Thigh mass in a patient with malignant pleural mesothelioma: Metastasis at an unusual site.

Soft tissue tumors are a highly heterogeneous group of lesions with varied clinical presentation. The majority is primary tumors and metastatic tumors are very rare. Malignant pleural mesothelioma presenting as a soft tissue mass at a distant site is even rarer and can cause diagnostic challenges both clinically and pathologically. We report a case of malignant pleural mesothelioma presenting as a soft tissue mass in the left thigh. A 59-year-old man, non-smoker, working in a cement factory since 30 years presented with complains of difficulty in walking since 1½ months. Review of his previous medical records revealed malignant pleural mesothelioma, which was diagnosed 9 months before. He had denied chemotherapy and was on Ayurvedic medication. The lesion involved the adjacent intercostal muscles. Few enlarged lymph nodes were noted in mediastinal and cervical regions. Biopsy of left supraclavicular and right cervical lymph nodes showed metastases. Metastasis from malignant pleural mesothelioma to the thigh was confirmed by immunohistochemistry. The tumor was positive for CK5/6, CK7, Calretinin and vimentin and immunonegative for CEA, Napsin A and TTF 1.

Diosgenin Supplementation Prevents Lipid Accumulation and Induces Skeletal Muscle-Fiber Hypertrophy in Rats.

Diosgenin (Dio) is a steroid sapogenin found in plants such as Dioscorea species, and is recognized as a phytochemical against various disorders as well as a natural precursor of steroidal drugs. The present study used rats fed high-cholesterol (Chol) diets supplemented with or without 0.5% Dio for 6 wk to investigate the effects of dietary Dio on lipid metabolism. Dio supplementation significantly increased serum high-density lipoprotein Chol concentrations and fecal Chol content, and significantly decreased fecal bile acid content compared rats fed a high-Chol diet alone, showing that dietary Dio may facilitate excretion of Chol rather than bile acids. A reduction in the liver triglyceride content and intra-abdominal visceral fat was observed in Dio-supplemented rats. Interestingly, dietary Dio also significantly increased the skeletal muscle-fiber diameter and area in the thigh muscles of the rats. Mouse myoblast-derived C2C12 cells were used to examine whether Dio directly affected skeletal muscle. Dio promoted fusion of myoblasts into multinucleated cells or myotubes. Furthermore, in myotube C2C12 cells, protein levels of phosphorylated AMP-activated protein kinase (AMPK) increased with Dio treatment in a dose-dependent manner. These results indicate that Dio may not only induce myoblast fusion and enhance skeletal muscle as an energy expenditure organ, but may also activate the catabolic pathway via AMPK in skeletal muscle cells. Thus, these effects of Dio on skeletal muscles may contribute to inhibition of visceral fat accumulation.

Case reports of diagnostic error: liposarcoma mistaken for hematoma in an obese female with concurrent ipsilateral thrombosis on rivaroxaban.

We report the case of a morbidly obese 49-year-old female found to have a 16×14×10 cm high grade myxoid liposarcoma of the thigh initially diagnosed as a hematoma. Recent initiation of rivaroxaban for a coincident ipsilateral popliteal vein thrombosis placed hematoma high in the differential diagnosis. Despite its large size, the mass was not directly appreciable on physical exam due to excess adjacent adipose tissue. Diagnostic success was achieved only after anchoring bias was abandoned and adaptive expertise was applied.

Necrotizing Myositis: A Rare Necrotizing Soft Tissue Infection Involving Muscle.

INTRODUCTION: Necrotizing myositis (NM) is an extremely rare necrotizing soft tissue infection involving muscle. Unlike similar infections (eg, necrotizing fasciitis, clostridial myonecrosis) that can be more readily diagnosed, NM can have a benign presentation then rapidly progress into a life-threatening condition with a mortality rate of 100% without surgical intervention. CASE REPORT: A 74-year-old man with a history of prostate cancer with radiation therapy, seed implants, and 2 transurethral resection procedures presented to the emergency department after a fall. He was initially diagnosed and treated for urosepsis. Sixteen hours after presentation, he complained of pain and swelling of his right groin. Computed tomography of the abdomen and pelvis showed gas findings suspicious for necrotizing infection of the bilateral thighs. Surgical exploration revealed NM. Separate cultures from the left thigh and bladder grew Streptococcus intermedius, Clostridium clostridioforme, and Peptostreptococcus, suggesting a possible common source of infection from the prostate gland or the osteomyelitic pubic symphysis, which subsequently spread to the bilateral thighs. CONCLUSIONS: To the best of the authors' knowledge, this is the first reported case of S intermedius and C clostridioforme causing NM. A high index of suspicion is required for extremely rare conditions like NM, because early diagnosis and surgical intervention significantly reduce mortality.

Activity of Meropenem-Vaborbactam in Mouse Models of Infection Due to KPC-Producing Carbapenem-Resistant Enterobacteriaceae.

Meropenem-vaborbactam (Vabomere) is highly active against Gram-negative pathogens, especially Klebsiella pneumoniae carbapenemase (KPC)-producing, carbapenem-resistant Enterobacteriaceae The objective of these studies was to evaluate the efficacy of meropenem alone and in combination with vaborbactam in mouse thigh and lung infection models. Thighs or lungs of neutropenic mice were infected with KPC-producing carbapenem-resistant Enterobacteriaceae, with meropenem MICs ranging from ≤0.06 to 8 mg/liter in the presence of 8 mg/liter vaborbactam. Mice were treated with meropenem alone or meropenem in combination with vaborbactam every 2 h for 24 h to provide exposures comparable to 2-g doses of each component in humans. Meropenem administered in combination with vaborbactam produced bacterial killing in all strains tested, while treatment with meropenem alone either produced less than 0.5 log CFU/tissue of bacterial killing or none at all. In the thigh model, 11 strains were treated with the combination of meropenem plus vaborbactam (300 plus 50 mg/kg of body weight). This combination produced from 0.8 to 2.89 logs of bacterial killing compared to untreated controls at the start of treatment. In the lung infection model, two strains were treated with the same dosage regimen of meropenem and vaborbactam. The combination produced more than 1.83 logs of bacterial killing against both strains tested compared to untreated controls at the start of treatment. Overall, these data suggest that meropenem-vaborbactam may have utility in the treatment of infections due to KPC-producing carbapenem-resistant Enterobacteriaceae.

Considerations about the Use of a Loading Dose of Daptomycin in a Neutropenic Murine Thigh Infection Model with Methicillin-Resistant Staphylococcus aureus Infection.

Previous clinical studies have showed the clinical benefits of the initiation of treatment with a daptomycin (DAP) loading dose, but only a few studies have evaluated its antimicrobial benefits. We evaluated the efficacy of a DAP loading dose against methicillin-resistant Staphylococcus aureus (MRSA) infections in a neutropenic murine thigh infection model. Three MRSA isolates (DAP MIC: 0.5, 1, and 2 mg/L) were tested. Four DAP regimens simulating human concentration-time profiles, i.e., (i) day 1: 8 mg/kg and day 2: 6 mg/kg, (ii) days 1 and 2: 6 mg/kg/day, (iii) day 1: 8 mg/kg and day 2: 4 mg/kg, and (iv) days 1 and 2: 4 mg/kg/day, were administered to the mice. Efficacy was calculated as the change in bacterial density. DAP loading-dose regimen iii showed greater antimicrobial activity against MRSA with MIC 1 mg/L than nonloading regimen iv (-3.10 ± 0.63 vs. -0.71 ± 0.34 log10 CFU; p < 0.01). Loading-dose regimen iii achieved greater log10 CFU changes than nonloading regimen ii, while the total DAP dose for 2 days was the same (-3.10 ± 0.63 vs. -1.46 ± 0.48 log10 CFU; p < 0.05). DAP loading-dose regimen iii showed enhanced antimicrobial activity against MRSA with DAP MIC 0.5 mg/L when compared with nonloading regimen iv. However, loading-dose regimens i and iii did not reduce bacterial density for MRSA with DAP MIC 2 mg/L. Our data suggest that a DAP loading-dose regimen would be an advantageous procedure for patients infected with MRSA with DAP MIC ≤1 mg/L.

11C-L-methyl methionine dynamic PET/CT of skeletal muscle: response to protein supplementation compared to L-[ring 13C6] phenylalanine infusion with serial muscle biopsy.

OBJECTIVE: The objective of this study was to determine if clinical dynamic PET/CT imaging with 11C-L-methyl-methionine (11C-MET) in healthy older women can provide an estimate of tissue-level post-absorptive and post-prandial skeletal muscle protein synthesis that is consistent with the more traditional method of calculating fractional synthesis rate (FSR) of muscle protein synthesis from skeletal muscle biopsies obtained during an infusion of L-[ring 13C6] phenylalanine (13C6-Phe). METHODS: Healthy older women (73 ± 5 years) completed both dynamic PET/CT imaging with 11C-MET and a stable isotope infusion of 13C6-Phe with biopsies to measure the skeletal muscle protein synthetic response to 25 g of a whey protein supplement. Graphical estimation of the Patlak coefficient Ki from analysis of the dynamic PET/CT images was employed as a measure of incorporation of 11 C-MET in the mid-thigh muscle bundle. RESULTS: Post-prandial values [mean ± standard error of the mean (SEM)] were higher than post-absorptive values for both Ki (0.0095 ± 0.001 vs. 0.00785 ± 0.001 min-1, p < 0.05) and FSR (0.083 ± 0.008 vs. 0.049 ± 0.006%/h, p < 0.001) in response to the whey protein supplement. The percent increase in Ki and FSR in response to the whey protein supplement was significantly correlated (r = 0.79, p = 0.015). CONCLUSIONS: Dynamic PET/CT imaging with 11C-MET provides an estimate of the post-prandial anabolic response that is consistent with a traditional, invasive stable isotope, and muscle biopsy approach. These results support the potential future use of 11C-MET imaging as a non-invasive method for assessing conditions affecting skeletal muscle protein synthesis.

An Anatomical Approach to Evaluating and Treating Cellulite.

Cellulite is the common rippling or dimpling of skin of the thighs and buttocks of women, formed from a confluence of skin laxity, tethering fibrous septa, and fat herniation. We describe an anatomical approach to evaluating the cellulite patient and selecting the best treatment from among available non-invasive, minimally invasive, and invasive therapies. It is crucial to consider the anatomy of the patient and the morphology of cellulite while choosing a treatment. Diffuse rippling represents increased adiposity and/or increased skin laxity which may stand to benefit from lipolytic and skin tightening modalities. Dimpling represents tethering by fibrous septa which may stand to improve from subcision by minimally invasive devices such as Cell na. Patients with both morphologies may be treated with a combination of treatments or Cellulaze. Careful evaluation of the patient can help identify the best therapeutic strategy. J Drugs Dermatol. 2017;16(1):58-61..

Effects of Light-Emitting Diode Therapy on Muscle Hypertrophy, Gene Expression, Performance, Damage, and Delayed-Onset Muscle Soreness: Case-control Study with a Pair of Identical Twins.

OBJECTIVE: The aim of this study was to verify how a pair of monozygotic twins would respond to light-emitting diode therapy (LEDT) or placebo combined with a strength-training program during 12 weeks. DESIGN: This case-control study enrolled a pair of male monozygotic twins, allocated randomly to LEDT or placebo therapies. Light-emitting diode therapy or placebo was applied from a flexible light-emitting diode array (λ = 850 nm, total energy = 75 J, t = 15 seconds) to both quadriceps femoris muscles of each twin immediately after each strength training session (3 times/wk for 12 weeks) consisting of leg press and leg extension exercises with load of 80% and 50% of the 1-repetition maximum test, respectively. Muscle biopsies, magnetic resonance imaging, maximal load, and fatigue resistance tests were conducted before and after the training program to assess gene expression, muscle hypertrophy and performance, respectively. Creatine kinase levels in blood and visual analog scale assessed muscle damage and delayed-onset muscle soreness, respectively, during the training program. RESULTS: Compared with placebo, LEDT increased the maximal load in exercise and reduced fatigue, creatine kinase, and visual analog scale. Gene expression analyses showed decreases in markers of inflammation (interleukin 1ß) and muscle atrophy (myostatin) with LEDT. Protein synthesis (mammalian target of rapamycin) and oxidative stress defense (SOD2 [mitochondrial superoxide dismutase]) were up-regulated with LEDT, together with increases in thigh muscle hypertrophy. CONCLUSIONS: Light-emitting diode therapy can be useful to reduce muscle damage, pain, and atrophy, as well as to increase muscle mass, recovery, and athletic performance in rehabilitation programs and sports medicine.

Neuromuscular electrical stimulation training increases intermuscular fascial length but not tendon cross-sectional area after spinal cord injury.

OBJECTIVE: To determine the effects of 12 weeks of neuromuscular electrical stimulation (NMES) training with ankle weights on intermuscular fascial length and patellar tendon cross-sectional area (CSA) in persons with spinal cord injury (SCI). METHODS: This study was a pre-post intervention. Seven men with motor complete SCI were randomly assigned to a resistance training plus diet (RT + diet) group (n = 4) or a diet control group (n = 3). Participants in the RT + diet group were enrolled in a 12-week leg extension weight-lifting program via surface NMES of the knee extensor muscle group. The length of mid-thigh intermuscular fascia and the patellar tendon CSA were measured using MRI. RESULTS: In the RT + diet group, a nonsignificant 8% increase in the CSA of the patellar tendon (P = .14) was noted. The length of the mid-thigh intermuscular fascia increased by 19% and 23% in the right (P = .029) and left (P = .015) legs, respectively, with no changes in the diet control group. Positive relationships were noted between skeletal muscle CSAs of the whole thigh (r = 0.77, P = .041) and knee extensors (r = 0.76, P = .048) and intermuscular fascial length. CONCLUSION: The preliminary results suggest that noncontractile connective tissue structures of the knee extensors respond differently to NMES training after SCI. Skeletal muscle hypertrophy is associated with an increase in the intermuscular fascial length.

Eravacycline (TP-434) is efficacious in animal models of infection.

Eravacycline is a novel broad-spectrum fluorocycline antibiotic being developed for a wide range of serious infections. Eravacycline was efficacious in mouse septicemia models, demonstrating 50% protective dose (PD50) values of ≤ 1 mg/kg of body weight once a day (q.d.) against Staphylococcus aureus, including tetracycline-resistant isolates of methicillin-resistant S. aureus (MRSA), and Streptococcus pyogenes. The PD50 values against Escherichia coli isolates were 1.2 to 4.4 mg/kg q.d. In neutropenic mouse thigh infection models with methicillin-sensitive S. aureus (MSSA) and S. pyogenes, eravacycline produced 2 log10 reductions in CFU at single intravenous (i.v.) doses ranging from 0.2 to 9.5 mg/kg. In a neutropenic mouse lung infection model, eravacycline administered i.v. at 10 mg/kg twice a day (b.i.d.) reduced the level of tetracycline-resistant MRSA in the lung equivalent to that of linezolid given orally (p.o.) at 30 mg/kg b.i.d. At i.v. doses of 3 to 12 mg/kg b.i.d., eravacycline was more efficacious against tetracycline-resistant Streptococcus pneumoniae in a neutropenic lung infection model than linezolid p.o. at 30 mg/kg b.i.d. Eravacycline showed good efficacy at 2 to 10 mg/kg i.v. b.i.d., producing up to a 4.6 log10 CFU reduction in kidney bacterial burden in a model challenged with a uropathogenic E. coli isolate. Eravacycline was active in multiple murine models of infection against clinically important Gram-positive and Gram-negative pathogens.

Sulfur spring dermatitis.

Thermal sulfur baths are a form of balneotherapy promoted in many cultures for improvement of skin conditions; however, certain uncommon skin problems may occur after bathing in hot sulfur springs. We report the case of a 65-year-old man who presented with multiple confluent, punched-out, round ulcers with peripheral erythema on the thighs and shins after bathing in a hot sulfur spring. Histopathologic examination revealed homogeneous coagulation necrosis of the epidermis and papillary dermis. Tissue cultures showed no evidence of a microbial infection. The histopathologic findings and clinical course were consistent with a superficial second-degree burn. When patients present with these findings, sulfur spring dermatitis should be considered in the differential diagnosis. Moreover, the patient's clinical history is crucial for correct diagnosis.

Neuromuscular electrical stimulation attenuates thigh skeletal muscles atrophy but not trunk muscles after spinal cord injury.

The current study examined the effects of 12weeks of surface neuromuscular electrical stimulation (NMES) and ankle weights on the cross-sectional areas (CSAs) of three thigh [Gracilis (Gra), Sartorious (Sar) and Adductor (Add)] as well as two trunk [hip flexor (HF) and back extensor (BE)] muscle groups in men with spinal cord injury (SCI). Seven individuals with chronic motor complete SCI were randomly assigned into a resistance training +diet (RT+diet; n=4) or diet control (n=3) groups. The RT+diet group underwent twice weekly training with surface NMES and ankle weights for 12weeks. Training composed of four sets of 10 repetitions of leg extension exercise while sitting in their wheelchairs. Both groups were asked to monitor their dietary intake. Magnetic resonance images were captured before and after 12weeks of interventions. Gra muscle CSA showed no change before and after interventions. A significant interaction (P=0.001) was noted between both groups as result of 9% increase and 10% decrease in the Gra muscle CSA of the RT+diet and diet groups, respectively. Sar muscle CSA increased [1.7±0.4-2.5±0.5cm(2); P=0.029] in the RT+diet group with no change [2.9±1.4-2.6±1.3cm(2)] in the diet group; with interaction noted between both groups (P=0.002). Analysis of covariance indicated that Add muscle CSA was 38% greater in the RT+diet compared to the diet group (P=0.025) after 12weeks; a trend of interaction was also noted between both groups (P=0.06). HF and BE muscle groups showed no apparent changes in CSA in both groups. The results suggested that surface NMES can delay the process of progressive skeletal muscle atrophy after chronic SCI. However, the effects are localized to the trained thigh muscles and do not extend to the proximal trunk muscles.

Methods for the assessment of the efficacy of products and slimming treatments for cellulite according to the Italian Interdisciplinary Group for the standardization of efficacy tests on cosmetic products.

Cellulite is a very common skin alteration with a complex pathogenesis; different degrees of severity of cellulite can be observed in most part of people after puberty, and numerous cosmetic or more invasive treatments have been proposed, with variable efficacy. Since reproducible methods of evaluation of the effectiveness of cellulite treatments are lacking, the purpose of our group was to define and set general testing principles for evaluating the efficacy of slimming products and treatments/remodeling methods for cellulite, to achieve a delineation of reliable and reproducible research steps following a well-designed and scientifically valid methodology. After a careful review of literature and textbooks and according to personal experience, we defined assessment protocols based on clinical and instrumental tools. In order to make studies reliable, reproducible and safe, a protocol standardization is needed. The sponsor is responsible for assuring quality and information concerning the product under investigation; moreover, investigators should be experienced on cellulite evaluation and treatment, and, finally, the duration and modalities of application of the product should be specified. A treated VS non treated area comparison can be performed, to evaluate the severity of cellulite and the clinical outcomes of the treatment. Besides clinical evaluation, instrumental methods should always be implemented to provide objective data for treatment outcome.

Applied kinesiology: distinctions in its definition and interpretation.

Modification of the motor system in assessing and treating as well as understanding one of the causes of musculoskeletal dysfunctions is a topic of growing importance in healthcare. Applied kinesiology (AK) addresses this interest in that it is a system which attempts to evaluate numerous aspects of health (structural, chemical, and mental) by the manual testing of muscles combined with other standard methods of diagnosis. It leads to a variety of conservative, non-invasive treatments which involve joint manipulations or mobilizations, myofascial therapies, cranial techniques, meridian and acupuncture skills, clinical nutrition and dietary management, counseling skills, evaluating environmental irritants, and various reflex techniques. The effectiveness of these ancillary treatments is believed to be consistent with the expanded construct validity of the manual muscle test (MMT), as described, although this assertion has primarily been tested in outcome studies. AK and its adjunctive procedures (challenge and therapy localization) are highlighted in this review providing details of its implementation as prescribed by an International College of Applied Kinesiology's Board of Examiners, cited for its scholarly and scientific activities. Because these procedures are believed to identify specific articular, soft tissue, biochemical, or emotional issues underlying muscle function, the applicability of this diagnostic method for all clinicians treating muscle imbalance disorders is described. As of yet, MMT efficacy in therapy localization and challenge techniques has not been established in published, peer-reviewed research. A variety of challenges likewise remain for professional AK to establish itself as an emerging science, with numerous gaps in the literature and testable hypotheses enumerated. Of particular concern are a multiplicity of derivatives of AK that have been described in the literature, which should be greeted with caution in light of the fact that they lack one or more of the essential attributes of AK as described in this report. The validity of these studies which have been critical of applied kinesiology appears in many instances to be no greater than several of the randomized controlled trials, cohort studies, case control studies, and case studies found in this communication to support various aspects of applied kinesiology.

Comparative in vitro and in vivo efficacies of human simulated doses of ceftazidime and ceftazidime-avibactam against Pseudomonas aeruginosa.

The combination of ceftazidime and avibactam possesses potent activity against resistant Gram-negative pathogens, including Pseudomonas aeruginosa. We compared the efficacies of human simulated doses of ceftazidime and ceftazidime-avibactam using a hollow-fiber system and neutropenic and immunocompetent murine thigh infection models. Twenty-seven clinical P. aeruginosa isolates with ceftazidime MICs of 8 to 128 mg/liter and ceftazidime-avibactam MICs of 4 to 32 mg/liter were utilized in neutropenic mouse studies; 15 of the isolates were also evaluated in immunocompetent mice. Six isolates were studied in both the hollow-fiber system and the neutropenic mouse. In both systems, the free drug concentration-time profile seen in humans given 2 g of ceftazidime every 8 h (2-h infusion), with or without avibactam at 500 mg every 8 h (2-h infusion), was evaluated. In vivo activity was pharmacodynamically predictable based on the MIC. Ceftazidime decreased bacterial densities by ≥0.5 log unit for 10/27 isolates, while ceftazidime-avibactam did so for 22/27 isolates. In immunocompetent animals, enhancements in activity were seen for both drugs, with ceftazidime achieving reductions of ≥0.3 log unit for 10/15 isolates, whereas ceftazidime-avibactam did so against all 15 isolates. In vitro, ceftazidime resulted in regrowth by 24 h against all isolates, while ceftazidime-avibactam achieved stasis or better against 4/7 isolates. Mutants with elevated ceftazidime-avibactam MICs appeared after 24 h from 3/7 isolates studied in vitro; however, no resistant mutants were detected in vivo. Against this highly ceftazidime-nonsusceptible population of P. aeruginosa, treatment with human simulated doses of ceftazidime-avibactam resulted in pharmacodynamically predictable activity, particularly in vivo, against isolates with MICs of ≤16 mg/liter, and this represents a potential new option to combat these difficult-to-treat pathogens.

In vivo efficacy of the novel aminoglycoside ACHN-490 in murine infection models.

Aminoglycosides are broad-spectrum antibiotics with particular clinical utility against life-threatening infections. As resistance to antibiotics, including aminoglycosides, continues to grow, there is a need for new and effective antimicrobial agents. ACHN-490 is a novel aminoglycoside in clinical development with activity against multidrug-resistant Gram-negative and select Gram-positive pathogens. Here we assess the in vivo efficacy of ACHN-490 against a variety of common pathogens in two murine models: the septicemia and neutropenic thigh models. When its activity against a gentamicin-susceptible strain of Escherichia coli was tested in the septicemia model, ACHN-490 improved 7-day survival with a dose-response profile similar to that of gentamicin, with 100% survival seen at doses of 1.6 mg/kg of body weight and above. In animals infected with a gentamicin-susceptible strain of Pseudomonas aeruginosa, treatment with either ACHN-490 or gentamicin led to 100% survival at doses of 16 mg/kg and above in the septicemia model. ACHN-490 was also effective in the neutropenic thigh model, reducing multidrug-resistant Enterobacteriaceae family and methicillin-resistant Staphylococcus aureus strains, as well as broadly susceptible strains, to static levels with dose-dependent activity. Against gentamicin-sensitive Enterobacteriaceae and methicillin-resistant S. aureus, the efficacy of ACHN-490 was comparable to that of gentamicin. However, gentamicin-resistant Enterobacteriaceae strains and those harboring the Klebsiella pneumoniae carbapenemase responded to ACHN-490 but not gentamicin, with static doses ranging from 12 mg/kg to 64 mg/kg for ACHN-490. These results suggest that ACHN-490 has the potential to become a clinically useful agent against drug-resistant pathogens, including Enterobacteriaceae, P. aeruginosa, and methicillin-resistant S. aureus, and support further development of this promising novel aminoglycoside.

The need for lumbar-pelvic assessment in the resolution of chronic hamstring strain.

A lumbar-pelvic assessment and treatment model based on a review of clinical and anatomical research is presented for consideration in the treatment of chronic hamstring strain. The origin of the biceps femoris muscle attaches to the pelvis at the ischial tuberosity and to the sacrum via the sacrotuberous ligament. The biomechanics of the sacroiliac joint and hip, along with lumbar-pelvic stability, therefore play a significant role in hamstring function. Pelvic asymmetry and/or excessive anterior tilt can lead to increased tension at the biceps origin and increase functional demands on the hamstring group by inhibiting its synergists. Joint proprioceptive mechanisms may play a significant role in re-establishing balance between agonists and antagonists. An appreciation of neuromuscular connections as well as overall lumbar-pelvic structural assessment is recommended in conjunction with lumbar-pelvic strengthening exercises to help resolve chronic hamstring strain.

fAUC/MIC is the most predictive pharmacokinetic/pharmacodynamic index of colistin against Acinetobacter baumannii in murine thigh and lung infection models.

OBJECTIVES: To elucidate the pharmacokinetic/pharmacodynamic (PK/PD) index that predicts colistin efficacy against Acinetobacter baumannii in neutropenic murine thigh and lung infection models, and to determine the extent of the emergence of resistance in vivo to colistin. METHODS: PK/PD of colistin was studied in thigh and lung infection models against A. baumannii ATCC 19606 and two multidrug-resistant clinical isolates (two of the three strains were colistin heteroresistant). Dose fractionation studies were conducted over a daily dose range of 1-160 mg/kg colistin sulphate. Bacterial burden in tissues was measured at 24 h. Non-linear least squares regression analyses were employed to determine the PK/PD index (fAUC/MIC, fC(max)/MIC or fT(>MIC)) best correlating with the efficacy of colistin in each model. Real-time population analysis profiles were conducted for tissue samples to monitor the emergence of resistance. RESULTS: The fAUC/MIC was the PK/PD index that correlated best with efficacy in both thigh (R(2) = 0.90) and lung (R(2) = 0.80) infection models. The fAUC/MIC targets required to achieve stasis and 1 log kill against the three strains were 1.89-7.41 and 6.98-13.6 in the thigh infection model, respectively, while the corresponding values were 1.57-6.52 and 8.18-42.1 in the lung infection model. Amplification of colistin-resistant subpopulations was revealed for all strains in both models after 24 h colistin treatment. CONCLUSIONS: This study indicates the importance of achieving adequate time-averaged exposure to colistin and defined target fAUC/MIC values for various magnitudes of kill. Amplification of resistant subpopulations indicates the importance of investigating rational combinations with colistin. The results will facilitate efforts to optimize colistin use in humans.

Determination of therapeutic equivalence of generic products of gentamicin in the neutropenic mouse thigh infection model.

BACKGROUND: Drug regulatory agencies (DRA) support prescription of generic products of intravenous antibiotics assuming therapeutic equivalence from pharmaceutical equivalence. Recent reports of deaths associated with generic heparin and metoprolol have raised concerns about the efficacy and safety of DRA-approved drugs. METHODOLOGY/PRINCIPAL FINDINGS: To challenge the assumption that pharmaceutical equivalence predicts therapeutic equivalence, we determined in vitro and in vivo the efficacy of the innovator product and 20 pharmaceutically equivalent generics of gentamicin. The data showed that, while only 1 generic product failed in vitro (MIC = 45.3 vs. 0.7 mg/L, P<0.05), 10 products (including gentamicin reference powder) failed in vivo against E. coli due to significantly inferior efficacy (E(max) = 4.81 to 5.32 vs. 5.99 log(10) CFU/g, P