tbuckley/cabot-search huggingface dataset:
Correlation of Spectral Phonoangiography and Carotid Angiography with Gross Pathology in Carotid Stenosis
Authors: J. Philip Kistler, Robert S. Lees, Arnold Miller, Robert M. Crowell, Glen Roberson
Journal: New England Journal of Medicine (1981)

Spectral phonoangiography, a noninvasive method for measurement of the residual-lumen diameter of carotid stenosis by bruit analysis, was compared with x-ray angiography and direct measurement of the pathological specimen at carotid endarterectomy in 39 bifurcations from 36 patients. In six studies, the bruit was too faint to analyze. In 31 of the other 33 studies, the phonoangiogram predicted the residual-lumen diameter to within 0.5 mm of the measured value. Of the 39 contrast angiograms, 35 showed residual lumens within 0.5 mm of the value measured in the specimen, two showed lumens between 0.5 and 1 mm, and the sizes of two could not be estimated because of vessel overlap in all planes. Spectral phonoangiography and contrast angiography are both accurate methods for evaluation of carotid stenosis. Since phonoangiography is noninvasive, it may be of particular value in determining the natural history in patients with carotid bruits.
Complete Deficiency of Adenine Phosphoribosyltransferase
Authors: Karel J. Van Acker, H. Anne Simmonds, Catherine Potter, J. Stewart Cameron
Journal: New England Journal of Medicine (1977)

We studied the clinical and biochemical manifestations of complete adenine phosphoribosyltransferase deficiency in the kindred of a male homozygous child excreting stones of 2,8-dihydroxyade-nine. Abnormal amounts of adenine, 8-hydroxyade-nine and 2,8-dihydroxyadenine (25 per cent of total purine metabolites) appeared in the urine of the propositus and his clinically normal brother, but not in heterozygotes or a control. Adenine phosphoribosyl-transferase activity in erythrocytes was less than 1 per cent of normal in both homozygotes and varied from 20 to 57 per cent of normal in six heterozygotes. Heterozygotes exhibited neither hyperuricemia nor gout. Treatment of the propositus with allopurinol and a low purine diet stopped stone formation. In addition, excretion of 2,8-dihydroxyadenine decreased. An autosomal recessive mode of inheritance with variable expression in the phenotype is indicated. Homozygotes may be detected by their raised urinary adenine levels or absence of detectable erythrocyte adenine phosphoribosyltransferase activity (or both).
Expression of p53, p63 and p73 family of genes in osteosarcoma: Single instituition study of 35 patients using tissue microarray
Authors: W. Chen, S. C. Aisner, J. Benevenia, F. Patterson, M. Hameed
Journal: Journal of Clinical Oncology (2005)

9044 Background: Osteosarcoma is the prototype of sarcomas where multimodality treatment including preop-chemotherapy, limb-sparing surgery and adjuvant chemotherapy has dramatically altered the overall survival from 25% to 70–80% in the last 30 years. The purpose of this study was to determine the role of p53 family of genes in the biology of Osteosarcoma Methods: 47 formalin fixed paraffin embedded blocks from 35 patients with osteosarcoma were chosen for the study. The ages of patients ranged from 6–74 years. Of the 35 patients, 32 patients were high grade conventional intramedullary osteosarcoma, and 3 were Paget osteosarcomas. Tumor locations included femur (22), proximal tibia (5), humerus (3), ilium (3), distal tibia (1), and foot (1). The clinical staging were as follows: Stage I (3), Stage II (22), Stage III (3), Stage IV (6) and Unknown (1). Fourteen patients had good response to chemotherapy (>90% necrosis) and 11 patients had poor response to chemotherapy (<90% necrosis). A tissue microarray was prepared using a manual tissue array instrument. A minimum of three cylindrical core biopsies (0.6mm) were taken from viable tumor (biopsy and/or resected specimens) and arrayed in a receipient paraffin tissue microarray block. Immunohistochemistry was performed using p53, p63 and p73 antibodies with standard protocols. Results: A semi-quantitative scoring system was used for all antibodies as follows: negative (<5% nuclear staining), positive (>5% nuclear staining). P53 was expressed in 10/35 (28.5%) and was not expressed by 25/35 (71.5%). P63 was expressed in 13/35 (37%) and was not expressed by 22/35 (63%), and p73 was expressed by 3/34 (9%) and was not expressed by 31/34 (91%). Conclusions: There is a significant relationship between clinical stage and overall survival (p<0.0001). The expression of p53, p63 and p73 did not correlate with clinical stage, overall survival and chemotherapy response. Even though there was no significant association between p53 and p63 expression (p=1.00), about one third of ostesarcomas appear to express these markers. Further studies with a larger group of patients are needed to elucidate the significance of p53 family of genes in osteosarcoma. No significant financial relationships to disclose.
Controversies in the Treatment of Elderly Patients With Newly Diagnosed Glioblastoma
Authors: Matthias Holdhoff, Marc C Chamberlain
Journal: Journal of the National Comprehensive Cancer Network (2013)

Approximately half of all patients with glioblastoma are older than 65 years and nearly one-quarter are older than 70 years, with a rising incidence of this disease in the elderly population. The life expectancy of elderly patients with glioblastoma is significantly shorter than in younger patients. Potential explanations for this abbreviated survival include differences in tumor biology, reduced use of therapies, enhanced toxicity of treatment, or diminished efficacy of available therapies with increasing age. The current standard treatment of newly diagnosed, protocol-eligible, nonelderly patients with glioblastoma is based on the randomized prospective EORTC/NCIC study that included patients aged 18 to 70 years with a performance status of ECOG 0 to 2. Limited single-institution retrospective series suggest that clinically fit elderly patients may benefit from a similar treatment regimen. However, no randomized trial has been performed in the elderly population using this regimen. Available prospective randomized clinical trials in the elderly population with glioblastoma have shown that radiotherapy is superior to supportive care only, that single-modality hypofractionated radiotherapy (reduced dose and shorter treatment schedule) is an alternative to single-modality standard fractionated radiotherapy, and that single-agent temozolomide is equivalent to radiotherapy alone. This article summarizes published data of current patterns of care in elderly patients and reviews published evidence as it pertains to the benefit of different treatment modalities in elderly patients with glioblastoma. Notwithstanding the previously mentioned randomized trials, the optimal treatment of elderly patients with glioblastoma remains controversial.
Carcinoma of the Thyroid Gland
Authors: A. H. Letton
Journal: JAMA (1961)

<h3>To the Editor:—</h3> The editorial comments which appeared inThe Journal,<b>174</b>:986 (Oct. 22) 1960, seen to approve the treatment of thyroid adenoma with thyroid extract. We cannot let this opportunity go by without condemning the treatment as a routine affair. Certainly, if the nodular area of the thyroid is due to hyperplasia and involution of the gland, then thyroid extract will suffice. However, if this nodular area is due to a neoplasm, either benign or malignant, then thyroid extract is insufficient. It is quite true that these neoplasms will reduce in size, but the malignant neoplasms, while it reduces, is not cured and will later renew its activity and, unless properly treated, will cause the death of the patient. It is unwise, therefore, for us to approve the treatment of nodular areas of the thyroid with thyroid extract. Certainly, before one applies thyroid extract on an area of
A phase II study of single-agent nab-paclitaxel as second-line therapy in patients with metastatic urothelial carcinoma.
Authors: S. S. Sridhar, C. M. Canil, S. D. Mukherjee, E. Winquist, C. Elser, A. Eisen, A. Chung, Y. Ko
Journal: Journal of Clinical Oncology (2010)

TPS231 Background: There is currently no standard second-line chemotherapy for metastatic urothelial cancer (UC) previously treated with a platinum-based regimen, representing a key unmet clinical need. In this setting, paclitaxel and docetaxel are commonly used despite overal response rates (ORR) of less than 20%. In this phase II multicenter study, we evaluated the efficacy and tolerability of nab-paclitaxel (Abraxane [ABI-007]), an albumin-bound nanoparticle formulation of paclitaxel as a single agent second-line chemotherapy for metastatic UC. Methods: Patients with unresectable locally advanced or metastatic urothelial cancer of the bladder, ureter or renal pelvis, who progressed on or after first-line platinum based chemotherapy were enrolled on this open-label, two-stage, multicenter clinical trial. Key eligibility criteria included measureable disease with predominantly transitional cell histology, ECOG performance status 0-2, and adequate organ function. Patients treated with prior taxanes for metastatic disease, pre-existing neuropathy ≥ grade 1 or uncontrolled brain metastases or other illnesses were excluded. All patients received a starting dose of 260mg/m2 IV every 3 weeks. Clinical evaluation, CBC and biochemistry were performed at baseline and before each cycle with CT scans of the chest, abdomen, and pelvis repeated every 2 cycles. The primary endpoint was RECIST- defined objective response. Responding patients had confirmatory CT scans performed at least one month following documentation of a response. Secondary endpoints were duration of response, disease control rate (stable disease ≥ 16 weeks, PR or CR), PFS, overall survival, safety and tolerability. All patients were treated until progressive disease or unacceptable toxicity. Abraxane will be considered active in this patient population if a response rate of ≥ 20% is observed. Using a two-stage design, a planned 21 patients will be accrued to stage 1. If more than 1 response is seen, an additional 20 patients will be accrued. Assuming a drop out rate of 10-15%, the planned total accrual is 48 patients. Currently stage 1 criteria have been met and there are 44 patients on study with accrual ongoing. No significant financial relationships to disclose.
Resin Hemoperfusion: A New Treatment for Acute Drug Intoxication
Authors: Jerry L. Rosenbaum, Mark S. Kramer, Rasib Raja, Christopher Boreyko
Journal: New England Journal of Medicine (1971)

A resin-column hemoperfusion system was used to treat four patients with profound, life-threatening drug intoxication. The column contained 650 g of pyrogen-free resin, Amberlite XAD-2. The resin is uncharged and has a cross-linked, polystyrene macroreticular structure with particular surface attraction for high-molecular-weight, lipid-soluble molecules. Blood was pumped through the column at a flow rate of 300 ml per minute for three hours. Two patients had secobarbital, one a mixture of glutethimide-butabarbital-ethchlorvynol, and one amobarbital intoxication. In all patients the column clearances of these drugs were markedly superior to known clearances with hemodialysis. A transient, modest fall in blood platelet concentration followed hemoperfusion. No serious clinical toxic effects were noted. The resin-column hemoperfusion system was technically simpler, consistently more effective and clinically superior to hemodialysis.
Clinical Use of Rabbit Antihuman Lymphocyte Globulin in Cadaver-Kidney Transplantation
Authors: John A. Mannick, Robert C. Davis, Sidney R. Cooperband, Arthur H. Glasgow, Lester F. Williams, John T. Harrington, Tito Cavallo, Gunther W. Schmitt, Beldon A. Idelson, Carl A. Olsson, Donald C. Nabseth
Journal: New England Journal of Medicine (1971)

Abstract Twenty-six consecutive recipients of cadaver-kidney transplants were treated with rabbit antihuman lymphocyte globulin (ALG) in addition to conventional immunosuppressive therapy. Each of the first 10 of these recipients has been followed for more than 12 months. The one-year transplant survival in this group was 90 per cent. Rabbit ALG administration was well tolerated. Most patients had no symptoms related to ALG injections. There were four acute transplant rejection episodes in the first 10 patients and four episodes in 16 subsequent patients followed for more than four months. All acute rejection episodes occurred six weeks or more after transplantation, and all were easily and promptly reversed by a temporary increase in the dose of steroid therapy. Immediate, hyperacute rejection by preformed antibodies was the only cause of kidney transplant loss in the entire series.
Reply to letter to the editor of<i>Gut</i>by Dickson and Cox
Authors: Jacqueline M Lankelma, Tim J Schuijt, W Joost Wiersinga
Journal: Gut (2016)

Dear editor,

We are thankful for the letter of Drs Dickson and Cox in response to our paper on the effect of the intestinal microbiota on host responses during pneumococcal pneumonia.1 We do agree that we cannot rule out that the antibiotics we used in our experiments could have influenced the microbiota in the airways and we do underwrite the importance of studying local host–microbe interactions within the respiratory tract during pneumonia. However, some points need to be addressed.

The relative importance of the microbiota of the lower airways, the area where alveolar macrophages reside, is a matter of debate. …
Accelerated Progression of Atherosclerosis in Coronary Vessels with Minimal Lesions That Are Bypassed
Authors: W. Linda Cashin, Miguel E. Sanmarco, Sharon A. Nessim, David H. Blankenhorn
Journal: New England Journal of Medicine (1984)

Accelerated progression of atherosclerosis is known to occur in surgically bypassed coronary arteries in which the preoperative stenosis was greater than 50 per cent. To assess the effect of coronary bypass on vessels with lesser degrees of stenosis, we studied 85 men who had undergone coronary bypass surgery. In this group we identified bypass grafts placed in 37 arteries with minimal atherosclerosis, which was defined as less than 50 per cent stenosis of the vessel diameter. In the same 85 men there were 93 coronary vessels with minimal atherosclerosis for which a bypass graft had not been placed. Progression of atherosclerosis, defined as further loss of at least 25 per cent of the lumen, during an average follow-up period of 37 months was more than 10 times as frequent (38 per cent vs. 3 per cent) in bypassed arteries with minimal atherosclerosis as in comparable arteries that were not bypassed. These findings support the view that minimally diseased coronary arteries should not be bypassed. (N Engl J Med 1984; 311:824–8.)
Posttranscriptional m 6 A Editing of HIV-1 mRNAs Enhances Viral Gene Expression
Authors: Edward M. Kennedy, Hal P. Bogerd, Anand V.R. Kornepati, Dong Kang, Delta Ghoshal, Joy B. Marshall, Brigid C. Poling, Kevin Tsai, Nandan S. Gokhale, Stacy M. Horner, Bryan R. Cullen
Journal: Cell Host & Microbe (2016)
Staphylococcal IgE Antibodies, Hyperimmunoglobulinemia E and<i>Staphylococcus aureus</i>Infections
Authors: K. Schopfer, K. Baerlocher, P. Price, U. Krech, P. G. Quie, S. D. Douglas
Journal: New England Journal of Medicine (1979)

IN 1966 Davis et al.1 described two girls with chronic eczema, recurrent staphylococcal infections and an abnormal inflammatory response with the formation of "cold" staphylococcal abscesses (Job's syndrome). Buckley et al.2 observed hyperimmunoglobulinemia E in two boys with severe recurrent skin and lung infections, and Clark et al.3 demonstrated depressed chemotaxis of polymorphonuclear leukocytes and hyperimmunoglobulinemia E in a girl with similar clinical manifestations. Subsequently, Hill et al.4 reported hyperimmunoglobulinemia E and defective chemotaxis of polymorphonuclear leukocytes in the two original cases of Job's syndrome. Several other patients with related disorders have recently been described.4 5 6 7 8 9 10 11 12 13 Cell-mediated immunity was abnormal in . . .
Case 16-1993
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Norman D. Rosenblum, Robert B. Colvin
Journal: New England Journal of Medicine (1993)

Presentation of CaseA 13-year-old girl was admitted to the hospital because of fever, cough, and hematuria.As a young child she had had recurrent pneumonia, with one episode of gross hematuria ascribed to urinary tract infection. At the age of nine years, shortly after arriving in the United States from the Dominican Republic, she was evaluated at this hospital. An x-ray film of the chest showed hazy linear and nodular consolidations in both lungs that were principally central in location and paratracheal and hilar lymphadenopathy. The urine, urea nitrogen, total protein, albumin, and globulin were normal. A tuberculin skin . . .
Prevention of Corticosteroid Osteoporosis -- A Comparison of Calcium, Calcitriol, and Calcitonin
Authors: Philip Sambrook, Joan Birmingham, Paul Kelly, Susan Kempler, Tuan Nguyen, Nicholas Pocock, John Eisman
Journal: New England Journal of Medicine (1993)

Prolonged corticosteroid therapy increases the risk of osteoporosis and fracture. We studied whether corticosteroid-induced osteoporosis could be prevented by treatment with calcium, calcitriol (1,25-dihydroxyvitamin D3), and calcitonin.
PTH-259 Sacral nerve stimulation for faecal incontinence – outcomes from a tertiary referral centre
Authors: M Quinn, S Hunt, H Koh, J Anderson, G MacKay
Journal: Gut (2015)

<h3>Introduction</h3> Neuromodulation therapies have gained recognition as effective treatment modalities for faecal incontinence. Sacral Nerve Stimulation (SNS) is the most widely used of these and has favourable short and medium term outcomes. No standard protocols exist for the follow up of these patients. This study aimed to audit our own practice and outcome`s in a tertiary referral centre. <h3>Method</h3> Retrospective analysis of prospectively collected data for all patients referred for SNS between January 2009–2013. Data collected included: demographics, test data, implant data, complications, and number of follow-up appointments (out-patient follow up was on a patient request only). <h3>Results</h3> 122 patients were referred for consideration of SNS (median age of 57 years (range 32–82)), of which 112 (91.8%) were female. 75 out of 122 patients underwent a test procedure. Of those that did not have a test, the reasons in 19 were unknown, 12 were no longer required after optimising other treatment modalities, 9 are still awaiting a test procedure, 3 patients were treated for prolapse and did not require SNS, 2 declined, and 2 failed to attend. Of the 75 patients who underwent a test procedure, 58 patients had a successful test, 17 failed the test. Of those patient who had a successful test 48 patients have been implanted to date. 1 patient declined implantation after a successful test and 9 patients are awaiting implantation. 47 of 48 patients (88%) have had a good result from implantation and 1 patient experienced treatment failure. The overall complication rate following implantation was 22.9% (11/48). 5 patients had wound infections, with 3 of these patients requiring device removal. 2 of these patients have been re-implanted successfully and 1 awaits re-implantation. 2 patients had post-operative pain, two required lead replacement, 1 had a superficial wound dehiscence, and 1 had a postoperative haematoma not requiring intervention. Median number of follow appointments was 1 (range 0–8). <h3>Conclusion</h3> Our success rates for SNS compare favourably with the published literature. Requests for out-patient follow up are low, suggesting patient-led follow up is feasible. <h3>Disclosure of interest</h3> None Declared.
Comparison of reduced-dose bortezomib plus thalidomide plus dexamethasone (vTD) to bortezomib plus dexamethasone (VD) as induction treatment prior to ASCT in de novo multiple myeloma (MM): Results of IFM2007-02 study.
Authors: P. Moreau, T. Facon, M. Attal, C. Doyen, C. Hulin, G. Marit, L. Garderet, M. Tiab, H. Avet-Loiseau, J. Harousseau
Journal: Journal of Clinical Oncology (2010)

8014 Background: The IFM has shown that induction treatment prior to ASCT with VD is superior to VAD. The Italian group has presented impressive results regarding response rates with VTD (Cavo ASH 2009). In both studies, peripheral neuropathy (PN) was the most frequent adverse event (9% Grade 3). Methods: We conducted a randomized trial comparing four 21-day cycles of induction with VD (V 1.3 mg/m2/d on days 1,4,8,11 plus D 40 mg/d on days 1-4 and 8-11) or vTD (v 1 mg/m2/d on days 1,4,8,11 plus thalidomide 100 mg/d d1-21 plus dexamethasone same dosing as for VD). The primary objective was the CR rate after induction treatment. Secondary objectives were achievement ≥ VGPR and ≥ PR, and toxicity including incidence of PN. Results: From 03/2008 to 01/2009, 205 patients with de novo MM (< 66 years) were randomized. The two groups were well balanced as regards initial prognostic parameters. As of January 10, 2010, according to investigators'assessment, on an intent-to-treat basis, the post-induction efficacy results are the following (VD vs vTD): CR rate 12% vs 14% (p= 0.68), CR + nCR 22% vs 31% (p = 0.15), ≥ VGPR 36% vs 50 % (p=0.047), ≥ PR 81%vs 90% (p= 0.096), stable disease 12% vs 5%, progression/failure 7% vs 4%. The post-ASCT results are the following (VD vs vTD): CR + nCR rate 47 vs 60% (p = 0.50), ≥ VGPR 54 vs 66% (p = 0.044), ≥ PR 84 vs 92% (p = 0.33). There was no difference regarding toxicity between the 2 arms of the study, except for peripheral neuropathy (PN). Grade > 2 PN occurred in 28% of the cases in the VD arm vs 16% in vTD (p = 0.04), and treatment was interrupted due to PN in 4 cases of the VD arm vs 0 (p = .12). Conclusions: Four cycles of induction treatment with vTD are more effective than 4 cycles of VD, since CR+VGPR rate is superior both before and after ASCT. Despite the addition of thalidomide, the incidence of PN was markedly reduced in the vTD arm. vTD as induction prior to ASCT is a new alternative with a very good efficacy/toxicity ratio. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene, Janssen-Ortho
Australian court orders Nurofen’s specific pain range off the shelves
Authors: Amy Coopes
Journal: BMJ (2015)

<h3>Abstract</h3> The brain and behavior are under energetic constraints, limited by mitochondrial energy production capacity. However, the mitochondria-behavior relationship has not been systematically studied on a brain-wide scale. Here we examine the association between multiple features of mitochondrial respiratory chain capacity and stress-related behaviors in mice with diverse behavioral phenotypes. Miniaturized assays of mitochondrial respiratory chain enzyme activities and mitochondrial DNA (mtDNA) content were deployed on 571 samples across 17 brain regions, defining specific patterns of mito-behavior associations that vary across brain regions and behaviors. Furthermore, multi-slice network analysis applied to our brain-wide mitochondrial dataset identified three large-scale networks of brain regions with shared mitochondrial signatures. A major network composed of cortico-striatal regions exhibited the strongest mitochondria-behavior correlations, suggesting that this mito-based network is functionally significant. Mito-based networks also overlap with regional gene expression and structural connectivity, thereby providing convergent multimodal evidence of mitochondrial respiratory chain functional organization anchored in gene, brain and behavior.