tbuckley/cabot-search huggingface dataset:
Association Between Hepatitis C Virus and Head and Neck Cancers
Authors: Parag Mahale, Erich M. Sturgis, David J. Tweardy, Ella J. Ariza-Heredia, Harrys A. Torres
Journal: JNCI Journal of the National Cancer Institute (2016)

Background: Hepatitis C virus (HCV) infection is associated with hepatocellular carcinoma and non-Hodgkin's lymphoma. In 2009, MD Anderson established the first US clinic for treating HCV-infected cancer patients, where we observed an unexpectedly large number of patients with head and neck cancers (HNCs). We sought to determine whether HCV is associated with HNCs. Methods: In this case-control study, medical records of cancer patients tested for HCV antibodies at our center from 2004 through 2014 were identified. Case subjects had new-onset primary oropharyngeal or nonoropharyngeal (oral cavity, nasopharynx, hypopharynx, or larynx) HNCs. Control subjects had smoking-associated (lung, esophagus, or urinary bladder) cancers. Biopsy reports of oropharyngeal cancers tested for human papillomavirus (HPV) were reviewed. Patients with lymphoma were excluded. Multivariable logistic regression models were constructed. All statistical tests were two-sided. Results: Of 34 545 cancer patients tested for HCV antibodies, 409 case subjects (164 oropharyngeal and 245 nonoropharyngeal) and 694 control subjects (378 lung, 168 esophagus, and 148 urinary bladder) were studied. The prevalence of HCV seropositivity was higher in oropharyngeal cancer patients (14.0%, 95% confidence interval [CI] = 8.7% to 19.4%, vs 6.5%, 95% CI = 4.6% to 8.3%), particularly HPV-positive oropharyngeal cancer patients (16.9%, 95% CI = 8.7% to 24.9%, vs 6.5%, 95% CI = 4.6% to 8.3%), and nonoropharyngeal HNC patients (20.0%, 95% CI = 14.9% to 25.0%, vs 6.5%, 95% CI = 4.6% to 8.3%) than in control subjects. Adjusted models showed a statistically significant association of HCV seropositivity with nonoropharyngeal (except nasopharyngeal) HNCs (odds ratio [OR] = 2.85, 95% CI = 1.38 to 5.88) and HPV-positive oropharyngeal cancers (OR = 2.97, 95% CI = 1.31 to 6.76). Conclusions: HCV is associated with nonoropharyngeal (except nasopharyngeal) and HPV-positive oropharyngeal HNCs. Further studies are required to explore the possible interaction between HCV and HPV, and the association between HCV and other HPV-related malignancies.
The evidence supports prequit use of nicotine patches
Authors: Colin P Mendelsohn
Journal: BMJ (2016)

Hartmann-Boyce and Aveyard state that there is insufficient evidence for starting nicotine replacement therapy (NRT) before quit day (prequit treatment or preloading).1 While this is true for oral NRT products such as the nicotine gum or lozenge, there is sufficient evidence that starting the nicotine patch two weeks before quit day significantly increases …
Increase in<i>Candida krusei</i>Infection among Patients with Bone Marrow Transplantation and Neutropenia Treated Prophylactically with Fluconazole
Authors: John R. Wingard, William G. Merz, Michael G. Rinaldi, Thomas R. Johnson, Judith E. Karp, Rein Saral
Journal: New England Journal of Medicine (1991)

In early 1990 fluconazole was introduced as a prophylactic antifungal agent after bone marrow transplantation. During the same year Candida krusei emerged as the chief candida pathogen among patients with bone marrow transplants.
Transdermal Granisetron Versus Palonosetron for Prevention of Chemotherapy-Induced Nausea and Vomiting Following Moderately Emetogenic Chemotherapy (Mec): a Multicenter, Randomized, Open-Label, Cross-Over, Active-Controlled, Phase Iv Study
Authors: Y.M. Seol
Journal: Annals of Oncology (2014)
Importance of Left Ventricular Chamber Size in Determining the Response to Hydralazine in Severe Chronic Heart Failure
Authors: Milton Packer, Jose Meller, Norma Medina, Richard Gorlin, Michael V. Herman
Journal: New England Journal of Medicine (1980)

To examine the importance of left ventricular chamber size in determing the response to vasodilator therapy, we performed echocardiography in 40 patients with chronic refractory heart failure before they were treated with oral hydralazine. The left ventricular end-diastolic dimension (LVEDD) correlated significantly with the per cent change in stroke volume (r = 0.77), left ventricular filling pressure (r = -0.68), and stroke work index (r = 0.87) during short-term drug administration. After 14 to 21 days of maintenance therapy, 15 of 24 patients with an LVEDD greater than or equal to 60 mm were improved, and one was worse; mean blood urea nitrogen decreased from 45.6 to 30.6 mg per deciliter in the 21 patients in this group who completed the study (16.3 to 10.9 mmol per liter) (P less than 0.001). In contrast, only two of 16 patients with an LVEDD less than 60 mm improved, whereas 10 showed clinical deterioration; blood urea nitrogen increased from 49.3 to 64.2 mg per deciliter in the 13 patients in this group who completed the study (17.6 to 22.9 mmol per liter) (P less than 0.01). These findings indicate that left ventricular chamber size is an important factor in the response to hydralazine in patients with severe chronic heart failure.
T2 Vitamin D supplementation reduces perioperative systemic and alveolar inflammation in patients undergoing oesophagectomy: Results of the Vindaloo Trial
Authors: RCA Dancer, D Parekh, A Scott, GD Perkins, DR Thickett
Journal: Thorax (2015)

<h3></h3> Vitamin D deficiency is associated with increased risk of ARDS post-oesophagectomy. We recruited patients to a double-blind, randomised controlled trial of high dose Vitamin D supplementation 3–14 days pre-oesophagectomy. 79 patients were randomised to receive placebo or 300,000 IU oral Vitamin D liquid 3–14 days prior to oesophagectomy. Blood samples were collected pre-dose, post-dose (pre-op) and post-op and analysed for 25-OH and 1,25-dOH Vitamin D, inflammatory cells and cytokines. Broncho-alveolar lavage fluid was collected at the end of the operation. PICCO biomarkers of alveolar capillary damage (EVLWI and PVPI) were measured pre- and post-op. Pre-operative supplementation with Vitamin D was well tolerated with no SUSARs and significantly increased circulating 25-OH and 1,25-OH Vitamin D (p &lt; 0.0001). This was associated with reduced systemic inflammation (IL-6 (p = 0.02) and IL-8 (p = 0.002)) and an increase in circulatory Treg (p = 0.027). Changes in PICCO biomarkers were lower in supplemented patients suggesting lower perioperative alveolar oedema (EVLWI p = 0.05, PVPI p = 0.04). This did not result in a significant difference in oxygenation at 24 h. Post-op, systemic and alveolar alarmin (IL-1B, IL-6, IL-8) response was similar in treated and untreated patients but the systemic release of IL-1ra (p = 0.046), sTNFR-1 (p = 0.05) and s-TNFR-2 (p = 0.02) were elevated in treated patients. There was also evidence of decreased alveolar macrophage efferocytosis in patients with Vitamin D deficiency (p = 0.003). Clinical diagnoses of ARDS were significantly lower in this cohort than in previous cohorts, but the study was not powered to detect that outcome. Mortality post-operative was not significantly different at 30 or 90 days but there is a significant difference after 300 days of follow-up (placebo 33% mortality, Vitamin D 8% mortality p = 0.033). In conclusion, vitamin D supplementation was a safe, well tolerated pre-operative intervention that reduced systemic inflammation and biomarkers of alveolar oedema. With evidence of enhanced anti-inflammatory mechanism that may have influenced longer term post-operative survival, Vitamin D deficiency should be identified and treated in patients at risk of ARDS.
Beta<sub>2</sub>Microglobulin and Lymphocytic Infiltration in Sjögren's Syndrome
Authors: Joseph P. Michalski, Troy E. Daniels, Norman Talal, Howard M. Grey
Journal: New England Journal of Medicine (1975)

We measured salivary beta2 microglobulin concentrations in 49 patients evaluated for Sjögren's syndrome with a labial salivary-gland biopsy. The salivary concentration was elevated and a significant correlation (P less than 0.001) was found between the concentration and the degree of inflammation seen in the biopsy. Serum concentrations were increased in 135 patients with Sjögren's syndrome. Striking elevations were seen in patients with associated renal or lymphoproliferative complications. Three patients have an increase in serum beta2 microglobulin concentration in association with exacerbation of their disease, and six a decrease after clinically efficacious therapy. These data indicate that determination of beta2 microglobulin in saiva may provide a simple, noninvasive technic for estimation of the degree of local inflammation in autoimmune disease.
The Treatment of Bacterial Arthritis with Penicillin
Authors: Harold L. Hirsh, Henry L. Feffer, Harry F. Dowling
Journal: New England Journal of Medicine (1946)

UNTIL the discovery of penicillin, the methods of treating the infectious arthritides were not entirely satisfactory. Although the sulfonamides were often valuable, the results obtained with them left much to be desired. The superior antibacterial action of penicillin in vitro justified a trial of this agent in certain bacterial infections of the joints. The present report is an account of our experience with penicillin in the treatment of 26 patients with bacterial arthritis.Gonococcal ArthritisSeventeen patients with gonococcal arthritis were treated with penicillin (Table 1). The diagnosis was made in 9 cases by culturing gonococci from the joint fluid . . .
Trial of Penicillamine in Advanced Primary Biliary Cirrhosis
Authors: E. Rolland Dickson, Thomas R. Fleming, Russell H. Wiesner, William P. Baldus, C. Richard Fleming, Jurgen Ludwig, John T. McCall
Journal: New England Journal of Medicine (1985)

A total of 227 patients with histologically advanced primary biliary cirrhosis entered a double-blind, randomized, controlled trial to determine whether penicillamine (1 g per day) was therapeutically effective; 111 patients received the drug, and 116 received placebo. The two groups were highly comparable at entry with regard to clinical, biochemical, and histologic features. Penicillamine therapy did not result in an overall improvement in survival as compared with placebo. Clinical symptoms and serial hepatic laboratory values reflected the progressive nature of the disease and were similar in both groups. There were no substantial differences between treatment groups in the morphologic features of sequential biopsy specimens. The development of major side effects led to permanent discontinuation of penicillamine in 22 per cent of the patients taking the drug. We conclude that penicillamine is not useful for patients with histologically advanced primary biliary cirrhosis. The trial is being continued in patients with early histologic disease whose better prognosis necessitates longer follow-up. (N Engl J Med 1985; 312: 1011–5.)
A phase I pharmacokinetic (PK) and molecular pharmacodynamic (PD) study of the combination of two anti-EGFR therapies, the monoclonal antibody (MAb) cetuximab (C) and the tyrosine kinase inhibitor (TKI) gefitinib (G), in patients (pts) with advanced colorectal (CRC), head and neck (HNC) and non-small cell lung cancer (NSCLC)
Authors: J. Baselga, P. Schöffski, F. Rojo, H. Dumez, F. J. Ramos, T. Macarulla, R. Cajal, O. Kisker, A. Van Oosterom, J. Tabernero
Journal: Journal of Clinical Oncology (2006)

3006 Background: C and G are two anti-EGFR agents with different mechanisms of action. We had previously shown a synergistic effect combining the two agents in preclinical models (Matar et al, Clin Cancer Res 2004). This study aims to explore safety, PK and PD changes in tumor and skin at different doses of C/G to define the recommended dose (RD) for further development. Methods: pts were treated at the RD of weekly iv C (400 mg/m 2 initial dose, 250 mg/m 2 weekly) and oral daily G (250 mg/d) as single agents (5 pts each) and in successive cohorts of combined C/G (3–6 pts each): C (320/200) / G (100), C (400/250) / G (100), C (400/250) / G (250), C (320/200) / G (500) &amp; C (400/250) / G (500) (ongoing). Dose escalation depended on dose limiting toxicity (DLT) rate during the first 28 d. Pre- &amp; on-treatment steady-state (14 d) tumor &amp; skin biopsies were obtained and have been evaluated by IHC for total (t) and phospho (p)-EGFR, p-MAPK, p-Akt, proliferation (Ki67), p27 expression and apoptosis by TUNEL. Gene profiling analysis is ongoing. Results: 35 pts have been treated so far: 20 CRC, 13 HNC &amp; 2 NSCLC; median KI 90 % (70–100); median age 60 years (38–80); 24 males, 11 females. DLTs occurred in 3 pts: 1 pt with G alone with reversible ILD; 1 pt with G (250) / C (400/250) with reversible deafness &amp; 1 pt with G (500) / C (320/200) with grade 3 anorexia and nausea. There were 1 CR (HNC) and 5 PRs (CRC) in the C/G cohorts, and 1 PR (CRC) in the C cohort. Overall, 5 out of 9 (56%) pts with CRC treated in the C/G cohorts presented a PR. PD studies show superior inhibition of p-EGFR, p-MAPK and p-Akt, reduction of proliferation and increased apoptosis (all p values &lt;0.05) in the tumors of pts treated with C/G compared with the single agent cohorts. PK evaluation shows no PK interactions with the 2 drugs. Conclusions: This combination of an anti-EGFR MAb (C) and a TKI (G) is feasible at the RD of both agents. Our findings show encouraging clinical activity, especially in CRC, and superior PD signaling inhibition with the combination without any significant PK interaction. Combined anti-EGFR therapy deserves further evaluation. [Table: see text]
Eye-blinking and cerebral ventricular size in chronic schizophrenic patients
Authors: J E Kleinman, C N Karson, D R Weinberger, W J Freed, K F Berman, R J Wyatt
Journal: American Journal of Psychiatry (1984)

Spontaneous eye-blinking, a possible measure of central dopaminergic activity, was studied in 55 drug-free chronic schizophrenic patients subdivided by cerebral ventricular size. Blink rates were higher in schizophrenic patients than in normal control subjects, regardless of cerebral ventricle size. Neuroleptics lowered blink rates in patients with normal ventricles but did not affect blink rates in patients with large ventricles. Insofar as blinking is a dopaminergic parameter, these findings suggest that the dopamine hypothesis of schizophrenia is most relevant in patients with normal ventricles.
THU0075 Tacrolimus Regulates the Expression of Endoplasmic Reticulum Stress-Mediated Osteoclastogenesis and Inflammation in Vitro and in Collagen-Induced Arthritis Mouse Model
Authors: W.S. Lee, Y.J. Choi, Y.-H. Cheon, M.-J. Hong, C.-H. Lee, M.S. Lee, S.-I. Lee, W.-H. Yoo
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Tacrolimus is a T cell specific, anti-inflammatory agent that has been used as a therapeutic agent for rheumatoid arthritis (RA). IL-1b- and thapsigargin (TG)-induced endoplasmic reticulum (ER) stress modulates the receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclastogenesis. <h3>Objectives</h3> This study was aimed at defining the effect of tacrolimus on endoplasmic reticulum stress-mediated osteoclastogenesis and inflammation and to elucidate the underlying mechanisms. <h3>Methods</h3> Bone marrow cells (BMCs) were obtained from 5-week-old male ICR mice and cultured to differentiate them into osteoclasts with M-CSF and RANKL in the presence or absence of IL-1β, TG, or TAC. The formation of osteoclasts was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and resorption pit assay with dentine slice. Collagen-induced arthritis (CIA) was induced by immunization of female Lewis rats with an emulsion of bovine type II collagen and incomplete Freund9s adjuvant. Lesions of bone and cartilage were assessed on the basis of histological changes in the knee joint and radiographic analysis of the hind paw. Tacrolimus at doses of 3.2 mg/kg or its placebo formulation was orally administered to rats for 28 days from the day after immunization. We examined the histopathological changes of osteolysis and the expression of specific ER stress-mediated inflammatory signaling pathway biomarkers (IRE1α, GRP78/Bip, c-Fos, and NF-κB). In addition, pro-inflammatory cytokines and osteoclastogenic molecules (RANKL, and M-CSF) were assessed in the knee and ankle joints in the CIA mouse model. <h3>Results</h3> In vitro, IL-1b- and thapsigargin (TG)-induced endoplasmic reticulum stress modulates the receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclastogenesis. In the mouse model, tacrolimus administration resulted in a dramatic amelioration of osteolysis and significant reduction in ER stress intensity. Simultaneously, tacrolimus lessened inflammatory cell infiltration, reduced the capability of osteoclastogenesis, and reduced the inflammatory response by reducing the levels of IRE1α, GRP78/Bip, c-Fos, and NF-κB. <h3>Conclusions</h3> These findings suggest that tacrolimus has the potential to inhibit the progression of joint damage by inhibiting endoplasmic reticulum stress as well as anti-inflammatory effects in established RA. <h3>Disclosure of Interest</h3> None declared
Prolonged Disease-Free Survival after Autologous Bone Marrow Transplantation in Patients with Non-Hodgkin's Lymphoma with a Poor Prognosis
Authors: Tak Takvorian, George P. Canellos, Jerome Ritz, Arnold S. Freedman, Kenneth C. Anderson, Peter Mauch, Nancy Tarbell, Felice Coral, Heather Daley, Beow Yeap, Stuart F. Schlossman, Lee M. Nadler
Journal: New England Journal of Medicine (1987)

Despite advances in the primary treatment of non-Hodgkin's lymphoma, relapse is common and treatment after relapse is unsatisfactory. Autologous bone marrow transplantation, although sometimes successful, has generally had disappointing results. We conducted a trial of such transplantation in patients with relapsed non-Hodgkin's lymphoma, using strict criteria in selecting patients; we included only those in whom disease was minimal after conventional treatment (nodal disease less than 2 cm and bone marrow involvement less than or equal to 5 percent on histologic examination) and whose tumor cells expressed the B1 antigen. Forty-nine patients meeting these criteria received cyclophosphamide and whole-body irradiation supported by transplantation of autologous bone marrow that had been treated in vitro with anti-B1 monoclonal antibody and complement. All patients had features of a poor prognosis, including relapse from primary chemotherapy, histologic conversion to more aggressive disease, and extra-nodal dissemination. Thirty-three patients had a history of bone marrow involvement--16 at the time that marrow was obtained. Hematologic and immunologic engraftment was achieved in all patients. Only two treatment-related deaths occurred, from venoocclusive disease of the liver and intracerebral hemorrhage, respectively. Disease-free remission without maintenance therapy has lasted from greater than 2 to greater than 52 months in 34 patients (median follow-up, greater than 11 months). These results are similar to those obtained in patients with advanced, high-grade non-Hodgkin's lymphoma treated with primary combination chemotherapy. This study demonstrates that autologous bone marrow transplantation has tolerable toxicity and high efficacy in a subset of patients who are otherwise incurable but still responsive to cytoreductive therapy. The results suggest a role for such transplantation in the treatment of selected patients with newly diagnosed non-Hodgkin's lymphoma.
Severe Pulmonary Disease Subsequent to Zenker's Diverticulum
Authors: Lloyd E. Hawes, James H. Walker
Journal: New England Journal of Medicine (1955)

IN any case of pulmonary disease of obscure origin an x-ray examination of the esophagus with barium may demonstrate some disease of the esophagus that causes regurgitation of food and saliva into the trachea. The cases of advanced pulmonary lesions reported below emphasize the importance of an esophageal examination since a Zenker diverticulum was easily demonstrated in each. Suppurative and lipoid pneumonia resulted from spillage of material from the high esophageal diverticulum into the trachea. In Case 1 an emergency closure of the diverticulum during convalescence from a lobectomy was necessary. The other patient (Case 2) died from a fulminating . . .
Cyclosporine-Associated Chronic Nephropathy
Authors: Bryan D. Myers, Jon Ross, Lynn Newton, John Luetscher, Mark Perlroth
Journal: New England Journal of Medicine (1984)

We evaluated glomerular filtration in 17 recipients of heart transplants who were treated for 12 months or longer with cyclosporine (cyclosporin A). The control group consisted of 15 heart-transplant recipients who were treated with azathioprine and who had also survived for at least 12 months. Despite an equivalent cardiac output, the glomerular filtration rate was depressed (51±4 vs. 93±3 ml per minute, P<0.005) in transplant recipients treated with cyclosporine. Cyclosporine treatment was also associated with reduced renal plasma flow (320±21 vs. 480±30 ml per minute, P<0.001). A trend toward restricted transglomerular transport of neutral dextrans (radii, 2.4 to 5.8 nm) in cyclosporine-treated recipients suggested an intrinsic loss of ultrafiltration capacity by glomerular capillaries rather than a hemodynamic basis for the reduced glomerular filtration rate. Histopathologic examination of the kidneys of five cyclosporine-treated patients with glomerular hypofiltration revealed a variable degree of tubulointerstitial injury accompanied by focal glomerular sclerosis. Among the 32 heart-transplant recipients treated for more than 12 months with cyclosporine at our center, end-stage renal failure developed in 2. We conclude that long-term cyclosporine therapy may lead to irreversible and potentially progressive nephropathy. We recommend that cyclosporine be used with restraint and caution until ways are found to mitigate its nephrotoxicity. (N Engl J Med 1984; 311: 699–705.)