tbuckley/cabot-search huggingface dataset:
Ovarian-Vein Thrombophlebitis
Authors: J. Kevin Lynch, V. Sreenivas, O. Pelliccia
Journal: New England Journal of Medicine (1966)

SINCE Reginald Fitz,1 in 1886, recognized and described the syndrome of acute appendicitis, many entities have been considered in its differential diagnosis. On exploration of a patient with the preoperative diagnosis of acute appendicitis, we discovered thrombophlebitis of the right ovarian vein. Because of the rarity of this condition and because it could not, on clinical grounds, be distinguished from acute appendicitis, we considered this case worthy of record.Case ReportA 28-year-old gravida 1, para 1, entered the hospital because of constant right-lower-quadrant pain of 2 days' duration. The pain, which was gradual in onset, became progressively more severe . . .
Potential of gene therapy as a treatment for heart failure
Authors: Roger J. Hajjar
Journal: Journal of Clinical Investigation (2013)

Advances in understanding the molecular basis of myocardial dysfunction, together with the evolution of increasingly efficient gene transfer technology, make gene-based therapy a promising treatment option for heart conditions. Cardiovascular gene therapy has benefitted from recent advancements in vector technology, design, and delivery modalities. There is a critical need to explore new therapeutic approaches in heart failure, and gene therapy has emerged as a viable alternative. Advances in understanding of the molecular basis of myocardial dysfunction, together with the development of increasingly efficient gene transfer technology, has placed heart failure within reach of gene-based therapy. The recent successful and safe completion of a phase 2 trial targeting the cardiac sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump (SERCA2a) has the potential to open a new era for gene therapy for heart failure.
Barrett's Esophagus with High-Grade Dysplasia
Authors: U Ladabaum, W M McDonnell
Journal: New England Journal of Medicine (1999)

Figure 1. A 73-year-old man underwent endoscopy after presenting with melena. A duodenal ulcer was seen, and Barrett's esophagus was found incidentally. One year later, esophageal-biopsy specimens obtained during surveillance endoscopy revealed high-grade dysplasia. The patient underwent transhiatal esophagectomy with cervical esophagogastric anastomosis. The resected specimen did not contain invasive carcinoma, and the lymph nodes were negative for cancer.
French patients will have to go through family doctors to access specialists
Authors: Brad Spurgeon
Journal: BMJ (2004)

The health minister, Philippe Douste-Blazy, last week unveiled the French government's plan to reorganise and streamline the country's healthcare system to reduce the €12.9bn (£8.7bn; $15.5bn) annual deficit and pay back the €32bn debt. It represents at least the fourteenth attempt to reform the French health system since 1975.

The plan, which he presented on television on 17 May, should save up to €15bn a year by 2007 by cutting costs and increasing charges. The most radical change requires patients to pay a non-reimbursable €1 for each medical consultation, to both save money and give people a “sense of responsibility” for their health care.

“Our system is failing, it is without a pilot, and no one is responsible,” said Mr Douste-Blazy. “I'm here to defend a new system.”

As part of the reorganisation, family doctors are to be the starting point for all medical consultations, and they will use a new computerised medical records system.

The family doctor—regardless of whether he or …
Advances in the Treatment of Mucopolysaccharidosis Type I
Authors: Joseph Muenzer, Amy Fisher
Journal: New England Journal of Medicine (2004)

The mucopolysaccharidoses are a group of lysosomal storage diseases caused by a deficiency of enzymes that degrade glycosaminoglycans.1 Mucopolysaccharidosis type I, an autosomal recessive disorder caused by a deficiency of the enzyme α-L-iduronidase, is characterized by multisystemic clinical disease. The α-L-iduronidase deficiency leads to the progressive accumulation of glycosaminoglycans, resulting in tissue and organ dysfunction. A wide range of clinical presentations, with variations in the severity of symptoms and the extent of central nervous system involvement, is observed in patients with iduronidase deficiency.In 1919, a German pediatrician named Gertrud Hurler provided the first description of mucopolysaccharidosis type I. Characteristics . . .
Abstract 1: Mcl-1 downregulation plays a crucial role in the synergistic anticancer activities between PI-3 kinase inhibitors and histone deacetylase inhibitors in primary NSCLC tumors <i>in vitro</i> and <i>in vivo</i>
Authors: Hao Zhang, Haikou Tang, Huanjie Shao, Chun Gao, Bonnie L. Hylander, Elizabeth A. Repasky, Grace K Dy, Wen Wee Ma, Chunrong Yu, Alex A. Adjei
Journal: Cancer Research (2011)

Abstract Interactions between the PI-3 kinase inhibitors and histone deacetylase inhibitors (HDACi) were examined in vivo using SCID mice bearing patient-derived primary NSCLC xenografts which contain the “hot spot” mutation PIK3CA [E545K (G1633A)] (K-Ras and EGFR wild-type), and in vitro using the primary cell cultures derived directly from the in vivo xenografts. Co-treatment of primary cell cultures to marginally toxic concentrations of GDC-0941 (1.0 uM) and HDACi LBH589 (2.5 nM) induced a striking increase of apoptosis, as evidenced by Annex V positive staining, cytochrome c release and caspase 3 cleavage. Similar effects were observed using other HDACis (e.g. SAHA or MS275). The combination was associated with profound Akt inactivation, GSK-3β activation and Mcl-1 attenuation without affecting other Bcl-2 family members. Although LBH589 induced p21CIP1/WAF1 expression, GDC-0941 blocked LBH589-mediated p21CIP1/WAF1 accumulation. Ectopic expression of the constitutively active (myristolated) Akt, dominant negative GSK-3β (K85A), Mcl-1, or p21CIP1/WAF1 significantly blocked apoptosis induced by this combination. Inactivation of GSK-3β by either shRNA knockdown or its pharmacological inhibitor markedly diminished GDC-0941/LBH589-induced cell death, and abrogated the Mcl-1 and p21CIP1/WAF1 downregulation seen with the combination, indicating that GSK-3β modulation is the process upstream of Mcl-1 and p21. However, overexpression of either Mcl-1 or p21CIP1/WAF1 did not demonstrate an interaction with each other under the co-treatment, suggesting an independent functional cascade for each Mcl-1 and p21CIP1/WAF1. The downregulation of Mcl-1 and p21CIP1/WAF1 was reversed by proteasome inhibitor, indicating a proteasome-dependent degradation of Mcl-1 and p21CIP1/WAF1. Lastly, the combination of GDC-0941/LBH589 in vivo inhibited the growth of primary tumor xenografts more efficiently than either agent alone. In vivo downregulation of Mcl-1 and p21CIP1/WAF1 was also observed, consistent with the modulation of molecular events presented in vitro. Taken together, our results demonstrate that GDC-0941 potentiates HDACi-mediated apoptosis through PI3K/Akt/GSK-3β pathway, and subsequently attenuates Mcl-1 and abrogates p21CIP1/WAF1 induction in primary NSCLC xenografts in vivo and the primary cell cultures in vitro, thereby suggesting a novel therapeutic approach for NSCLC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1. doi:10.1158/1538-7445.AM2011-1
Electronic health records may not be available in secondary care until 2015
Authors: Michael Cross
Journal: BMJ (2008)

Patients who have confounded doctors with signs and symptoms that elude diagnosis are to be offered the expertise of hundreds of doctors in a unique programme from the US National Institutes of Health."Physicians deal with about 6600 conditions and 6000 of them are quite rare.Even common diseases have many subtypes," the institutes' director Elias A Zerhouni said during a telephone news conference with reporters earlier this week.He said it was not surprising that many can go undiagnosed for years.The programme aims to combine the revolution in tools and information at the molecular level with the expertise of the 1600 doctors at the NIH Clinical Center "to assist patients around the country and their doctors."It will add to the knowledge base by creating a phenotype atlas of disease."We are doing this now because of the advances that have been made over the last five years at the fundamental level.We have many more biologic markers, the significance of which is not always understood." Dr Zerhouni said that for the first time his organisation was going to apply these sophisticated laboratory tests to human diseases on a large scale.Under the current system of research at the NIH Clinical Center, patients with challenging conditions "are triaged to a specific institute or protocol programme, and are assessed by one team," said John I Gallin, director of the centre.Participants in the new programme "will be assessed by a large spectrum of teams."Candidate patients must be referred by a healthcare provider and will have to submit exhaustive medical records that will be reviewed by a multidisciplinary team of 25 senior doctors.Those who are accepted into the programme will travel to the centre for an evaluation, which is likely to take at least a week.Details are available at http://rarediseases.info.nih.gov/
A CASE OF FRACTURE OF THE THYROID CARTILAGE—RECOVERY WITHOUT TRACHEOTOMY.
Authors: THOMAS B. EASTMAN
Journal: JAMA (1895)

Of the thirty cases of fracture of the thyroid cartilage reported by Durham, but ten of these recovered and most of them after a tracheotomy. Indeed, most authorities unqualifiedly condemn any delay in operating, Cohen saying: "Unless forestalled by precautionary tracheotomy and insertion of a tube, suffocative phenomena may intervene at any time from edema, displacement of fragments, or occlusion of the caliber of the air tube with blood clots."<sup>1</sup>He further says, "better far that an unnecessary tracheotomy should occasionally be performed without detriment to the patient than that a number of cases should be allowed to terminate fatally for the want of it." Stimson says:<sup>2</sup>"It is not safe to wait until it (dyspnea) has become extreme, for its increase at the last is often so rapid and so sudden that death takes place before relief can be given. It is therefore the part of prudence
Primary CTL response magnitude in mice is determined by the extent of naive T cell recruitment and subsequent clonal expansion
Authors: Nicole L. La Gruta, William T. Rothwell, Tania Cukalac, Natasha G. Swan, Sophie A. Valkenburg, Katherine Kedzierska, Paul G. Thomas, Peter C. Doherty, Stephen J. Turner
Journal: Journal of Clinical Investigation (2010)

CD8+ T cell responses to viral infection are characterized by the emergence of dominant and subdominant CTL populations. The immunodominance hierarchies of these populations are highly reproducible for any given spectrum of virus-induced peptide-MHCI complexes and are likely determined by multiple factors. Recent studies demonstrate a direct correlation between naive epitope-specific CD8+ T cell precursor (CTLp) frequency and the magnitude of the response after antigen challenge. Thus, the number of available precursors in the naive pool has emerged as a key predictor of immunodominance. In contrast to this, we report here no consistent relationship between CTLp frequency and the subsequent magnitude of the immune response for 4 influenza virus–derived epitopes following intranasal infection of mice with influenza A virus. Rather, the characteristic, antigen-driven T cell immunodominance hierarchy was determined by the extent of recruitment from the available pool of epitope-specific precursors and the duration of their continued expansion over the course of the infection. These findings suggest possibilities for enhancing protective immune memory by maximizing both the size and diversity of typically subdominant T cell responses through rational vaccine design.
Effect of hypercapnia and hypocapnia on myocardial blood flow and performance in anaesthetized dogs
Authors: C. S. ALEXANDER, S.-M. LIU
Journal: Cardiovascular Research (1976)

The effects of hypercapnia and hypocapnia on haemodynamics, coronary blood flow, and lactate metabolism were evaluated in anaesthetized closed chest dogs. Coronary flow increased with increased pCO2 and oxygen consumption and left ventricular performance were well maintained. Hypocapnia reduced coronary flow, oxygen consumption, and left ventricular functional performance.
Metabolism of halogenated ethylenes.
Authors: K C Leibman, E Ortiz
Journal: Environmental Health Perspectives (1977)

The metabolism of the chlorinated ethylenes may be explained by the formation of chloroethylene epoxides as the first intermediate products. The evidence indicates that these epoxides rearrange with migration of chlorine to form chloroacetaldehydes and chloroacetyl chlorides. Thus, monochloroacetic acid, chloral hydrate, and trichloroacetic acid have been found in reaction mixtures of 1,1-dichloroethylene, trichloroethylene, and tetrachloroethylene, respectively, with rat liver microsomal systems. Rearrangements of the chloroethylene, and glycols formed from the epoxides by hydration may also take place, but would appear, at least in the case of 1,1-dichloroethylene, to be quantitatively less important. The literature on the metabolism of chlorinated ethylenes and its relationship to their toxicity is reviewed.
Abstract P3-14-06: Residual tumor autophagy marker LC3B is a prognostic marker in local advanced breast cancer underwent neoadjuvant chemotherapy
Authors: S Chen, Y-Z Jiang, L Huang, Y Liu, K-D Yu
Journal: Cancer Research (2013)

Abstract Purpose A membrane-bound microtubule-associated protein chain 3B(LC3B) is known as one of the most specific biomarker for autophagy. The goal of this study is to investigate the prognostic value of autophagy marker LC3B in patients with residual tumors after neoadjuvant chemotherapy(NCT) for local advanced breast cancer(LABC) Patients and Methods Expression of LC3B in residual breast cancer cells were assessed by immunohistochemistry in surgical specimens from 229 patients who were diagnosed with histological proven invasive breast cancer. All patients had undergone neoadjuvant chemotherapy followed by mastectomy, and were considered as non pathological complete responders(non-pCR)after pathological evaluation. The density of positive staining of LC3B was measured with the use of a computerized image system. Prognostic value of various clinicopathologic factors was combined and evaluated by using Cox regression model. Results LC3B density was similar in the peripheral and central area of tumor(P = 0.328), however, it was siginifcantly lower in the extratumoral area(P&amp;lt;0.001 and P&amp;lt;0.001, respectively). High LC3B density was more likely to be observed in patients with PR-negative at diagnosis(P = 0.033), Beclin-1-positive(P&amp;lt;0.001) at surgery and higher Ki-67 index at surgery(P = 0.029). Breast cancer subtype was also correlated to LC3B expression(P = 0.003), an obvious lower proportion of LC3B-high density was detected in luminal-A patients than in other subtypes(32.4% in luminal-A, 59.4% in luminal-B, 65.4% in HER-2+, and 46.7% in TNBC). In survival analysis, only LC3B and residual nodal status after NCT resulted significant predictors of both RFS(HR = 1.180,P = 0.012 and HR = 3.067, 6.103, P&amp;lt;0.001, respectively) and overall survival(HR = 2.428, P = 0.008 and HR = 1.809,4.283, P = 0.003, respectively). Ki-67 was also an indepentent predictor for RFS(HR = 1.122, P = 0.019). The prognostic value of LC3B was most significant in triple-negative patients than in other subtypes. With a combination of LC3B expression and status of residual involved lymph nodes, patients were classified into four groups with different risk of relapse and death(P&amp;lt;0.001 for RFS and P = 0.003 for OS). Patients with no positive node residual and low LC3B expression were at low risk of relapse and death, with 5-year RFS and OS of 97% and 97%, respectively. However, the 5-year RFS and OS for patients with a positive node satus and high LC3B were only 52% and 66%, respectively. Conclusion LC3B is a prognostic marker in non-pCR patient after neoadjuvant chemotherapy for breast cancer, which highlighting the importance of autophagy in the biological behavior of chemo-resistence cancer cells. Evaluating and targeting autophagy in neoadjuvant setting may help in prevention of disease relapse in non-pCR patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-06.
Authors' reply (Finland)
Authors: P. K Verkasalo, K. V Heikkila, E. Pukkala, M. Y Hongisto, J. E Valjus, P. J Jarvinen, M. Koskenvuo
Journal: BMJ (1994)

EDITOR,--We are well aware that magnetic fields from sources other than power lines will, if carcinogenic, mask and decrease the observed association. Our exposure assessment was based on the assumption that magnetic fields of high voltage power lines usually increase the overall exposures of children living in the vicinity of the lines compared with other children. Calculation of magnetic fields generated by power lines provided no more than a tool for classifying study subjects according to their overall exposure levels. The subcohorts of children with maximal annual average exposure of >/=0.20 μT or cumulative exposure of >/=0.40 μT years were considered to be exposed in our study; the rest were investigated solely to compare …
In vivo p53 response and immune reaction underlie highly effective low-dose radiotherapy in follicular lymphoma
Authors: Laurent Knoops, Rick Haas, Sanne de Kemp, Donné Majoor, Annegien Broeks, Eric Eldering, Jan Paul de Boer, Marcel Verheij, Conny van Ostrom, Annemieke de Vries, Laura van't Veer, Daphne de Jong
Journal: Blood (2007)
IMMUNOREACTIVE BASEMENT MEMBRANE ANTIGENS IN NORMAL HUMAN URINE AND SERUM
Authors: J. J. McPhaul, Frank J. Dixon
Journal: The Journal of Experimental Medicine (1969)

Using a sheep antiserum to human glomerular basement membrane (GBM), studies of urine from healthy adults showed the presence of two cross-reactive antigens. These antigens were purified partially by preparative electrophoresis and electrofocusing, and separated on G-200; both appeared to be acidic, of high molecular weight, and carbohydrate rich. Their immunologic relationship to human GBM solubilized by several techniques was deduced from lines of identity with the native GBM digests in double diffusion analyses. These antigens will combine with homologous anti-GBM antibodies and block their fixation to human kidney sections, and will evoke heterologous anti-GBM antibody production in the rabbit. Fractionation studies of normal human serum indicated the presence of trace amounts of basement membrane antigens in the circulation. Although the serum antigens appear immunologically identical to the urinary antigens, the precise anatomic structures from which both are derived is not certain. Demonstration of immunoreactive basement membrane antigens in the circulation provides a plausible source of immunogen for the potential development of anti-GBM antibody-mediated glomerulonephritis as well as a clue to a mode for reestablishment of tolerance in such an autoimmune disorder.
RAPID RESPONSES FROM BMJ.COM
Authors: Sidha S Sambandan
Journal: BMJ (2004)

Following are edited excerpts from the Rapid Responses generated by this article, all of which can be read in their entirety at http://bmj.bmjjournals.com/cgi/content/full/328/7444/869#responses.-Editor 

Having used methylprednisolone and lidocaine (80 mg) for more than 15 years for osteoarthritis of the knee that did not respond to conservative treatment, I have found that a significant proportion of patients have had pain relief lasting up to five years. …
The Dynamic Nature of Coronary Artery Lesion Morphology Assessed by Serial Virtual Histology Intravascular Ultrasound Tissue Characterization
Authors: Takashi Kubo, Akiko Maehara, Gary S. Mintz, Hiroshi Doi, Kenichi Tsujita, So-Yeon Choi, Osamu Katoh, Kenya Nasu, Andreas Koenig, Michael Pieper, Jason H. Rogers, William Wijns, Dirk Böse, M. Pauliina Margolis, Jeffrey W. Moses, Gregg W. Stone, Martin B. Leon
Journal: Journal of the American College of Cardiology (2010)

We used virtual histology intravascular ultrasound (VH-IVUS) to investigate the natural history of coronary artery lesion morphology. Plaque stability is related to its histological composition. We performed serial (baseline and 12-month follow-up) VH-IVUS studies and examined 216 nonculprit lesions (plaque burden ≥40%) in 99 patients. Lesions were classified into pathological intimal thickening (PIT), VH-IVUS–derived thin-capped fibroatheroma (VH-TCFA), thick-capped fibroatheroma (ThCFA), fibrotic plaque, and fibrocalcific plaque. At baseline, 20 lesions were VH-TCFAs; during follow-up, 15 (75%) VH-TCFAs “healed,” 13 became ThCFAs, 2 became fibrotic plaque, and 5 (25%) VH-TCFAs remained unchanged. Compared with VH-TCFAs that healed, VH-TCFAs that remained VH-TCFAs located more proximally (values are median [interquartile range]) (16 mm [15 to 18 mm] vs. 31 mm [22 to 47 mm], p = 0.013) and had larger lumen (9.1 mm2[8.2 to 10.7 mm2] vs. 6.9 mm2[6.0 to 8.2 mm2], p = 0.021), vessel (18.7 mm2[17.3 to 28.6 mm2] vs. 15.5 mm2[13.3 to 16.6 mm2]; p = 0.010), and plaque (9.7 mm2[9.6 to 15.7 mm2] vs. 8.4 mm2[7 to 9.7 mm2], p = 0.027) areas; however, baseline VH-IVUS plaque composition did not differ between VH-TCFAs that healed and VH-TCFAs that remained VH-TCFAs. Conversely, 12 new VH-TCFAs developed; 6 late-developing VH-TCFAs were PITs, and 6 were ThCFAs at baseline. In addition, plaque area at minimum lumen sites increased significantly in PITs (7.8 mm2[6.2 to 10.0 mm2] to 9.0 mm2[6.5 to 12.0 mm2], p < 0.001), VH-TCFAs (8.6 mm2[7.3 to 9.9 mm2] to 9.5 mm2[7.8 to 10.8 mm2], p = 0.024), and ThCFAs (8.6 mm2[6.8 to 10.2 mm2] to 8.8 mm2[7.1 to 11.4 mm2], p < 0.001) with a corresponding decrease lumen areas, but not in fibrous or fibrocalcific plaque. Most VH-TCFAs healed during 12-month follow-up, whereas new VH-TCFAs also developed. PITs, VH-TCFAs, and ThCFAs showed significant plaque progression compared with fibrous and fibrocalcific plaque.
Cutaneous lip tumours treated with Mohs micrographic surgery: clinical features and surgical outcome
Authors: I. Leibovitch, S.C. Huilgol, D. Selva, R. Paver, S. Richards
Journal: British Journal of Dermatology (2005)

Journal Article Cutaneous lip tumours treated with Mohs micrographic surgery: clinical features and surgical outcome Get access I. Leibovitch, I. Leibovitch Oculoplastic and Orbital Division, Department of Ophthalmology and Visual Sciences, Royal Adelaide Hospital, University of Adelaide, South Australia Igal Leibovitch. E‐mail: leiboigal5@yahoo.com.au Search for other works by this author on: Oxford Academic Google Scholar S.C. Huilgol, S.C. Huilgol Department of Dermatology, Royal Adelaide Hospital, University of Adelaide, and Wakefield Clinic, Adelaide, South Australia Search for other works by this author on: Oxford Academic Google Scholar D. Selva, D. Selva Oculoplastic and Orbital Division, Department of Ophthalmology and Visual Sciences, Royal Adelaide Hospital, University of Adelaide, South AustraliaDepartments of Surgery and Medicine, University of Adelaide, Adelaide, South Australia Search for other works by this author on: Oxford Academic Google Scholar R. Paver, R. Paver Skin and Cancer Foundation Australia, Sydney, New South Wales, Australia Search for other works by this author on: Oxford Academic Google Scholar S. Richards S. Richards Skin and Cancer Foundation Australia, Sydney, New South Wales, Australia Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 153, Issue 6, 1 December 2005, Pages 1147–1152, https://doi.org/10.1111/j.1365-2133.2005.06903.x Published: 01 December 2005 Article history Accepted: 23 May 2005 Published: 01 December 2005