tbuckley/cabot-search huggingface dataset:
How long is a life?
Authors: T. Dalrymple
Journal: BMJ (2010)

<h3>Introduction</h3> Very little is known about the influence of socioeconomic status on type 1 diabetes mellitus (T1DM) complications. Our aim was to determine whether socioeconomic level is a risk factor for the development of diabetic retinopathy (DR) in patients with T1DM. <h3>Research design and methods</h3> A cohort of 150 patients with T1DM were studied prospectively over 9 years. Socioeconomic status was assessed using a neighborhood-level measure based on an index of deprivation. The contribution of other variables such as hypertension, dyslipidemia, diabetic nephropathy and smoking habit was evaluated. Cox proportional hazards models were used to quantify the associations. <h3>Results</h3> The incidence of DR was 21.6 cases per 1000 patient-years. Multivariable analyses showed that for each percentage point increase in glycated hemoglobin (HbA1c), the risk of developing DR increased by 58% (HR 1.58, 95% CI 1.19 to 2.10). Patients with T1DM onset &gt;18 years of age and resident in areas of lower socioeconomic levels presented with almost triple the risk of developing DR (HR 2.95, 95% CI 1.08 to 8.00) compared with those with onset &lt;18 years of age and resident in less deprived areas. We did not find significant relationships with other variables studied such as hypertension, dyslipidemia, diabetic nephropathy and smoking habit. <h3>Conclusions</h3> Low socioeconomic level is a risk factor, independent of glycemic control, in the development of DR in patients with T1DM when the onset of diabetes is in adulthood. This finding indicates that socioeconomic status and age of onset need to be considered in population screening for DR in patients with T1DM.
Pharmacological Stimulation of the Cholinergic Antiinflammatory Pathway
Authors: Thomas R. Bernik, Steven G. Friedman, Mahendar Ochani, Robert DiRaimo, Luis Ulloa, Huan Yang, Samridhi Sudan, Christopher J. Czura, Svetlana M. Ivanova, Kevin J. Tracey
Journal: The Journal of Experimental Medicine (2002)

Efferent activity in the vagus nerve can prevent endotoxin-induced shock by attenuating tumor necrosis factor (TNF) synthesis. Termed the “cholinergic antiinflammatory pathway,” inhibition of TNF synthesis is dependent on nicotinic α-bungarotoxin-sensitive acetylcholine receptors on macrophages. Vagus nerve firing is also stimulated by CNI-1493, a tetravalent guanylhydrazone molecule that inhibits systemic inflammation. Here, we studied the effects of pharmacological and electrical stimulation of the intact vagus nerve in adult male Lewis rats subjected to endotoxin-induced shock to determine whether intact vagus nerve signaling is required for the antiinflammatory action of CNI-1493. CNI-1493 administered via the intracerebroventricular route was 100,000-fold more effective in suppressing endotoxin-induced TNF release and shock as compared with intravenous dosing. Surgical or chemical vagotomy rendered animals sensitive to TNF release and shock, despite treatment with CNI-1493, indicating that an intact cholinergic antiinflammatory pathway is required for antiinflammatory efficacy in vivo. Electrical stimulation of either the right or left intact vagus nerve conferred significant protection against endotoxin-induced shock, and specifically attenuated serum and myocardial TNF, but not pulmonary TNF synthesis, as compared with sham-operated animals. Together, these results indicate that stimulation of the cholinergic antiinflammatory pathway by either pharmacological or electrical methods can attenuate the systemic inflammatory response to endotoxin-induced shock.
Drug-Induced Depression
Authors: Scott B. Patten, Edgar J. Love
Journal: Psychotherapy and Psychosomatics (1997)

Certain drugs may contribute to the etiology of depressive symptoms and depressive disorders. The objective of this review is to critically appraise the literature concerned with these potential etiological associations.The review was based on papers uncovered in electronic literature searches using Medline, Psychlit and Psychological Abstracts. Statistical power calculations were used to assist in the interpretation of negative results.A large number of publications were uncovered, but most of these were case reports. There were relatively few empirical studies. Corticosteroids, certain calcium channel blockers and digoxin have been associated with depression by replicated, well conducted studies. Psychostimulant withdrawal is also associated with prominent depressive symptoms. Preliminary evidence suggests that antihyperlipidemic agents, angiotensin converting enzyme inhibitors, sedative hypnotics, psychostimulants and certain hormonal agents may also cause depression. Despite an extensive literature, the potential association between beta-blockers and depressive symptoms remains controversial. There is no substantial evidence that l-dopa or histamine-2-receptor blockers cause depression and the literature is relatively conclusive in determining that thiazide diuretics are not associated with depressive symptoms.A small, but growing, literature confirms that certain drug exposures can contribute to the biopsychosocial etiology of depressive symptoms and disorders. Current beliefs and diagnostic conventions classify drug-induced depression into a distinct category (Substance-Induced Mood Disorder): but this approach is not specifically supported by the existing literature.
Further advances and uses of assisted conception technology
Authors: S. Pickering
Journal: BMJ (2003)

Assisted conception technology has led to a variety of new techniques that can help subfertile couples. However, many now go beyond simply improving the capacity to procreate. They also affect areas outside reproductive biology and present new ethical dilemmas.

   ![][1] 

During cooling of an oocyte for cryopreservation, the normal metaphase spindle (left) can become dismantled (right), which could result in the production after fertilisation of a karyotypically abnormal embryo

Long term survival rates for cancer have improved substantially because of the use of aggressive chemotherapy and radiotherapy. However, in young women this comes at a price—many women lose ovarian function because oocytes or their support cells are damaged by the treatment. A technique ensuring successful cryopreservation of oocytes would benefit women recently diagnosed with cancer who want to retain their fertility potential. In addition, cryopreservation could help women with a family history of premature menopause as they could store their gametes before their pool of oocytes is depleted.

### Cryopreservation of oocytes

In contrast to the success of embryo freezing, which is now a routine procedure in most in vitro fertilisation clinics, cryopreservation of oocytes has been less successful. Only a few live births after egg freezing have been achieved since the first one in 1986. Some problems have been reduced by improving cryoprotectant regimens and by using intracytoplasmic sperm injection to overcome the block to fertilisation, resulting in a few pregnancies and live births. However, the success rate remains low—about 1 in 100 eggs that are frozen results in a live birth.

   ![][2] 

Live births after egg freezing are rare and can make headline news

### Cryopreservation of ovarian tissue and maturation of oocytes and follicles in vitro

An alternative approach is cryopreservation of slices or biopsies of ovarian tissue, which contain many thousands of immature oocytes. These oocytes are quiescent and their chromatin is in a stable phase of meiosis.

Autografting and in vitro maturation could be …

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 [2]: /embed/graphic-2.gif
THE CONTROL OF VENEREAL DISEASE IN THE ARMY
Authors: Frank Thomas Woodbury
Journal: JAMA (1918)

infections" ; for rhinitis with the claims that acute coryza can be aborted within twenty-four hours ; for pneumonia in which it is advised for all stages ; for laryngitis, for bronchitis, and for asthma.No acceptable evidence was submitted as to the value of the product in the treatment of any of the foregoing con¬ ditions.In view of what is known about non-specific reac¬ tions, it seems likely that any influence which this vaccine may have on the divers conditions enumerated by the manu¬ facturer, is due to this, rather than to the combination of organisms used in its preparation.
Abstract 5147: drugCARD: a database of anticancer treatment regimens and drug combinations.
Authors: Eric Fernandez, Jianxiong Pang, Chris Snell, Cathy Derow, Frances Brightman, Christophe Chassagnole, Robert Jackson
Journal: Cancer Research (2013)

Abstract Physiomics and Pharmacometrics have collaborated to design a new database of anti-cancer drugs and therapeutic treatment information. The objective is to provide a database of anti-neoplastic agents, regimens and combinations for use by clinicians and researchers in oncology. The drugCARD database, accessible through the web, offers data on more than 130 anti-cancer drugs (small molecules and biologics) used in research and in the clinic. It contains information on drug combinations as well as several hundreds of cancer chemotherapy regimens used routinely in the clinic. The data are classified according to tumour type, species and experimental system (in vitro or in vivo). This database will be regularly expanded and curated with the most current information. Individual drug information contained within the database comprises pharmacokinetic profiles, mechanisms of action and resistance, dose-response effect, dosing limits, therapeutic index and immunosuppression data. Drug combinations are also referenced. The database covers synergy or antagonism, and includes the combination therapeutic index and cross-resistance information. Drug combinations where the level of synergy is dependent upon the drug schedule, drug sequence or administration timing are also referenced and thoroughly discussed. The user can browse and compare chemotherapeutic regimens, and analyse the overall drug dose over a course of treatment, by tumour type, in animal and clinical models. Moreover, the database enables users to design new combinations and regimens that obey dosing constraints (such as MLD and MTD), and can be used to determine drug candidates that could be combined with a new chemical or biological entity, given the respective mechanisms of action and other PK/PD data. Data can be exported for analysis in spreadsheets, modelling software or simulation packages. Advanced functions will include the ability to carry out statistical analysis on drug usage and dosing in various contexts. Finally, the database allows the expression and nomenclature of chemotherapy regimens to be standardized, which is of paramount importance in improving efficacy, as well as reducing medication errors (Kohler et al 1998). Citation Format: Eric Fernandez, Jianxiong Pang, Chris Snell, Cathy Derow, Frances Brightman, Christophe Chassagnole, Robert Jackson. drugCARD: a database of anticancer treatment regimens and drug combinations. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5147. doi:10.1158/1538-7445.AM2013-5147
Immune Monitoring for Rejection of Kidney Transplants
Authors: Jean-Paul Soulillou
Journal: New England Journal of Medicine (2001)

Kidney transplantation is the best treatment for patients with end-stage renal disease. The first six months after a technically successful transplantation is, however, often complicated by episodes of renal dysfunction that may have various causes. Rapid diagnosis of these episodes, which is difficult in patients with poor basal kidney function, is important in order to treat acute rejection or to stop further immunosuppression if rejection is not the cause. In most cases the clinical findings allow an accurate diagnosis to be made. However, clinicians confronted with such episodes can be misled because findings suggestive of rejection can also be the . . .
Acellular Pertussis Vaccine Hailed for Infants
Authors: Charles Marwick
Journal: JAMA (1995)

CHILDHOOD immunization against diphtheria-tetanus-pertussis using an acellular pertussis vaccine for the first three doses has moved measurably closer. Data from two large field trials, one in Italy and one in Sweden, have now been analyzed, and they show clear evidence of efficacy and fewer side effects compared with the control group that received whole-cell pertussis vaccine. See also p 450. Three of the four vaccines used in the trials showed 84% to 85% efficacy. The fourth was only 58% effective. The randomized, double-blind trials began in 1992 and involved more than 25000 children. <h3>The Swedish Trial</h3> In the Swedish trial, 9630 infants were vaccinated at age 2, 4, and 6 months with one of two types of acellular pertussis vaccine combined with diphtheria and tetanus toxoids, or with diphtheria and tetanus toxoids combined with a whole-cell pertussis vaccine, or with diphtheria-tetanus alone. Efficacy data were obtained and analyzed when the
SO-04 * INTERNATIONAL CONSENSUS GUIDELINES FOR POST-OPERATIVE STEREOTACTIC BODY RADIATION THERAPY (SBRT) FOR MALIGNANT SPINE TUMORS
Authors: K. Redmond, S. Lo, E. Chang, P. Gerszten, S. Chao, L. Rhines, S. Ryu, M. Fehlings, I. Gibbs, A. Sahgal
Journal: Neuro-Oncology (2014)

Emerging data suggests that post-operative SBRT for malignant spinal tumors may improve local control compared to conventional radiation therapy. However, few guidelines exist. The purpose of this study was to develop consensus guidelines to guide safe, effective treatment. Twenty spine specialists representing 19 centers in 4 countries with a collective experience of >1300 cases completed survey. Responses were defined as follows: 1) consensus: selected by ≥75%, 2) predominant: selected by ≥50%, 3) controversial: no single response selected by a majority of respondents. Consensus indications include: radio-resistant primary, 1-2 levels of adjacent disease and/or prior RT to same site. Contra-indications include: >3 contiguous vertebral bodies involved, ASIA score A (complete spinal cord injury without preservation of motor or sensory function), post-operative Bilsky grade 3 residual (cord compression without any CSF around the cord). For treatment planning, predominance of physicians co-register pre-operative MRI and post-operative T1 post-gadolinium MRI and delineate cord on T2 variant MRI or CT myelogram in cases of significant hardware artifact. Consensus GTV is post-operative residual tumor based on MRI. CTV is predominantly post-operative bed defined as entire extent of pre-operative tumor & anatomic compartment plus residual disease. Consensus is that hardware and scar do not need to be included. PTV expansion is controversial (range: 0-2 mm). Predominant prescription dose for initial treatment is 18 Gy x 1 with max point to cord <12-14 Gy (prescription range: 16-48.5 Gy in 1-10 fractions). For re-treatment, physicians predominantly account for repair and time interval between prior RT and spinal SBRT in calculating cord constraints. Acceptable PTV coverage is controversial, but physicians predominantly compromise coverage to meet cord constraint and/or fractionate to improve coverage while meeting cord constraint. Future investigation will be critical in better understanding areas of controversy including circumferential treatment of epidural space, margin for paraspinal extension and optimal dose/fractionation.
Catheter Design Influences Recurrence of Catheter-Related Bloodstream Infection in Children With Cancer
Authors: Patricia M. Flynn, Brian Willis, Aditya H. Gaur, Jerry L. Shenep
Journal: Journal of Clinical Oncology (2003)

Multiple studies have demonstrated that catheter-related bloodstream infections (CRBI) can be successfully treated without catheter removal (in situ therapy), but there is insufficient information available to determine if catheter design can influence the eradication of bacteremia or recurrence.Bacteremic episodes in patients at St Jude Children's Research Hospital between January 1996 and May 2001 were identified and patient records were reviewed.A total of 172 unique episodes of CRBI were identified. In situ therapy resulted in successful eradication of bacteremia in 87% of the episodes. Bacteremia recurred in 10% of the episodes. Although catheter design (Hickman and Broviac versus totally implantable central venous catheter) did not influence short-term eradication of bacteremia, totally implantable central venous catheters were significantly associated with recurrence of bacteremia (odds ratio, 10; 95% confidence interval, 3.1 to 33.3). In a multivariable analysis, this association between catheter design and recurrence remained statistically significant after adjustment for other factors that influenced recurrence in this study (isolation of coagulase-negative staphylococci and inadequate duration of initial antibiotic therapy).This study demonstrates that patients with CRBI with a totally implantable central venous catheter in place are more likely to develop recurrent bacteremia. Management strategies to prevent recurrence in this setting should be explored.
Catheter ablation of ventricular tachycardia in patients with structural heart disease using cooled radiofrequency energy
Authors: Hugh Calkins, Andrew Epstein, Douglas Packer, Amelia M. Arria, John Hummel, David M. Gilligan, Janet Trusso, Mark Carlson, Richard Luceri, Harry Kopelman, David Wilber, J.Marcus Wharton, William Stevenson
Journal: Journal of the American College of Cardiology (2000)
The Case for Primary Care — A Medical Student's Perspective
Authors: Ishani Ganguli
Journal: New England Journal of Medicine (2010)

Ms. J. was no stranger to medical students. The year before I came along, she'd worked with another student, and she took unabashed pleasure in sharing the teachable complexities of her health problems — diabetes, depression, obesity, and osteoarthritis. She arrived at our first appointment, in the fall of my third year, adorned in a hot-pink feathered hat with matching sweatshirt and oversized hoop earrings. She labored to the exam room using a walker, and as we chatted, the buoyancy of her Trinidadian lilt was undercut with a sadness that would take months for me to even begin to unpack. . . .
Abstract 3138: Development of a tetracycline-inducible lentiviral system for RNAi screen in PDX tumors.
Authors: Lei Chen, Yi Geng, Dave Fruhling, Wenyan Zhong, Veronica Diesl, Jing Pan, Christine Loreth, Elizabeth Wang, Yaroslava Bulynko, Kim Arndt, Maximillian Follettie
Journal: Cancer Research (2013)

Abstract Patient-derived xenograft (PDX) tumors are believed to be more clinically relevant pre-clinical models for cancer target identification and validation. We used a tetracycline-inducible lentiviral vector that delivers shRNA expression which is tightly linked to a GFP reporter in PDX cells. Using shRNAs against PLK1 (polo-like kinase 1) as positive controls, we demonstrated that three of the four PLK1 hairpins resulted in growth inhibition of HT29 and A549 cells upon dox induction. Correspondingly, these 3 hairpins showed significant knockdown of PLK1 mRNA. To facilitate RNAi in PDX tumors, we have established an in vitro system to culture PDX tumor cells. Gene expression and IHC study demonstrated that tumors regenerated from colon PDX cells grown in vitro retained features of their parental tumors. PDX cells cultured in vitro also remained tumorigenic. When GFP/shRNA-transduced colon PDX cells were re-implanted in mice to form tumors, approximately 30% of the new tumor cells was GFP-positive, enabling us to capture shRNA-expressing cells by flow cytometry. Initial shRNA drop-out screens were carried out in HT29 and colon PDX cells transduced with a pool of ∼600 shRNAs targeting a set of potential cancer associated genes. Included amongst the hairpins demonstrating statistically significant depletion in HT29 were the exact same three PLK1 shRNAs previously functionally validated. These results demonstrated that we have established a robust in vivo shRNA drop-out screening platform in PDX tumors for identification of novel cancer drug targets. Citation Format: Lei Chen, Yi Geng, Dave Fruhling, Wenyan Zhong, Veronica Diesl, Jing Pan, Christine Loreth, Elizabeth Wang, Yaroslava Bulynko, Kim Arndt, Maximillian Follettie. Development of a tetracycline-inducible lentiviral system for RNAi screen in PDX tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3138. doi:10.1158/1538-7445.AM2013-3138
Effectiveness of interferon alfa on incidence of hepatocellular carcinoma and decompensation in cirrhosis type C
Authors: Giovanna Fattovich, Giuliano Giustina, Francoise Degos, Giulio Diodati, Federico Tremolada, Frederik Nevens, Piero Almasio, Antonio Solinas, Johannes T Brouwer, Howard Thomas, Giuseppe Realdi, Roberto Corrocher, Solko W Schalm
Journal: Journal of Hepatology (1997)
Functional Cone Rescue by RdCVF Protein in a Dominant Model of Retinitis Pigmentosa
Authors: Ying Yang, Saddek Mohand-Said, Aude Danan, Manuel Simonutti, Valérie Fontaine, Emmanuelle Clerin, Serge Picaud, Thierry Léveillard, José-Alain Sahel
Journal: Molecular Therapy (2009)

In retinitis pigmentosa (RP), a majority of causative mutations affect genes solely expressed in rods; however, cone degeneration inevitably follows rod cell loss. Following transplantation and in vitro studies, we demonstrated the role of photoreceptor cell paracrine interactions and identified a Rod-derived Cone Viability Factor (RdCVF), which increases cone survival. In order to establish the clinical relevance of such mechanism, we assessed the functional benefit afforded by the injection of this factor in a frequent type of rhodopsin mutation, the P23H rat. In this model of autosomal dominant RP, RdCVF expression decreases in parallel with primary rod degeneration, which is followed by cone loss. RdCVF protein injections induced an increase in cone cell number and, more important, a further increase in the corresponding electroretinogram (ERG). These results indicate that RdCVF can not only rescue cones but also preserve significantly their function. Interestingly, the higher amplitude of the functional versus the survival effect of RdCVF on cones indicates that RdCVF is acting more directly on cone function. The demonstration at the functional level of the therapeutic potential of RdCVF in the most frequent of dominant RP mutations paves the way toward the use of RdCVF for preserving central vision in many RP patients.