tbuckley/cabot-search huggingface dataset:
<i>VEGFA</i> Genomic Amplification Tailors Treatment of HCCs with Sorafenib
Authors: Xiaolin Luo, Gen-Sheng Feng
Journal: Cancer Discovery (2014)

In this issue of Cancer Discovery, Horwitz and colleagues identified a subtype of hepatocelluar carcinoma (HCC) bearing VEGFA genomic amplification that is particularly sensitive to VEGFA inhibition and is also more sensitive to sorafenib treatment. Taken conjointly, these data suggest that VEGFA genomic amplification can be used as a biomarker for personalized treatment of HCC with sorafenib.
Surgical Ineligibility and Mortality Among Patients With Unprotected Left Main or Multivessel Coronary Artery Disease Undergoing Percutaneous Coronary Intervention
Authors: Stephen W. Waldo, Eric A. Secemsky, Cashel O’Brien, Kevin F. Kennedy, Eugene Pomerantsev, Thoralf M. Sundt, Edward J. McNulty, Benjamin M. Scirica, Robert W. Yeh
Journal: Circulation (2014)

Background— Decisions to proceed with surgical versus percutaneous revascularization for multivessel coronary artery disease are often based on subtle clinical information that may not be captured in contemporary registries. The present study sought to evaluate the association between surgical ineligibility documented in the medical record and long-term mortality among patients with unprotected left main or multivessel coronary artery disease undergoing percutaneous coronary intervention. Methods and Results— All subjects undergoing nonemergent percutaneous coronary intervention for unprotected left main or multivessel coronary artery disease were identified at 2 academic medical centers from 2009 to 2012. Documentation of surgical ineligibility was assessed through review of electronic medical records. Cox proportional hazard models adjusted for known mortality risk factors were created to assess long-term mortality in patients with and without documentation of surgical ineligibility. Among 1013 subjects with multivessel coronary artery disease, 218 (22%) were deemed ineligible for coronary artery bypass graft surgery. The most common explicitly cited reasons for surgical ineligibility in the medical record were poor surgical targets (24%), advanced age (16%), and renal insufficiency (16%). After adjustment for known risk factors, documentation of surgical ineligibility remained independently associated with an increased risk of in-hospital (odds ratio, 6.26; 95% confidence interval, 2.16–18.15; P &lt;0.001) and long-term mortality (hazard ratio, 2.98; 95% confidence interval, 1.88–4.72, P &lt;0.001) after percutaneous coronary intervention. Conclusions— Documented surgical ineligibility is common and associated with significantly increased long-term mortality among patients undergoing percutaneous coronary intervention with unprotected left main or multivessel coronary disease, even after adjustment for known risk factors for adverse events during percutaneous revascularization.
Viral Shedding and Biodistribution of G207, a MuItimutated, Conditionally Replicating Herpes Simplex Virus Type 1, after Intracerebral Inoculation in Aotus
Authors: Tomoki Todo, Frank Feigenbaum, Samuel D. Rabkin, Fred Lakeman, Joseph T. Newsome, Paul A. Johnson, Erin Mitchell, Daniel Belliveau, Jeffrey M. Ostrove, Robert L. Martuza
Journal: Molecular Therapy (2000)

G207 is a multimutated, conditionally replicating herpes simplex virus type 1 (HSV-1) that is currently in clinical trial for patients with malignant glioma. G207 exhibits an efficient oncolytic activity in tumor cells, yet minimal toxicity in normal tissue when injected into the brains of HSV-susceptible mice or nonhuman primates. In this study, we evaluated the shedding and biodistribution of clinical-grade G207 after intracerebral inoculation (3 × 107 pfu) in four New World owl monkeys (Aotus nancymae). Using PCR analyses and viral cultures, neither infectious virus nor viral DNA was detected from tear, saliva, or vaginal secretion samples at any time point up to 1 month postinoculation. Analyses of tissues obtained at necropsy at 1 month from two of the four monkeys, plus one monkey inoculated with laboratory-grade G207 (109 pfu) 2 years earlier, showed the distribution of G207 DNA restricted to the brain, although infectious virus was not isolated. Histopathology revealed normal brain tissues including the sites of inoculation. A measurable increase of serum anti-HSV antibody titer was observed in all monkeys, as early as 21 days postinoculation. The results ascertain the safety of G207 in the brain and indicate that strict biohazard management may not be required for G207-treated patients. G207 is a multimutated, conditionally replicating herpes simplex virus type 1 (HSV-1) that is currently in clinical trial for patients with malignant glioma. G207 exhibits an efficient oncolytic activity in tumor cells, yet minimal toxicity in normal tissue when injected into the brains of HSV-susceptible mice or nonhuman primates. In this study, we evaluated the shedding and biodistribution of clinical-grade G207 after intracerebral inoculation (3 × 107 pfu) in four New World owl monkeys (Aotus nancymae). Using PCR analyses and viral cultures, neither infectious virus nor viral DNA was detected from tear, saliva, or vaginal secretion samples at any time point up to 1 month postinoculation. Analyses of tissues obtained at necropsy at 1 month from two of the four monkeys, plus one monkey inoculated with laboratory-grade G207 (109 pfu) 2 years earlier, showed the distribution of G207 DNA restricted to the brain, although infectious virus was not isolated. Histopathology revealed normal brain tissues including the sites of inoculation. A measurable increase of serum anti-HSV antibody titer was observed in all monkeys, as early as 21 days postinoculation. The results ascertain the safety of G207 in the brain and indicate that strict biohazard management may not be required for G207-treated patients.
Acute cardiomyopathy with rhabdomyolysis in chronic alcoholism.
Authors: B I Seneviratne
Journal: BMJ (1975)

Of five chronic alcoholics with acute skeletal muscle necrosis (rhabdomyolysis) three developed acute heart failure with disturbances of rhythm and conduction. Symptoms came on abruptly after a period of intensified drinking. Myocardial infarction, thiamine deficiency, and cobalt intoxication were excluded. Probably the whole spectrum of muscle disease in chronic alcoholism may be commoner than has been suspected.
SUICIDE CONSULTATION: A PSYCHIATRIC SERVICE TO SOCIAL AGENCIES
Authors: MARVIN N. KAPHAN, R. E. LITMAN
Journal: American Journal of Psychiatry (1966)

The Suicide Prevention Center in Los Angeles, in its diagnostic and referral services focusing on the problem of suicide, has worked toward a community program of early detection of potentially suicidal individuals and location of suitable treatment services for them and has, in this endeavor, put considerable emphasis upon collaboration with social agencies. In the course of this collaboration, the agencies have been accorded a consultation service providing evaluations of suicide risk, treatment indications and suitability for casework handling. The S.P.C. has received from the agencies increased cooperation and willingness to accept patients who under other circumstances might have been rejected, as well as an opportunity to disseminate knowledge about the phenomenon of suicide. An important factor in this collaboration has been the development of methods of sharing responsibility without taking control of the case from the agency. One by-product of the consultation service has been the reexamination by the social agencies of their usual policies regarding such stereotyped categories as "severely disturbed," "psychotic" and "suicidal" clients. The paper includes discussion of some of the criteria used in the consultation, case illustrations and examples of policy changes in community facilities.
Reply from Authors re: Michael Baum. Screening for Prostate Cancer: Can We Learn from the Mistakes of the Breast Screening Experience? Eur Urol 2013;64:540–1
Authors: Monique J. Roobol, Ries Kranse, Chris H. Bangma, Suzie J. Otto, Theo H. van der Kwast, Leonard P. Bokhorst, Harry J. de Koning, Fritz H. Schröder
Journal: European Urology (2013)
Reverse Remodeling of the Left Cardiac Chambers After Catheter Ablation After 1 Year in a Series of Patients With Isolated Atrial Fibrillation
Authors: Patricia Reant, Stephane Lafitte, Pierre Jaïs, Karim Serri, Rukshen Weerasooriya, Meleze Hocini, Xavier Pillois, Jacques Clementy, Michel Haïssaguerre, Raymond Roudaut
Journal: Circulation (2005)

Background— Isolated atrial fibrillation (AF) is associated with mild enlargement of the left atrium (LA) and left ventricular (LV) diastolic dysfunction. The impact of ablation of isolated AF on left chamber size and function is unclear, and whether diastolic dysfunction is the cause or the consequence of AF remains unknown. The objective of this prospective study was to evaluate the impact of sinus rhythm restoration by catheter ablation on LV diastolic dysfunction, LA morphology, and mechanical function. Methods and Results— Forty-eight patients with isolated AF were studied by serial echocardiographic studies at baseline and at 1-, 3-, 6-, 9-, and 12-month intervals after radiofrequency ablation. LA dimensions and mechanical function and LV systolic and diastolic functions were evaluated at each time interval. Diastolic function was assessed with conventional Doppler parameters and new indexes such as tissue Doppler imaging, mitral flow propagation velocity, and combined criteria. LV diastolic dysfunction was present in paroxysmal and chronic AF patients with a reduction of tissue Doppler imaging lateral early diastolic peak velocity in 37% ( P &lt;0.001) and 48% ( P &lt;0.01), respectively, compared with healthy control subjects. At the end of the follow-up, LA area decreased significantly by 18% ( P &lt;0.001) in paroxysmal and 23% ( P &lt;0.05) in chronic AF patients. Diastolic function improved significantly with an increase in lateral early diastolic peak velocity of 29% ( P &lt;0.001) in paroxysmal AF and 46% ( P &lt;0.05) in chronic AF patients. A significant increase in LV ejection fraction was also noted for both groups: 7.7% and 18.8%, respectively. Conclusions— This study demonstrates reverse morphological remodeling of the LA and improvement of LV diastolic and systolic functions after restoration of sinus rhythm by ablation for isolated AF. Because patients with isolated AF have none of the traditional causes of LV diastolic dysfunction, our findings suggest that AF may be partly the cause rather than the consequence of diastolic dysfunction.
Absence of end diastolic frequencies in umbilical artery: a sign of fetal hypoxia and acidosis.
Authors: K. H. Nicolaides, C. M. Bilardo, P. W. Soothill, S. Campbell
Journal: BMJ (1988)

Internal radiation therapy using intrahepatic arterial injection of <sup>90</sup>Y-labeled glass microspheres (<sup>90</sup>Y-microspheres) has proven to be a promising therapeutic modality for inoperative liver tumor. Recently, direct intratumoral injection of <sup>90</sup>Y-microspheres has been performed with even more encouraging results. The purpose of this study was to compare the treatment efficacy of these 2 methods using <sup>90</sup>Y-microspheres. <b>Methods:</b> Forty-eight male rats, each bearing a hepatic tumor, were divided into 4 groups (12 rats in each group) to evaluate the efficacy of treatment. Group 1 received an intratumoral injection of 37 MBq (1 mCi) <sup>90</sup>Y-microspheres. Group 2 received an intratumoral injection of 0.1 mL normal saline as the control group. Group 3 received an intra-arterial injection of 37 MBq (1 mCi) <sup>90</sup>Y-microspheres. Group 4 received an intra-arterial injection of 0.1 mL normal saline as the control group. Tumor size was measured by liver sonography before injection as well as at 2 and 4 wk after injection. Survival time was calculated from the day of treatment to 2 mo after treatment by Kaplan-Meier survival analysis. The response rate was evaluated by the change in tumor size and survival time. Fisher9s exact, 2-tailed test was used to compare response rates. <b>Results:</b> In the rats treated by intratumoral injection of <sup>90</sup>Y-microspheres, 83.3% (10/12) showed a good response. In contrast, all 12 rats in the control group showed a poor response. The difference was significant (<i>P</i> &lt; 0.00001). Eighty-three percent (10/12) of the rats survived &gt;60 d after intratumoral injection of <sup>90</sup>Y-microspheres, whereas only 25% (3/12) of the control rats survived &gt;60 d. The difference was significant (<i>P</i> = 0.0068). In the rats treated by intra-arterial injection of <sup>90</sup>Y-microspheres, 58.3% (7/12) showed a good response to the treatment. All rats in the control group showed a poor response. The difference was significant (<i>P</i> = 0.0023). Sixty-six percent (8/12) of the rats survived &gt;60 d after intra-arterial injection of <sup>90</sup>Y-microspheres, whereas only 16.7% (2/12) of the control rats survived &gt;60 d. The difference was significant (<i>P</i> = 0.0385). However, the response rate and survival time between the intratumoral treatment group and the intra-arterial treatment group showed no significant difference (<i>P</i> = 0.3707 and 0.3988, respectively). <b>Conclusion:</b> Both methods (intratumoral treatment and intra-arterial treatment) showed a significantly good response rate and prolonged survival time compared with those of the control groups. However, no significant difference was found in the response rate or survival time between intratumoral treatment and intra-arterial treatment.
Factitious hypoglycaemia: chlorpropamide self-administration by a non-diabetic.
Authors: K G Alberti, J M Oxbury, G Higgins
Journal: BMJ (1972)

suggestions as highly unlikely and investigations are being undertaken to exclude them.It is also possible that the three patients suffering from non-neoplastic bowel disease were carrying occult cancers.They are being kept under surveillance.The lower proportion of positive faeces in patients whose cancers were proximal to the large bowel bears out the findings of Gold and Freedman (1956) that the concentration of C.E.A. in alimentary cancers diminishes from below upwards.It is clearly of the first importance to apply a quantitative technique to the demonstration of C.E.A. in faeces.It may be possible to define "normal limits" of faecal C.E.A. in the healthy population above which a diagnosis of alimentary carcinoma should be considered.This question is receiving attention.It remains to be seen whether serum or faeces is the best material to examine with a view to designing a diagnostic test.
Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis
Authors: A Cortes, W P Maksymowych, B P Wordsworth, R D Inman, P Danoy, P Rahman, M A Stone, M Corr, Lianne S Gensler, D Gladman, A Morgan, H Marzo-Ortega, M M Ward, T J Learch, J D Reveille, M A Brown, M H Weisman
Journal: Annals of the Rheumatic Diseases (2014)

Objective To identify genetic associations with severity of radiographic damage in ankylosing spondylitis (AS). Method We studied 1537 AS cases of European descent; all fulfilled the modified New York Criteria. Radiographic severity was assessed from digitised lateral radiographs of the cervical and lumbar spine using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A two-phase genotyping design was used. In phase 1, 498 single nucleotide polymorphisms (SNPs) were genotyped in 688 cases; these were selected to capture &gt;90% of the common haplotypic variation in the exons, exon–intron boundaries, and 5 kb flanking DNA in the 5′ and 3′ UTR of 74 genes involved in anabolic or catabolic bone pathways. In phase 2, 15 SNPs exhibiting p&lt;0.05 were genotyped in a further cohort of 830 AS cases; results were analysed both separately and in combination with the discovery phase data. Association was tested by contingency tables after separating the samples into ‘mild’ and ‘severe’ groups, defined as the bottom and top 40% by mSASSS, adjusted for gender and disease duration. Results Experiment-wise association was observed with the SNP rs8092336 (combined OR 0.32, p=1.2×10 −5 ), which lies within RANK (receptor activator of NFκB), a gene involved in osteoclastogenesis, and in the interaction between T cells and dendritic cells. Association was also found with the SNP rs1236913 in PTGS1 (prostaglandin-endoperoxide synthase 1, cyclooxygenase 1), giving an OR of 0.53 (p=2.6×10 −3 ). There was no observed association between radiographic severity and HLA-B*27 . Conclusions These findings support roles for bone resorption and prostaglandins pathways in the osteoproliferative changes in AS.
Behind an enteric neuron there may lie a glial cell
Authors: Michael D. Gershon
Journal: Journal of Clinical Investigation (2011)

The enteric nervous system (ENS) controls the gastrointestinal system. Enteric glia have long been regarded as the essential "glue" of the ENS. Now, however, two independent reports in this issue of the JCI provide compelling evidence that mouse enteric glia can also be neuronal precursors. These reports show that enteric glia give rise to neurons in vitro and that neurogenesis can be experimentally induced to occur in vivo in the adult mouse ENS. Unfortunately, glia do not constitutively replace neurons, and neurogenesis is not easily provoked. Although these new observations make it clear that clinical trials using glia to replace enteric neurons are more than premature, they are enticing for future research.
PET and NIR optical imaging using self-illuminating 64 Cu-doped chelator-free gold nanoclusters
Authors: Hao Hu, Peng Huang, Orit Jacobson Weiss, Xuefeng Yan, Xuyi Yue, Molly Gu Zhang, Yuxia Tang, Liming Nie, Ying Ma, Gang Niu, Kaichun Wu, Xiaoyuan Chen
Journal: Biomaterials (2014)
Geographic Variation in Medicare Spending
Authors: Arnold M. Epstein
Journal: New England Journal of Medicine (2010)

In my third and fourth years of medical school at Duke University, I was totally engaged in learning clinical strategies and algorithms: when to admit a patient with chest pain from the emergency ward, when and how to work up dyspepsia, when to schedule laboratory work and ambulatory follow-up for stable hypertension. These protocols are the nuts and bolts of day-to-day practice. I learned them as an apprentice, trailing fellows and attending physicians on ward rounds and in the clinic, since the level of detail needed to guide these decisions never seemed to be in the scientific literature. After finishing . . .
Carcinoma Arising in Choledochocele
Authors: T. Ohtsuka, K. Inoue, J. Ohuchida, T. Nabae, S. Takahata, H. Niiyama, K. Yokohata, Y. Ogawa, K. Yamaguchi, K. Chijiiwa, M. Tanaka
Journal: Endoscopy (2001)

Background and Study Aims: Choledochocele has a potential for carcinogenesis, but no report has described malignant changes of the choledochocele in relation to pancreaticobiliary reflux because its anatomic form does not fit the criteria of pancreaticobiliary malunion (PBM). The aims of this study were to analyze the amylase level in bile in patients with choledochocele and to clarify whether the presence of a choledochocele predisposed to carcinoma.
What if the government refuses to ban smoking in public places?
Authors: Jammi N Rao
Journal: BMJ (2004)

I came across a new TLA (that's “three letter acronym”) the other day: KDM. It stands for key decision maker. It was in a great big document that was in my post on how to go about persuading the great and the good to do something to reduce people's exposure to secondhand smoke in public places.

According to this framework for action a large number of public health professionals should devote a great deal of energy to winning the hearts and minds of city councillors, business leaders, trade unions, company bosses, and community leaders to act to limit or ban smoking in public places and in places of work. These people and organisations are the KDMs that we should be influencing.

That's all very well—but the thought occurred to me that there's one KDM that matters …
Religious fundamentalism in medical school
Authors: P. Ney
Journal: BMJ (1985)

need at least 800 to 1000 cases a year, about half of which would be needed for training the next generation of surgeons (D D Trunkey, personal communication).The medical profession in general, and surgeons in particular, must take the manage- ment of major injuries seriously.Until they relinquish their demand that every district general hospital accident and emergency department should receive the seriously in- jured, and until they persuade the government to establish trauma centres in selected hospitals, injured patients will continue to die un- necessarily.
The Harveian Lecture ON FRACTURES OF THE PATELLA AND THEIR SURGICAL TREATMENT: Delivered before the Harveian Society of London
Authors: C. B. Lockwood
Journal: BMJ (1911)

IT is fortunate that the knee cap is ebldom broken.'AU, fractures into joints are especially serious both at the time and afterwards.The joint is, sure to become in- flamed and cause pain and suffering, and it may in the end be stiff.But a broken knee'-cap has a further evil.It is more likely than other fractures to end in bad union and a weak and unreliable limb.In the past this' has always been a grave misfortune to the wage-earner, but in
Colposcopy in a family planning clinic: a future model?
Authors: H C Kitchener, R A Burnett, E S Wilson, J W Cordiner
Journal: BMJ (1987)

The first year9s experience of a satellite colposcopy clinic in the Glasgow Family Planning Centre was analysed. Establishment of the clinic was supervised by an experienced member of the colposcopy team at the department of gynaecology, Western Infirmary, Glasgow, who trained one of the family planning centre9s staff. Close links were thus maintained with the hospital clinic to which patients were referred for treatment. The policy at the new colposcopy clinic was to study prospectively all women in the hospital catchment area whose cervical smears were reported as abnormal. In 58 of 162 such patients there was at least moderate dyskaryosis and the cytologist9s recommendation had been referral for colposcopy. In 104 cases the changes were either atypia alone or mild dyskaryosis and a repeat smear was recommended within three to 12 months; 18 of these patients had grade II or III cervical intraepithelial neoplasia on biopsy, and relying on repeat smears would have resulted in an 11.7% false negative rate. If an atypical cytological picture is to be an indication for colposcopy clinics attached to family planning centres may have an important role, given satisfactory training and close links with central specialist colposcopy clinics.