tbuckley/cabot-search huggingface dataset:
Monitoring and management of acidosis in calf diarrhoea
Authors: D H Grove-White
Journal: Journal of the Royal Society of Medicine (1998)

Neonatal diarrhoea is a major cause of morbidity and mortality in calves during the first three weeks of life, resulting in considerable economic loss. Aetiological agents include enterotoxigenic Escherichia coli, Salmonella spp, rotavirus, coronavirus and Cryptosporidium parvum, mixed infection being common1-3. As in other species, the cardinal biochemical features of calf diarrhoea are hypovolaemia, hyponatraemia, pre-renal failure and metabolic acidosis-8. There is no relationship between severity of dehydration and acidosis7. In previous studies7'8, acidosis was found to be widespread and severe amongst diarrhoeic suckler calves, and collapsed calves requiring intravenous fluid therapy (IF) were more severely acidotic than those manageable by oral fluid therapy. Calves less than 6 days old were less acidotic than older calves (Figure 1). Recording similar observations, Naylor4 postulated that the age-related difference in severity of acidosis might be explained in terms of susceptibilities to enteric pathogens: the younger calf is likely to be affected by enterotoxigenic E. coil, with consequent rapid dehydration, reduced tissue perfusion and production of lactic acid by the tissues together with intestinal loss of bicarbonate, whereas the older calf is more
Usefulness of monitoring serum carcinoembryonic antigen (CEA) to define response to chemotherapy and its correlation with survival in patients with non-small cell lung cancer with abnormal baseline CEA levels.
Authors: D. Pachuca, O. Peña, M. Morales, A. Astorga, J. G. De La Garza, L. M. Martinez, O. G. Arrieta Rodriguez
Journal: Journal of Clinical Oncology (2010)

e18044 Background: Carcinoembryonic antigen (CEA, CEACAM5) is an oncofetal protein that functions as a cell-adhesion molecule. It is usually over-expressed in a variety of neoplasms; moreover, high serum CEA levels are an independent prognostic factor for recurrence and survival in patients with non small-cell lung cancer (NSCLC). To date, there are no markers that satisfactorily predict objective response to chemotherapy in NSCLC. Methods: The aim of the study was to evaluate the relationship of a change in serum CEA levels at baseline and after two cycles of treatment, to compare them with objective response (measured by RECIST) and to correlate it with progression free-survival (PFS) and overall survival (OS). Results: 182 (67.4%) of 270 patients had a baseline CEA serum level > 5 ng/mL (range 5-7,440). Treatment was platinum-based chemotherapy in 169 (92.9%) patients and a tyrosine kinase inhibitor was used in 13 (7.1%). The mean follow-up time was 12.6 mo. After two cycles of treatment, objective global response was 29.7% and ≤ 25% CEA reduction was found in 32.4%. One hundred percent of patients with complete response had a ≤ 25% CEA reduction value, 60% for partial response, 24.7% for stable disease and 9.3% for progressive disease (Pearson's X2 value 38.49, p < 0.0001). Sensitivity, specificity, positive predictive value and negative predictive value were 80%, 62%, 57% and 83% respectively. PFS was longer in patients with a 25% reduction in CEA (11.3 mo [CI 95% 9.5-13.1] vs 8.7 mo [CI 95% 7.5-9.8], p = 0.04) and OS showed a tendency for longer survival (19.9 mo [CI 95%12.3-27.5] vs 14.7 mo [CI 95% 13.2-16.1] p = 0.09). Conclusions: A 25% reduction from baseline CEA is associated with objective response and PFS. CEA is an accurate and specific predictor of objective response to treatment in locally advanced and advanced NSCLC. No significant financial relationships to disclose.
Voluntary Interruption of Pregnancy with Mifepristone (RU 486) and a Prostaglandin Analogue
Authors: Louise Silvestre, Catherine Dubois, Maguy Renault, Yvonne Rezvani, Etienne-Emile Baulieu, André Ulmann
Journal: New England Journal of Medicine (1990)

In 2115 women seeking voluntary termination of pregnancy after 49 days of amenorrhea or less, we studied the effect of a single 600-mg dose of mifepristone (RU 486), followed 36 to 48 hours later by the administration of one of two prostaglandin analogues, either gemeprost (1 mg by vaginal suppository) or sulprostone (0.25, 0.375, or 0.5 mg by intramuscular injection). The women were monitored for four hours after prostaglandin administration. Efficacy was indicated by the complete expulsion of the conceptus without the need of an additional procedure. All other results were considered failures, and the pregnancy was then terminated by a surgical method.
Long-Term Tissue Culture of Neuroblastomas. III. &lt;italic&gt;In Vitro&lt;/italic&gt; Studies of a Nerve Growth-Stimulating Factor in Sera of Children With Neuroblastoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: José A. Burdman, Milton N. Goldstein
Journal: JNCI Journal of the National Cancer Institute (1964)

Sera from children with neuroblastomas contained increased amounts of a nerve growth factor that stimulated the outgrowth of axons in explanted 8-day chick-embryo spinal-ganglia cultures. This factor could not be detected in normal human sera. The nerve growth factor was neutralized by an antiserum prepared in goats against purified nerve growth-stimulating protein isolated from mouse submaxillary glands. The cross-reactivity between the human nerve growth factor and the antisera against the mouse protein was low. The data indicate that neutralization of neuroblastoma sera can be markedly increased by an antiserum prepared from nerve growth-stimulating protein isolated from human tissue. The effect of a nerve growth-promoting protein and its antisera on normal human sympathetic nerve cells and human neuroblastoma cells growing in vitro is discussed and is currently being investigated.
Nonobstructive Hydronephrosis and Hydroureter Associated with Peritonitis
Authors: Sudesh P. Makker, Arthur S. Tucker, Robert J. Izant, Walter Heymann
Journal: New England Journal of Medicine (1972)

Three patients with peritonitis (ruptured appendix in two and primary in one) were found to have associated hydronephroses and hydroureters. The hydronephroses and hydroureters were of the nonobstructive type, were not accompanied by urinary-tract infection, and disappeared spontaneously within four to 20 months after onset. It is possible that, as in paralytic ileus, the kidney pelvis and ureter participate in impaired peristalsis associated with peritonitis and thus produce reversible, nonobstructive hydronephrosis and hydroureter.
Abstract 2906: Role of autophagy in Wnt5A-mediated melanoma invasion and metastasis
Authors: Abibatou Ndoye, Anna Budina, Marie Webster, Amanpreet Kaur, Reeti Behera, Maureen Murphy, Ashani T. Weeraratna
Journal: Cancer Research (2015)

Abstract Melanoma is the most aggressive type of skin cancer and the leading cause of death from skin disease. With increasing incidence of the disease, it is crucial to further investigate the cellular mechanisms and molecular pathways that lead to invasion, metastasis, and drug resistance. Recent studies have revealed that high autophagy correlates with melanoma tumor aggressiveness and poor survival in clinical samples, as it is a common mechanism of resistance to therapy. Autophagy inhibition leads to reduced levels in Wnt5A in a breast cancer model, suggesting a cross-talk of Wnt5A and autophagy in cancer. β catenin, a mediator of canonical Wnt signaling, has been shown to act as a negative regulator of both basal and induced autophagy in a colorectal cancer model. Our laboratory showed that high levels of Wnt5A correlate with increased invasion and metastasis in melanoma and that Wnt5A downregulates β catenin; therefore, we hypothesize that autophagy might drive invasion and metastasis in aggressive melanoma through the regulation of Wnt signaling. To study the role of autophagy in Wnt5A-mediated melanoma invasion, we inhibited autophagy in highly invasive melanoma cells using lentivirus-mediated shATG5 knockdown or hydroxychloroquine and evaluated the effects of autophagy inhibition on Wnt5A expression, β catenin, and invasion using 3D spheroid models. Analysis of autophagy flux confirms that highly invasive melanoma cells have high autophagy compared to non-invasive cell lines. The inhibition of autophagy by hydroxychloroquine or shATG5 both resulted in significant decrease in invasion. By western blot analysis, we also observed a decrease in Wnt5A in these cells. These results demonstrate that autophagy inhibition in highly invasive melanoma leads to decrease in invasion in a 3D model that mimics the tumor microenvironment of melanoma. Further dissection of the molecular mechanisms that are involved in this process will enable the identification of novel autophagy targets in aggressive melanoma. Citation Format: Abibatou Ndoye, Anna Budina, Marie Webster, Amanpreet Kaur, Reeti Behera, Maureen Murphy, Ashani T. Weeraratna. Role of autophagy in Wnt5A-mediated melanoma invasion and metastasis. [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 2906. doi:10.1158/1538-7445.AM2015-2906
Soundings: An afternoon of alternative medicine
Authors: Kevin Barraclough
Journal: BMJ (2001)

The doctor started in a slightly apologetic tone. He was lecturing to a group of colleagues about his use of alternative medicines. The lunch had been good, the afternoon was warm, and his audience was sleepily indulgent. It was, after all, courageous of him to stand up before a group of non-believers.

My attention drifted a little to the paintings that hung on the wall. Had Harold Pinter painted, he might have painted pictures like these—large expanses of white with the odd blob. Each of the pictures in the series was rather similar, except that the blob moved around a bit. The title of the sequence was enigmatic—“Studies of the London skyline,” or something of that ilk.

I returned to the lecturer, who was warming to his theme. He had started cautiously with a few pragmatic claims, but, clearly emboldened by the odd sympathetic question from the audience, he began to drop in a few yins and yangs, energy lines, and so on.

I roused myself and asked him why we should believe anything he was saying. The question fell rather awkwardly through the benign afternoon sunlight, clattering crudely on the floor like an inappropriately sexist joke. I sensed a certain antipathy, somewhat muted by the lunch, from my fellow listeners. My question had been intended in a genuine spirit of interested inquiry, but was clearly seen as unduly combative. I kept my head down, and examined my soul for signs of unreasonable prejudice.

The difficulty I have with alternative medicine is the difficulty I have with Tracy Emin's bed, the blobs from the London skyline, or Parisian haute couture. How do we know that they're not charlatans? Ah! say the cognoscenti, you have to keep an open mind: Van Gogh wasn't recognised in his own time.

But if keeping an open mind means suspending scepticism, on the basis that it is tainted with prejudice, then surely we are all lost. We are at the mercy of every opportunist who flicks paint at a canvas, every shaman who claims to cure cancer. If we suspend systematic doubt in medicine, an area fraught with emotive self interest, then we risk plunging into an abyss of humbuggery.

And the trouble is, when it comes to humbuggery, the history of medicine is not squeaky clean.
Pathology of Gastric Carcinoma in Japanese Populations: Comparisons Between Miyagi Prefecture, Japan, and Hawaii 2
Authors: Pelayo Correa, Nobuaki Sasano, Grant N. Stemmermann, William Haenszel
Journal: JNCI Journal of the National Cancer Institute (1973)

The pathology and related epidemiologic aspects of gastric cancer in Japanese populations of Japan and Hawaii were studied through data and specimens from 407 cases in Miyagi prefecture, Japan, and 256 cases in Hawaii. The estimated incidence rates for diffuse carcinomas were the same in both localities, but the corresponding rates for intestinal, mixed, and other (IMO) types were substantially lower in Hawaii. The slopes of the IMO incidence curves were similar in the 4 subgroups considered, but the curves were displaced horizontally to the right (to older ages) in Hawaii as compared to Japan and in females as compared to males. The slope of the incidence curves for diffuse were less steep than for IMO types and did not exhibit horizontal displacement. The slopes and displacement of the type-specific incidence curves can be reconciled with the variation in sex ratios by age observed in Japan and Hawaii. An association with blood group A in the Japanese populations studied was limited to diffuse-type tumors.
Studies of a Second Family With the Quebec Platelet Disorder: Evidence That the Degradation of the α-Granule Membrane and Its Soluble Contents Are Not Secondary to a Defect in Targeting Proteins to α-Granules
Authors: Catherine P.M. Hayward, Elisabeth M. Cramer, William H. Kane, Shilun Zheng, Madeleine Bouchard, Jean-Marc Massé, Georges E. Rivard
Journal: Blood (1997)
Antibody Formation in Hodgkin's Disease
Authors: Alan G. Aisenberg, Sidney Leskowitz
Journal: New England Journal of Medicine (1963)

ALTHOUGH it has been generally agreed that an early loss of delayed hypersensitivity is commonly found in Hodgkin's disease1 2 3 4 5 6 7 there has been argument about the antibody-forming ability of these patients. The majority of investigators have found that, in contrast to the cutaneous anergy, antibody formation is intact in Hodgkin's disease,4 , 5 , 8 , 9 but several workers, employing varying technics,3 , 9 , 10 have reported a defect in antibody synthesis. We decided that the antibody-forming ability of patients with Hodgkin's disease was of sufficient interest to merit reinvestigation, particularly of the ability of the patient with known cutaneous anergy to form antibody. We have recently studied delayed . . .
Rituximab plus gemcitabine, ifosfamide, oxaliplatin (R-GIFOX) as salvage therapy for recurrent Hodgkin lymphoma
Authors: G. Corazzelli, F. Frigeri, G. Marcacci, G. Capobianco, M. Arcamone, C. Becchimanzi, F. Russo, A. Pinto
Journal: Journal of Clinical Oncology (2009)

8579 Background: Gemcitabine (G), ifosfamide (Ifo), oxaliplatin (Ox) and rituximab (R) have been accounted of cross-synergy in preclinical and early clinical studies in Hodgkin lymphoma (HL). We assessed activity, toxicity and stem cells (SCs) mobilizing capacity of a bi-weekly salvage combination with these agents in HL recurring after conventional or high dose therapy (HDT). Methods: Patients were scheduled to receive 3 R-GIFOX courses followed by SCs mobilization and HDT if elegible for autologous transplantation (ASCT) or 3 more courses if not. R-GIFOX consisted of R 375 mg/m 2 D1, G 1000 mg/m 2 D2, Ox 130 mg/m 2 D3 and Ifo 5 g/m 2 D3, as a 24-h single infusion, G-CSF 5 mcg/kg/d DD 7–11 (10 mcg/kg/d, 3rd course until SCs mobilization). Results: Twenty-one patients (median age 33 yrs, r 22–64) with relapsed (n = 16) [post-ASCT (n=6), &lt;12 mo.s (n=7), &gt; 12 mo.s (n=3)] or primary progressive (n = 5) HL, were prospectively accrued. Ten patients (48%) had received ≥ 2 previous CHT lines and 15 (78%) had GHLSG recurring HL prognostic score ≥ 2. Eighty-three total courses were delivered (median 3, r 3–6). CTCAE v3.0 G4 thrombocytopenia occurred in 18% of courses, G4 infection in 11%. Ifosfamide was withdrawn at the 4th course in 2 patients, both aged 64 yrs, due to tachyarrhythmia and encephalopathy. Actual dose intensity of the first 3 courses was 82%, 86%, 92 % for G, Ifo and Ox, respectively. The overall response according to FDG-PET/IWC criteria after 3 courses was 86%, with 2 partial and 16 complete responses (CRs) (76%; CR=10, CRu=6). Four CRs were achieved among the 6 patients with post-ASCT relapses. Eight of 14 eligible patients had effective CD34+ cells harvest [median 4,35 × 10 6 /kg (r 2,91–11.45)] and proceeded to subsequent ASCT. Five ’bad mobilizers’ had previously undergone radiation therapy (n=3) and radioimmunotherapy (n=2). At 42 mo.s. Failure Free Survival was 57%. At a median f.u. of 12 mo.s for CRs, Disease Free Survival was 79% in patients eligible for ASCT and 41% in those unfit treated with additional R-GIFOX. Conclusions: R-GIFOX retains an attractive therapeutic potential in recurring HL, enabling pre-ABMT cytoreduction and mobilization, and also a safe delivery of a full salvage program to patients unfit for HDT. No significant financial relationships to disclose.
Vitamin D receptor expression and associated gene signature in tumour stromal fibroblasts predict clinical outcome in colorectal cancer
Authors: Gemma Ferrer-Mayorga, Gonzalo Gómez-López, Antonio Barbáchano, Asunción Fernández-Barral, Cristina Peña, David G Pisano, Ramón Cantero, Federico Rojo, Alberto Muñoz, María Jesús Larriba
Journal: Gut (2016)

<h3>Objective</h3> Colorectal cancer (CRC) is a major health concern. Vitamin D deficiency is associated with high CRC incidence and mortality, suggesting a protective effect of vitamin D against this disease. Given the strong influence of tumour stroma on cancer progression, we investigated the potential effects of the active vitamin D metabolite 1α,25-dihydroxyvitamin D<sub>3</sub> (1,25(OH)<sub>2</sub>D<sub>3</sub>) on CRC stroma. <h3>Design</h3> Expression of vitamin D receptor (VDR) and two 1,25(OH)<sub>2</sub>D<sub>3</sub> target genes was analysed in 658 patients with CRC with prolonged clinical follow-up. 1,25(OH)<sub>2</sub>D<sub>3</sub> effects on primary cultures of patient-derived colon normal fibroblasts (NFs) and cancer-associated fibroblasts (CAFs) were studied using collagen gel contraction and migration assays and global gene expression analyses. Publicly available data sets (n=877) were used to correlate the 1,25(OH)<sub>2</sub>D<sub>3</sub>-associated gene signature in CAFs with CRC outcome. <h3>Results</h3> High VDR expression in tumour stromal fibroblasts was associated with better overall survival (OS) and progression-free survival in CRC, independently of its expression in carcinoma cells. 1,25(OH)<sub>2</sub>D<sub>3</sub> inhibited the protumoural activation of NFs and CAFs and imposed in CAFs a 1,25(OH)<sub>2</sub>D<sub>3</sub>-associated gene signature that correlated with longer OS and disease-free survival in CRC. Furthermore, expression of two genes from the signature, CD82 and S100A4, correlated with stromal VDR expression and clinical outcome in our cohort of patients with CRC. <h3>Conclusions</h3> 1,25(OH)<sub>2</sub>D<sub>3</sub> has protective effects against CRC through the regulation of stromal fibroblasts. Accordingly, expression of VDR and 1,25(OH)<sub>2</sub>D<sub>3</sub>-associated gene signature in stromal fibroblasts predicts a favourable clinical outcome in CRC. Therefore, treatment of patients with CRC with VDR agonists could be explored even in the absence of VDR expression in carcinoma cells.
Low-Dose Filgrastim Therapy for Chronic Neutropenia
Authors: Richard S. Kaczmarski, Ghulam J. Mufti
Journal: New England Journal of Medicine (1993)

To the Editor: Filgrastim (recombinant human granulocyte colony-stimulating factor) is available for the treatment of chemotherapy-induced neutropenia. It is currently being investigated for use in...
Variation in the Use of Cardiac Procedures after Acute Myocardial Infarction
Authors: Edward Guadagnoli, Paul J. Hauptman, John Z. Ayanian, Chris L. Pashos, Barbara J. McNeil, Paul D. Cleary
Journal: New England Journal of Medicine (1995)

There are large geographic differences in the frequency with which coronary angiography and revascularization are performed. We attempted to assess whether differences in case mix or in the treatment of specific groups of patients may explain this variability. We also assessed the consequences of various patterns of treatment.
Xanthinuria and Hemochromatosis
Authors: John H. Ayvazian
Journal: New England Journal of Medicine (1964)

IN 1954 Dent and Philpot1 presented an account of xanthinuria observed in a four-year-old girl. She had only traces of uric acid in the blood and urine. Urinary excretion of purines consisted mainly of xanthine, the immediate metabolic precursor of uric acid. The xanthine was excreted in amounts comparable, mole for mole, to that of the expected normal uric acid excretion. The authors postulated that the defect was either a deficiency of liver xanthine oxidase or a renal tubular defect with greatly increased renal tubular clearance of xanthine. In 1959 the same patient was reinvestigated by Dickinson and Smellie,2 who . . .
Dissection of anti-CTLA4-induced cytotoxic T-cell responses in melanoma.
Authors: John B. A. G. Haanen, Pia Kvistborg, Daisy Philips, Sander Kelderman, Bianca Heemskerk, Christian Ottensmeier, Daniel E Speiser, Olivier Alain Michielin, Emanuela Romano, Christian U. Blank, Ton Schumacher
Journal: Journal of Clinical Oncology (2013)

9078 Background: There is strong evidence that melanoma-reactive T cells induced by immunotherapeutic interventions such as anti-CTLA4 therapy can exert clinically effects. However, there is very little information on how these therapies influence tumor-specific T cell responses. Furthermore, as the number of potential melanoma-associated antigens to which these responses can be directed is very high, classical strategies to map cytotoxic T cell reactivity do not suffice. Knowledge of such reactivities would be useful to design targeted strategies, selectively aiming to induce immune reactivity against these antigens. Methods: We have addressed these issues by designing MHC class I molecules occupied with UV-sensitive ‘conditional’ ligands, thereby allowing the production of very large collections of pMHC complexes for T cell detection. Secondly, we have developed a ‘combinatorial coding’ strategy that allows parallel detection of dozens of different T cell populations within a single sample. The combined use of MHC ligand exchange and combinatorial coding allows the high-throughput dissection of disease- and therapy-induced CTL immunity. We have used this platform to monitor immune reactivity against a panel of 145 melanoma-associated epitopes in patients receiving Ipilimumab treatment. Results: Comparison of PBMC samples from 32 melanoma patients pre- and post-therapy indicated a significant increase in the number of detectable melanoma-associated T cell responses (p=0.004). Furthermore, kinetic data on T cell responses during therapy suggests that this broadening generally occurs within weeks after start of therapy. The magnitude of melanoma-specific T cell responses that was detectable prior to start of therapy was not significantly altered (p=0.8). Conclusions: These results establish the pattern of melanoma-specific T-cell reactivity induced by anti-CTLA4 treatment and form a benchmark for evaluation of other immunotherapeutic interventions, like anti-PD1 treatment, that are currently undergoing clinical evaluation. Furthermore, our data suggests that the clinical activity of Ipilimumab may be mostly due to epitope spreading, rather than through enhancement of pre-existing immune activity.
258P Clinical experience of tyrosine kinase inhibitors in metastatic renal cell carcinoma: results from a cancer center in Eastern India
Authors: D. Dabkara, B. Biswas, A.D. Dwary, I. Ghosh, S. Mukherjee, S. Gupta, I. Mallick, P. Mondal
Journal: Annals of Oncology (2015)