTP2. Exercise protocols that rely solely on the HRT in CF will lead to excessive exertion during exercise training programs in these patients. According to these results the HRT of Conconi is not a suitable method to determine appropriate exercise levels in CF training programs and might even be harmful in CF patients. These results also indicate the need to test the reliability of a diagnostic procedure that has been developed only for healthy people.

[Dual sensor-controlled rate adaptation in non-dynamical exercise]. / Dual-Sensor-gesteuerte Frequenzanpassung bei nicht-dynamischen Belastungen: Wie physiologisch sind frequenzadaptive Dual-Sensor-Schrittmacher wirklich?

Single sensor and dual sensor systems are used to reach physiological rate adaptation in pacemaker therapy. The purpose of the present study was to examine the sensor-controlled heart rate reaction and adaptability of a dual sensor (QT + activity) with 3 different tests. Nine chronotropically incompetent patients (group 1), 3 females and 6 males, mean age 74.1±8.43 years, were implanted 5 VVIR and 4 DDDR pacemakers (Vitatron, The Netherlands). The control group included 10 chronotropically competent patients (group 2) (2 females, 8 males, mean age 58.2±12.6 years). Both groups underwent 3 different tests: 1) a mental test, 2) an isometric test and 3) an activity (=tap) test. Heart rate was measured every 30 seconds by the recorded surface ECG. We measured an unsatisfaying heart rate response of the pacemaker patients in all 3 tests: During isometric exercise the pacing rate decreased from 63±3.5bpm to 65±3.4bpm (-0.97±0.71bpm/min) (p=0.1829) in contrast to an increase of the heart rate in the control group: from 77.8±15.8bpm to 92.5±19.9bpm (3.76±1.29bpm/min) (p=0.0048). During mental stress testing the pacing rate increased from 63±3.5bpm to 65±3.4bpm (0.66±0.20bpm/min) (p=0.0199) in the pacemaker group, compared to an increase of the heart rate in the control group from 75.8±15.8bpm to 83.6±17.3bpm (2.04±0.74bpm/min) (p=0.0076). Tapping on the pacemaker case produced an increase of the pacing rate from 65.9±2.8bpm to 73.6±3.8bpm (2.83±0.73bpm/min) (p=0.0004), whereas the heart rate decreased from 76.8±13.0bpm to 75.0±1.9bpm (-0.19±0.61bpm/min) (p=0.7522) in the control group. Compared to the physiologically chronotropic function of the control group, the sensor-controlled heart rate response was inadaequate during these tests. The expectations of sensor cross checking could not be fulfilled with the previous sensor combination (QT + activity).

Tricuspid annular plane systolic excursion assessed using MRI for semi-quantification of right ventricular ejection fraction.

OBJECTIVE: Accurate determination of right ventricular volume and ejection fraction (RVEF) is established using MRI. Automatic contour detection of the right ventricular endocardial border is not established in clinical practice, resulting in considerable manual efforts to quantify RVEF. Using transthoracic echocardiography (TTE), the tricuspid annular plane systolic excursion (TAPSE) has proved its worth for quantification of RVEF and risk prediction. Therefore, the aim of this study was to clarify whether TAPSE assessed with MRI as a fast and easily obtainable parameter correlated with volumetric quantification of RVEF. METHODS: Right ventricular volumes and RVEF were measured with the standardised slice-summation method at MRI. MRI-TAPSE was defined as maximum apical excursion of lateral tricuspid annular plane and measured in a four-chamber view using steady-state free precession sequences. Additionally, MRI-TAPSE was compared with TAPSE assessed using TTE. RESULTS: 76 consecutive patients (aged 58±17 years) were examined. At MRI, right end-diastolic volumes were 97±36 ml, right end-systolic volumes were 57±27 ml and the mean RVEF was 42±14%. MRI-TAPSE was determined with 19±6 mm and correlated well at linear regression analysis with volumetric RVEF (r=0.72, p<0.001). Furthermore, MRI-TAPSE discriminated sufficiently between patients with impaired and normal RVEF. Multiplying MRI-TAPSE by 2.5 led to values close to the RVEF by volumetry. Additionally, MRI-TAPSE correlated well with TAPSE determined using TTE. The inter- and intra-observer variabilities of MRI-TAPSE determination were low (3.1% and 1.8%). CONCLUSION: TAPSE assessed with MRI is a fast and easily obtainable parameter which correlates well with volumetric quantification of RVEF.

Comparison of dual-source and electron-beam CT for the assessment of coronary artery calcium scoring.

OBJECTIVE: Cardiac CT allows the detection and quantification of coronary artery calcification (CAC). Electron-beam CT (EBCT) has been widely replaced by high-end CT generations in the assessment of CAC. The aim of this study was to compare the CAC scores derived from an EBCT with those from a dual-source CT (DSCT). METHODS: We retrospectively selected 92 patients (61 males; mean age, 60.7 ± 12 years) from our database, who underwent both EBCT and DSCT. CAC was assessed using the Agatston score by two independent readers (replicates: 1, 2; 3=mean of reading 1 and 2). RESULTS: EBCT scores were on average slightly higher than DSCT scores (281 ± 569 vs 241 ± 502; p<0.05). In regression analysis R(2)-values vary from 0.956 (1) to 0.966 (3). We calculated a correction factor as EBCT=(DSCT+1)(1.026)-1. When stratifying into CAC categories (0, 1-99, 100-399, 400-999 and ≥1000), 79 (86%) were correctly classified. From those with positive CAC scores, 7 out of 61 cases (11%, κ=0.81) were classified in different categories. Using the corrected DSCT CAC score, linear regression analysis for the comparison to the EBCT results were r=0.971 (p<0.001), with a mean difference of 6.4 ± 147.8. Five subjects (5.4%) were still classified in different categories (κ=0.84). CONCLUSION: CAC obtained from DSCT is highly correlated with the EBCT measures. Using the calculated correction factor, agreement only marginally improved the clinical interpretation of results. Overall, for clinical purposes, face value use of DSCT-derived values appears as useful as EBCT for CAC scoring.

Scaffold-free 3D cellulose acetate membrane-based cultures form large cartilaginous constructs.

Scaffold-free three-dimensional (3D) cultures provide clinical potential in cartilage regeneration. The purpose of this study was to characterize a scaffold-free 3D membrane-based culture system, in which human articular chondrocytes were cultivated on a cellulose acetate membrane filter, and compare it to pellet and monolayer cultures. Chondrocytes were expanded in monolayer culture for up to 5 passages, transferred to membrane-based or pellet cultures and harvested after 7 or 21 days. The chondrogenic potential was assessed by histology (toluidine blue, safranin-O), immunohistochemistry for collagen type II and quantitative analysis of collagen type II α(1) (COL2A1). Membrane-based cultures (P1) formed flexible disc-like constructs (diameter 4000 µm, thickness 150 µm) with a large smooth surface after 7 days. Positive safranin-O and collagen type II staining was found in membrane-based and pellet cultures at P1-3. Expression of COL2A1 after 7 days was increased in both culture systems compared to monolayer culture up to P3, whereas cells from monolayer > P3 did not redifferentiate. The best results for COL2A1 expression were obtained from membrane-based cultures at P1. After 21 days the membrane-based cultures did not express COL2A1. We concluded that membrane-based and pellet cultures showed the ability to promote redifferentiation of chondrocytes expanded in monolayer culture. The number of cell passages had an impact on the chondrogenic potential of cells. Membrane-based cultures provided the highest COL2A1 expression and a large, smooth and cartilage-like surface. As these are appropriate features for clinical applications, we assume that membrane-based cultures might be of use in cartilage regeneration if they displayed similar results in vivo.

Influence of design and bearing material on polyethylene wear particle generation in total knee replacement.

Periprosthetic osteolysis is one of the main reasons for revision of arthroplasty. The osteolytic reaction is influenced by the dose, size and shape of the wear particles. For arthroplasty, a low number and biologically less active particles are required. This is the first study which analyzes the impact of different knee designs, combined with crosslinked polyethylenes (sequentially irradiated and annealed as well as remelted techniques), on the amount, size and shape of particles. Overall, six material combinations, four of them with crosslinked polyethylene (XPE) and two of them with ultra-high molecular weight polyethylene (UHMWPE) inserts, including fixed and mobile bearings, were tested in a knee joint simulator. After isolation nearly 100,000 particles were analyzed in size, shape and number by scanning electron microscopy and image analysis. For all the designs, the wear was predominantly smooth and granular with few fibrillar particles. The Scorpio design with the X3 insert, the Natural Knee II design with the Durasul insert and the LCS design, also combined with a crosslinked polyethylene insert, generated statistically significant (P<0.05) lower particle numbers. The particle size was independent of the radiation dose. The wear generated by the LCS knee design (XPE and UHMWPE) had a higher percentage fraction of particles >1microm in size (equivalent circle diameter). The NexGen design, tested with the Prolong insert, showed a high number of particles in the biologically active size range compared with the other crosslinked designs, which could be a predictor for higher biological reactivity.

Randomized comparison of effects of suture-based and collagen-based vascular closure devices on post-procedural leg perfusion.

BACKGROUND: Vascular closure devices (VCD) are well established to facilitate hemostasis after cardiac catheterization procedures. However, impairment of flow due to the reduction of femoral artery diameter remains a major concern. The present study aims to evaluate leg perfusion before and after application of collagen- and suture-based vascular closure devices. METHODS: A total of 366 patients (age: 64.3 years+/-10.7, male: 71.3%) were randomized to receive femoral access site closure with either a collagen-based closure device (group A) (n=214) or a suture-mediated device (group B) (n=152), immediately following coronary catheterization procedures. In all patients, the ankle-brachial-index (ABI) was measured before and the day after closure device application. RESULTS: In group A, mean ABI at baseline was 1.09+/-0.2, in group B 1.11+/-0.2. In both groups, there was a significant, albeit clinically not relevant, reduction in post-procedural ABI (group A: 1.04+/-0.2, p<0.01 vs baseline, group B: 1.06+/-0.2, p<0.01 vs baseline). DeltaABI was not different between both VCD groups (p=0.55). In patients with peripheral vascular disease (PVD), neither the Angioseal device (mean ABI at baseline 0.76+/-0.1) nor the Perclose-device (mean ABI at baseline 0.79+/-0.1) induced a remarkable impairment of leg perfusion (Angioseal: 0.77+/-0.1, p=0.9 vs baseline, Perclose: 0.78+/-0.1, p=1.0 vs baseline). Clinically, no aggravation of claudication was observed in the PVD patient group. CONCLUSION: Both vascular closure devices are not associated with clinically relevant reduction in ABI. There was no difference between the two groups with respect to the level of flow impairment. Both devices may be safely used in patients with reduced ABI.

[Results of emergency bypass operation following percutaneous transluminal coronary angioplasty]. / Ergebnisse der notfallmässigen Bypass-Operation nach perkutaner transluminaler Koronarangioplastie.

Between 1980 and 1988, percutaneous transluminal coronary angioplasty (PTCA) was performed in 1,514 patients. Fifty-five patients (3.6%) underwent emergency coronary bypass surgery because of an acute occlusion of the vessel or a dissection with sustained angina and signs of ischemia on the electrocardiogram. Twenty-five of these 55 patients had a myocardial infarction and 5 patients died, 3 perioperatively, 2 after hospital discharge. The degree of stenosis of the dilated vessel significantly influenced the incidence of infarction, while left ventricular ejection fraction prior to PTCA significantly influenced mortality. Patients who underwent surgery with an occluded vessel experienced myocardial infarction significantly more often (87%) than patients with a patent vessel (24%). The incidence of infarction was 27% when reperfusion of the vessel occluded during PTCA was achieved with a reperfusion catheter, repeated PTCA or intracoronary lysis. The patients' age, presence of unstable angina, left ventricular ejection fraction prior to PTCA, the dilated vessel, the extent of coronary artery disease, collateralization of the dilated vessel, and the time between the onset of the event necessitating bypass surgery and the beginning of extracorporeal circulation were found to have no influence on the incidence of infarction. Patients who died had a significantly lower ejection fraction before PTCA than survivors and all patients who died had experienced a large perioperative myocardial infarction.

Comparative pharmacokinetics of intravenous ofloxacin and ciprofloxacin.

In ten volunteers the pharmacokinetics of ofloxacin and ciprofloxacin were determined after crossover administration of 100 and 200 mg intravenously (30 min constant infusion). Concentrations in serum and urine were measured by HPLC. Concentrations in serum following parenteral ofloxacin dosages demonstrated dose dependency with long biological half-lives. Pharmacokinetic parameters were calculated on the basis of an open three-compartment model, which resulted in a high volume of distribution for both substances (166-246 1 for ofloxacin, 178-2611 for ciprofloxacin). AUC for ofloxacin was three times higher than that for ciprofloxacin. Approximately 80% of ofloxacin and 57% of ciprofloxacin were eliminated through the kidneys. Ciprofloxacin had a considerable amount of extrarenal clearance, whereas only 19% of ofloxacin were eliminated by extrarenal mechanisms. Only 4.3% of ofloxacin after iv dosing could be detected as metabolites in urine.

Pharmacokinetics of ofloxacin after parenteral and oral administration.

In 10 volunteers, the pharmacokinetics of ofloxacin [HOE 280, DL 8280; (+/-)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H -pyrido-[1,2,3-de] [1,4]benzoxacine-6-carboxylic acid] was determined after administration of 25, 50, 100, and 200 mg intravenously (30-min infusion) as well as 200 and 400 mg orally. Concentrations in serum and urine were measured by high-pressure liquid chromatography. Concentrations in serum following different parenteral ofloxacin dosages demonstrated dose dependency with long biological half-lives of 231 to 267 min. Pharmacokinetic parameters were calculated on the basis of open two- and three-compartment models, which yielded nearly identical results. High volumes of distribution (1.2 to 1.4 liters/kg of body weight) suggested effective diffusion into the extravascular space. High total and renal clearances indicated primarily renal excretion with additional elimination pathways, such as tubular secretion and extrarenal elimination. After oral administration, absorption was excellent, and the absolute bioavailability following 200 mg of ofloxacin could be calculated at greater than 0.95. Maximal concentrations in serum were attained 1.2 to 1.9 h after dosing; areas under the curve increased in proportion to dose between 200 and 400 mg of oral ofloxacin. The amount of known metabolites (demethyl and N-oxide compounds) excreted in urine reached only 4.3% (intravenously) and 4.0% (orally). Transient headaches in some volunteers were the only side effects registered.

[Significance of ear lobe biopsy in the diagnosis of angiopathies inflammatory-rheumatic diseases]. / Die Bedeutung der Ohrläppchenbiopsie zur Diagnostik von Angiopathien bei entzündlich-rheumatischen Erkrankungen

Biopsy of the ear lobule in inflammatory rheumatic and collagen diseases is not a suitable method for detecting vascular involvement. A perivascular cell infiltration van often be found but it non-specific. The intensity of cell infiltration did not correlate with duration, severity or activity of the disease process.

Pharmacokinetics of ciprofloxacin in healthy volunteers after oral and intravenous administration.

The pharmacokinetics of ciprofloxacin was studied in three groups of healthy volunteers comprising a total of 16 males and 16 females (age 21-35 years; body weight 52-80 kg). Single oral doses of 50, 100, 250, 500 and 750 mg were given to fasting subjects. The 250 mg dose was repeated after a breakfast. Intravenous doses of 50, 100 and 200 mg were given by short infusion in a randomized cross-over sequence. Concentrations of the drug in serum and urine were determined by high-performance liquid chromatography and by a microbiological assay. Mean peak concentrations between 0.37 +/- 0.49 mg/l (100 mg dose) and 1.97 +/- 0.50 (750 mg dose) were measured 60-75 min after oral administration. Twelve hours after 750 mg ciprofloxacin, serum concentrations were 0.15 +/- 0.05 mg/l. Taking a breakfast reduced absorption by 15-20% compared to the fasting state, as judged by peak concentrations, AUC and renal excretion. After 200 mg i.v. (20 min infusion period), initial serum concentrations of 4.0 +/- 1.2 mg/l were observed which declined 12 h later to 0.070 +/- 0.025 mg/l. Mean cumulated recovery of ciprofloxacin from urine over 24 h varied between 25.5% and 33.6% of oral doses and between 53.2% and 57.4% of intravenous doses. Two of the three metabolites seen in the chromatograms were identified as M1 and M3 (oxo-ciprofloxacin). Cumulated renal excretion after an oral 250 mg dose was 1.2 +/- 0.4% of M1 and 5.5 +/- 1.6% of M3.(ABSTRACT TRUNCATED AT 250 WORDS)