tbuckley/cabot-search huggingface dataset:
Motor Cars for Medical Men: Next Week's Motor Show
Authors: H. M. Buist
Journal: BMJ (1926)

THE resumed series of motor car shows in the Grand Palais, Paris, closes to-morrow (Sunday) night, and the twentieth yearly International Passenger Car Show, organized by the Society of Motor Maniufacturers and Traders, under the patronage of the King, will open at Olympia, Kensington', 'on Friday next, October 22nd.It will remain open daily, Sunday excluded, until 10 o'clock on Saturday night, October 30th, the prices for admission being 5s. each day, with the exception of the Fridays and Saturdays, when the charge will be reduced to 2s. 6d,.The scale of accommoda- tion afforded in the enlarged building may be judged from the fact that, set end-to-end, there will be nlearly three and a half miles of exhibits, the cars ranging in cost from £100 to nearly £4,000 each. CONSIDERATIONS OF COST.From the point of view of the average medical man cost takes precedence of all other considerations in respect of his motoring comilmitments.By cost I mean ex-pendi- ture not onily upon the acquisition but uponi the maill- tenance (thlat is, the wearing life) of a car, since this matter has to be considered as a whole if one is to aim at obtaining the best value for money.This conisiderationi
Estrogen, not intrinsic aging, is the major regulator of delayed human wound healing in the elderly
Authors: Matthew J Hardman, Gillian S Ashcroft
Journal: Genome biology (2008)

Multiple processes have been implicated in age-related delayed healing, including altered gene expression, intrinsic cellular changes, and changes in extracellular milieu (including hormones). To date, little attempt has been made to assess the relative contribution of each of these processes to a human aging phenomenon. The objective of this study is to determine the contribution of estrogen versus aging in age-associated delayed human wound healing.Using an Affymetrix microarray-based approach we show that the differences in gene expression between male elderly and young human wounds are almost exclusively estrogen regulated. Expression of 78 probe sets was significantly decreased and 10 probe sets increased in wounds from elderly subjects (with a fold change greater than 7). A total of 83% of down-regulated probe sets and 80% of up-regulated probe sets were estrogen-regulated. Differentially regulated genes were validated at the level of gene and protein expression, with genes identified as estrogen-regulated in human confirmed as estrogen-dependent in young estrogen depleted mice in vivo. Moreover, direct estrogen regulation is demonstrated for three array-identified genes, Sele, Lypd3 and Arg1, in mouse cells in vitro.These findings have clear implications for our understanding of age-associated cellular changes in the context of wound healing, the latter acting as a paradigm for other age-related repair and maintenance processes, and suggest estrogen has a more profound influence on aging than previously thought.
Association Between Hospital Recognition for Nursing Excellence and Outcomes of Very Low-Birth-Weight Infants
Authors: Eileen T. Lake, Douglas Staiger, Jeffrey Horbar, Robyn Cheung, Michael J. Kenny, Thelma Patrick, Jeannette A. Rogowski
Journal: JAMA (2012)

<h3>Context</h3>Infants born at very low birth weight (VLBW) require high levels of nursing intensity. The role of nursing in outcomes for these infants in the United States is not known.<h3>Objective</h3>To examine the relationships between hospital recognition for nursing excellence (RNE) and VLBW infant outcomes.<h3>Design, Setting, and Patients</h3>Cohort study of 72 235 inborn VLBW infants weighing 501 to 1500 g born in 558 Vermont Oxford Network hospital neonatal intensive care units between January 1, 2007, and December 31, 2008. Hospital RNE was determined from the American Nurses Credentialing Center. The RNE designation is awarded when nursing care achieves exemplary practice or leadership in 5 areas.<h3>Main Outcome Measures</h3>Seven-day, 28-day, and hospital stay mortality; nosocomial infection, defined as an infection in blood or cerebrospinal fluid culture occurring more than 3 days after birth; and severe (grade 3 or 4) intraventricular hemorrhage.<h3>Results</h3>Overall, the outcome rates were as follows: for 7-day mortality, 7.3% (5258/71 955); 28-day mortality, 10.4% (7450/71 953); hospital stay mortality, 12.9% (9278/71 936); severe intraventricular hemorrhage, 7.6% (4842/63 525); and infection, 17.9% (11 915/66 496). The 7-day mortality was 7.0% in RNE hospitals and 7.4% in non-RNE hospitals (adjusted odds ratio [OR], 0.87; 95% CI, 0.76-0.99; P = .04). The 28-day mortality was 10.0% in RNE hospitals and 10.5% in non-RNE hospitals (adjusted OR, 0.90; 95% CI, 0.80-1.01; P = .08). Hospital stay mortality was 12.4% in RNE hospitals and 13.1% in non-RNE hospitals (adjusted OR, 0.90; 95% CI, 0.81-1.01; P = .06). Severe intraventricular hemorrhage was 7.2% in RNE hospitals and 7.8% in non-RNE hospitals (adjusted OR, 0.88; 95% CI, 0.77-1.00; P = .045). Infection was 16.7% in RNE hospitals and 18.3% in non-RNE hospitals (adjusted OR, 0.86; 95% CI, 0.75-0.99; P = .04). Compared with RNE hospitals, the adjusted absolute decrease in risk of outcomes in RNE hospitals ranged from 0.9% to 2.1%. All 5 outcomes were jointly significant (P &lt; .001). The mean effect across all 5 outcomes was OR, 0.88 (95% CI, 0.83-0.94; P &lt; .001). In a subgroup of 68 253 infants with gestational age of 24 weeks or older, the ORs for RNE for all 3 mortality outcomes and infection were statistically significant.<h3>Conclusion</h3>Among VLBW infants born in RNE hospitals compared with non-RNE hospitals, there was a significantly lower risk-adjusted rate of 7-day mortality, nosocomial infection, and severe intraventricular hemorrhage but not of 28-day mortality or hospital stay mortality.
Superiority of cisplatin or carboplatin in combination with teniposide and vincristine in the induction chemotherapy of small-cell lung cancer. A randomized trial with 5 years follow up
Authors: U. Lassen, P.E.G. Kristjansen, K. Østerlind, B. Bergman, T.C. Sigsgaard, F.R. Hirsch, M. Hansen, P. Dombernowsky, H.H. Hansen
Journal: Annals of Oncology (1996)
Translating the A1C Assay
Authors: Richard Kahn, Vivian Fonseca
Journal: Diabetes Care (2008)

In the clinical management of diabetes, the A1C assay has become indispensable. Used worldwide to monitor chronic glycemia, the assay is an essential tool to determine whether a patient has achieved the core goal of therapy for diabetes: a marked and sustained reduction in plasma glucose to achieve as close to a normal level as can be safely attained. With the publication of the A1c-Derived Average Glucose (ADAG) study in this issue of Diabetes Care (1), the evolution of the A1C assay continues and an important milestone has been reached. To better appreciate this recent report, a brief and admittedly incomplete historical perspective may be useful.

It was 60 years ago that Allen et al. (2) showed that hemoglobin A (which makes up about 97% of total hemoglobin) contains three minor components, designated HbA1a, HbA1b, and HbA1c (A1C). In the decades that followed, we learned that a hexose molecule is attached to these components (3) and that hemoglobin A actually has two more minor glycated derivatives. The five altogether comprise ∼5–7% of the HbA molecule (4).

In the early course of the biochemical dissection of hemoglobin, Huisman and Dozy (5) noted, virtually in passing, that the level of glycated hemoglobin components was increased in a few individuals they studied who happened to have diabetes. It took 4 more years, however, for Rahbar and colleagues (6,7) to document that diabetes is clearly associated with an elevation in glycated hemoglobin. The Rahbar reports stimulated other investigators to confirm these initial findings and to seek an explanation for how glucose binds to hemoglobin. It was not for another few years, in 1972, that Bunn et al. (8) elegantly showed that the cause of the increased glycated hemoglobin in diabetes, which was predominantly the A1C component, …
Massive ex Vivo Expansion of Human Natural Regulatory T Cells (T <sub>regs</sub> ) with Minimal Loss of in Vivo Functional Activity
Authors: Keli L. Hippen, Sarah C. Merkel, Dawn K. Schirm, Christine M. Sieben, Darin Sumstad, Diane M. Kadidlo, David H. McKenna, Jonathan S. Bromberg, Bruce L. Levine, James L. Riley, Carl H. June, Phillip Scheinberg, Daniel C. Douek, Jeffrey S. Miller, John E. Wagner, Bruce R. Blazar
Journal: Science Translational Medicine (2011)

A good manufacturing grade–compatible approach generates massive numbers of natural regulatory T cells that retain suppressive function in vivo.
Caveolin-1 Reduces Osteosarcoma Metastases by Inhibiting c-Src Activity and Met Signaling
Authors: Lara Cantiani, Maria Cristina Manara, Cinzia Zucchini, Paola De Sanctis, Monia Zuntini, Luisa Valvassori, Massimo Serra, Martina Olivero, Maria Flavia Di Renzo, Mario Paolo Colombo, Piero Picci, Katia Scotlandi
Journal: Cancer Research (2007)

Abstract Caveolin-1 (Cav-1) is highly expressed in normal osteoblasts. This article reports that Cav-1 down-regulation is part of osteoblast transformation and osteosarcoma progression and validates its role as oncosuppressor in human osteosarcoma. A survey of 6-year follow-up indicates a better overall survival for osteosarcoma expressing a level of Cav-1 similar to osteoblasts. However, the majority of primary osteosarcoma shows significantly lower levels of Cav-1 than normal osteoblasts. Accordingly, Met-induced osteoblast transformation is associated with Cav-1 down-regulation. In vitro, osteosarcoma cell lines forced to overexpress Cav-1 show reduced malignancy with inhibited anchorage-independent growth, migration, and invasion. In vivo, Cav-1 overexpression abrogates the metastatic ability of osteosarcoma cells. c-Src and c-Met tyrosine kinases, which are activated in osteosarcoma, colocalize with Cav-1 and are inhibited on Cav-1 overexpression. Thus, Cav-1 behaves as an oncosuppressor in osteosarcoma. Altogether, data suggest that Cav-1 down-modulation might function as a permissive mechanism, which, by unleashing c-Src and Met signaling, enables osteosarcoma cells to invade neighboring tissues. These data strengthen the rationale to target c-Src family kinases and/or Met receptor to improve the extremely poor prognosis of metastatic osteosarcoma. [Cancer Res 2007;67(16):7675–85]
Bad smells are good
Authors: L. Farrell
Journal: BMJ (2002)

I'm pretty hardy, and not overly sensitive to bad smells; delicacy is not a virtue in this job. Humans can apparently distinguish up to 10 000 different scents, which is useful for docs, as every body fluid has its own distinct aroma, and when these have been percolating for a few weeks or more they can become a heady brew. Smegma, the stuff from infected sebaceous cysts, really stale urine, navel fluff that has been there for a generation, dead bodies, steatorrhoea, purulent phlegm, bad …
Series Elastic and Contractile Elements in Vascular Smooth Muscle
Authors: PHILIP B. DOBRIN, THOMAS R. CANFIELD
Journal: Circulation Research (1973)

Segments of dog common carotid artery were excised, cannulated, and restored to in situ length. They were immersed in a Krebs-Ringer's bath and inflated with 100% O 2 under nonoscillating pressure. Diameter was continuously monitored with a linear displacement transducer. The vessel segments were relaxed and then treated isometrically with norepinephrine to excite the muscle. These continuously contracted vessels were subjected to 10- or 25-mm Hg quick release steps to 0 mm Hg. Then the muscle was inactivated with potassium cyanide, and the quick releases were repeated to study the parallel elastic elements. Finally, vessel wall volumes were determined radiographically. Computations were performed to compute series elastic element stiffness for both the Maxwell and the Voigt model of the arterial wall. These experiments indicated that the series elastic element stiffness was dependent on the applied stress and independent of muscle length provided that the vessels were excited at initial strains less than 0.70. Vessels excited isometrically at various initial pressures up to 150 mm Hg yielded identical stress-series elastic element stiffness curves. The computed series elastic element extension at an applied stress of 1.0 x 10 6 dynes/cm was 18.9% for the Hill model and 14.7-17.9% for the Voigt model; these values are percents of the vessel diameter at 0 mm Hg after application of potassium cyanide. The values were reduced to 11.2% for the Maxwell model and 8.6-10.5% for the Voigt model when they were expressed as a percent of the circumferential length associated with the peak in the length-tension curve. Vessels excited isometrically at pressures higher than 150 mm Hg exhibited greater series elastic element extensibility.
Despite a massive increase in cortisol secretion in women during parturition, there is an equally massive increase in prostaglandin synthesis. A paradox?
Authors: M L Casey, P C MacDonald, M D Mitchell
Journal: Journal of Clinical Investigation (1985)

In this investigation, we sought to resolve the apparent paradox that is posed by the fact that there is a simultaneous increase in the production of prostaglandin and cortisol in women during labor. A paradox obtains, since in most tissues, cortisol acts to inhibit prostaglandin formation. Using previously characterized model systems for the in vitro study of arachidonic acid metabolism in amnion, decidua, and myometrium, we found that prostaglandin production by amnion and endometrial stromal cells in monolayer culture was not decreased by glucocorticosteroid treatment. On the other hand, prostaglandin production by myometrial smooth muscle cells in culture was inhibited by greater than 90% in response to dexamethasone (10(-7) M) treatment. Importantly, the major prostaglandin produced by myometrium, as well as myometrial smooth muscle cells in culture, is prostacyclin, a prostaglandin that acts to cause uterine quiescence. We suggest that the immunity of amnion and decidua to the action of glucocorticosteroids may allow for the accelerated production of prostaglandins E2 and F2 alpha, which act to cause myometrial contractions; simultaneously, glucocorticosteroid produced in large quantities in women in labor may lead to decreased production of prostacyclin by myometrium, thereby reducing uterine quiescence. In this coordinated manner, the uterine contractions that culminate in delivery of the fetus may proceed uninterrupted in the face of increased cortisol production.
Acute Mitral Regurgitation Due to a Torn Porcine Bioprosthetic Cusp
Authors: Jagdish Butany, Bryan Dias, Pratibha Iyengar, Richard Leask, Stephanie Brister
Journal: Circulation (2002)

A 46-year-old man presented with a 48-hour history of fevers, sweats, and dyspnea.He had bacterial endocarditis of the native mitral valve 12 years earlier with subsequent mitral valve replacement (MVR) with a Hancock II porcine valve (Medtronic Inc).Examination revealed a Grade 3/6 holosystolic murmur at the apex radiating into the axilla with crackles heard halfway up both lung fields.A diagnosis of infective endocarditis with acute mitral regurgitation (MR) was made and serial blood cultures drawn.Transesophageal echocardiogram (TEE) revealed severe MR (Figure 1).The MR was transvalvular with no perivalvular leak. 1-3A large mobile linear echodense mass (lengthϭ2.0cm) was seen in the left ventricle and this prolapsed across the valve into the left atrium (LA, Figure 2 through 4) along with partial prolapse of one of the leaflets of the valve (Figure 3 and4).The patient underwent urgent mitral valve replacement where the tissue bioprosthesis was replaced with a 29-mm St Jude Medical bileaflet mechanical valve (St Jude Medical Inc).The left atrium was closed with a patch.Postoperatively, the patient developed complete heart block and required a permanent pacemaker.Blood and tissue cultures were sterile.
Insulin-Like Growth Factor-I Activates Gene Transcription Programs Strongly Associated With Poor Breast Cancer Prognosis
Authors: Chad J. Creighton, Angelo Casa, ZaWaunyka Lazard, Shixia Huang, Anna Tsimelzon, Susan G. Hilsenbeck, Charles Kent Osborne, Adrian V. Lee
Journal: Journal of Clinical Oncology (2008)

Purpose Substantial evidence implicates insulin-like growth factor-I (IGF-I) signaling in the development and progression of breast cancer. To more clearly elucidate the role of IGF in human breast cancer, we identified and then examined gene expression patterns of IGF-I–treated breast cancer cells. Methods MCF-7 cells were stimulated with IGF-I for 3 or 24 hours and were profiled for greater than 22,000 RNA transcripts. We defined an IGF-I signature pattern of more than 800 genes that were up- or downregulated at both time points. The gene signature was examined in clinical breast tumors and in experimental models that represented other oncogenic pathways. The signature was correlated with clinical and pathologic variables and with patient outcome. Results IGF-I caused temporal changes in gene expression that were strongly associated with cell proliferation, metabolism, and DNA repair. Genes with early and sustained regulation by IGF-I were highly enriched for transcriptional targets of the estrogen receptor (ER), Ras/extracellular signal-related kinase 1/2, and phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin pathways. In three large, independent data sets of profiled human breast tumors, the IGF-I signature was manifested in the majority of ER-negative breast tumors and in a subset (approximately 25%) of ER-positive breast tumors. Patients who had tumors that manifested the IGF-I signature (including patients who did not receive adjuvant therapy) had a shorter time to a poor outcome event. The IGF gene signature was highly correlated with numerous poor prognostic factors and was one of the strongest indicators of disease outcome. Conclusion Transcriptional targets of IGF-I represent pathways of increased aggressiveness and possibly hormone independence in clinical breast cancers.
Stimulation of collagen gene expression and protein synthesis in murine mesangial cells by high glucose is mediated by autocrine activation of transforming growth factor-beta.
Authors: F N Ziyadeh, K Sharma, M Ericksen, G Wolf
Journal: Journal of Clinical Investigation (1994)

Previous investigations have demonstrated that growing mesangial cells in high glucose concentration stimulates extracellular matrix synthesis and also increases the expression of TGF-beta. We tested whether the stimulation of extracellular matrix production is mediated by autocrine activation of TGF-beta, a known prosclerotic cytokine. Addition of neutralizing anti-TGF-beta antibody, but not normal rabbit IgG, significantly reduced the high glucose-stimulated incorporation of 3[H]proline. Denaturing SDS-PAGE revealed that mainly collagen types I and IV were stimulated by high (450 mg/dl) D-glucose. This high glucose-mediated increase in collagen synthesis was reduced by the anti-TGF-beta antibody. Treatment of mesangial cells grown in normal (100 mg/dl) D-glucose with 2 ng/ml recombinant TGF-beta 1 mimicked the effects of high glucose. Furthermore, the anti-TGF-beta antibody significantly reduced the increase in mRNA levels encoding alpha 2(I) and alpha 1(IV) collagens induced by high glucose. Thus, the high glucose-stimulated increase of collagen production in mesangial cells is mediated, at least in part, by autocrine TGF-beta activation. We postulate that the interception of the glomerular activity of TGF-beta may be an effective intervention in the management of diabetic nephropathy.
The determinants of atrioventricular nodal re-entrance with premature atrial stimulation in patients with dual A-V nodal pathways.
Authors: P Denes, D Wu, F Amat-y-Leon, R Dhingra, C R Wyndham, K M Rosen
Journal: Circulation (1977)

In patients with dual atrioventricular (A-V) nodal pathways, atrial extrastimulus testing induces either no echoes, single atrial echoes (Ae), or repetitive re-entrance (repetitive atrial and ventricular beating). We examined the fast and slow pathways properties in 38 patients with dual pathways in order to delineate the determinants of re-entrance. Seventeen patients had no Ae. Of these, six had no V-A conduction and 11, intact V-A conduction. The mean paced ventricular cycle length producing retrograde V-A block (VABCL) in this group (a measure of retrograde fast pathway refractoriness) was 552 +/- 32 msec (mean +/- SEM; 10 pts). In contrast, all 21 patients with Ae had intact V-A conduction with mean VABCL of 382 +/- 21 msec (14 pts) (P less than 0.05). Repetitive re-entrance occurred only when Ae conducted to the ventricles. Seven patients had only single Ae. The mean paced atrial cycle length producing Wenckebach periodicity (CLAWP) in this group (a measure of antegrade slow pathway refractoriness) was 490 +/- 31 msec (5 pts). Fourteen patients had repetitive re-entrance. The mean CLAWP in this group was 399 +/- 18 msec (8 pts) (P less than 0.05). In conclusion, our results suggest that in patients with dual pathway, the occurrence of single or repetitive re-entry is dependent upon measurable slow and fast pathway properties.
Transfusion of minor histocompatibility antigen–mismatched platelets induces rejection of bone marrow transplants in mice
Authors: Seema R. Patel, Chantel M. Cadwell, Arielle Medford, James C. Zimring
Journal: Journal of Clinical Investigation (2009)

Bone marrow transplantation (BMT) represents a cure for nonmalignant hematological disorders. However, compared with the stringent conditioning regimens used when performing BMT to treat hematological malignancies, the reduced intensity conditioning regimen used in the context of nonmalignant hematological disorders leads to substantially higher rates of BMT rejection, presumably due to an intact immune system. The relevant patient population typically receives transfusion support, often including platelets, and the frequency of BMT rejection correlates with the frequency of transfusion. Here, we demonstrate that immunity to transfused platelets contributes to subsequent BMT rejection in mice, even when the BMT donor and recipient are MHC matched. We used MHC-matched bone marrow because, although immunity to transfused platelets is best characterized in relation to HLA-specific antibodies, such antibodies are unlikely to play a role in clinical BMT rejection that is HLA matched. However, bone marrow is not matched in the clinic for minor histocompatibility antigens, such as those carried by platelets, and we report that transfusion of minor histocompatibility antigen–mismatched platelets induced subsequent BMT rejection. These findings indicate previously unappreciated sequelae of immunity to platelets in the context of transplantation and suggest that strategies to account for minor histocompatibility mismatching may help to reduce the chance of BMT rejection in human patients.