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At least 793 records · Page 44Linked to original sources

Pharmacodynamics of daptomycin in a murine thigh model of Staphylococcus aureus infection.

Daptomycin is a lipopeptide antibiotic with activity against gram-positive bacteria, including Staphylococcus aureus. We defined the pharmacodynamic parameters that determine the activity of daptomycin for S. aureus using in vitro methods and the Craig (W. A. Craig, J. Redington, and S. C. Ebert, J. Antimicrob. Chemother. 27[Suppl. C]:29--40, 1991) neutropenic mouse thigh infection model. In Mueller-Hinton broth, the MICs for three S. aureus isolates were 0.1 to 0.2 microg/ml. In mouse serum, the MICs were 1.0 microg/ml. The protein binding of daptomycin was 90 to 92.5% in mouse serum. Single-dose intraperitoneal (i.p.) pharmacokinetic studies with infected mice showed a linear relationship between dose versus the maximum concentration of drug in serum and dose versus the area under the concentration-time curve (AUC). The serum half-life of daptomycin in infected mice was approximately 1.8 h. In single-dose, dose-ranging studies using mice, daptomycin showed a dose-response effect described by an inhibitory sigmoid E(max) (maximum effect) curve (r = 0.974; P << 0.001). The density of S. aureus in untreated controls was 8.26 log(10) CFU/g, and the E(max) was 3.97 log(10) CFU/g. The 50% effective dose (ED(50)) was 3.7 mg/kg of body weight i.p. and the stasis dose was 7.1 mg/kg. Dose fractionation studies at schedules of Q6h, Q12h, and Q24h, for total 24-h ED(30), ED(60), and ED(80) doses of 2.5, 5.6, and 15 mg/kg i.p., showed no difference in effect at each total 24-h dose level by schedule, indicating that the AUC/MIC ratio is the dynamically linked variable.

Animals↗

Pharmacodynamics of oritavancin (LY333328) in a neutropenic-mouse thigh model of Staphylococcus aureus infection.

The pharmacokinetics and pharmacodynamics of oritavancin (LY333328), a glycopeptide antibiotic with concentration-dependent bactericidal activity against gram-positive pathogens, in a neutropenic-mouse thigh model of Staphylococcus aureus infection were studied. Plasma radioequivalent concentrations of oritavancin were determined by using [(14)C]oritavancin at doses ranging from 0.5 to 20 mg/kg of body weight. Peak plasma radioequivalent concentrations after an intravenous dose were 7.27, 12.56, 69.29, and 228.83 micro g/ml for doses of 0.5, 1, 5, and 20 mg/kg, respectively. The maximum concentration of drug in serum (C(max)) and the area under the concentration-time curve (AUC) increased linearly in proportion to the dose. Neither infection nor neutropenia was seen to affect the pharmacokinetics of oritavancin. Intravenous administration resulted in much higher concentrations in plasma than the concentrations obtained with subcutaneous administration. Single-dose dose-ranging studies suggested a sigmoid maximum effect (E(max)) dose-response relationship, with a maximal effect evident at single doses exceeding 2 mg/kg. The oritavancin dose (stasis dose) that resulted in a 24-h colony count similar to the pretreatment count was 1.53 (standard error [SE], 0.35) mg/kg. The single oritavancin dose that resulted in 50% of maximal bacterial killing (ED(50)) was 0.95 (SE, 0.20) mg/kg. Dose fractionation studies suggested that single doses of 0.5, 1, 2, 4, and 16 mg/kg appeared to have greater bactericidal efficacy than the same total dose subdivided and administered multiple times during the 24-h treatment period. When using an inhibitory E(max) model, C(max) appears to correlate better with bactericidal activity than do the time during which the concentration in plasma exceeds the MIC (T>MIC) and AUC. These data suggest that optimal oritavancin dosing strategies will require regimens that favor high C(max) concentrations rather than long periods during which unbound concentrations in plasma exceed the MIC.

Animals↗

Pharmacodynamic profile of ertapenem against Klebsiella pneumoniae and Escherichia coli in a murine thigh model.

The pharmacodynamic profile of ertapenem was evaluated in a neutropenic mouse thigh infection model. Extended-spectrum beta-lactamase (ESBL)-positive and ESBL-negative clinical strains of Escherichia coli and Klebsiella pneumoniae were studied. MICs ranged from 0.0078 to 0.06 microg/ml with standard inoculum tests. Ertapenem doses were administered once to five times daily to achieve various exposures, reported as the percentage of the dosing interval that the concentration of free ertapenem was in excess of the MIC (%T>MIC(free)). Mean values for the static exposure and 80% maximally effective exposure (ED(80)) were 19% (range, 2 to 38%) and 33% (range, 13 to 65%) T>MIC(free), respectively. Differences in exposure requirements based on the presence of an ESBL resistance mechanism or bacterial species were not evident. In addition, experiments using a 100-fold higher inoculum did not decrease the magnitude of the reduction in bacterial density from baseline achieved compared to lower-inoculum studies. The pharmacodynamic parameter of %T>MIC(free) correlated well with bactericidal activity for all isolates, and the static and ED(80) exposures are consistent with those reported previously for carbapenems.

Animals↗

Acute compartment syndrome of the anterior thigh following quadriceps strain in a footballer.

A rare case is presented of acute anterior compartment syndrome in the thigh of a footballer caused by an acute quadriceps strain, exacerbated by poor first aid and alcohol ingestion. Decompressive fasciotomy with subsequent split skin grafting of the wound defect resulted in a satisfactory outcome. The diagnosis requires a high index of suspicion lest it be overlooked with inevitably disastrous consequences.

Acute Disease↗

Spontaneous complete hamstring avulsion causing posterior thigh compartment syndrome.

Complete avulsion of the hamstring muscle group from its ischial origin is an uncommon condition, and has been mostly reported in young athletes. A case is presented in which a middle aged man sustained this injury and developed a compartment syndrome of the thigh, which has not been previously reported. The surgical management of this patient is described.

Compartment Syndromes↗

Best evidence topic report. No evidence found that a femoral nerve block in cases of femoral shaft fractures can delay the diagnosis of compartment syndrome of the thigh.

A short cut review was carried out to establish whether a femoral nerve block may mask the signs and symptoms of thigh compartment syndrome. No relevant papers were found using the reported search. There is no evidence to associate a femoral nerve block with a delayed or missed diagnosis of compartment syndrome.

Compartment Syndromes↗

Metastatic Crohn's disease of thigh and forearm.

Cutaneous involvement with Crohn's disease at a site separated from the gastrointestinal tract by normal skin is termed metastatic Crohn's disease. Such a complication is extremely rare and previous reports have emphasised the flexural distribution of the ulcerated lesions. We report a patient who developed Crohn's disease involving the skin of the thigh and forearm several months after a panproctocolectomy for colorectal Crohn's disease.

Aged↗

Appendix sepsis tracking along the lateral cutaneous nerve of the thigh.

A patient presented with tracking of pus from a chronic appendiceal abscess along the lateral cutaneous nerve of the thigh. In the absence of such a tunnel, which is only present in a small proportion of individuals, the infection would have resulted in a subinguinal psoas abscess. Although pus may conceivably extend in any direction, the reason for this unusual complication remains poorly understood.

Abscess↗

Clostridial myonecrosis in association with etoposide therapy presenting as severe thigh pain.

The case is described of a 68 year old man who was immunosuppressed as a result of receiving chemotherapy for small cell lung cancer and who presented with severe right thigh pain. This proved to be due to clostridial myonecrosis with none of the classical clinical features of clostridial infection. This is believed to be the first reported case of spontaneous clostridial infection associated with etoposide administration.

Aged↗

Effects of strength and endurance training on thigh and leg muscle mass and composition in elderly women.

The effects of 18 wk of intensive strength and endurance training on knee extensor, knee flexor, and lower leg muscle mass and composition were studied in 76- to 78-yr-old women. Muscle cross-sectional area (CSA), lean tissue CSA, and relative proportion of fat were determined using computed tomography. The strength-trained women increased their total muscle lean tissue CSA of the thigh (1.5%; P = 0.035), quadriceps CSA (4.5%; P = 0.021), quadriceps lean tissue CSA (5.8%, P = 0.009), and mean Hounsfield unit of the lower leg muscles (11.2%; P = 0.035) compared with the changes that occurred in the control group during the experiment. The change in quadriceps lean tissue CSA because of the strength training was also significant compared with that in the endurance group. The relative proportion of fat within the quadriceps muscle decreased due to the strength training compared with the changes that occurred in the endurance group. The results show that intensive strength training can induce skeletal muscle hypertrophy in elderly women and thereby also reduce the relative amount of intramuscular fat, whereas the effects of endurance training are negligible.

Aged↗

Prenatal diagnosis of a fibrosarcoma of the thigh: a case report.

We report a rare case of fibrosarcoma of the thigh suspected prenatally. At 27 weeks of gestation a voluminous, vascularised mass was discovered at ultrasound on the foetus' left leg, suggestive of haemangioma or a fibrosarcoma. There were no signs of heart failure. A rapid increase in the tumour mass was noted and a caesarean section was carried out at 39 weeks because of abnormal foetal heart rate. Postnatal ultrasound examination was comparable to that carried out prenatally; pathological examination of the mass biopsied and immunohistochemical investigation provided a diagnosis of congenital fibrosarcoma. After neoadjuvant chemotherapy and surgery the infant is now in complete remission without amputation.

Adult↗

A new approach to lateral cutaneous nerve of thigh block.

A new approach to the lateral cutaneous nerve of thigh is described. It depends on locating the depth of the canal through which the nerve passes immediately medial to the anterior superior iliac spine. Anatomical dissections show that it lies deep to the attachments of external oblique aponeurosis, the internal oblique muscle, and a deep fascial layer. Two district 'pops' or loss of resistance can be identified during insertion of a short-bevelled needle. Location of the canal by the technique described has been confirmed radiographically.

Anesthesia, Local↗

Recurrent compartment syndrome in the posterior thigh. Report of a case.

Recurrent compartment syndromes of the lower extremity, which usually occur in conjunction with intense use of muscle groups, can be briefly defined as an uncomfortable circulatory disturbance associated with a pathologic increase in total intramuscular pressure. This syndrome has been reported in each of the four compartments of the leg but not in the thigh. Characteristic features of clinical presentation and physical examination are reviewed in this report. We have found that an intracompartmental pressure test (Whitesides Jr, TE, Haney TC, Morimoto K, et al: Tissue pressure measurements as a determinant for the need of fasciotomy. Clin Orthop 113: 43-51, 1975) is an invaluable diagnostic aid. A case involving the medial hamstring groups, with characteristic historical presentation, intracompartmental pressure elevation, and excellent response to fasciotomy, is presented and discussed. The only effective treatment in this case was fasciotomy.

Acute Disease↗

The synergistic action of the anterior cruciate ligament and thigh muscles in maintaining joint stability.

The synergistic action of the ACL and the thigh muscles in maintaining joint stability was studied experimentally. The EMG from the quadriceps and hamstring muscle groups was recorded and analyzed in three separate experimental procedures in which the knee was stressed. The test revealed that direct stress of the ACL has a moderate inhibitory effect on the quadriceps, but simultaneously it directly excites the hamstrings. Similar responses were also obtained in patients with ACL damage during loaded knee extension with tibia subluxation, indicating that an alternative reflex arc unrelated to ACL receptors was available to maintain joint integrity. The antagonist muscles (hamstrings) were clearly demonstrated to assume the role of joint stabilizers in the patient who has a deficient ACL. The importance of an appropriate muscle-conditioning rehabilitation program in such a patient is substantiated.

Adolescent↗

The effect of thigh and goniometer restraints on the reproducibility of the genucom knee analysis system.

We compared the reproducibility of measurements made with the Genucom knee analysis system using two methods of restraint. The first method was that suggested by the manufacturer and consisted of clamping the thigh to the examination chair with 70 N of vertical force and 110 N of mediolateral force and used a single elastic strap to secure the electrogoniometer cuff to the leg. In the second, or enhanced, method, the vertical and mediolateral clamping forces were each increased to 156 N, and an additional strap was used to secure the cuff to the leg. Tests performed were the anteroposterior stress tests at 20 degrees and 90 degrees of knee flexion, and the varus-valgus stress test, the internal-external rotation stress test, and the medial and lateral pivot shift tests at 20 degrees. Five normal subjects were installed and tested on 6 different days with the manufacturer's suggested securing method and on 12 different days with the enhanced securing method. The enhanced method of restraint resulted in significantly reduced day-to-day variance for all tests performed except the varus-valgus stress test.

Adult↗

Quantitative ultrasound tissue characterization in shoulder and thigh muscles--a new approach.

BACKGROUND: The echogenicity patterns of ultrasound scans contain information of tissue composition in muscles. The aim was: (1) to develop a quantitative ultrasound image analysis to characterize tissue composition in terms of intensity and structure of the ultrasound images, and (2) to use the method for characterization of ultrasound images of the supraspinatus muscle, and the vastus lateralis muscle. METHODS: Computerized texture analyses employing first-order and higher-order grey-scale statistics were developed to objectively characterize ultrasound images of m. supraspinatus and m. vastus lateralis from 9 healthy participants. RESULTS: The mean grey-scale intensity was higher in the vastus lateralis muscle (p < 0.05) than in the supraspinatus muscle (average value of middle measuring site 51.4 compared to 35.0). Furthermore, the number of spatially connected and homogeneous regions (blobs) was higher in the vastus lateralis (p < 0.05) than in the supraspinatus (average for m. vastus lateralis: 0.092 mm(-2) and for m. supraspinatus: 0.016 mm(-2)). CONCLUSION: The higher intensity and the higher number of blobs in the vastus lateralis muscle indicates that the thigh muscle contained more non-contractile components than the supraspinatus muscle, and that the muscle was coarser. The image analyses supplemented each other and gave a more complete description of the tissue composition in the muscle than the mean grey-scale value alone.

Adult↗

Cross-sectional thigh components: computerized tomographic assessment.

The purpose of this study was to examine the efficacy of the Picker Synerview Fourth Generation CT Scanner in assessing cross-sectional areas of muscle, bone, and subcutaneous fat of the thigh. A secondary purpose was to resolve individual muscle bellies using the CT scanner and to determine the effects of body composition in isolating those muscles. Both limbs of one cadaver were used to compare actual cross-sectional areas with the CT images. Each limb was dissected and photographed. Accuracy of repeated measurements was assessed using human volunteers. Absolute and percent error between the CT measurements and the measurements of the cross-sectional areas differed most at the bone. No differences were found between repeat scans. CT images and photographic measurements of individual muscles were generally quite similar, as assessed by absolute and percent error. The gracilis and sartorious were reasonably well defined in those individuals with more than 8% body fat. The results are discussed in terms of possible applications of the CT scanner in sports medicine research.

Adipose Tissue↗