Current Alternative-medicine News Results

Possibility of paclitaxel as an alternative radiosensitizer to 5-fluorouracil for colon cancer.

Oncol Rep. 2010 Oct; 24(4): 1029-34
Hiro J, Inoue Y, Toiyama Y, Yoshiyama S, Tanaka K, Mohri Y, Miki C, Kusunoki M

To evaluate the feasibility of paclitaxel (PTX) radiosensitization for colon cancer, we investigated the cytotoxic and G2/M checkpoint protein (Chk1, Wee1, Bub1, MAD2) effects of 5-fluorouracil (5-FU) or PTX combined with radiation in the human colon cancer cell line LoVo. Cytotoxicity and radiocytotoxicity were evaluated for each drug by the WST-8 colorimetric assay. The IC20 for each drug was determined as a cytotoxic concentration from a survival curve. LoVo cells were exposed to the IC20 of each drug for 24 h and then irradiated. Expressions of the G2/M checkpoint proteins were confirmed by Western blot analysis. Cytotoxicity was induced by 5-FU or PTX alone in a time- and dose-dependent manner. The IC20 of PTX caused higher radiosensitivity than the IC20 of 5-FU (P<0.05). Western blot analysis revealed different expression patterns of the G2/M checkpoint proteins between 5-FU and PTX pre-treatments. 5-FU combined with radiation tended to decrease the expressions of all G2/M checkpoint proteins in a time-dependent manner. PTX combined with radiation maintained high expressions of Chk1 and MAD2 proteins for 24 h post-radiation and, in particular, MAD2 protein was strongly induced by PTX with high-dose radiation. PTX showed higher radio-sensitization than 5-FU for the colon cancer cell line LoVo and may be an alternative radiosensitizer to 5-FU in the clinical setting.

Identification of novel inhibitors of dietary lipid absorption using zebrafish.

PLoS One. 2010; 5(8):
Clifton JD, Lucumi E, Myers MC, Napper A, Hama K, Farber SA, Smith AB, Huryn DM, Diamond SL, Pack M

Pharmacological inhibition of dietary lipid absorption induces favorable changes in serum lipoprotein levels in patients that are at risk for cardiovascular disease and is considered an adjuvant or alternative treatment with HMG-CoA reductase inhibitors (statins). Here we demonstrate the feasibility of identifying novel inhibitors of intestinal lipid absorption using the zebrafish system. A pilot screen of an unbiased chemical library identified novel compounds that inhibited processing of fluorescent lipid analogues in live zebrafish larvae. Secondary assays identified those compounds suitable for testing in mammals and provided insight into mechanism of action, which for several compounds could be distinguished from ezetimibe, a drug used to inhibit cholesterol absorption in humans that broadly inhibited lipid absorption in zebrafish larvae. These findings support the utility of zebrafish screening assays to identify novel compounds that target complex physiological processes.

Exercise training can attenuate preeclampsia-like features in an animal model.

J Hypertens. 2010 Sep 1;
Falcao S, Bisotto S, Michel C, Lacasse AA, Vaillancourt C, Gutkowska J, Lavoie JL

OBJECTIVE: Exercise training benefits have been widely investigated and used as alternative treatment for different pathological conditions. Since preeclampsia is a severe pregnancy-associated disease for which no treatment is available, our aim was to investigate the protective role of exercise training on pregnancy outcome using a mouse model of the disease. METHODS: We used transgenic female mice overexpressing human angiotensinogen, which develop preeclampsia when mated with human renin-overexpressing males. Females were placed in exercise cages 4 weeks prior to mating, and remained in these throughout gestation. Blood pressure was measured by telemetry, and proteinuria was quantified by ELISA. Placentas were assessed by histology and immunohistochemistry, whereas vascular endothelial growth factor was measured by real-time PCR and immunoblot. Endothelial function was assessed in isolated mesenteric arteries. RESULTS: Conversely to sedentary transgenic females (131.20 +/- 4.08 mmHg), trained dam's mean arterial pressure was no longer different from normal mice at the end of gestation (117.5 +/- 10.6 vs. 112.3 +/- 5.5 mmHg). Proteinuria observed in transgenic dams (3.364 +/- 1.62 mug/mg) was absent in trained mice (0.894 +/- 0.43 mug/mg). Placental disease and cardiac hypertrophy were also normalized, whereas vascular reactivity was significantly ameliorated. Furthermore, placental vascular endothelial growth factor was normalized in trained transgenic mice. CONCLUSIONS: To our knowledge, we are the first to clearly demonstrate that exercise training both before and during gestation can reduce preeclampsia features in a mouse model. Consequently, women at risk for this disease could benefit from exercise training to protect themselves and their future fetuses.

Analysis of nasal periosteum and nasofrontal suture with clinical implications for dorsal nasal augmentation.

Plast Reconstr Surg. 2010 Sep; 126(3): 1037-47
Tsai FC, Liao CK, Fong TH, Lin JY, Wu ST

BACKGROUND:: Subperiosteal placement of nasal implants has been performed widely for dorsal nasal augmentation in Asia. The authors introduced anatomical and biomechanical studies to investigate the influence of the periosteum on the subperiosteal technique. METHODS:: Nasal periosteum on 20 cadavers was investigated by hematoxylin and eosin staining and biomechanical methods. Nasal profiles (n = 160) and motility testing (n = 1317) were used to analyze patients who underwent augmentation rhinoplasty between 2003 and 2008. An alternative high-split subperiosteal technique was developed for higher placement of the nasal implant. RESULTS:: In the cadaver study, the authors discovered that the periosteum and bone were bound together by Sharpey's fibers below the nasion (1.3 +/- 0.6 mm) that penetrated into the nasofrontal suture. The nasal periosteum above the nasofrontal suture (1.77 +/- 0.19 mm) was thicker than the one below the suture (0.83 +/- 0.15 mm) (p < 0.001). Men had relatively thicker periosteum (1.41 +/- 0.49 mm) compared with women (1.18 +/- 0.5 mm), and the difference was statistically significant (p < 0.001). Motility testing for clinical cases revealed that there was a higher percentage of the mobilized implant in women than in men (p = 0.042). When the subperiosteal technique was compared with the subcutaneous technique, analysis of the Poisson ratio for the periosteum (0.33 +/- 0.02) indicated greater strength than in the subcutaneous tissue (0.45 +/- 0.02). The alternative high-split subperiosteal technique significantly shortened the radix-to-glabella distance, increased the radix height, and made the nasofrontal angle more obtuse than the conventional subperiosteal technique (p < 0.001, p < 0.001, and p = 0.02, respectively). CONCLUSION:: Analysis of the nasal periosteum provided scientific support for using the subperiosteal technique in dorsal nasal augmentation.

The temporoparietal fascial flap is an alternative to free flaps for orbitomaxillary reconstruction.

Plast Reconstr Surg. 2010 Sep; 126(3): 880-8
Kim JY, Buck DW, Johnson SA, Butler CE

BACKGROUND:: The temporoparietal fascial flap is a thin, pliable, well-vascularized, locoregional flap that can be a reasonable alternative to traditional free flap reconstruction, but its utility for reconstruction of orbitomaxillary defects is often overlooked. The authors investigated the rationale for and benefits of the use of this flap over free tissue transfer in a well-defined subset of head and neck cancer cases. METHODS:: The records of all patients who underwent temporoparietal fascial reconstruction for orbitomaxillectomy between 1993 and 2008 were reviewed. Demographic data, preoperative plans, operative details, and outcomes were assessed to (1) determine the overall outcomes for the temporoparietal fascial flap and (2) analyze preoperative and intraoperative factors that led to the choice of this flap instead of the originally planned free flap. RESULTS:: Nineteen patients (mean age, 56 years) were included in this study. Ten (53 percent) were initially considered for free flap reconstruction. Among them, the principal reasons for electing the temporoparietal fascial flap were (1) smaller-than-anticipated extent of resection, (2) need for coverage of implant or bone or thin prosthesis support, and (3) patient comorbidities. Nine resections (47 percent) involved the orbit alone, two (11 percent) involved the maxilla alone, and eight (42 percent) involved a combination of the two. Five patients (26 percent) received neoadjuvant radiation. Four (21 percent) experienced complications (flap failure, ectropion, enophthalmos with intraoral mesh extrusion, and partial skin graft loss). Mean follow-up time was 36 +/- 27 months. CONCLUSION:: The temporoparietal fascial flap is a viable alternative to free flaps for orbitomaxillary defects when orbital resection is limited, when obturator reconstruction is desired, or when comorbidities preclude microvascular surgery.

Breast implant infections: is cefazolin enough?

Plast Reconstr Surg. 2010 Sep; 126(3): 779-85
Feldman EM, Kontoyiannis DP, Sharabi SE, Lee E, Kaufman Y, Heller L

BACKGROUND:: Bacterial infection is a well-known risk of breast implant surgery, occurring in 2.0 to 2.5 percent of cosmetic cases and up to 20 percent of reconstructive cases. The Centers for Disease Control and Prevention recommends a first-generation cephalosporin for perioperative prophylaxis; however, no guidelines exist for the empiric treatment of established breast implant infections. A recent increase in methicillin-resistant Staphylococcus aureus infections has prompted interest in using alternative antibiotics with anti-methicillin-resistant S. aureus activity for both prophylactic and empiric therapy. The goal of the present study was to assess the bacteriology and antibiotic susceptibility of breast implant-related infections at two tertiary care hospitals in the Texas Medical Center to determine whether a baseline for empiric therapy for breast implant infections could be established. METHODS:: A retrospective review of patients who developed periprosthetic infections within 1 month after breast implant placement between 2001 and 2006 was completed. One hundred six patients with 116 infected breasts were identified. Patients were included in the study only if they had documented culture data. RESULTS:: Thirty-one breasts in 26 patients met inclusion criteria. Sixty-seven percent of the infected breasts had S. aureus infections; of these, 68 percent were methicillin-resistant S. aureus infections and 32 percent were methicillin-susceptible S. aureus infections. We noted Gram-negative rods and sterile cultures in 6 percent and 26 percent of breasts, respectively. CONCLUSIONS:: Because of the high incidence of methicillin-resistant S. aureus infections in breast implant recipients, we believe that choosing an antibiotic with anti-methicillin-resistant S. aureus activity is justified for empiric treatment of breast implant infections, until culture and sensitivity data, if obtained, become available.

PECAM-1 Regulates the Proangiogenic Properties of Endothelial Cells through Modulation of Cell-Cell and Cell-Matrix Interactions.

Am J Physiol Cell Physiol. 2010 Sep 1;
Park S, Dimaio TA, Scheef EA, Sorenson CM, Sheibani N

Platelet/endothelial cell adhesion molecule-1 (PECAM-1/CD31) is a member of the immunoglobulin super family of the cell adhesion molecules with important roles in angiogenesis and inflammation. However, the molecular and cellular mechanisms, and the role specific PECAM-1 isoforms play in these processes, remain elusive. We recently showed attenuation of retinal vascular development and neovascularization in PECAM-1-deficient (PECAM-1-/-) mice. To gain further insight into the role of PECAM-1 in these processes, we isolated primary retinal endothelial cells (EC) from wild type (PECAM-1 +/+) and PECAM-1 -/- mice. Lack of PECAM-1 had a significant impact on endothelial cell-cell and cell-matrix interactions resulting in attenuation of cell migration and capillary morphogenesis. Mechanistically these changes were associated with a significant decrease in expression of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) bioavailability in PECAM-1 -/- retinal EC. PECAM-1 -/- retinal EC also exhibited a lower rate of apoptosis under basal and challenged conditions, consistent with their increased growth rate. Furthermore, re-expression of PECAM-1 was sufficient to restore migration and capillary morphogenesis of null cells in an isoform specific manner. Thus, PECAM-1 expression modulates pro-angiogenic properties of EC, and these activities are significantly influenced by alternative splicing of its cytoplasmic domain.

Interferon-gamma-release assays: Better than tuberculin skin testing?

Cleve Clin J Med. 2010 Sep; 77(9): 606-11
Miranda C, Tomford JW, Gordon SM

Although the tuberculin skin test has long been the standard for detecting latent tuberculosis infection, it has many limitations. Interferon-gamma-release assays are gaining acceptance as an alternative. In this paper we present cases to illustrate how these new tests can be used and how to interpret the results.

It's Not Easy Being Green: The Viridans Group Streptococci with a Focus on Pediatric Clinical Manifestations.

J Clin Microbiol. 2010 Sep 1;
Doern CD, Burnham CA

The viridans group streptococci (VGS) are a heterogeneous group of organisms that can be human commensals, colonizing the gastrointestinal and genitourinary tracts in addition to the oral mucosa. VGS are generally considered to be of low pathogenic potential in immunocompetent individuals. However, in certain patient populations, VGS can cause invasive disease, such as endocarditis, intraabdominal infection, and shock. Within the VGS, the rate and pattern of antimicrobial resistance varies greatly depending upon the species identification and the patient population. In general, Streptococcus mitis group organisms are resistant to more antimicrobial agents than the other VGS species. This review addresses current VGS taxonomy in addition to the current methodologies being used in clinical microbiology labs for identification of VGS. Automated systems struggle overall with species level identification and susceptibility testing for VGS. MALDI-TOF identification is emerging as a potential alternative for organism identification. A review of recent pediatric specific data regarding the clinical manifestations of VGS reveals that the Streptococcus anginosus group organisms may be important pathogens in pediatric patients, and that the VGS may contribute to disease in patients with cystic fibrosis. It also appears that rates of antimicrobial resistance in VGS in pediatric patients is surpassing that of the adult population.

Epstein-Barr virus SM protein utilizes cellular splicing factor SRp20 to mediate alternative splicing.

J Virol. 2010 Sep 1;
Verma D, Bais S, Gaillard M, Swaminathan S

Epstein Barr virus (EBV) SM protein is an essential nuclear protein produced during the lytic cycle of EBV replication. SM is an RNA binding protein with multiple mechanisms of action. SM enhances expression of EBV genes by stabilizing mRNA and facilitating nuclear export. SM also influences splicing of both EBV and cellular pre-mRNAs. SM modulates splice site selection of the host cell STAT1 pre-mRNA, directing utilization of a novel 5' splice site that is used only in the presence of SM. SM activates splicing in the manner of SR proteins but does not contain canonical RS domains typical of cellular splicing factors. Affinity purification and mass spectrometry of SM complexes from SM-transfected cells led to the identification of the cellular SR splicing factor SRp20 as an SM-interacting protein. The regions of SM and SRp20 required for interaction were mapped by in vitro and in vivo assays. The SRp20 interaction was shown to be important for the effects of SM on alternative splicing by the use of STAT1 splicing assays. Overexpression of SRp20 enhanced SM-mediated alternative splicing and knockdown of SRp20 inhibited the SM effect on splicing. These data suggest a model whereby SM, a viral protein, recruits and co-opts the function of cellular SRp20 in alternative splicing.

Personal Protective Equipment for Care of Pandemic Influenza Patients: A Training Workshop for the Powered Air Purifying Respirator.

Anesth Analg. 2010 Sep 1;
Tompkins BM, Kerchberger JP

Virulent respiratory infectious diseases may present a life-threatening risk for health care professionals during aerosol-generating procedures, including endotracheal intubation. The 2009 Pandemic Influenza A (H1N1) brings this concern to the immediate forefront. The Centers for Disease Control and Prevention have stated that, when performing or participating in aerosol-generating procedures on patients with virulent contagious respiratory diseases, health care professionals must wear a minimum of the N95 respirator, and they may wish to consider using the powered air purifying respirator (PAPR). For influenza and other diseases transmitted by both respiratory and contact modes, protective respirators must be combined with contact precautions. The PAPR provides 2.5 to 100 times greater protection than the N95, when used within the context of an Occupational Safety and Health Administration-compliant respiratory protection program. The relative protective capability of a respirator is quantified using the assigned protection factor. The level of protection designated by the APF can only be achieved with appropriate training and correct use of the respirator. Face seal leakage limits the protective capability of the N95 respirator, and fit testing does not assure the ability to maintain a tight face seal. The protective capability of the PAPR will be defeated by improper handling of contaminated equipment, incorrect assembly and maintenance, and improper don (put on) and doff (take off) procedures. Stress, discomfort, and physical encumbrance may impair performance. Acclimatization through training will mitigate these effects. Training in the use of PAPRs in advance of their need is strongly advised. "Just in time" training is unlikely to provide adequate preparation for groups of practitioners requiring specialized personal protective equipment during a pandemic. Employee health departments in hospitals may not presently have a PAPR training program in place. Anesthesia and critical care providers would be well advised to take the lead in working with their hospitals' employee health departments to establish a PAPR training program where none exists. User instructions state that the PAPR should not be used during surgery because it generates positive outward airflow, and may increase the risk of wound infection. Clarification of this prohibition and acceptable solutions are currently lacking and need to be addressed. The surgical hood system is not an acceptable alternative. We provide on line a PAPR training workshop. Supporting information is presented here. Anesthesia and critical care providers may use this workshop to supplement, but not substitute for, the manufacturers' detailed use and maintenance instructions.

Click-words: Learning to Predict Document Keywords from a User Perspective.

Bioinformatics. 2010 Sep 1;
Islamaj Dogan R, Lu Z

MOTIVATION: Recognizing words that are key to a document is important for ranking relevant scientific documents. Traditionally, important words in a document are either nominated subjectively by authors and indexers, or selected objectively by some statistical measures. As an alternative, we propose to use documents' words popularity in user queries to identify click-words, a set of prominent words from the users' perspective. Although they often overlap, click-words differ significantly from other document keywords. RESULTS: We developed a machine learning approach to learn the unique characteristics of click-words. Each word was represented by a set of features that included different types of information, such as semantic type, part of speech tag, TF-IDF weight and location in the abstract. We identified the most important features and evaluated our model using six months of PubMed click-through logs. Our results suggest that, in addition to carrying high TF-IDF weight, clickwords tend to be biomedical entities, to exist in article titles, and to occur repeatedly in article abstracts. Given the abstract and title of a document, we are able to accurately predict words likely to appear in user queries that lead to document clicks. CONTACT: luzh@ncbi.nlm.nih.gov.

Contrast-enhanced dynamic magnetic resonance nephrography in healthy dogs.

Vet J. 2010 Aug 30;
Fonseca-Matheus JM, Pérez-García CC, Ginja MM, Altónaga JR, Orden MA, Gonzalo-Orden JM

Twenty-three healthy mixed-breed male adult dogs were examined using serial magnetic resonance (MR) renograms. The images were obtained using a dynamic gradient-echo, fast SPGR, T1-weighted sequence and low doses of gadolinium chelates (0.025mmol/kg). Time-intensity curves were obtained to assess typical urinary excretion parameters, namely, time to vascular peak (TVP), time to vascular drop (TVD), time to glomerular peak (TGP), parenchymal phase length (PPL), gradient of parenchymal phase (GPP) and pattern of excretory segment. The mean TVP, TVD, TGP and PPL were 31.6+/-11.8, 43.4+/-11.2, 154.0+/-36.2 and 115.2+/-37.7s, respectively. The GPP was 24.1+/-8.6% of signal intensity per min. The excretory segment was concave in all cases, and at the end of the examination, 87.1% of kidneys had shown a reduction in signal intensity of 50%. This MR nephrography protocol can provide adequate time-intensity curve parameters for the urinary system of dogs, offers excellent anatomical detail, and represents an alternative to radionuclide nephrography.

Integrative Medicine: Enhancing Quality in Primary Health Care.

J Altern Complement Med. 2010 Sep 1;
Grace S, Higgs J

Abstract Objectives: Integrative medicine (IM) is an emerging model of health care in Australia. However, little is known about the contribution that IM makes to the quality of health care. The aim of the research was to understand the contribution IM can make to the quality of primary care practices from the perspectives of consumers and providers of IM. Design: This interpretive research used hermeneutic phenomenology to understand meanings and significance that patients and practitioners attach to their experiences of IM. Various qualitative research techniques were used: case studies; focus groups; and key informant interviews. Data sets were generated from interview transcripts and field notes. Data analysis consisted of repeatedly reading and examining the data sets for what they revealed about experiences of health care and health outcomes, and constantly comparing these to allow themes and patterns to emerge. Setting: The setting for this research was Australian IM clinics where general medical practitioners and CAM practitioners were co-located. Results: From the perspective of patients and practitioners, IM: (1) provided authentically patient-centered care; (2) filled gaps in treatment effectiveness, particularly for certain patient populations (those with complex, chronic health conditions, those seeking an alternative to pharmaceutical health care, and those seeking health promotion and illness prevention); and (3) enhanced the safety of primary health care (because IM retained a general medical practitioner as the primary contact practitioner and because IM used strategies to increase disclosure of treatments between practitioners). Conclusions: According to patients and practitioners, IM enhanced the quality of primary health care through its provision of health care that was patient-centered, effective (particularly for chronic health conditions, nonpharmaceutical treatments, and health promotion) and safe.

A Meta-Analysis of Prehospital Airway Control Techniques Part II: Alternative Airway Devices and Cricothyrotomy Success Rates.

Prehosp Emerg Care. 2010 Oct-Dec; 14(4): 515-30
Hubble MW, Wilfong DA, Brown LH, Hertelendy A, Benner RW

Abstract Background. Airway management is a key component of prehospital care for seriously ill and injured patients. Oral endotracheal intubation (OETI) is the definitive airway of choice in most emergency medical services (EMS) systems. However, OETI may not be an approved skill for some clinicians or may prove problematic in certain patients because of anatomic abnormalities, trauma, or inadequate relaxation. In these situations alternative airways are frequently employed. However, the reported success rates for these devices vary widely, and established benchmarks are lacking. Objective. We sought to determine pooled estimates of the success rates of alternative airway devices (AADs) and needle cricothyrotomy (NCRIC) and surgical cricothyrotomy (SCRIC) placement through a meta-analysis of the literature. Methods. We performed a systematic literature search for all English-language articles reporting success rates for AADs, SCRIC, and NCRIC. Studies of field procedures performed by prehospital personnel from any nation were included. All titles were reviewed independently by two authors using prespecified inclusion criteria. Pooled estimates of success rates for each airway technique were calculated using a random-effects meta-analysis model. Results. Of 2,005 prehospital airway titles identified, 35 unique studies were retained for analysis of AAD success rates, encompassing a total of 10,172 prehospital patients. The success rates for SCRIC and NCRIC were analyzed across an additional 21 studies totaling 512 patients. The pooled estimates (and 95% confidence intervals [CIs]) for intervention success across all clinicians and patients were as follows: esophageal obturator airway-esophageal gastric tube airway (EOA-EGTA) 92.6% (90.1%-94.5%); pharyngeotracheal lumen airway (PTLA) 82.1% (74.0%-88.0%); esophageal-tracheal Combitube (ETC) 85.4% (77.3%-91.0%); laryngeal mask airway (LMA) 87.4% (79.0%-92.8%); King Laryngeal Tube airway (King LT) 96.5% (71.2%-99.7%); NCRIC 65.8% (42.3%-83.59%); and SCRIC 90.5% (84.8%-94.2%). Conclusions. We provide pooled estimates for prehospital AAD, NCRIC, and SCRIC airway interventions. Of the AADs, the King LT demonstrated the highest insertion success rate (96.5%), although this estimate is based on limited data, and data regarding its ventilatory effectiveness are lacking; more data are available for the ETC and LMA. The ETC, LMA, and PTLA all had similar-but lower-success rates (82.1%-87.4%). NCRIC has a low rate of success (65.8%); SCRIC has a much higher success rate (90.5%) and should be considered the preferred percutaneous rescue airway.

Empirical constrained Bayes predictors accounting for non-detects among repeated measures.

Stat Med. 2010 Aug 30;
Moore RH, Lyles RH, Manatunga AK

When the prediction of subject-specific random effects is of interest, constrained Bayes predictors (CB) have been shown to reduce the shrinkage of the widely accepted Bayes predictor while still maintaining desirable properties, such as optimizing mean-square error subsequent to matching the first two moments of the random effects of interest. However, occupational exposure and other epidemiologic (e.g. HIV) studies often present a further challenge because data may fall below the measuring instrument's limit of detection. Although methodology exists in the literature to compute Bayes estimates in the presence of non-detects (Bayes(ND)), CB methodology has not been proposed in this setting. By combining methodologies for computing CBs and Bayes(ND), we introduce two novel CBs that accommodate an arbitrary number of observable and non-detectable measurements per subject. Based on application to real data sets (e.g. occupational exposure, HIV RNA) and simulation studies, these CB predictors are markedly superior to the Bayes predictor and to alternative predictors computed using ad hoc methods in terms of meeting the goal of matching the first two moments of the true random effects distribution. Copyright (c) 2010 John Wiley & Sons, Ltd.

Cord Blood Stem Cells for Hematopoietic Transplantation.

Stem Cell Rev. 2010 Sep 1;
Stanevsky A, Shimoni A, Yerushalmi R, Nagler A

Cord blood (CB) is an important alternative source of hematopoietic stem cells (HSCs) for transplantation today. The principal drawbacks of cord blood transplantation are the limited number of hematopoietic stem cells and a long time to engraftment. Several promising approaches for engraftment enhancement are under intensive investigation. Such are transplantation with two cord blood units, co transplantation of cord blood and haploidentical HSCs and different methods for expansion of cord blood hematopoietic stem cells. In addition there are several ways for improving of homing of HSCs such as co- infusion of CB hematopoietic stem cells and mesenchymal stem cells, administration of parathyroid hormone (PTH), intra- bone transplantation and targeting the CXCR4/SDF1 system. These strategies are expected to increase the availability of transplantation to adults, for whom the chance to find a cord blood suitable for a single unit transplant is small. Recent advances in elucidation of the molecular mechanisms responsible for the proliferation and self-renewal of hematopoietic stem cells may bring further improvement of the outcomes of cord blood transplantation. This review summarizes the recent progress in the field of cord blood derived hematopoietic stem cells. It presents the strategies applied and points out directions for the future.

Incidental detection of pseudodiverticulum of sigmoid colon on (18)F-FDG-PET/CT in a patient with lymphoma.

Hell J Nucl Med. 2010 May-Aug; 13(2): 171-2
Karuppuswamy Kamaleshwaran K, Chakraborty D, Kashyap R, Bhattacharya A, Singh B, Mittal BR

To the Editor: Incidental pathologic findings have been reported on myocardial perfusion scintigraphy as well as on fluorine-18 fluorodesoxyglucose-positron emission tomography/ computerized tomography ((18)F-FDG-PET/CT) by Kotsalou et al and Bertagna et al respectively and published in HJNM. The present case illustrates the potential pitfalls in (18)F-FDG-PET of the abdomen imaging. A 75 years old woman presenting with pain in the right hip was found to have an expansile bone lesion in the posterior pillar of the acetabulum and their adjoining ischium along with involvement of the adjacent muscles. Computerized tomography (CT) guided biopsy, from soft tissue showed B cell type of non-Hodgkin's lymphoma (NHL). A (18)F-FDG-PET/CT scan for the initial evaluation of disease activity showed intense (18)F-FDG uptake in a soft tissue mass (7.5x6x3cm) surrounding the right hip joint causing lytic destruction of the posterior part of acetabulum and the ischium and of the right obturator internus in association with the mass. Another focal, circumferentially increased uptake was noted in the distal part of the sigmoid colon. Repeated (18)F-FDG-PET/CT scan for response evaluation after 4 courses of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy showed no (18)F-FDG avidity in the right hip. However, focal uptake in the sigmoid colon persisted. This was unrelated to primary pathology and colonoscopy confirmed a pseudodiverticulum at this site of (18)F-FDG uptake.The routine use of (18)F-FDG-PET to evaluate lymphoma, especially its management, significantly increases the probability of detecting unexpected diseases in the same scan. Incidental abdominal findings involving the digestive tract have been reported to occur in 1.3% of the scanned patients without significant difference in the intensity of (18)F-FDG uptake within malignant, premalignant, and benign lesions. However, focal, fusiform, or lobulated abnormalities are significantly more intense than physiological uptake elsewhere in the bowel, particularly if associated with a structural abnormality and may sometimes warrant endoscopic examination. In conclusion, as (18)F-FDG is not lymphoma-specific, any unusual (18)F-FDG avidity should be correlated with further investigations and/or an alternative diagnosis. A follow-up (18)F-FDG- PET, performed after 2-3 months, is useful in providing a specific diagnosis which in 88% of the cases is related to malignancies.

Use of complementary and alternative medicine in children with asthma.

Can Respir J. 2010 Jul-Aug; 17(4): 183-7
Torres-Llenza V, Bhogal S, Davis M, Ducharme F

BACKGROUND: Because of the potential risk of interaction with, and underuse of, conventional medications, it is important to document the prevalence of the use of complementary and alternative medicines (CAMs) in asthmatic children.OBJECTIVE: To ascertain the prevalence and type of CAMs, and to identify factors associated with their use.METHODS: A cross-sectional survey of children who presented to the Asthma Centre of The Montreal Children's Hospital (Montreal, Quebec) between 1999 and 2007 was conducted. At the initial consultation, parents completed a questionnaire inquiring, in part, about CAM use. Computerized health records provided information regarding patient characteristics and their condition.RESULTS: The median age of the 2027 children surveyed was 6.1 years (interquartile range 3.3 to 10.5 years); 58% were male and 59% of children had persistent asthma. The prevalence of CAM use was 13% (95% CI 12% to 15%). Supplemental vitamins (24%), homeopathy (18%) and acupuncture (11%) were the most commonly reported CAMs. Multivariable logistic regression analysis confirmed the association of CAM use with age younger than six years (OR 1.86; 95% CI 1.20 to 2.96), Asian ethnicity (OR 1.89; 95% CI 1.01 to 3.52), episodic asthma (OR 1.88; 95% CI 1.08 to 3.28) and poor asthma control (OR 1.98; 95% CI 1.80 to 3.31).CONCLUSION: The prevalence of reported CAM use among Quebec children with asthma remained modest (13%), with vitamins, homeopathy and acupuncture being the most popular modalities. CAM use was associated with preschool age, Asian ethnicity, episodic asthma and poor asthma control.

Polyphosphate Kinase 2: A Novel Determinant of Stress Responses and Pathogenesis in Campylobacter jejuni.

PLoS One. 2010; 5(8):
Gangaiah D, Liu Z, Arcos J, Kassem II, Sanad Y, Torrelles JB, Rajashekara G

BACKGROUND: Inorganic polyphosphate (poly P) plays an important role in stress tolerance and virulence in many bacteria. PPK1 is the principal enzyme involved in poly P synthesis, while PPK2 uses poly P to generate GTP, a signaling molecule that serves as an alternative energy source and a precursor for various physiological processes. Campylobacter jejuni, an important cause of foodborne gastroenteritis in humans, possesses homologs of both ppk1 and ppk2. ppk1 has been previously shown to impact the pathobiology of C. jejuni. METHODOLOGY/PRINCIPAL FINDINGS: Here, we demonstrate for the first time that the deletion of ppk2 in C. jejuni resulted in a significant decrease in poly P-dependent GTP synthesis, while displaying an increased intracellular ATP:GTP ratio. The Deltappk2 mutant exhibited a significant survival defect under osmotic, nutrient, aerobic, and antimicrobial stresses and displayed an enhanced ability to form static biofilms. However, the Deltappk2 mutant was not defective in poly P and ppGpp synthesis suggesting that PPK2-mediated stress tolerance is not ppGpp-mediated. Importantly, the Deltappk2 mutant was significantly attenuated in invasion and intracellular survival within human intestinal epithelial cells as well as in chicken colonization. CONCLUSIONS/SIGNIFICANCE: Taken together, we have highlighted the role of PPK2 as a novel pathogenicity determinant that is critical for C. jejuni survival, adaptation, and persistence in the host environments. PPK2 is absent in humans and animals; therefore, can serve as a novel target for therapeutic intervention of C. jejuni infections.