tbuckley/cabot-search huggingface dataset:
Pituitary prolactinoma and estrogen contraceptives. (Editorial)
Authors: Vaisrub S
Journal: JAMA (1979)

Recent diagnostic and therapeutic advances have propelled the galactorrhea-amenorrhea syndrome to the forefront of medical awareness and many more cases of pituitary prolactinemia are being diagnosed treated and reported.  But the increase cited in this editorial goes beyond refinement of diagnositic tests;  other factors are cited as causing a real increased incidence.  1 factor is the use of estrogen-containing oral contraceptives.  In a series of 30 patients with galactorrhea and amenorrhea 23 had hyperprolactinemia.  In 19 of these symptoms followed the use of oral contraceptives and in 4 they appeared after parturition.  3/19 had radiographic evidence of a pituitary tumor.  A temporal link between the manifestations of prolactinemia and oral contraceptive use or childbirth is evident in a series of 42 patients with amenorrhea-galactorrhea and hyperprolactinemia who underwnet transsphenoidal resection of histologically verified pituitary adenomas.  In 31 of these patients symptoms developed in close association with the use or discontinued use of oral contraceptives or after childbirth.  Therefore estrogens are thought to promote growth of preexisting silent pituitary lesions.
Abstract 1818: Medium Term Outcomes of Coronary Artery Bypass Graft Surgery On vs Off pump: Result From a Randomized Controlled Trial
Authors: Wojtek Karolak, Gregory Hirsch, Karen Buth, Jean-Francois Legare
Journal: Circulation (2006)

Objective: Despite the proposed advantages of off pump CABG surgery some controversy remains as to its advantages compared to on pump CABG. The present study evaluates medium term outcomes from pat...
Age is an independent risk factor for the presence of clinically significant prostate pancer in men over the age of 75
Authors: Sandeep Mistry, Wesley Mayer, Gustavo Ayala, Brian Miles
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

2545 

Introduction: Prostate cancer is the most common non-skin malignancy affecting men and is the second-leading cause of cancer death. The incidence of prostate cancer increases dramatically with age. However, many health authorities advocate ceasing routine prostate cancer screening in men over 75 due to the belief that most patients will have a clinically insignificant cancer and will not benefit from therapy. The true prevalence of clinically significant prostate cancer in elderly men is not known. Methods: We analyzed 1,446 needle biopsies of the prostate of men ages 75 or older. All pathologic reviews were conducted by the Pathology Department at The Methodist Hospital in Houston, TX. Data was collected from pathology reports, hospital and clinic databases, and medical records when available. Data obtained included age at biopsy, prostate-specific antigen (PSA), number of positive core biopsies, and Gleason’s Score. Statistical analysis was performed using STATA (Stata Corp., College Station,TX). Clinically significant cancer is defined by the pathologic presence of Gleason’s score 6 adenocarcinoma in more than one biopsy core or the presence of any Gleason 4 or 5 component in the biopsy. Results: The average age of the patients included was 78.8 and 95% of the patients were between the ages of 75 and 85. Average PSA for patients biopsied was 12.8. Of all biopsies reviewed, 52.6% of biopsies were positive for prostate cancer and 78% of these would be defined as clinically significant cancer. Regression analysis revealed age to be a significant (p>0.05) factor for increased Gleason’s score found on positive biopsies. Logistic regression revealed age as a significant factor (p>0.05) for clinically significant prostate cancer even when controlling for PSA. A PSA threshold value of 6.5 would have missed 38% of significant cancer and a PSA threshold of 4.0 would have missed 8% of significant cancers. Conclusions: Our findings suggest that the prevalence of clinically significant prostate cancer in the elderly population may be higher than previously thought. As the population continues to live healthier longer, confronting prostate cancer morbidity in the elderly population will become more common. Using higher PSA thresholds to eliminate unnecessary biopsies in older men does not appear to help identify patients at greater risk of having clinically significant prostate cancer. Patients with prostate cancer having aggressive clinical features may benefit from treatment of their prostate cancer well into their eighth and ninth decades of life. Screening and diagnostic recommendations should reflect the potential benefit of identifying patients with aggressive prostate cancer even after age 75.
Abstract 4451: Impact of Low Responsiveness to Thienopyridine Antiplatelet Agents Before Elective Drug Eluting Stent Implantation on Subsequent Adverse Cardiac Events
Authors: Hironori Ueda, Chikaaki Motoda, Yasuhiko Hayashi, Yoshiko Masaoka, Tadamichi Sakuma, Yuji Muraoka, Hidekazu Hirao, Mamoru Toyofuku, Tomokazu Okimoto, Masaya Otsuka, Hiromichi Tamekiyo, Shinnji Mito, Takehito Tokuyama, Ryo Takeda, Tomoharu Kawase
Journal: Circulation (2008)

Background: Dual antiplatelet therapy with aspirin and clopidogrel is the gold standard after drug eluting stents (DES) implantation. However, large inter-individual variability in the response to thienopyridines is known to exist. Recent data show that poor responsiveness to clopidogrel is associated with an increased risk of thrombotic events in patients treated with DES. Therefore, this study was designed to determine whether low response to thienopyridines correlates with the occurrence of major adverse cardiac events (MACE) in patients treated with DES. Methods: The study group consisted of 230 consecutive patients (mean age 70.1 ± 10.6 yrs) who successfully underwent elective implantation of DES at our hospital from January to July 2007 (total; 304 coronary lesions). All patients received chronic dual antiplatelet agents (aspirin and ticlopidine or clopidogrel). We analyzed the platelet aggregation activity in those patients and 46 control patients undergoing coronary angiography without antiplatele...
Pioglitazone Improves Myocardial Blood Flow and Glucose Utilization in Nondiabetic Patients With Combined Hyperlipidemia
Authors: Rossi P. Naoumova, Heiko Kindler, Lucia Leccisotti, Marco Mongillo, Muhammad T. Khan, Clare Neuwirth, Mary Seed, Paul Holvoet, John Betteridge, Paolo G. Camici
Journal: Journal of the American College of Cardiology (2007)
Abstract 3599: Resistance mechanisms to HER2-targeting treatment in HER2-positive gastric cancer
Authors: Kyo Hwa Kang, Ah-Rong Nam, Ji Eun Park, Ju-Hee Bang, Jin Ling, Mei Hua Jin, Tae Yong Kim, Sae-Won Han, Sang-Hyun Song, Seock-Ah Im, Tae-You Kim, Do-Youn Oh, Yung-Jue Bang
Journal: Cancer Research (2015)

Abstract Background: HER2 is the first validated therapeutic target in advanced gastric cancer (GC). Trastuzumab in combination with chemotherapy is used as a first-line treatment of GC. The resistance mechanisms to trastuzumab have not been widely known in GC. We investigated the resistance mechanisms to HER2-targeting agents in HER2-positive gastric cancer cells. Methods: SNU216 and NCI-N87 are HER2 amplified gastric cancer cells. Using these cells, we established trastuzumab-resistant cells (SNU216-HR, N87-HR) and dacomitinib (panHER inhibitor)-resistant cells (SNU216-PR). Acquired resistance of the established cell lines was verified by MTT assay and western blotting. We compared various receptor tyrosine kinase activities and protein expression levels between parental and resistant cells by RTK arrays and western blotting. We used many targeted agents (HER family inhibitor, PI3K inhibitor, mTOR inhibitor, MEK inhibitor, Src inhibitor, HSP90 inhibitor, etc) to overcome the resistance. Results: Resistant cells displayed more rapid growth rate and different morphology compared with parent cells. Resistant cells showed increased levels of pEGFR, pHER2, pHER3, pMET, pIGF1R, pAXL, pSTAT3, pAKT, pFAK, and TS compared with the parental cells in western blot. With the treatment of trastuzumab, HR cells showed elevated levels of EGFR, pHER2, AXL, pAXL, pMEK, pSRC, pSTAT3, pAKT, pERK and TS compared with the parental cells. With the treatment of dacominitib, PR cells showed elevated levels of pEGFR, pAXL, pIGF1R, pMEK, pSRC, pERK and TS compared with the parental cells in western blot. The RTK arrays also showed the similar findings. These resistant cells were more sensitive to Src inhibitor and PI3K inhibitor than parent cells. Conclusion: Resistance mechanisms to HER2-targeting strategy in gastric cancer include activation of HER, MET, FAK and Src pathway. Targeting these pathways is needed to overcome resistance. Citation Format: Kyo Hwa Kang, Ah-Rong Nam, Ji Eun Park, Ju-Hee Bang, Jin Ling, Mei Hua Jin, Tae Yong Kim, Sae-Won Han, Sang-Hyun Song, Seock-Ah Im, Tae-You Kim, Do-Youn Oh, Yung-Jue Bang. Resistance mechanisms to HER2-targeting treatment in HER2-positive gastric cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3599. doi:10.1158/1538-7445.AM2015-3599
Dissecting Aneurysm of the Aorta
Authors: H. S. Shucksmith, I. Macpherson
Journal: BMJ (1949)

Haemoglobin (g.%) 16-6 (120%) 13-6 (98%) 12-4 (90%) 12-7 (92%) 15-5 (112%) Colour index .. 1.00 1.00 099 0.99 1-00 Leucocytes (per c.mm.).. 15,
Talactoferrin is a novel maturation factor for human dendritic cells
Authors: Michela Spadaro, Cristiana Caorsi, Patrizia Ceruti, Federica Pericle, Atul Varadhachary, Guido Forni, Mirella Giovarelli
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

259 

Background: Talactoferrin alfa(TLF) is a unique recombinant version of human lactoferrin, an important immunomodulatory protein present in exocrine secretions and in the secondary granules of neutrophils. Talactoferrin has demonstrated anti-cancer activity in preclinical studies and in Phase II clinical trials in patients with Renal Cell Cancer and non-small cell lung cancer. Talactoferrin is now entering Phase III clinical development. We have previously shown that orally administered TLF acts through the gut and the gut-associated lymphoid tissue (GALT) - the largest lymphoid organ in the body - inducing a strong systemic innate and adaptive immune response, cellular infiltration of distant tumors and tumor-cell death. We have also shown that CD8+ lymphocytes and NK-T cells are required for TLF’s anti-cancer activity.    Methods and Results: In this work, we evaluated the role played by dendritic cells (DC) in this activity. We now show that talactoferrin, at physiologically relevant concentrations (100 μg/ml) up-regulates the expression of HLA class II, CD83, CD80 and CD86 costimulatory molecule and CXCR4 and CCR7 chemokine receptors, acting primarily through the p38MAPK signaling pathway. DCs matured by talactoferrin displayed an enhanced release of IL-8 and CXCL10, and a significantly reduced production of IL-6, IL-10, and CCL20. They also display a reduced ability to take up antigen, and increased capacity to trigger proliferation and release IFNγ in the presence of allogeneic human T cells. Talactoferrin-matured DC are able to prime naive T cells to respond to KLH antigen and display a significantly increased capacity to present Flu-MA58-66 peptide to HLA-A2 matched T cells.    Conclusions: These data suggest that the linkage of the innate and adaptive immunity through DC maturation is a key immune function mediated by TLF. Thus, TLF, a first-in-class anti-cancer molecule entering Phase III clinical trials, acts through a novel immunomodulatory mechanism of action involving dendritic cell activation.
Long-Term Outcome and its Predictors Among Patients With ST-Segment Elevation Myocardial Infarction Complicated by Shock
Authors: Mandeep Singh, Jennifer White, David Hasdai, Patricia K. Hodgson, Peter B. Berger, Eric J. Topol, Robert M. Califf, David R. Holmes
Journal: Journal of the American College of Cardiology (2007)
Spheroid formation affects the response of mouse ovarian cancer cells to natural and synthetic sphingoid bases.
Authors: Eva Schmelz, Paul Roberts
Journal: Cancer Research (2008)

3051   We have recently isolated mouse ovarian surface epithelium (MOSE) cells that spontaneously undergo transformation in vitro and characterized distinct transitional states. As the cells progress from a non-tumorigenic to a highly aggressive malignant phenotype, our ovarian cancer model undergoes distinct changes in proliferation, anchorage-independent growth, and tumor formation in vivo. Comparable to the formation of ascites in women, these cells also form spheroids when cell attachment is prohibited. In the present study, we investigated if the response of the MOSE cells to sphingolipids, lipid second messengers involved in the regulation of cell growth, differentiation and cell death, is altered by the spheroid formation. Our results show that sphingolipid treatment did not affect spheroid formation. However, although there was no difference in the uptake of natural and synthetic sphingoid bases between cells grown in monolayers or as spheroids, the toxicity of both sphingosine and the synthetic analog enigmol was drastically reduced in spheroids in a structure-, time- and concentration dependent manner, and signaling pathways leading to cell death were altered. These results suggest a limitation of the use of sphingolipids as anti-cancer agents against ascites in women.  Supported by AICR grant 04B071 (to EMS), and NIH R01 CA118846 (to EMS and PCR)
Abstract 1176: The effect of resveratrol combined with dichloroacetate (DCA) on breast cancer cell lines and MCF-10a noncancerous cells
Authors: Sarah Piepenbrink, Dan Sisler, Russ Feirer
Journal: Cancer Research (2015)

Abstract Resveratrol, (3,5,49-trihydroxy-trans-stilbene), was first reported to act as a chemo-preventative anticancer compound in mice by Jang et al. in 1997 and has been shown to induce apoptosis and reduce both cell viability and mitotic index in many cancer cell lines. Earlier work in our lab found that it affects glucose utilization by decreasing glucose uptake by MCF-7 cells. The present study examined combinations of resveratrol with DCA, a compound that affects mitochondrial metabolism (reversing the Warburg Effect). A goal of this study was to determine if DCA might sensitize cancer cells to other chemotherapeutic compounds that affect glucose metabolism, such as resveratrol. Glucose uptake and lactate production by treated cells were measured, and Western blots were used to estimate levels of several proteins, including cleaved PARP and p21. Both resveratrol and DCA were found to reduce cell viability of treated breast cancer cell lines. Resveratrol, but not DCA, was found to induce caspase-3,7, a measure of apoptosis. This suggests that resveratrol and DCA may affect viability via different mechanisms. More importantly, a synergistic effect of these compounds on cell viability was observed, where DCA was found to enhance the anti-proliferative effect of resveratrol. Citation Format: Sarah Piepenbrink, Dan Sisler, Russ Feirer. The effect of resveratrol combined with dichloroacetate (DCA) on breast cancer cell lines and MCF-10a noncancerous cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1176. doi:10.1158/1538-7445.AM2015-1176
Private practice
Authors: Andrew Cole
Journal: BMJ (2008)

APMS (Alternative Provider of Medical Services) was once just another of the myriad health service acronyms that English general practitioners (GPs) were expected to master. But in recent months the APMS procurement process has become all too familiar and has led to fears it could threaten the foundations of general practice.

It’s a surprising turnaround. When APMS was launched it was billed as an unexceptional, indeed laudable, attempt to bring new blood into areas where practices had failed or had severe doctor shortages. In those situations contracts would be put out to tender and would be open to all comers—the private or voluntary sector or existing NHS practices.

Initially that’s how it worked. But recently the number of APMS schemes has risen sharply while the criteria for choosing this tendering method seem to have widened. The trend gained momentum with the government’s edict late last year that 100 new general practices and 150 polyclinics be procured through APMS.

A survey by the general practitioners’ magazine Pulse in January showed a third of trusts were now tendering for APMS contracts compared with just 10% six months earlier. And when it comes to the procurement process itself, the private sector seems to be winning hands down. Another survey by the same magazine suggests that although around half of shortlisted bids come from NHS practices, only one in 10 is successful, with 91% going to private companies. Private companies are also consistently undercutting practices on price, often by as much as 25%.
Abstract 15518: Novel SNPs Associated with Warfarin Dose in a Large Multicenter Cohort of African Americans: Genome Wide Association Study and Replication Results
Authors: Minoli A Perera, Nita A Limdi, Larisa Cavallari, Eric R Gamazon, Anuar Konkashbaev, Anna Pluzhnikov, Jelai Wang, Nianjun Liu, Michael J Wagner, Alan Wu, Dan M Roden, Dana C Crawford, James K Burmester, Jennifer Evertson, Matthew Tector, Taisai Mushiroda, Michiaki Kubo, Russ B Altman, Teri E Klein, Mark J Rieder, Yusuke Nakamura, Nancy J Cox, Julie A Johnson
Journal: Circulation (2011)

Warfarin has consistently shown large interindividual differences in therapeutic dose and has a high potential for adverse events due to over and under-dosing. Several genome wide association studi...
Evaluation of the Proliferative Potential of Gliomas by KI 67 Immunolabelling of Stereotactic Biopsy Samples
Authors: M. Parent, S. Blond, P. Gosset, F. Dubois, R. Assaker, J. L. Christiaens, A. Dupont
Journal: Neuro-Oncology (1991)

Using the monoclonal antibody (mAB) Ki 67, proliferating cells were demonstrated immunocytochemically in 50 stereotactic brain glioma biopsies. The antibody, which reacts with a nuclear protein antigen expressed during the G1, S, G2 and M phases of the cycle (GERDES J. and al 1985) was demonstrated in smear preparation using the peroxidase antiperoxidase method. The degree of proliferative activity was estimated by determining the percentage of Stained tumor cells. The Ki 67 labelling index (LI) was in agreement with the histologic grade but somes cases of low grade gliomas demonstrated a high Ki 67 LI. Marked variations of the Ki 67 LI were found in morphologically similar high grade gliomas. The Ki 67 LI complements the findings of the standard histological examination of cerebral gliomas. This is an additional diagnostic mean to evaluate the proliferative potential of these tumors.
Frequency of Nosocomial Transmission of HIV Infection among Health Care Workers
Authors: G P Wormser, C S Rabkin, C Joline
Journal: New England Journal of Medicine (1988)

Documented HIV seroconversion in health care workers from patient contact has occurred.  The risk of HIV seroconversion from a single needle-stick accident from an infected patient has been shown to be about 0.35% on the basis of composite analysis of 8 seroprevalence studies.  Needle-stick injury is the most important risk for health care workers occurring quite commonly.  The frequency of injuries in workers caring for HIV infected patients in our hospital has declined from 4.6 needle-sticks/1000 HIV infected patient-days in 1984 to 1.9/1000 days from 1/1/86 to 6/30/87.  The probability of nosocomial transmission of HIV in our institution can be calculated.  105000 HIV infected patient-days would yield a 50% chance of at least 1 case of HIV transmission to a health care worker.  This number of patient days will be exceeded in many large urban medical centers over the next 4 years.  Many institutions are likely to have to face the prospect of nosocomial transmission to a member of their staff in the next few years.  Prevention of needle-stick injuries is a critical factor in avoiding this outcome.
Understanding the comorbidity between early-onset dysthymia and cluster B personality disorders: a family study
Authors: L P Riso, D N Klein, T Ferro, K L Kasch, C M Pepper, J E Schwartz, T A Aronson
Journal: American Journal of Psychiatry (1996)

A number of studies have documented significant comorbidity between dysthymia and axis II personality disorders, particularly those grouped in cluster B. However, the nature of this comorbidity is poorly understood. The purpose of this investigation was to use the family study method to test five competing models of the comorbidity between early-onset dysthymia and cluster B personality disorders.Proband groups consisted of subjects with early-onset dysthymia and a co-occurring cluster B personality disorder (N = 28), subjects with early-onset dysthymia without a cluster B personality disorder (N = 69), and a comparison group of subjects who had never been psychiatrically ill (N = 45). The groups were compared on rates of dysthymia with a cluster B personality disorder, dysthymia without a cluster B personality disorder, and cluster B personality disorders without dysthymia in their first-degree relatives (N = 675).The relatives of both subgroups of dysthymic probands exhibited higher rates of dysthymia with a cluster B personality disorder, dysthymia without a cluster B personality disorder, and cluster B personality disorders without dysthymia than the relatives of the never ill probands. In addition, the relatives of probands with comorbid dysthymia exhibited higher rates of cluster B personality disorders without dysthymia than the relatives of probands with noncomorbid dysthymia.This pattern of results is consistent with the notion that dysthymia and cluster B personality disorders co-occur because of shared etiological factors. This was the only one of five models of the comorbidity between dysthymia and cluster B personality disorders that was supported by the family data.