tbuckley/cabot-search huggingface dataset:
Abstract OT3-2-05: Randomized phase II study of fulvestrant with or without ganetespib in patients (pts) with hormone receptor (HR)-positive metastatic breast cancer
Authors: NU Lin, L Whitesell, R Gelman, E Mayer, IE Krop, S Santagata, A Lowe, D Proia, S Farooq, M Brown, M Iannone, S Lindquist, EP Winer
Journal: Cancer Research (2013)

Abstract Background: In pts with HR-positive metastatic breast cancer, endocrine resistance is a major clinical problem. Ganetespib is a small molecule inhibitor of heat shock protein 90 (HSP90), a molecular chaperone protein that regulates post-translational folding of numerous client proteins including estrogen and progesterone receptor. In preclinical HR-positive breast cancer models, ganetespib impairs endocrine resistance and reduces heterogeneity in the disease control achievable by hormonal therapies. Trial Design and Eligibility: This is a randomized phase II study designed to evaluate the efficacy of ganetespib in combination with fulvestrant compared to fulvestrant alone. Pts with endocrine-resistant, HR-positive metastatic breast cancer and up to 1 prior line of metastatic chemotherapy are eligible. Endocrine resistance is defined as relapse while on or within 1 year of completion of adjuvant endocrine therapy (ET) or progression through at least one line of ET for advanced disease. Patients are treated with fulvestrant 500 mg IM on Cycle 1 Day 1 (C1D1) and C1D15, C2D1, and D1 of each subsequent 28-day cycle. Ganetespib is administered at a starting dose of 200 mg/m2 IV on Days 1, 8, and 15 of each cycle. Pts undergo optional research biopsies at baseline and time of progression. Pts with accessible disease undergo a required research biopsy on C2D9. Circulating tumor cells (CTCs) and peripheral blood mononuclear cells (PBMCs) are collected at baseline, C2D8, C2D9, and time of progression. Pts who progress on fulvestrant may cross over to the combination. Aims: The primary endpoint is progression-free survival. Secondary endpoints include safety and tolerability, objective response rate by RECIST 1.1, clinical benefit rate, and overall survival. Correlative aims include comparison of biomarkers on the C2D9 biopsy in pts treated with fulvestrant alone versus the combination of fulvestrant plus ganetespib, analysis of CTCs and pharmacodynamic markers in PMBCs. Statistical Methods: Pts will be randomized 1:2 to receive fulvestrant alone or the combination of fulvestrant plus ganetespib. The total accrual goal is 71 pts. The expected accrual rate is 3.5-4.5 pts per month over a period of ∼20 months; it is anticipated at ∼15% of pts may be censored for PFS, with similar probability on both arms. There will be 80% power to detect a prolongation of true median PFS from 4.0 months to 8.0 months, using a one-sided 0.05 log-rank test. Acrrual: To date, 15 of 71 planned pts have been enrolled. Funding: The trial is supported by a grant from the Susan G. Komen foundation and funding from Synta Pharmaceuticals. Contact information: nlin@partners.org. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT3-2-05.
Elevated Hip Fracture Risk in Type 1 Diabetic Patients
Authors: Junmei Miao, Kerstin Brismar, Olof Nyrén, Anna Ugarph-Morawski, Weimin Ye
Journal: Diabetes Care (2005)

OBJECTIVE—Patients with type 1 diabetes often have low bone mineral density, but epidemiological data on fracture risk are sparse and imprecise, particularly for men. RESEARCH DESIGN AND METHODS—In the Swedish Inpatient Register, we identified a population-based cohort of 24,605 patients (12,551 men and 12,054 women) who were hospitalized for diabetes before age 31 years during 1975 through 1998. Follow-up for hip fracture was accomplished through cross-linkage in the Inpatient Register until the end of 1998. Censoring information was obtained from the registers of Death and Migration. Using the Kaplan-Meier method, we calculated the cumulative probability of getting a hip fracture. Standardized hospitalization ratios and their 95% CIs estimated relative risks with the age-, sex-, and calendar period–matched Swedish general population as reference. RESULTS—In total, 70 and 51 first hip fractures were ascertained in men and women, respectively, corresponding to a cumulative probability (both sexes) of 65.8/1,000 until age 65 years. Markedly elevated risks were observed in both men and women (standardized hospitalization ratios = 7.6 [95% CI 5.9–9.6] and 9.8 [7.3–12.9], respectively), increasing with follow-up time. Ophthalmic, nephropathic, neurological, and cardiovascular complications were indicators of particularly high risks. CONCLUSIONS—Both male and female type 1 diabetic patients are at increased risk for hip fracture. Although optimal preventive measures still need to be defined, the co-occurrence with other diabetes complications suggests that tighter metabolic control might reduce the risk.
Industry group created bogus websites to hijack browsers
Authors: R. Moynihan
Journal: BMJ (2003)

<h3>Abstract</h3> Determining the impact that the <i>KIAA0319</i> gene has on primate brain morphology can provide insight into the evolution of human cognition and language systems. Here, we tested whether polymorphisms in <i>KIAA0319</i> in chimpanzees account for gray matter volumetric variation in brain regions implicated in language and communication (particularly within the posterior superior temporal gyrus and inferior frontal gyrus). First, we identified the nature and frequencies of single nucleotide variants (SNVs) in <i>KIAA0319</i> in a sample of unrelated chimpanzees (<i>Pan troglodytes</i> spp.). Next, we genotyped a subset of SNVs (those important for gene regulation or likely to alter protein structure/function) in a sample of chimpanzees for which <i>in vivo</i> T1-structural magnetic resonance imaging scans had been obtained. We then used source-based morphometry (SBM) to test for whole-brain gray matter covariation differences between chimpanzees with different <i>KIAA0319</i> alleles. Finally, using histologic sections of 15 postmortem chimpanzee brains, we analyzed microstructural variation related to <i>KIAA0319</i> polymorphisms in the posterior superior temporal cortex. We found that the SNVs were associated with variation in gray matter within several brain regions, including the posterior superior temporal gyrus (a region associated with language comprehension and production in humans). The microstructure analysis further revealed hemispheric differences in neuropil fraction, indicating that <i>KIAA0319</i> expression may be involved in regulation of processes related to the formation and maintenance of synapses, dendrites, or axons within regions associated with communication.
Recovery From Disseminated Intravascular Coagulation Without Heparin Therapy
Authors: Ruth Andrea Seeler
Journal: JAMA (1971)

<h3>To the Editor.—</h3> Data from a recent report by Corrigan and Jordan<sup>1</sup>cast doubt on the effectiveness of heparin sodium in improving the survival of patients with disseminated intravascular coagulation (DIC). Experience with a patient with<i>Neisseria meningitidis</i>septicemia and meningitis, who responded to treatment for shock, supports the concept of treating the patient, not the importance of the clotting studies. <h3>Report of a Case.—</h3> A 23-month-old boy was brought to the hospital because of irritability, refusal to eat, and fever. The child was acutely ill, with a temperature of 105 F, a pulse rate of 126 beats per minute, respiratory rate of 36 per minute, and a blood pressure of 90/60 mm Hg. Petechiae were present in the conjunctiva, and skin of the trunk and extremities. Lumbar puncture yielded clear cerebrospinal fluid (CSF) with 145 neutrophils per cubic millimeter. Gram-negative diplococci were found in the smear. The CSF
Oral efficacy of a leukotriene B4 receptor antagonist in colitic cotton-top tamarins.
Authors: D Fretland, T Sanderson, P Smith, L Adams, R Carson, J Fuhr, J Tanner, N Clapp
Journal: Gut (1995)

Leukotriene B4 (LTB4) is a potent neutrophil activator and chemotaxin that is present in increased concentrations in the colonic tissue and rectal dialysates of acute ulcerative colitis patients. Cotton-top tamarins (CTTs) with confirmed active colitis were treated with the second generation LTB4 receptor antagonist, SC-53228 ((+)-(S)-7-[3-(2-cyclopropyl-methyl)-3-methoxy-4-[(methylamino) carbonyl]phenoxy]propoxy]-3,4-dihydro-8-propyl-2H-1-benzopyran-2- propanoic acid), 20 mg/kg bodyweight by gavage, twice daily for 56 days. End points were body weights, stool consistency, colonic endoscopy, assay of inflammatory mediators, and haematology and clinical chemistry tests. LTB4 and prostaglandin E (PGE) values were measured in rectal dialysates at pretreatment, 28 day and 56 day time points. LTB4 concentrations were reduced from pretreatment mean (SEM) values of 37.3 (0.8) ng/ml to 3.7 (0.8) ng/ml (p < 0.001) and 2.3 (0.5) ng/ml (p < 0.01) at days 28 and 56, respectively. On the other hand, mucosal protective PGE values remained constant or slightly increased during SC-53228 treatment (pre: 6.9 (2.2) ng/ml; day 28: 6.7 (1.4) ng/ml; day 56: 9.9 (1.6) ng/ml). Furthermore, assessment of a panel of 35 clinical chemistry and haematology parameters throughout the treatment showed there were no significant untoward effects of drug treatment. Six CCTs finished the eight week treatment and five of six gained weight (ranging from 27-121 grams each) while one CTT lost weight (50 g). Stool condition improved in five of six animals while one of six remained unchanged. All CCTs showed dramatic improvement histologically, with no or only minimally active colitis after treatment. The histological changes plus significant weight gains and improvement of stool condition (quality of life parameters) after eight weeks of SC-53228 treatment were remarkable. Furthermore, in follow up biopsies seven months after treatment ceased, three of six CTTs had no active colitis. This is the first time afflicted CTTs have not had recurring colitic exacerbations after a treatment regimen was stopped. It is concluded that in colitic CTTs, SC-53228 has shown both an immediate and a long acting anticolitic activity. It is also concluded that reduced LTB4 concentrations during treatment inhibited neutrophil infiltration of the colonic tissue and this, coupled with the maintenance of mucosal protective prostaglandins, contributed to the dramatic anticolitic efficacy. The treatment was safe over eight weeks. A compound such as SC-53228 may be useful in the medical treatment of human inflammatory bowel disease.
Questionary on General Practice
Authors: R. Maxwell
Journal: BMJ (1964)

MIAJOURNA.88Ldoes not care and the greedy gets as much -attention as he can).Similarly, should he fail to call the doctor at the proper time and have to call later, he has no means of compensat- ing the doctor for his extra trouble.He feels guilty, fears hostility, and may project it back at the doctor in a demanding attitude.Thus the natural divergence of interest of patient and doctor, which is reconciled by fee pay- ment, is exacerbated by the capitation system.So long as we continue to work in the present system we have an individual and collective responsibility for the poor standards of work and relationships which it entails.Since there is no prospect of any Government voluntarily reorganizing the Service as we advise (report of House of Commons debate, 1 August, p. 319) it is our duty to bring this about by withdrawing from it now and treating our patients privately.Nowadays we could all afford to waive our fees in the few cases of real financial hardship.The Government would, of course, always be at liberty, if it really has the patients' welfare at heart, to introduce a State-subsidized insurance scheme on the lines of the successful schemes in Australia, Norway, etc., London E.4.
Carney complex: report of a kindred with predominantly cutaneous manifestations
Authors: D.K.B. ARMSTRONG, A.D. IRVINE, J.M. HANDLEY, M.Y. WALSH, D.R. HADDEN, E.A. BINGHAM
Journal: British Journal of Dermatology (1997)

We report a four-generation kindred with the complex of myxomas, spotty pigmentation and endocrine overactivity. This kindred demonstrates a relatively limited phenotypic expression with predominance of cutaneous features. Male-to-male transmission confirms the autosomal dominant nature of the condition. We propose that pilonidal sinus may be an associated manifestation in this kindred.
Drug War Intelligence Gathering: Risky, but Useful to Physicians
Authors: Jody W. Zylke
Journal: JAMA (1988)

A PATIENT in the emergency department says he has been taking milk, and he doesn't mean the homogenized, pasteurized kind. How can a physician find out what he has taken? The patients in most practices are asking more questions about illicit drugs, but physicians may not be aware which of these are circulating in the community. How do they get more information? If you live in New York City, you might call William Hopkins. Hopkins is the supervisor of the Street Research Unit in the New York State Division of Substance Abuse Services. The unit, the only one of its kind, has been so successful that the National Institute on Drug Abuse has contacted Hopkins about starting similar programs in other parts of the country. At a recent American Academy of Pediatrics meeting, Hopkins spoke about his unit and the drug information it gathers on the street. He says more
Physician and Population Determinants of Rates of Middle-Ear Surgery in Ontario
Authors: Peter C. Coyte
Journal: JAMA (2001)

Small-area variations in surgical rates raise concerns about access to care, treatment appropriateness, and the quality and cost of care.To measure small-area variations in rates of myringotomy with insertion of tympanostomy tubes (TTs) and to identify determinants of rate variation.Retrospective analyses using hospital discharge data for patients who had undergone a myringotomy with insertion of TT by county in Ontario between April 1, 1996, and March 31, 1999. Information on possible determinants was taken from a survey of otolaryngologists and primary care physicians in 1996 and from the 1996 Canadian census and physician demographic databases for 1996-1999.A total of 75 358 hospitalizations for TT placement of children and adolescents (aged </=14 years).Small-area variation in rates of TT.An almost 10-fold difference between the areas with the highest and lowest rates was found (extremal quotient, 9.6; 95% confidence interval [CI], 8.2-11.1; P<.001). Higher rates occurred in counties with higher percentages of high school graduates (parameter estimate, 0.01; 95% CI, 0-0.02; P =.049); and where referring physicians were more likely to be male (parameter estimate, 0.01; 95% CI, 0-0.02; P =.01), North American-trained (parameter estimate, 0.01; 95% CI, 0.01-0.02; P<.001), and have higher propensities to refer for surgery (parameter estimate, 0.40; 95% CI, 0.09-0.72; P =.02). Otolaryngologist opinion was not a significant predictor.Substantial area variation in TT rates was observed. The opinion of primary care physicians was the dominant modifiable determinant, suggesting an area of research that may be important in reducing area variation in TT procedures.
Gout is associated with more comorbidities, poorer health-related quality of life and higher healthcare utilisation in US veterans
Authors: J A Singh, V Strand
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> To better understand the impact of gout on functional status, health-related quality of life (HRQoL), mortality and healthcare utilisation in US veterans. <h3>Methods:</h3> All veterans seen in Veterans Integrated Service Network-13 from 1 October 1996 to 31 March 1998 received mailed surveys asking about demographic characteristics; performance of activities of daily living and HRQoL by Short Form-36 (SF-36) for Veterans. Administrative data included demographics; inpatient/outpatient healthcare utilisation; ICD-9 codes for gout, medical comorbidities and arthritis excluding gout—"arthritic comorbidity" and 1-year mortality. Multivariable estimates compared results between veterans with/without gout using least means squared. <h3>Results:</h3> Subjects with gout were significantly older, retired, not married, current non-smokers, with more comorbidities. Multivariable-adjusted bodily pain was somewhat worse (49.7 vs 47.1, p&lt;0.01) and mental health (66.7 vs 68.6, p&lt;0.01) domain scores somewhat better in patients with gout, both differences significant but not clinically meaningful (less than threshold of 5–10 points); other SF-36 domain and summary scores and functional limitations were similar. Medical or arthritic comorbidities predicted clinically/statistically lower adjusted scores in all SF-36 domains and physical domains (physical component summary), respectively. Patients with gout had significantly more annual primary care visits (3.5 vs 2.7, p&lt;0.001) and admissions to hospital (18.3% vs 15.1%, p&lt;0.01), fewer mental health visits (10.1% vs 13.7%, p&lt;0.01) and similar mortality (2.6% vs 2.2%, p = 0.23). <h3>Conclusions:</h3> Gout is independently associated with higher medical and arthritic comorbidity, primary care and inpatient utilisation. Poorer HRQoL, functional limitation and higher mortality noted in univariate analyses in patients with gout were attributable to higher comorbidity and sociodemographic characteristics.
B cell depletion therapy for patients with systemic lupus erythaematosus results in a significant drop in anticardiolipin antibody titres
Authors: Y Ioannou, A Lambrianides, G Cambridge, M J Leandro, J C W Edwards, D A Isenberg
Journal: Annals of the Rheumatic Diseases (2007)

B cell depletion therapy (BCDT) has recently been used with success to treat patients with rheumatoid arthritis and systemic lupus erythematosus (SLE). As antiphospholipid antibodies have been implicated in the pathogenesis of the antiphospholipid syndrome (APS), we asked the question whether BCDT affects levels of IgG anticardiolipin antibodies (aCL) in our cohort of 32 SLE patients given this treatment.We identified seven SLE patients who had undergone BCDT and had had at least two moderate positive aCL titres at least 12 weeks apart. Of these only one patient had APS. IgG aCL were measured at time 0 and 6-9 months post BCDT.At time 0, the mean IgG aCL level was 20.6 standardized IgG antiphospholipid units (GPLU) (range (SD) 10-32, (10.1), normal level <5). At 6-9 months post depletion the IgG aCL levels in six of the seven patients was undetectable and in the other patient the level reduced from 25 GPLU to 15 GPLU (p<0.005, two-tailed paired t test). At baseline, only one patient had a mildly positive anti-beta(2)-glycoprotein I (beta(2)GPI) antibody level at 30% (compared to an in-house standard), which fell to 5% post-BCDT.This small observational study in patients with SLE is the first to demonstrate that BCDT results in a significant reduction in levels of IgG aCL.
Incidence of Myoendothelial Gap Junctions in the Proximal and Distal Mesenteric Arteries of the Rat Is Suggestive of a Role in Endothelium-Derived Hyperpolarizing Factor–Mediated Responses
Authors: Shaun L. Sandow, Caryl E. Hill
Journal: Circulation Research (2000)

Abstract —Although the chemical nature of endothelium-derived hyperpolarizing factor (EDHF) remains elusive, electrophysiological evidence exists for electrical communication between smooth muscle cells and endothelial cells suggesting that electrotonic propagation of hyperpolarization may explain the failure to identify a single chemical factor as EDHF. Anatomical evidence for myoendothelial gap junctions, or the sites of electrical coupling, is, however, rare. In the present study, serial-section electron microscopy and reconstruction techniques have been used to examine the incidence of myoendothelial gap junctions in the proximal and distal mesenteric arteries of the rat where EDHF responses have been reported to vary. Myoendothelial gap junctions were found to be very small in the mesenteric arteries, the majority being &lt;100 nm in diameter. In addition, they were significantly more common in the distal compared with the proximal regions of this arterial bed. Pentalaminar gap junctions between adjacent endothelial cells were much larger and were common in both proximal and distal mesenteric arteries. These latter junctions were frequently found near the myoendothelial gap junctions. These results provide the first evidence for the presence of sites for electrical communication between endothelial cells and smooth muscle cells in the mesenteric vascular bed. Furthermore, the relative incidence of these sites suggests that there may be a relationship between the activity of EDHF and the presence of myoendothelial gap junctions.
Peripheral Neuropathy in Rheumatoid Arthritis
Authors: C. A. Pallis, J. T. Scott
Journal: BMJ (1965)

Sporadic references to peripheral neuropathy complicating rheumatoid arthritis appeared as long ago as the last century.The early literature is reviewed by Irby, Adams, and Toone (1958) and by Hart and Golding (1960).During the past ten years neuropathy has been mentioned in a number of papers dealing primarily with the vascular complications of rheumatoid arthritis or with treatment of the disease with corticosteroid hormones.A recent comprehensive account of arteritis in rheumatoid disease by Schmid, Cooper, Ziff, and McEwen (1961) reviews these communications in detail.Hart, Golding, and Mackenzie (1957) were the first to describe a definitive series of patients with neuropathy and rheumatoid disease.Similar publications then followed from Mason and Steinberg (1958), Irby et al. (1958), Johnson, Smyth, Holt, Lubchenco, and Valentine (1959), Ansell (1960), Hart and Golding (1960), Steinberg (1960), and Ferguson and Slocumb (1961).The association has become well recognized by those treating large numbers of patients with rheumatoid arthritis, but is perhaps less familiar to neurologists and general physicians.Moreover, certain features of the condition have not yet received adequate attention.The present paper describes 30 cases of rheumatoid arthritis' and peripheral neuropathy personally examined at Hammer- smith Hospital and at the Canadian Red Cross Memorial Hospital, Taplow, during the past two years.These comprise most patients with rheumatoid neuropathy attending the two centres during this period. Clinical ExaminationThe examination of patients with rheumatoid arthritis and neurological complications is difficult and time-consuming.The history of arthritis is usually long, the details of its fluctuating course being more or less accurately recorded in voluminous dossiers.Patients often have difficulty in giving accurate information if to their arthritic symptoms are added neuritic ones, which may themselves evolve in a variety of ways.Neuritic pains may be confused with those of arthritis, the distribution of numbness may be difficult to recall, and com- plaints of weakness are notoriously hard to evaluate.For example, many patients with rheumatoid arthritis complain of weak hands, when what they mean is a combination of stiffness,
Analgesia for children in intensive care.
Authors: D Southall, C Harrison-Sewell, B Cronin, M Samuels, H Hartmann, A O'Higgins
Journal: BMJ (1993)

the 120 experienced young patients interviewed, 13 (aged 8 to 15 years) said that they were the "main decider" about proposed surgery, and their parents agreed.Health professionals discussed the wish of certain children, aged from 7 years, to refuse or postpone treatment.This was respected in cases of proposed surgical leg lengthening, spinal fusion for scoliosis, amputation (of toes), heart-lung transplantation, and growth hormone treatment.Articles reporting empirical studies of child patients' decision making are more likely to further the spirit of the 1989 Children Act than is abstract debate.They would help to ensure that clinical practice is not unduly influenced by retiring judges, and that legal judgments are influenced by reasonable doctors3 in daily contact with young patients.