tbuckley/cabot-search huggingface dataset:
Screening of newborns for hearing impairment: Statement from the US Preventive Services Task Force
Authors: Steven H Woolf
Journal: BMJ (2003)

This article originally appeared in BMJ USA 

The US Preventive Services Task Force (www.ahrq.gov/clinic/uspstfab.htm) recently completed a review of the evidence for routine screening of newborns for hearing impairment,1 and issued a policy statement based on that review in October 2001 (www.ahrq.gov/clinic/3rduspstf/newhearrr.htm). The task force concluded that there is insufficient evidence …
Encyclopedia of Medical Sources.
Authors: Karl A. Baer
Journal: Annals of Internal Medicine (1949)

To read a note in the Amiable Autocrat you must turn back and see what chapter you are reading and then go to the back of the book and find the notes on that chapter.Maddening!Miss Tilton has obviously taken Cushing's Life of Osler as her model.Dr. Cushing knew Sir William, and his plan in giving a painstaking account of his life, and including much correspondence, was simply to compile the "memoires pour servir".Everyone knows how the Cushing touch has enhanced the glow that is inseparable from all that is Oslerian.Miss Tilton's touch unfortunately is a kiss of death.The minute I finished the book I went to DeWolfe Howe's Dr. Holmes of the Breakfast Table, and at once fell under the spell, both of Mr.
A case of obstructive sleep apne syndrome with bilateral vocal cord paralysis
Authors: Önder Öztürk, Ulughbik Khayri, Yücel Kurt, Mehmet Has, Ibrahim Metin Çiris, Mustafa Tüz, Ahmet Akkaya, Meltem Çetin
Journal: European Respiratory Journal (2011)

Aim: Bilateral vocal cord paralysis (BVCP) often caused by trauma, is a rare, but life-threathening condition in patients. Although the most comon symptom seen in BVCP is respiratory distress, hoarseness and the symptoms of sleep apnea are rare. Here we present an interesting and educative case of BVCP, caused obstructive sleep apnea syndrome (OSAS).

Results: A 46- year-old male patient who had a history of snoring, apnea, excessive daytime sleepiness (EDS), admitted to our outpatient clinic with complaints of dypsnea and hoarseness. He had these symptoms for a year, but progressed during the last two months. He had also a history of diabetus mellitus and COPD for a year, smoked 25 pack-years. Full-night polysomnography revealed that his apnea–hypopnea index was 67.7/h and minimal oxygen saturation level was 75%, diagnosed as severe OSAS. His pulmonary function test demonstrated variable extrathoracic airway obstruction. The ear-nose-throat consultation revealed that vocal cords were bilaterally paralytic at the median border. His chest film, Thorax CT and neck CT were normal. The histopathologic examination of biopsies from subglottic region and left vocal cord was reported as edema, hyperemia and chronic inflamation. The paient did not benefit from CPAP titration and the tracheostomy was opened due to the progression of respiratory distress. Later, right arytenoidectomy operation was done. The patient indicated that snoring,apnea,EDS,hoarseness and dypsnea were improved after the operation.

Conclusion: BVCP rarely causes OSAS. Thus, a multidisciplinary approach in the diagnosis and treatment of these cases should be done urgently to have a better survival.
Islamic State creates jihadi health service
Authors: D. Gardham
Journal: BMJ (2015)

Feature, doi:10.1136/bmj.h3479

Many doctors in war zones seek to remain independent, but the situation in Syria and Iraq is forcing them to take sides, Duncan Gardham reports

Since the militant group Islamic State took over large tracts of Syria and Iraq about a year ago local doctors have been forced to pledge allegiance or flee, aid workers have retreated, and the group is attempting to train or recruit a health service workforce made up of medical jihadists from around the world.

On 24 March Omar Hussain, a British man from High Wycombe, tweeted: “O Muslim doctors, stop treating the Kuffaar [infidels] & come Sham [Syria] & help the injured mujaahideen [holy fighters]! Imagine the reward of helping a bro go back 2 batle!”

The group of medical students who left Sudan to work for Islamic State in March drew international attention to what seems to have been a steady flow of Western educated Muslim doctors drawn to support the militant group.

One, who describes himself as a “muhajir [emigrant] medical doctor” was tweeting under the alias Abu Layla al-Shami and featured a photograph with a stethoscope and handgun. He wrote in January that he would be “posting medical advice to the mujahideen, including first aid tips” along with “health updates from the Islamic state” and the inevitable “analysis & advice regarding issues of jihad & aqeedah [belief].”

However, it was his tweet on 3 January that gained most attention from supporters of Islamic State, who re-tweeted it as proof that the group was able to run itself as a fully fledged state.

“First glimpses …
A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis
Authors: Sandra S. Strautnieks, Laura N. Bull, Alexander S. Knisely, Samuel A. Kocoshis, Niklas Dahl, Henrik Arnell, Etienne Sokal, Karine Dahan, Sarah Childs, Victor Ling, M. Stuart Tanner, Amir F. Kagalwalla, Antal Németh, Joanna Pawlowska, Alastair Baker, Giorgina Mieli-Vergani, Nelson B. Freimer, R. Mark Gardiner, Richard J. Thompson
Journal: Nature Genetics (1998)
UK law on consent: broad consent or authorisation for research?
Authors: M. A. Crouch
Journal: BMJ (2015)

I read Edozien’s editorial1 and the rapid responses with interest, in particular Ilangaratne’s quote “the basic principles—and the resulting duty of care—defined in Montgomery are likely to be applied to all aspects of the provision of advice given to patients by medical and nursing staff.”2

This concern extends beyond direct patient care.

At the recent European Society …
CVX-045: A novel thrombospondin-1 (TSP-1) mimetic CovX-Body that potentiates chemotherapy in preclinical colon cancer models
Authors: N. J. Levin, T. A. Leedom, V. R. Doppalapudi, L. Li, J. Lai, K. Johnson, J. D. Rizzo, R. W. Lappe, C. W. Bradshaw, G. Woodnutt
Journal: Journal of Clinical Oncology (2007)

14011 Background: TSP-1 reduces angiogenesis and tumor growth in vivo, and induces endothelial cell apoptosis in vitro. CVX-045 was produced by fusing a peptide derived from TSP-1, known to have anti-vascular activity, to a proprietary monoclonal antibody. CVX-045 possesses the potency and specificity of the TSP-1 mimetic peptide, along with the advantageous PK of an antibody. Methods: Anti-tumor activity of CVX-045 was evaluated in A549, A431, and HT-29 human adenocarcinoma xenograft models. Cells were implanted SC in female nu/nu mice, and tumors were staged to 300–400 mm 3 prior to initiation of weekly treatments: CVX-045 IV 10–30 mg/kg; 5-FU or CPT-11 IP 100 mg/kg. Results: CVX-045 (10 mg/kg) significantly reduced A549 and A431 tumor growth 73% (day 49) and 51% (day 22), respectively, but was not effective in the HT-29 xenograft (10 or 30 mg/kg). CVX-045 demonstrated significant anti-vascular activity, reducing tumor microvessel density 51% in A549, 49% in A431, and 36% in HT-29 xenografts. CVX-045 (30 mg/kg) plus 5- FU significantly decreased HT-29 tumor growth 70% and microvessel density 61.2% on day 30 (both P&lt;0.01), effects significantly greater than either agent alone. Co-treatment with CVX-045 (30 mg/kg) plus CPT-11 decreased HT-29 tumor volume 91% on day 28 (P&lt;0.001), also significantly greater than either agent alone. As a surrogate measurement of survival, mice remained on treatment until tumors reached 2000 mm 3 . CPT-11 alone extended the time to reach tumor load from day 28 to day 39, while the combination of CPT-11 with CVX-045 extended this further to day 60. Conclusions: CVX-045 exhibits significant anti-angiogenic activity in several tumor models and enhances anti-tumor activity in combination with standard chemotherapies in a highly aggressive colon tumor model. No significant financial relationships to disclose.
R-Dhaox, high dose chemotherapy (HDC) and rituximab maintenance as salvage treatment in relapsed/refractory (R/R) follicular (F) and mantle cells (MC) lymphomas (NHL)
Authors: M. Rupolo, M. Michieli, M. Spina, P. Bulian, M. Degan, M. Mazzucato, L. Abbruzzese, U. Tirelli
Journal: Journal of Clinical Oncology (2007)

8036 Second line regimens in NHL are mainly based on cisplatin (DDP). The substitution of DDP with oxaliplatin in DHAP- like regimens may result in lower toxicity and higher activity. In R/R CD20+ follicular (F) and mantle cell (MC) NHL the sinergistic activity of rituximab with chemotherapy and the maintenance immunotherapy obtain and prolong clinical and molecular remission. We assessed the tolerability and the activity in terms of clinical and molecular remission of R-Dhaox (rituximab 375 mg/m 2 i.v., day 1, dexametazone 40 mg i.v. days 1–4, Oxaliplatin 130 mg/m 2 , day 2 and cytarabine 2,000 mg/m 2 i.v. twice a day day 3) regimen for 4 courses in phase II study. The pts in response underwent to HDC with the scheme BEAM-R and further were treated with maintenance therapy with rituximab 375 mg/m 2 i.v. 75+ from ABMT. After three monthly doses, pts were treated with further five every 4 months (for a total of two years). From June 2002 to September 2006, 31 pts were enrolled. 19 were male and 12 female. Median age was 51 (30–66). 21 (68%) pts were follicular G1-G2, 9 (29%) mantle cells and 1 a transformed follicular. The stage was III for 8 (26%) and IV for 23 (74%) pts. 22 (70%) pts were previous treated with rituximab and 30 (96%) with adryamicin based schedules. CD34+ harvest was after 4 th cycle with a median collection of 5,5 ×10 6 /Kg (2,1–20); 2 were positive for BCL-2 and 1 for BCL-1. Overall clinical response before ABMT was 94% for F and 100% for MC. 26 pts underwent ABMT with the schedule BEAM-R. At relapse 54% (12/22) of F were BCL-2 positive and 66% (6/9) of MC for BCL-1. Before ABMT 4/17 pts were BCL-2 positive and 1/9 for BCL-1. Among F, 3 pts relapsed after ABMT: 2 with reexpression of BCL-2 and 1 without. No relapse among MC, all negative for BCL-1 after ABMT. No pt showed severe or fatal infections during maintenance immunotherapy. Three- year projected free survival was 100% for MC and 68% for F NHL. These preliminary data suggested that R-DHAOX, HDC and rituximab maintenance is a novel approach highly effective for R/R F and MC NHL. No significant financial relationships to disclose.
Nontuberculous mycobacteria and aspergillus coexistence in pulmonary disease – Retrospective analysis
Authors: Hans Dabó, Vanessa Santos, Adelina Amorim, Angelica Ramos, Teresa Carvalho, Manuela Ribeiro, Anabela Marinho
Journal: European Respiratory Journal (2014)

Introduction:  Nontuberculous mycobacteria (NTM) and Aspergillus are ubiquitous in nature. Lung disease associated to coexistence of both has been increasingly reported in the literature.   Objective:  Characterize the incidence of related lung disease to Aspergillus in patients (pts) with NTM isolated in pulmonary specimens.   Methods:  Retrospective analysis of pts followed in Pulmonology department (Jan/08 to Dec/12) with the isolation of NTM in at least one respiratory specimen, and evaluation of the microbiological and serological Aspergillus profile.   Results:  202 pts had NTM isolated from respiratory specimens and treatment was realized in 18% (89% with ATS/IDSA criteria). Pulmonary comorbidities: COPD in 36% pts, bronchiectasis 31% and sequelae of tuberculosis 20%. Aspergillus was isolated in 12% (25) pts (54 isolates): 39  A.fumigatus  (AF), 11  A.niger , 3  A.Flavus  and 1  A.terreus . Immunology AF (available in about 1/3 pts): median IgG 26.10 (2.06 to 200), IgE positive in 6% (13) pts (0.14 to 10.70), precipitins positive in 5% (10) pts and median total IgE 42 (   Conclusion:  There was significant isolation of Aspergillus, particularly AF, but Aspergillus related lung disease was rare. The coexistence of Aspergillus and NTM related lung disease may exist, and clinicians should be aware.
The antitumor effect of tanshinone IIA on anti-proliferation and decreasing VEGF/VEGFR2 expression on the human non-small cell lung cancer A549 cell line
Authors: Jun Xie, Jiahui Liu, Heng Liu, Shihui Liang, Meigui Lin, Yueyu Gu, Taoli Liu, Dongmei Wang, Hui Ge, Sui-lin Mo
Journal: Acta Pharmaceutica Sinica B (2015)

The effects of tanshinone IIA on the proliferation of the human non-small cell lung cancer cell line A549 and its possible mechanism on the VEGF/VEGFR signal pathway were investigated. The exploration of the interaction between tanshinone IIA and its target proteins provides a feasible platform for studying the anticancer mechanism of active components of herbs. The CCK-8 assay was used to evaluate the proliferative activity of A549 cells treated with tanshinone IIA (2.5−80 μmol/L) for 24, 48 and 72 h, respectively. Flow cytometry was used for the detection of cell apoptosis and cell cycle perturbation. VEGF and VEGFR2 expression were studied by Western blotting. The binding mode of tanshinone IIA within the crystal structure of the VEGFR2 protein was evaluated with molecular docking analysis by use of the CDOCKER algorithm in Discovery Studio 2.1. The CCK-8 results showed that tanshinone IIA can significantly inhibit A549 cell proliferation in a dose- and time-dependent manner. Flow cytometry results showed that the apoptosis rate of tested group was higher than the vehicle control, and tanshinone IIA-treated cells accumulated at the S phase, which was higher than the vehicle control. Furthermore, the expression of VEGF and VEGFR2 was decreased in Western blot. Finally, molecular docking analysis revealed that tanshinone IIA could be stably docked into the kinase domain of VEGFR2 protein with its unique modes to form H-bonds with Cys917 and π–π stacking interactions with Val848. In conclusion, tanshinone IIA may suppress A549 proliferation, induce apoptosis and cell cycle arrest at the S phase. This drug may suppress angiogenesis by targeting the protein kinase domains of VEGF/VEGFR2.
Efficacy and safety of briakinumab vs. etanercept and placebo in patients with moderate to severe chronic plaque psoriasis
Authors: A.B. Gottlieb, C. Leonardi, F. Kerdel, S. Mehlis, M. Olds, D.A. Williams
Journal: British Journal of Dermatology (2011)

The anti-interleukin-12/23p40 monoclonal antibody briakinumab has been shown in a phase II study to be effective psoriasis treatment.The aim of the current study was to assess the efficacy, safety and tolerability of briakinumab compared with etanercept and placebo in patients with moderate to severe chronic plaque psoriasis.In this phase III, 12-week study (M10-114, NCT00691964), 347 patients were randomized in a 2 : 2 : 1 ratio to receive 200 mg briakinumab at weeks 0 and 4 followed by 100 mg briakinumab at week 8 (n = 138); 50 mg of etanercept twice weekly 3-4 days apart at weeks 0-11 (n = 141); or placebo injections matching active treatment (n = 68). The co-primary efficacy endpoints were the proportion of patients achieving a Physician's Global Assessment (PGA) of 0/1 at week 12, and the proportion of patients achieving a Psoriasis Area and Severity Index (PASI) 75 response at week 12.Of the briakinumab-treated patients, 71·0% achieved a PGA of 0/1 at week 12 as compared with 39·7% of etanercept-treated patients and 2·9% of placebo-treated patients, (P < 0·001, for both comparisons). Of the briakinumab-treated patients 81·9% achieved a PASI 75 response at week 12 as compared with 56·0% of etanercept-treated and 7·4% of placebo-treated patients (P < 0·001, for both comparisons). Serious adverse event rates were reported in four (2·9%) patients receiving briakinumab, one (0·7%) patient receiving etanercept and one (1·5%) placebo-treated patient.In patients with moderate to severe psoriasis, briakinumab had superior efficacy to both placebo and etanercept at 12 weeks as administered in this study.
Postoperative pulmonary complications
Authors: S. Sabanathan, R. Shah, J. Richardson
Journal: BMJ (1996)

paper focused on discrimination in its widest sense and the hypothesis that this might explain differences in outcome.Thus we looked at two groups that had different risks of discrimination: people of Caribbean origin and white British people.Evidence suggests that Irish people are discriminated against in the United Kingdom,3 so we excluded them.We were interested in culture only as it might affect discrimination, which is consistent with our statement that we aimed to demarcate a white group that was "as culturally homogeneous...as possible to decrease difficulties in interpreting results."Azuonye highlights the problem of how to use data on the minority of patients of Caribbean origin who are not ofAfrican ancestry.Because we did not know what level of discrimination they would suffer and no systematic evidence exists, we set our criteria to include such patients.We were unable to assess this question as our sample contained only people ofAfrican ancestry.The paper in the Psychiatric Bulletin to which Azuonye refers relates to culture, not discrimina- tion.4It was aimed at helping researchers to choose the most appropriate variables when comparing ethnic groups.We believe that by using populations at differing levels of risk we chose the most appropriate variables.
Demographic and microbial characteristics of childhood tuberculosis in Istanbul: Evaluation of 1541 cases
Authors: Erkan Cakir, Ela Erdem, Nagihan Ozlu, Engin Seber, Serap Gencer, Zeki Kilicaslan
Journal: European Respiratory Journal (2013)

Introduction:  Although tuberculosis (TB) is frequently seen in Turkey, there are limited and generally one center studies on childhood TB.  Aim:  To describe clinical and laboratory findings of children with TB in Istanbul, Turkey, including the drug resistances.  Methods:  The data of children who were diagnosed with TB between 2006 and 2010 were reviewed.  Results:  The study included 1541 cases. Forty-four percent of the patients were male with a mean age of 8.86±4.19. Fifty-five percent of the patients had pulmonary TB, 39% had extrapulmonary TB and 6% had both pulmonary and extrapulmonary TB. The most common extrapulmonary involvement sites were the pleura, lymph nodes and central nervous system. Forty-one percent of the patients were evaluated microbiologically and 35% of them were positive. For the total study group, 14% of them were positive. A drug susceptibility test was performed on 108 patients. Drug resistance to at least one drug was detected in 16%, to isoniazid in 15%, streptomycin in 12%, rifampicin in 9%, ethambutol in 7% and multidrug resistance in 8% of patients. All of the patients tolerated the treatment well and there was no case with treatment failure.  Conclusion:  This is the first multicenter study about childhood TB in Turkey both for demographic features and for drug resistance. In Turkey, the rate of microbiological diagnosis is low, similar to rates worldwide. More microbiological studies and drug resistance tests should be done and annual changes should be followed with multicenter studies.
Pharmacokinetic, pharmacodynamic, and phase II study of gefitinib in patients with malignant pleural effusion from non-small cell lung cancer.
Authors: A. Kubo, Y. Koh, T. Hori, S. Isa, J. Fukuoka, T. Kawaguchi, A. Masahiko, I. Okamoto, M. Kitaichi, M. Takada
Journal: Journal of Clinical Oncology (2010)

3096 Background: Pharmacokinetics and pharmacodynamics of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in NSCLC with malignant pleural effusion (MPE) are unknown. We conducted an exploratory phase II study of gefitinib in patients (pts) with MPE from non-small cell lung cancer (NSCLC), with pharmacokinetic and pharmacodynamic assessments. Methods: Single agent gefitinib 250 mg was given PO daily with concurrent tube drainage and sampling of MPE from NSCLC. Pleural effusion and blood samples were collected at 0, 3, 8, 24, and 72 hrs on gefitinib therapy. Tumor cell-enriched cell blocks were prepared from serial MPE samples and analyzed for EGFR signaling pathway. MPE and serum samples were measured for gefitinib concentration, transforming growth factor-alpha (TGFα), and amphiregulin (AR). Tumor response was assessed by RECIST. Results: From Sep 2006 to Aug 2008, twenty pts were enrolled onto the study. All pts were evaluable for efficacy, toxicity, and biologic outcomes. Patient characteristics include: female, 60%; adenocarcinoma, 100%; and EGFR mutation positive, 65%. Median survival and median progression-free survival were 10.0 months and 5.0 months, respectively. One, nine, and two pts achieved CR, PR, and SD. With single gefitinib dosing, geometric mean Cmax in MPE was 60.3 ng/ml reached at 18.9 ± 13.8 h (mean ± S.D.) following Cmax in plasma of 237.4 ng/ml reached at 6.0 ± 4.8 h. Geometric mean gefitinib concentration in MPE increased from 55.7 ng/ml 24 h after initial dosing to 133.0 ng/ml 24 h after 3-day dosing, suggesting accumulation of gefitinib in MPE. While levels of TGFα in MPE were comparable to those in serum, AR levels in MPE were × 5 higher than in serum and they decreased at 72 h on therapy. In several responders, apoptosis of tumor cells in MPE became detectable as early as 3 h on therapy. Further intensive pharmacodynamics is to be presented. Conclusions: Gefitinib showed clinical efficacy and acceptable toxicity in pts with MPE from NSCLC. MPE seems to be a suitable condition for intensive pharmacokinetic and pharmacodynamic assessments of molecular targeting agents which have less hematologic toxicities. No significant financial relationships to disclose.
Aneuploidy and chromosomal instability caused by CENP-E heterozygosity contribute to tumorigenicity.
Authors: Beth A. Weaver, Alain D. Silk, Frances R. Putkey, Don W. Cleveland
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5641 

Aneuploidy and chromosomal instability are frequent characteristics of human tumors. Based on this correlation, aneuploidy was hypothesized to be a cause of carcinogenesis approximately 100 years ago. However, this hypothesis has remained untested due to the technical difficulty of selectively generating aneuploidy. We have discovered that CENP-E heterozygous mice develop aneuploidy in vitro and in vivo due to chromosomal instability in the absence of other known defects. CENP-E is a mitosis-specific microtubule motor protein that localizes to the centromeric region of mitotic chromosomes. CENP-E participates in making and/or maintaining the connections between chromosomes and the microtubules of the mitotic spindle. CENP-E also participates in the mitotic checkpoint, the major cell cycle control mechanism guarding against aneuploidy. As a result, CENP-E heterozygous cells, which lack approximately 50% of the protein expressed in wild type cells, missegregate small numbers of chromosomes at high frequency, resulting in aneuploidy and chromosomal instability. More than half of primary CENP-E heterozygous cells are aneuploid after 12 days in culture and these cells exhibit some characteristics of transformed cell growth. CENP-E heterozygous cells form foci on plastic and, when immortalized with the SV40 large T antigen (SV40T), exhibit anchorage independent growth in soft agar. These latter cells form tumors when injected into nude mice, while SV40T immortalized wild type cells with normal CENP-E levels do not. In vivo, one-third of spleen cells from 8 month old CENP-E heterozygous animals exhibit aneuploidy. Fluorescence In Situ Hybridization (FISH) analysis of colon sections reveals that aged (19 month old) CENP-E heterozygous animals have elevated levels of aneuploidy (assayed for chromosome 2 and the Y chromosome). As a result, aged CENP-E heterozygous animals have elevated levels of spleen and lung tumors. One-third of female CENP-E heterozygous animals also exhibit ovarian abnormalities. However, CENP-E heterozygous animals are not hypersensitive to treatment with the chemical carcinogen DMBA. These results indicate that aneuploidy and chromosomal instability can facilitate tumorigenesis, but do not do so in all contexts.