tbuckley/cabot-search huggingface dataset:
Recent developments in lactamases and extended spectrum lactamases
Authors: J. N Samaha-Kfoury
Journal: BMJ (2003)

Resistance to β lactam antibiotics is an increasing problem worldwide. This review describes the classification and mechanism of action of βlactamases and the options available for detecting, treating, and controlling extended spectrum β lactamases

βlactam antimicrobial agents are the most common treatment for bacterial infections (table 1).1 Rates of bacterial resistance to antimicrobial agents are increasing worldwide, including in Lebanon.2 Production of β lactamases is the most common mechanism of bacterial resistance (table 2).1 3 These enzymes are numerous, and they mutate continuously in response to the heavy pressure of antibiotic use, leading to the development of extended spectrum β lactamases (ESBLs).4 Examples are the mutated TEM and SHV genes, mainly found in strains of Escherichia coli and Klebsiella pneumoniae respectively. Infections with ESBL producing bacterial strains are encountered singly or in outbreaks, especially in critical care units in hospitals, resulting in increasing costs of treatment and prolonged hospital stays. We aim to present a simplified review of this highly complex subject, in the hope that it will guide the practising physician in appropriate decisions relating to the use of β lactams in patient care.

View this table:

Table 1 
Groups and examples of β lactam antimicrobial agents



View this table:

Table 2 
Antimicrobial agents, their modes of action, and the corresponding mechanisms of bacterial resistance



We examined new information from the most recent relevant literature retrieved from PubMed and the internet.

The β lactams are a family of antimicrobial agents consisting of four major groups: penicillins, cephalosporins, monobactams, and carbapenems (table 1). They all have a β lactam ring, which can be hydrolysed by β lactamases. The groups differ from each other by additional rings (thiazolidine ring for penicillins, cephem nucleus for cephalosporins, none for monobactams, double ring structure for carbapenems). The various antibiotics in each group differ by the nature of one …
Induction of an Inflammatory and Prodegradative Phenotype in Autologous Fibroblast‐like Synoviocytes by the Infrapatellar Fat Pad From Patients With Knee Osteoarthritis
Authors: Florent Eymard, Audrey Pigenet, Danièle Citadelle, Charles‐Henri Flouzat‐Lachaniette, Alexandre Poignard, Chantal Benelli, Francis Berenbaum, Xavier Chevalier, Xavier Houard
Journal: Arthritis & Rheumatology (2014)

The infrapatellar fat pad (IFP) of the knee joint has an inflammatory phenotype in osteoarthritis (OA). Its close proximity to the synovial membrane suggests that the IFP could be involved in the induction of OA synovitis. This study was undertaken to investigate the response of fibroblast-like synoviocytes (FLS) to autologous IFP and subcutaneous adipose tissue (SCAT) from patients with severe knee OA.Samples of IFP, SCAT, and autologous synovial membrane tissue close to the IFP were harvested during surgery from 28 patients with end-stage knee OA. FLS from 14 patients were stimulated with autologous IFP- or SCAT-conditioned medium, and levels of messenger RNA (mRNA) expression and protein release of interleukin-6 (IL-6), IL-8, secretory phospholipase A2 (sPLA2 ), cytosolic PLA2 , cyclooxygenase 2 (COX-2), microsomal prostaglandin E synthase, prostaglandin E2 (PGE2 ), and matrix metalloproteinases (MMPs) 1, 3, 9, and 13 were evaluated. Both IFP- and SCAT-conditioned medium were evaluated by enzyme-linked immunosorbent assay for secretion of IL-6, soluble IL-6 receptor (sIL-6R), IL-8, tumor necrosis factor α (TNFα), PGE2 , IL-1β, and interferon-γ. In addition, OA FLS were treated with PGE2 receptor antagonists to evaluate the contribution of IFP-derived PGE2 to the inflammatory response of FLS to the IFP.Stimulation of OA FLS with IFP-conditioned medium induced the mRNA expression and protein release of IL-6, IL-8, sPLA2 , COX-2, PGE2 , and MMPs 1, 3, 9, and 13. The extent of stimulation was consistently stronger with IFP-conditioned medium than with SCAT-conditioned medium. Moreover, secretion of IL-6, sIL-6R, IL-8, TNFα, and PGE2 was greater in IFP-conditioned medium than in SCAT-conditioned medium, especially PGE2 , whose secretion was 75-fold stronger in IFP-conditioned medium (P < 0.0001). PGE2 receptor antagonists dose-dependently inhibited the release of IL-6, IL-8, and PGE2 by IFP-stimulated FLS.This study showed that the IFP has a potential role in the induction of synovial inflammation in patients with severe knee OA. Furthermore, secretion of PGE2 by the IFP may be involved in the OA inflammatory process.
The costs of computing for primary care groups
Authors: A. Willis
Journal: BMJ (1998)

From next April about £38bn of public money will come under the direct influence of primary care groups. If these new organisations are to succeed in taking over much of the planning of local services there are inevitable resource implications in terms of people, time, and information systems. So far, however, ministers have offered remarkably little public recognition of the resource requirements, particularly with regard to the period up to next April. This is in sharp contrast to the endeavour put in at the beginning of fundholding, when a national specification for software was developed and extra money released to reimburse fundholders for computing and personnel costs.

All practices will be included in primary care groups, and much of the information required to …
The Tama River in Autumn
Authors: M. Therese Southgate
Journal: JAMA (1999)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 284: Impact of Target Core Temperature on Neurological Outcome of Cardiac Arrest Patients Treated With Therapeutic Hypothermia
Authors: Shunji Kasaoka, Ryosuke Tsuruta, Ken Nagao, Naohiro Yonemoto, Hiroyuki Yokoyama, Hiroshi Nonogi, J-PULSE-Hypo Investigators
Journal: Circulation (2010)

Introduction: Therapeutic hypothermia improves neurological outcome in patients with out-of-hospital cardiac arrest. However, ideal target core temperature remains unclear. We investigated the effe...
Abstract 4318: Is Female Gender Still an Independent Predictor of In-Hospital Mortality After STEMI in the Era of Primary PCI? Insights From the Greater Paris Area PCI Registry
Authors: Hakim Benamer, Muriel Tafflet, Sophie Bataille, Sylvie Escolano, Xavier Mouranche, Jean-Pierre Tresca, Bernard Livarek, Vincent Fourchard, Christophe Caussin, Emmanuel Teiger, Philippe Garot, Yves Lambert, Xavier Jouven, Christian Spaulding
Journal: Circulation (2009)
The Mozart Effect
Authors: Rob M F van der Weiden
Journal: Journal of the Royal Society of Medicine (2001)

Dr James suggests that some cases of ‘road rage’ in motorists might be due to an overdose of pop music at the wheel (June 2001 JRSM, pp. 316-317). More likely there exist fundamental (psychological) differences between motorists listening to Mozart and motorists enjoying uncivilized music. I should not be surprised if motorists eager to mow down the odd cyclist prefer uncivilized music to Mozart.
678. Cytoskeleton as the Principal Determinant of the Size-Dependent DNA Mobility in Cytoplasm: A New Barrier for Non-Viral Gene Transfer
Authors: Emmanuel Dauty, Alan S. Verkman
Journal: Molecular Therapy (2004)

Gene delivery by synthetic vectors is a multi-step process that relies on the endocytosis of the DNA particles, escape from endosomes, and diffusion of the DNA through the cytosol before the import in the nucleus. The cytoplasm of mammalian cells is a complex environment containing a fluid phase, a high concentration of soluble proteins, and a network of cytoskeletal filaments. We found previously that the translational diffusion of small DNAs (  250 bp) were greatly slowed (Dcyto/Dw/Dw< 0.05) (J. Biol. Chem. 275:1625–1629, 2000). To investigate the mechanisms responsible for size-dependent DNA diffusion, we measured by fluorescence correlation spectroscopy the diffusion of fluorescent linear, double-stranded DNAs in saline and artificial crowded solutions, cytosol extracts, actin network and cell cytoplasm. DNA fragments containing a single rhodamine green molecule were generated by PCR. In saline solution, DNA diffusion coefficients decreased with DNA size according to: Dw = 8.1 × 10−6cm2/s × (base pair) −0.71. In solutions containing the inert crowding agent Ficoll-70, DNA mobility was reduced exponentially with the Ficoll-70 concentration (5-fold at 18 wt% Ficoll-70); however, neither Ficoll-70 nor concentrated cytosolic soluble fractions reproduced size-dependent reduction in Dcyto/Dw as found in intact cells. In contrast, reduced Dcyto/Dw with increasing DNA size was reproduced in saline solutions crowded with actin filaments, the principal component of the cytoskeleton. Compact globular macromolecules of same size were not slowed, implicating the extended conformation of the DNA in its impaired diffusion. In intact cells microinjected with the fluorescent DNAs, Dcyto/Dw was greatly reduced as found in prior photobleaching measurements; however, the size-dependent reduction in Dcyto/Dw was eliminated with cytoskeletal disrupters (cytochalasin D, latrunculin B) and was dependent on cell volume. Our results implicate actin cytoskeleton as the principal determinant of the restricted DNA mobility in cytoplasm, thus identifying a new barrier in restricting DNA movement to the nucleus.
Abstract 16608: Building of a Right Ventricular Conduit in Native Outflow Tract in Preparation of Edwards Sapien Valve Implantation
Authors: M. Giulia Gagliardi, Mara Pilati, Alessandra Cristofaletti, Salvatore Giannico, Aurelio Secinaro, Giacomo Pongiglione
Journal: Circulation (2014)

Background: Percutaneous valve implantation (PPVI) is now considered feasible and safe especially in patients with conduit between the right ventricle and the pulmonary arteries. However there are still no clear indications on valvolization in native outflow tract (RVOT), traditionally considered at risk because of the dynamic characteristics of the RVOT Aim: The aim of this study is to demonstrate the feasibility and safety of building a percutaneous conduit using a stent in the native RVOT before valve implant performing PPVI two months after stent implant, on the basis of previous animal studies, where endotelitation of the stent was shown to be reached within 60 days. Methods: From October 2010 to April 2014, 19 pts, with tetralogy of Fallot, (mean age 15 ± 6 yrs) previously corrected by transannular patch technique, underwent a cardiac catheterization in order to build a stent-conduit in the native RVOT. After a complete right catheterization a balloon was inserted through a long sheath in the RVOT. During the inflation of the balloon a right ventricular angiography and a left coronary artery angiography are performed. In the presence of a complete occlusion of the RVOT and no coronary compression, a stent was deployed in the RVOT. Two months later an Edwards Sapien Pulmonary valve was implanted. Results: Twenty two stents were implanted in 19 pts. The mean time of the procedures was 185 ± 89 min with a mean fluoroscopy time of 72 ± 33 min. Two main complications occurred: in 1 pt the stent partially occluded the right pulmonary artery and in a second pt the stent was dislocated in RVOT. In both cases the patients were treated surgically. In all other patients the procedure was successful and patients were discharged home two days later, on Aspirin therapy. The correct position of the stent was confirmed at the 1 month of follow-up by echocardiographic examination. Among the 19 pts , 152 underwent implantation of Edwards Sapien Pulmonary Valve, two months later. No complications occurred during the procedure and during the FU. Two patients are still waiting PPVI procedure Conclusions: A two-step procedure approach increases the safety of PPVI with no impact on clinical conditions or complications
Augmentation of plasminogen activator inhibitor-1 by free fatty acids in breast cancer cells
Authors: Chang Hyun Byon, Robert Hardy, Danny Welch, Jay McDonald, Yabing Chen
Journal: Cancer Research (2006)

4374   Plasminogen activator inhibitor-1 (PAI-1) is the primary inhibitor of urokinase- and tissue type-plasminogen activators. Increases in the expression of PAI-1 have been demonstrated in many tumor cells, including breast cancer cells. By contrast, retarded tumor development has been shown in PAI-1 deficient mice. Emerging clinical studies have pointed to PAI-1 as a key prognostic factor in breast cancer. Obesity is a high risk factor for breast cancer and increased plasma concentrations of free fatty acids (FFA) and PAI-1 are associated with obesity. We and others have demonstrated that FFA induced PAI-1 expression in a variety of cells. Accordingly, we hypothesized that FFA increase the expression of PAI-1 in breast cancer cells and facilitate breast cancer progression. The effects of FFA on PAI-1 expression in breast cancer cells were determined in MDA-MB-231 and Hs578T. FFA with different saturation and chain lengths including palmitic, palmitoleic, stearic, oleic, and linoleic acid at physiological and pathological concentrations (50 μM to 500 μM) were studied. FFA were prepared in fatty acid free-BSA and experiments were performed in serum-free DMEM/F12 media. Secretion of PAI-1 in culture media was determined by ELISA. Intracellular PAI-1 was determined by Western blotting and PAI-1 mRNA was assessed by RT-PCR. PAI-1 secretion levels were higher in MDA-MB-231 compared with Hs578T (fold = 5.7 ± 0.8 MDA-MB-231 Vs. Hs578T, n = 4, p = 0.002). Linoleic and oleic acids induced PAI-1 in MDA-MB-231 and Hs578T in a dose-dependent manner, whereas palmitic, palmitoleic, and stearic acids (at all concentrations studied) had no effect on the expression of PAI-1 (n = 4). The greatest induction of PAI-1 was observed with linoleic acid (500 μM) in both MDA-MB-231 (fold = 1.8 ± 0.2, n = 4, p = 0.004) and Hs578T (fold = 3.4 ± 1.1, n = 4, p = 0.002). Increased PAI-1 mRNA was demonstrated in MDA-MB-231 (fold = 1.4 ± 0.3, n = 3, p  in vitro  Matrigel invasion assay, whereas other FFA had no effects. In summary, we have demonstrated that linoleic acid induced the greatest level of PAI-1 expression in breast cancer cell lines MDA-MB-231 and Hs578T. Increased invasion of MDA-MB-231 cells was also induced by linoleic acid, but not other FFA. These results are consistent with previous observations that linoleic acid (ω-6) is associated with cancer progression. The present study provides new insight into understanding the important role of PAI-1 in mediating the effects of FFA on breast cancer progression.
Serum cholesterol concentrations in parasuicide
Authors: M R Law, N J Wald
Journal: BMJ (1995)

promote contraception through safer sex cam- paigns have undoubtedly been successful in increasing the proportion of teenagers who use condoms.Most people have assumed that increas- ing the use of contraception leads to a reduction in unplanned teenage pregnancies.4Yet my analysis shows that this has not happened.A plausible explanation is that the main factor in unplanned teenage conceptions is contraceptive failure, not the lack of contraceptive knowledge and availability.The findings of Pearson and colleagues support this view.A further question is whether increasing the availability of contraception leads to an increase in sexual activity.If this is the case-and the national survey of sexual behaviour reports a large increase over the past two decades in the proportion of teenagers who are sexually active-then it is not surprising that the rate of teenage conceptions continues to increase.The answer is not more contraception or emergency contraception but a change in attitude towards sexual behaviour.
Amplification of genomic DNA demonstrates the presence of the t(2;5) (p23;q35) in anaplastic large cell lymphoma, but not in other non- Hodgkin's lymphomas, Hodgkin's disease, or lymphomatoid papulosis
Authors: AH Sarris, R Luthra, V Papadimitracopoulou, M Waasdorp, MA Dimopoulos, JA McBride, F Cabanillas, M Duvic, A Deisseroth, SW Morris, WC Pugh
Journal: Blood (1996)
Abstract 2808: GD2-specific genetically engineered NK cell therapy is effective in a drug-resistant neuroblastoma xenograft mouse model
Authors: Diana Seidel, Anastasia Shibina, C. Patrick Reynolds, Winfried S. Wels, Nicole Huebener, Holger N. Lode
Journal: Cancer Research (2014)

Abstract Background: Drug-resistant neuroblastoma remains a major challenge in pediatric oncology. A human NK cell line NK-92-scFv(ch14.18)-z engineered to express a GD2-specific chimeric antigen receptor (CAR) may help to address this problem. We investigated the cytotoxicity of NK-92-scFv(ch14.18)-z in a panel of GD2+ drug-resistant neuroblastoma cell lines and analyzed the anti-tumor efficacy of NK-92-scFv(ch14.18)-z in a drug-resistant neuroblastoma xenograft mouse model. Methods Cytotoxic activity of GD2-specific NK-92-scFv(ch14.18)-z towards a panel of GD2+ cell lines (CHLA-20, SK-N-BE(2), CHLA-136, CHLA-79, LA-N-1, LA-N-5), some of which exhibit partial or multidrug resistance, was analyzed in a 51Cr release assay. We investigated the impact of GD2 recognition on NK-92-scFv(ch14.18)-z-mediated lysis by blocking the CAR through the addition of an anti-idiotype antibody (anti-IdAb) and also by downregulating GD2 on target cells induced by the glucosylceramide synthase (GCS) inhibitor PPPP. We then employed ELISA to determine the production of effector molecules granzyme B and perforin in response to activation with immobilized GD2. Anti-tumor efficacy of NK-92-scFv(ch14.18)-z and IL-2 was analyzed in a drug-resistant GD2+ xenograft mouse model by peritumoral injections of the GD2-specific NK cell line. Results NK-92-scFv(ch14.18)-z effectively lysed GD2+ drug-resistant NB cell lines. This effect was almost completely abrogated by blocking the CAR with an anti-IdAb. Decreased GD2 expression on target cells also resulted in diminished lysis mediated by NK-92-scFv(ch14.18)-z. Quantification of granzyme B and perforin production with ELISA revealed that the plate-bound antigen GD2 alone was sufficient to induce activation of NK-92-scFv(ch14.18)-z. Importantly, repeated peritumoral subcutaneous injections of a combination of NK-92-scFv(ch14.18)-zeta and IL-2 significantly prolonged survival time of mice challenged with aggressively growing subcutaneous CHLA-20 tumors in a xenograft mouse model. Conclusions These encouraging results indicate that GD2-directed immunotherapy with genetically engineered NK cells is an appropriate treatment strategy especially in relapsed NB that exhibit drug resistance. Citation Format: Diana Seidel, Anastasia Shibina, C. Patrick Reynolds, Winfried S. Wels, Nicole Huebener, Holger N. Lode. GD2-specific genetically engineered NK cell therapy is effective in a drug-resistant neuroblastoma xenograft mouse model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2808. doi:10.1158/1538-7445.AM2014-2808
Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages
Authors: Takafumi Yokota, Kenji Oritani, Isao Takahashi, Jun Ishikawa, Akifumi Matsuyama, Noriyuki Ouchi, Shinji Kihara, Tohru Funahashi, Andrea J. Tenner, Yoshiaki Tomiyama, Yuji Matsuzawa
Journal: Blood (2000)
A Dictionary of Terms Used in Medicine and the Collateral Sciences.
Authors: Richard D. Hoblyn, Isaac Hays
Journal: JAMA (1900)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal