tbuckley/cabot-search huggingface dataset:
Antenatal screening
Authors: C. Baillie, J. Hewison, E. Dormandy, T Fitzgerald
Journal: BMJ (1999)

Editor—McFayden et al stated that first trimester ultrasound screening “should include the accurate presentation of all available information before screening to ensure that consent is truly informed.”1 In 1997 we evaluated the content and readability of the leaflets used in 14 centres offering first trimester nuchal translucency screening using a number of predefined variables.2

Only one of the leaflets met all of the criteria deemed necessary for an informed choice to be made. Thirteen of the leaflets indicated that ultrasound scanning was used to screen for Down’s syndrome and chromosomal abnormalities, although only two leaflets gave any description of the syndrome, and this was limited to “mental handicap.” Few of the leaflets gave information on the sensitivity or specificity of the test, or on interpreting results. Eight mentioned diagnostic testing, and two referred to the option of termination. Nine leaflets explained that nuchal translucency screening was separate from other elements of the early pregnancy scan, and four leaflets indicated that written consent was required.

The content and readability of the leaflets used to inform women of the aims and limitations of screening for nuchal translucency varied widely but the majority could be considered as failing to meet the criteria for informed choice. Even under conditions of informed choice, however, uptake of ultrasound screening is markedly above that which would be expected for other prenatal screening tests. This high uptake has been attributed to expectant couples’ overwhelming desire to “see the baby.”3

Since the first centre was accredited by the Fetal Medicine Foundation (a charity established to provide training and audit of first trimester ultrasound screening) in 1993, uptake of nuchal translucency screening has fallen from 96.9% to 86.6% of all women having ultrasound screening (R Snijders, personal communication). This decline shows that offering the option of “selective consent” has the potential to overcome the previously reported high uptake of ultrasound screening.

Selective consent can be easily accommodated by the early pregnancy scan because its pregnancy monitoring functions (assessing gestation and viability, and identifying multiple pregnancies) are distinct from its screening functions. Therefore, couples who wish to decline screening for chromosomal abnormalities do not have to forgo “seeing the baby” or accurately dating the pregnancy. The data suggest that an increasing, albeit small, percentage of women who have ultrasound scans are making an informed choice to selectively decline screening for chromosomal abnormalities. It may be that the way forward in facilitating informed choice for ultrasound screening is to separate “scanning” (to monitor the pregnancy) from “screening” (for fetal abnormality).
KPC-2-producing Klebsiella pneumoniae infections in Greek hospitals are mainly due to a hyperepidemic clone
Authors: P Giakkoupi, H Maltezou, M Polemis, O Pappa, G Saroglou, A Vatopoulos, Collective the Greek System for the Surveillan
Journal: Eurosurveillance (2009)

To verify the presence of Klebsiella pneumoniae carbapenemase-producing (KPC–producing) Klebsiella pneumoniae in Greece, we asked 40 Greek hospitals participating in the Greek System for the Surveillance of Antimicrobial Resistance (GSSAR) to apply a combination of the modified Hodge test plus EDTA synergy test on all K. pneumoniae clinical isolates obtained from February 2008 which displayed reduced susceptibility to carbapenems (MIC of imipenem ≥ 1 mg/L). The presence of the blaKPC gene was confirmed by PCR and sequencing. This procedure revealed the presence of KPC-2 in isolates from 173 patients in 18 hospitals during a period of 11 months. Of these, 166 isolates belonged to a single pulsotype a fact consistent with possible epidemic spread, whereas the remaining seven isolates were further classified into four different pulsotypes. BlaKPC-2 gene was found to be transferable by conjugation in the four pulsotypes other than the prevailing one. The emergence of a new carbapenemase gene in Greece, where high resistance rates to carbapenems in K. pneumoniae due to the spread of the VIM type metalloenzyme have been observed, emphasises the urgent need for the implementation of public health measures in the field of infection control and antibiotic consumption. It also underlines the need to supplement surveillance systems based on susceptibility data with the surveillance of resistance mechanisms.
455. Neutrophils Interact with Adenovirus Vectors Via the β2-Integrin CD11b
Authors: Hoyin S. Mok, Michael A. Barry
Journal: Molecular Therapy (2004)

First generation adenoviruses constitute as one of the most common used vectors in gene therapy clinical trials. However, these recombinant vectors are limited by their abilities to provoke strong innate and adaptive responses in vivo. In addition, the administration of human serotypes of adenovirus to individuals previously exposed to the virus may trigger a more severe inflammatory response to the vector than their unexposed counterparts. Neutralizing antibodies are also problematic from these individuals which could blunt vector transduction entirely within hours. Previous work has demonstrated that chemical modification of adenovirus with polyethylene glycol (PEG) can protect the vectors from pre-existing and new adaptive immune responses by reducing non-specific protein-protein interaction. Here we have optimized the PEGylation process for first generation adenoviral vectors and evaluated vector transduction, vector persistence, toxicity and innate immune responses against virus. We demonstrate that increasing PEGylation of the vector ablates in vitro, but not in vivo gene delivery. In vivo biodistribution was the same despite slighty higher transduction levels for PEGylated versus non-PEGylated vectors. In addition, vector levels in the serum were up to 100-fold higher for PEGylated vectors relative to unmodified vectors 24 hour after injection. Comparison of innate immune responses using serum IL-6 levels between mice injected with PEGylated or unmodified adenovirus systemically demonstrated a reduction of up to 70% from PEG-modified viruses at 6 hour after injection. Furthermore, the integrated amount of IL-6 release from unmodified vectors was 10-fold higher than PEGylated viruses during the 48 hour period after injection. Consistent with the reduction in IL-6 levels in vivo, we found that PEGylation reduced IL-6 expression 70% in RAW264.7 macrophages when exposed to the viruses in vitro. These data suggest that macrophages may play an important role in the acute immune response to adenoviral vectors and that PEG-modified vectors may attenuate this inflammatory response by reducing macrophage activation. In summary, this work demonstrates that PEGylation of adenovirus ablates in vitro, but not in vivo transduction, increases vector persistence, and reduces innate immune responses.
Metabolic Flare: Indicator of Hormone Responsiveness in Advanced Breast Cancer
Authors: Joanne E. Mortimer, Farrokh Dehdashti, Barry A. Siegel, Kathryn Trinkaus, John A. Katzenellenbogen, Michael J. Welch
Journal: Journal of Clinical Oncology (2001)

PURPOSE: The purpose of this study was to investigate whether positron emission tomography (PET) with the glucose analog [ 18 F]fluorodeoxyglucose (FDG) and the estrogen analog 16 alpha-[ 18 F]fluoroestradiol-17 beta (FES), performed before and after treatment with tamoxifen, could be used to detect hormone-induced changes in tumor metabolism (metabolic flare) and changes in available levels of estrogen receptor (ER). In addition, we investigated whether these PET findings would predict hormonally responsive breast cancer. PATIENTS AND METHODS: Forty women with biopsy-proved advanced ER-positive (ER + ) breast cancer underwent PET with FDG and FES before and 7 to 10 days after initiation of tamoxifen therapy; 70 lesions were evaluated. Tumor FDG and FES uptake were assessed semiquantitatively by the standardized uptake value (SUV) method. The PET results were correlated with response to hormonal therapy. RESULTS: In the responders, the tumor FDG uptake increased after tamoxifen by 28.4% ± 23.3% (mean ± SD); only five of these patients had evidence of a clinical flare reaction. In nonresponders, there was no significant change in tumor FDG uptake from baseline (mean change, 10.1% ± 16.2%; P = .0002 v responders). Lesions of responders had higher baseline FES uptake (SUV, 4.3 ± 2.4) than those of nonresponders (SUV, 1.8 ± 1.3; P = .0007). All patients had evidence of blockade of the tumor ERs 7 to 10 days after initiation of tamoxifen therapy; however, the degree of ER blockade was greater in the responders (mean percentage decrease, 54.8% ± 14.2%) than in the nonresponders (mean percentage decrease, 19.4% ± 17.3%; P = .0003). CONCLUSION: The functional status of tumor ERs can be characterized in vivo by PET with FDG and FES. The results of PET are predictive of responsiveness to tamoxifen therapy in patients with advanced ER + breast cancer.
Management of deliberate self poisoning
Authors: E. Williams, C. Mitchell, J. Preston, K. Augarde, R. Barber, J. Catalan, B. Jones, R. Brogan, K. Ullyatt, A. Pelosi
Journal: BMJ (1998)

Early diagnosis allows option of prenatal diagnosis in subsequent pregnanciesEditor-Like Wald and Morris, we do not advocate neonatal screening for cystic fibrosis, although the situation is not as simple as they seem to suggest.The benefits of screening are not limited to early treatment of affected children; early diagnosis allows parents to have the options of prenatal diagnosis in subsequent pregnancies, although only a minority of carrier couples can be detected in this way.
A mutation in OTOF, encoding otoferlin, a FER-1-like protein, causes DFNB9, a nonsyndromic form of deafness
Authors: Shin'ichiro Yasunaga, M'hamed Grati, Martine Cohen-Salmon, Aziz El-Amraoui, Mirna Mustapha, Nabiha Salem, Elie El-Zir, Jacques Loiselet, Christine Petit
Journal: Nature Genetics (1999)
R to Q Amino Acid Substitution in the GFFKR Sequence of the Cytoplasmic Domain of the Integrin IIb Subunit in a Patient With a Glanzmann’s Thrombasthenia-Like Syndrome
Authors: O. Peyruchaud, A.T. Nurden, S. Milet, L. Macchi, A. Pannochia, P.F. Bray, N. Kieffer, F. Bourre
Journal: Blood (1998)
Randomized Trial of Peribulbar Triamcinolone Acetonide with and without Focal Photocoagulation for Mild Diabetic Macular Edema
Authors: E Chew, S Strauber, R Beck, L P Aiello, A Antoszyk, N Bressler, D Browning, R Danis, J Fan, C Flaxel, S Friedman, A Glassman, C Kollman, H Lazarus
Journal: Ophthalmology (2007)
A quantitative multigene RT-PCR assay for prediction of recurrence in stage II colon cancer: Selection of the genes in four large studies and results of the independent, prospectively designed QUASAR validation study
Authors: D. Kerr, R. Gray, P. Quirke, D. Watson, G. Yothers, I. C. Lavery, M. Lee, M. J. O’Connell, S. Shak, N. Wolmark
Journal: Journal of Clinical Oncology (2009)

4000 Background: New clinical tools are needed to improve risk assessment and treatment decisions in stage II colon cancer. Four development studies [Surgery (Sx) alone: NSABP C-01/C-02 (n=270) and CCF study (n=765); Sx+5FU/LV: NSABP C-04 (n=308) and C-06 (n=508)] were performed to select the genes for prediction of recurrence and 5FU/LV benefit. To determine clinical utility of the prespecified assay, we performed a large, independent, prospectively designed, clinical validation study in stage II colon cancer pts from the QUASAR trial. Methods: Gene expression was quantitated by RT-PCR from 30 μm manually microdissected fixed paraffin-embedded primary colon cancer tissue. Recurrence-free interval (RFI), disease-free survival (DFS), and overall survival (OS) were analyzed using Cox regression. Results: Combined analysis of the four development studies (total n=1,851; 761 candidate genes) identified 48 genes significantly associated with recurrence risk and 66 genes predictive of 5FU/LV benefit. Multivariate analysis, in the context of stage, grade, nodes examined, and MSI status, yielded 18 genes (7 prognostic genes, 6 predictive genes, 5 reference genes) and separate prognostic recurrence score (RS) and predictive treatment score (TS) algorithms. In the QUASAR validation study, tumor blocks were collected for 68% of pts; 1,490 pts with blocks had stage II colon cancer and RT-PCR was successful in 1,436 eligible pts (711 Sx, 725 Sx+5FU/LV). Median FU=6.6 yrs. In the primary analysis of RFI in pts following Sx, the RS predicted recurrence risk (HR/25 units=1.58, 95% CI 1.15–2.15; p=0.004). The RS also predicted DFS (p=0.01) and OS (p=0.04). Recurrence risk increased monotonically with increasing RS. In multivariate analyses, RS retained prognostic significance (p=0.008) independent of mismatch repair (MMR), T stage, nodes examined, grade, and lymphovascular invasion. MMR deficiency (HR=0.31, 95% CI 0.15–0.63; p&lt;0.001) and T4 stage (HR=1.94, 95% CI 1.35–2.79; p=0.005), together ∼25% of pts, also were independently prognostic. 5FU/LV benefit was significant (p&lt;0.001). However, TS was not validated as a predictor of 5FU/LV benefit (interaction p=0.19). Conclusions: The colon cancer recurrence score is a validated, independent predictor of individualized recurrence risk for stage II colon cancer patients following surgery. [Table: see text]
Relationship of smoking change with the 40-year change of the symptoms of chronic bronchitis among Eastern Finnish men
Authors: Pekka Jousilahti, Katja Borodulin, Tiina Laatikainen, Tari Haahtela, Erkki Vartiainen
Journal: European Respiratory Journal (2013)

Introduction : Smoking is a major risk factor of chronic bronchitis. During the past 40 years smoking prevalence and symptoms of chronic bronchitis have decreased markedly among men in Finland.   Aim : To study the relationship of the decrease of smoking prevalence with the change of the prevalence of the classical symptoms of chronic bronchitis among eastern Finnish men.   Methods : Study population consists of 18595 men aged 30 to 59 years who participated in the National FINRISK Study between 1972 and 2012 (total of nine surveys). Data on smoking and symptoms of chronic bronchitis: cough with sputum a) in winter mornings, b) during day and night during winter and c) during the most days and nights at least three months during a year, were collected using standardized questionnaires. Association of smoking with the symptoms, and their change, were analyzed using logistic regression models.   Results : Prevalence of the symptoms decreased markedly between 1972 and 2007: from 34.2 % to 14.6% (57% reduction) for morning symptom, 30.5-14.7 % (52% reduction) for day and night symptoms, and 25.4-13.5 % (47% reduction) for the symptoms lasting at least three months. During the same period, smoking prevalence reduced from 50.8% to 30.6%. Decrease of smoking explained 34%, 30% and 33% from the observed reduction in the symptoms, respectively. A small increase of the symptoms was observed between 2007-2012 which may be explained by the increase of smoking prevalence among older men between 2007 and 2012.   Conclusions : Decrease in smoking explained one third of the reduction in the symptoms of chronic bronchitis. Tobacco control is a major tool for improvement of respiratory health.
Treatment of childhood acute lymphoblastic leukemia in second remission with allogeneic bone marrow transplantation and chemotherapy: ten-year experience of the Italian Bone Marrow Transplantation Group and the Italian Pediatric Hematology Oncology Association.
Authors: C Uderzo, M G Valsecchi, A Bacigalupo, G Meloni, C Messina, P Polchi, G Di Girolamo, G Dini, R Miniero, F Locatelli
Journal: Journal of Clinical Oncology (1995)

PURPOSE To compare the results of allogeneic bone marrow transplantation (AlloBMT) with those obtained with chemotherapy (CHEMO) in children with acute lymphoblastic leukemia (ALL) in second complete remission (CR) after a marrow relapse. The experience of the Italian Bone Marrow Transplantation Group and the Italian Pediatric Hematology Oncology Association is summarized. PATIENTS AND METHODS All children who had a relapse in the period 1980 to 1989 in 27 centers in Italy were eligible for the study. Of 287 eligible patients, 230 were treated with CHEMO, most of them (93%) according to a standard multiple-drug relapse protocol. The remaining 57 children underwent AlloBMT. Preparative regimens included total-body irradiation and chemotherapy (n = 51) or chemotherapy alone (n = 6). Statistical analysis was performed with a Cox regression model adjusting for waiting time to transplant and prognostic factors. RESULTS In the whole series, minimum and median follow-up after second CR were 3 and 6.2 years, respectively; at 8 years from second CR, disease-free survival (DFS) was 20.0% (SE 2.5) and survival was 26.4% (SE 2.9). In the group of patients with an early first relapse, DFS was significantly longer after AlloBMT than after CHEMO (relative risk [RR] = 0.45, P = .002). No significant advantage of AlloBMT over CHEMO was found for patients with a late relapse (&gt; 30 months since diagnosis). Duration of first CR significantly influenced prognosis in the CHEMO group (RR = 0.32, P = .0001 for patients with late first relapse versus patients with early first relapse). CONCLUSION Results suggest an advantage in DFS of AlloBMT over CHEMO in ALL patients who experienced an early first medullary relapse. Prospective trials are needed to address efficacy of AlloBMT versus CHEMO in patients with late bone marrow relapse.
Uremic plasma contains factors inhibiting 1 alpha-hydroxylase activity.
Authors: C H Hsu, S Patel
Journal: Journal of the American Society of Nephrology (1992)

The effect of uremic plasma ultrafiltrate on calcitriol synthesis was investigated. Renal 1 alpha-hydroxylase activity was measured in normal rats infused for 20 h with 20 mL of normal or uremic plasma ultrafiltrate. Renal 1 alpha-hydroxylase activity was determined by the generation of calcitriol measured 5, 10, 20, and 30 min after the reaction was initiated by the addition of cold 25(OH)D3. The activity was significantly lower in rats infused with uremic plasma ultrafiltrate. Kidney homogenates preincubated for 3 h with uremic plasma ultrafiltrate also had significantly lower renal 1 alpha-hydroxylase activity than did those preincubated with normal plasma ultrafiltrate. In addition, the effect of the putative uremic toxin, guanidinosuccinic acid (GSA), on renal 1 alpha-hydroxylase activity was studied. Normal rats infused for 20 h with 20 mL of saline solution containing 1.5 mg/dL of GSA had significantly lower renal 1 alpha-hydroxylase activity than did rats infused with normal saline. The enzyme activity was also lower in kidney homogenates preincubated for 3 h with 4 mg/dL of GSA. Enzyme kinetic analysis revealed that the inhibition of renal 1 alpha-hydroxylase by GSA was noncompetitive. It was concluded that uremic plasma contains substances that directly inhibit renal 1 alpha-hydroxylase activity.
Extramedullary leukemia adversely affects hematologic complete remission rate and overall survival in patients with t(8;21)(q22;q22): results from Cancer and Leukemia Group B 8461.
Authors: J C Byrd, R B Weiss, D C Arthur, D Lawrence, M R Baer, F Davey, E S Trikha, A J Carroll, R Tantravahi, M Qumsiyeh, S R Patil, J O Moore, R J Mayer, C A Schiffer, C D Bloomfield
Journal: Journal of Clinical Oncology (1997)

PURPOSE To examine the prognostic significance of extramedullary leukemia (EML) at presentation in patients with t(8;21)(q22;q22) karyotype. PATIENTS AND METHODS Consecutive patients with t(8;21) treated on Cancer and Leukemia Group B de novo acute myeloid leukemia (AML) treatment studies were examined for the presence of EML (granulocytic sarcoma, subcutaneous nodules, leukemia cutis, or meningeal leukemia) at initial presentation. Clinical features and outcome of t(8;21) patients with and without EML were compared. RESULTS Of 84 patients with t(8;21), eight (9.5%) had EML manifesting as granulocytic sarcoma (five paraspinal, one breast, and one subcutaneous) or symptomatic meningeal leukemia (n = 1). The pretreatment prognostic variables of t(8;21) patients with and without EML were similar. The hematologic complete remission (CR) rate for t(8;21) patients with EML was 50% versus 92% for those without EML (P=.006). The median CR duration for EML patients was 14.7 months. Patients with EML had a shorter survival (P = 0.002, median 5.4 months versus 59.5 months). This poor outcome may relate to inadequate local (radiation or intrathecal) therapy for patients with spinal or meningeal EML, resulting in residual/recurrent EML following induction chemotherapy (n = 2) or at relapse (n = 1) and permanent neurologic deficits (n = 4). Only one of the EML patients received high-dose cytarabine (HDAC) intensification; this is the only EML patient remaining alive in CR. CONCLUSION Patients with t(8;21) and EML have a low CR rate and overall survival. An aggressive local and systemic induction therapy should be considered for this patient subset. The effectiveness of HDAC intensification in t(8;21) patients with EML is uncertain and warrants further study.
... and Northern Ireland
Authors: C E Goldsmith, J E Moore, P G Murphy
Journal: BMJ (1996)

EDITOR,—Alan P Johnson and colleagues state that while the prevalence of resistance to penicillin in pneumococci in England and Wales is increasing, resistance to cefotaxime is still rare.1 We report data from similar studies at the Northern Ireland Public Health Laboratory.

In a study of 488 consecutive routine clinical isolates of Streptococcus pneumoniae sent to this laboratory in 1988, only four (0.8%) were found to be resistant to penicillin (minimum inhibitory concentration >/=0.1 mg/l).2 Subsequently, in the late 1980s and early 1990s, sporadic isolates that were resistant to penicillin were detected—on average …