tbuckley/cabot-search huggingface dataset:
Effects of Laser Printer–Emitted Engineered Nanoparticles on Cytotoxicity, Chemokine Expression, Reactive Oxygen Species, DNA Methylation, and DNA Damage: A Comprehensive <i>in Vitro</i> Analysis in Human Small Airway Epithelial Cells, Macrophages, and Lymphoblasts
Authors: Sandra V. Pirela, Isabelle R. Miousse, Xiaoyan Lu, Vincent Castranova, Treye Thomas, Yong Qian, Dhimiter Bello, Lester Kobzik, Igor Koturbash, Philip Demokritou
Journal: Environmental Health Perspectives (2015)

Engineered nanomaterials (ENMs) incorporated into toner formulations of printing equipment become airborne during consumer use. Although information on the complex physicochemical and toxicological properties of both toner powders and printer-emitted particles (PEPs) continues to grow, most toxicological studies have not used the actual PEPs but rather have primarily used raw toner powders, which are not representative of current exposures experienced at the consumer level during printing.We assessed the biological responses of a panel of human cell lines to PEPs.Three physiologically relevant cell lines--small airway epithelial cells (SAECs), macrophages (THP-1 cells), and lymphoblasts (TK6 cells)--were exposed to PEPs at a wide range of doses (0.5-100 μg/mL) corresponding to human inhalation exposure durations at the consumer level of 8 hr or more. Following treatment, toxicological parameters reflecting distinct mechanisms were evaluated.PEPs caused significant membrane integrity damage, an increase in reactive oxygen species (ROS) production, and an increase in pro-inflammatory cytokine release in different cell lines at doses equivalent to exposure durations from 7.8 to 1,500 hr. Furthermore, there were differences in methylation patterns that, although not statistically significant, demonstrate the potential effects of PEPs on the overall epigenome following exposure.The in vitro findings obtained in this study suggest that laser printer-emitted engineered nanoparticles may be deleterious to lung cells and provide preliminary evidence of epigenetic modifications that might translate to pulmonary disorders.
Cetuximab with oxaliplatin and capecitabine (CAPOX)in patients with metastatic colorectal cancer (mCRC) refractory to standard chemotherapy
Authors: W. Grothe, D. Arnold, S. Peinert, W. Voigt, L. Mantovani Loeffler, R. Siewczynski, G. Steps, J. Boehme, U. Graeven, H.-J. Schmoll
Journal: Journal of Clinical Oncology (2005)

3669 Background: Cetuximab is an EGFR-targeting IgG1 monoclonal antibody that has demonstrated activity as single agent or in combination with irinotecan in patients with mCRC (pts) refractory to chemotherapy. Conceivably as a result of chemosenzitation, pts with irinotecan-refractory tumors are more likely to respond to the combination with irinotecan when compared to single agent cetuximab. In combination with 5FU/LV/Oxaliplatin, two recent trials reported the highest response rates ever achieved in 1st-line treatment of mCRC. Aim of this study was to evaluate efficacy and toxicity of cetuximab in combination with oxaliplatin plus capecitabine in mCRC pts refractory to oxaliplatin. Methods: Pts refractory to standard chemotherapy (incl. 5FU, oxaliplatin, and irinotecan in all pts) were assigned to treatment with cetuximab (400mg/m2 d1 followed by weekly 250mg/m2) and CAPOX: oxaliplatin (70mg/m2 d1 and 8; qd22) plus capecitabine (2000 mg/m2 d1–14; qd22). All tumors showed EGFR expression by IHC. Pts with sensory neurotoxicity > grade 1 resulting from previous oxaliplatin treatment were excluded. Tumor assessment was performed 9-weekly. Results: Since Jan 04, 15 pts have been prospectively evaluated: 9m/6f, median ECOG PS 1 [0–2], median age 59 yrs [32–75]. No. of previous treatment lines: Two 9 pts, three 5 pts, four 1 pt. Pretreatment included 5FU, oxaliplatin and irinotecan in all pts., MMC and gefitinib in 4 pts each. In 1 pt treatment was stopped due to a grade 4 hypersensitivity reaction. Further NCI-CTC grade 3/4 toxicities were (15 pts): leukopenia 1 pt, sensory neuropathy 1 pt, skin 2 pts, diarrhea 1 pt. Efficacy analysis of 15 pts: PR 27%, SD 27% (4 pts each), PD 46%. Currently median PFS is 2.5 mos (0.25+-9.6), median overall survival is 5.5+ mos (0.6–10.9+) (7 pts ongoing). Conclusion: Combination of Cetuximab plus CAPOX has significant clinical activity in patients with colorectal cancer refractory to standard chemotherapy. The observed toxicities allow treatment even in this group of heavily pretreated patients. These promising results are currently further evaluated in an expanded phase II setting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche, sanofi-aventis Roche, sanofi-aventis
Case 23-1994
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, David W. Rattner, Michael R. Pins
Journal: New England Journal of Medicine (1994)

Presentation of CaseA 37-year-old man was admitted to the hospital because of a pancreatic-duct lesion and several bouts of acute pancreatitis.The patient had been in excellent health until 2 1/2 years earlier, when acute pancreatitis developed, with severe abdominal pain, vomiting, and watery diarrhea. A second attack occurred two years later. Both episodes required admission to a hospital for several days.Five months before admission, an endoscopic retrograde cholangiopancreatographic examination (Figure 1), performed elsewhere, showed two small nodular filling defects in the pancreatic duct near the ampulla of Vater; the main pancreatic duct upstream of the defects and . . .
Identification of Spirochetes Related to<i>Treponema pallidum</i>in Necrotizing Ulcerative Gingivitis and Chronic Periodontitis
Authors: George R. Riviere, Murriel A. Wagoner, Sharon A. Baker-Zander, Kathryn S. Weisz, Donald F. Adams, Lloyd Simonson, Sheila A. Lukehart
Journal: New England Journal of Medicine (1991)

Spirochetes are commonly asciated with periodontal disease, but it is not known whether these treponemes are pathogenic or merely opportunistic. We sought to determine whether spirochetes present in periodontal disease share antigens thought to be unique to spirochetes that are known pathogens.
Small Pituitary Fossa in Cushing's Syndrome Due to Adrenal Neoplasm
Authors: Howard L. Steinbach, Max Noetzli, M. B. Ozonoff
Journal: New England Journal of Medicine (1963)

IN the differentiation of adrenal hyperplasia from adrenal neoplasm as the cause of Cushing's syndrome the size of the pituitary fossa may be a useful diagnostic aid. Previous studies have indicated that the sella is enlarged in approximately 10 to 15 per cent of patients in whom Cushing's syndrome resulted from adrenal hyperplasia.1 , 2 In the case presented below a thirteen-and-a-half-year-old boy had Cushing's syndrome due to adrenal adenoma. In this patient the initially small pituitary fossa increased to normal size after removal of the adrenal neoplasm.Case ReportA 13 1/2-year-old boy of Portuguese descent had begun 3 years previously . . .
Effects of Diabetes Mellitus on Bone Mass in Juvenile and Adult-Onset Diabetes
Authors: Marvin E. Levin, Vincenza C. Boisseau, Louis V. Avioli
Journal: New England Journal of Medicine (1976)

To assess the influence of diabetes mellitus on bone metabolism, we measured skeletal mass in the forearms of 35 patients with juvenile diabetes on insulin and 101 stable patients with adult-onset diabetes, on diet alone, insulin, or oral hypoglycemic agents. There was a significant loss of bone mass in both juvenile and adult-onset diabetes (P less than 0.01) as compared to controls matched for age and sex. The decrease was already present in patients with diabetes of less than five years' duration. Bone loss and duration of the diabetes did not correlate; the greatest decrease in bone mass was observed in the patients receiving oral agents. These data are consistent with the hypothesis that the loss of skeletal tissue in diabetes reflects the underlying disease since it occurs early and is not related to severity as evidenced by the need for insulin, to duration, or to treatment with insulin or diet alone.
Evidence of Prostacyclin Deficiency in the Syndrome of Hyporeninemic Hypoaldosteronism
Authors: Jerry L. Nadler, Frederick O. Lee, Willa Hsueh, Richard Horton
Journal: New England Journal of Medicine (1986)

Hyporeninemic hypoaldosteronism is an important cause of hyperkalemia and is characterized by low renin secretion. We found that prostacyclin, a potent vasodilator and renin secretagogue, was markedly reduced — as reflected by its stable urinary metabolite 6-keto-prostaglandin F1α — in seven patients with hyporeninemic hypoaldosteronism as compared with seven matched controls with renal insufficiency and as compared with 12 normal volunteers (mean±SE, 42±7 vs. 185±37 and 164±20 ng per gram of creatinine, respectively; P<0.001). In contrast, renal prostaglandin E2 excretion was similar in all three groups. A low-dose infusion of calcium or norepinephrine (known stimulants of prostacyclin) increased renal prostacyclin release in normal subjects and controls with renal insufficiency. Neither agonist, however, increased the low basal prostacyclin excretion in the patients (49.6±11 [basal] vs. 62±20 [norepinephrine] and 47.5±16 [calcium]; P>0.8). To evaluate the functional importance of the altered prostacyclin production, we studied the responses of renal blood flow and blood pressure to the calcium infusion. The calcium infusion did not alter blood pressure or renal blood flow in the normal subjects or the controls with renal insufficiency. In contrast, the same dose of calcium in the patients with hyporeninemic hypoaldosteronism produced a rise in mean blood pressure (from 91±6 to 104±8 mm Hg, P<0.05) and a fall in renal blood flow (from 673±58 to 560±42 ml per minute per 1.73 m2, P<0.05). These results indicate that a deficiency of prostacyclin could explain the low active-renin concentration and altered vasomotor tone seen in hyporeninemic hypoaldosteronism. (N Engl J Med 1986; 314:1015–20.)
Buyer beware transplantation
Authors: Jeremy R. Chapman, Francis L. Delmonico
Journal: Kidney International (2016)

Poor long-term outcomes of commercial transplantation of transplant tourists reinforce the need to prevent this form of human trafficking. The development of an International Convention by the Council of Europe is highlighted and the implications for physicians of the criminalizing of organ trafficking are considered. The causes of poor outcomes from transplant tourism are considered, with the actions needed to provide both equity and sufficiency of access to transplantation as critical deterrent measures.
Aspirin and Thromboembolism — A Possible Dilemma
Authors: Aaron J. Marcus
Journal: New England Journal of Medicine (1977)

A report by Harris and his associates in this issue of the Journal is of great interest and potential importance (p. 1246). Patients who underwent total hip replacement — a group at high risk for postoperative thromboembolism — were shown to benefit from prophylactic therapy with aspirin. Each subject was over the age of 40, had no prior history of thromboembolic disease or venous operations and received 600 mg of aspirin twice daily. Whereas a thromboembolic complication developed in 45 per cent of patients on placebo, only 25 per cent of those receiving aspirin acquired a deep vein thrombus as . . .
Chemoimmunotherapy of Disseminated Malignant Melanoma with Dimethyl Triazeno Imidazole Carboxamide and Bacillus Calmette-Guérin
Authors: Jordan U. Gutterman, Giora Mavligit, Jeffrey A. Gottlieb, Michael A. Burgess, Charles E. McBride, Lawrence Einhorn, Emil J. Freireich, Evan M. Hersh
Journal: New England Journal of Medicine (1974)

Eighty-nine patients with disseminated malignant melanoma were treated with a combination of dimethyl triazeno imidazole carboxamide (DTIC) administered intravenously and bacillus Calmette–Guérin (BCG) administered by scarification. The results were compared to those in a comparable retrospective group of 111 patients treated with DTIC alone. Metastatic areas regional to BCG immunization showed an augmented response to chemotherapy. Thus, chemoimmunotherapy-treated patients with lymph-node metastasis had a remission rate of 55 per cent compared to one of 18 per cent for patients treated with chemotherapy alone (p = 0.025). The duration of remissions and survival was significantly longer for patients (both nonvisceral and visceral metastases) treated with chemoimmunotherapy than for those treated with chemotherapy alone (p = 0.05, 0.001, respectively). A good prognosis was associated with immunocompetence before treatment or an increase in immunocompetence during treatment. Chemoimmunotherapy was well tolerated without serious morbidity. Further trials of chemoimmunotherapy are indicated in patients with disseminated malignant melanoma as well as other disseminated solid tumors. (N Engl J Med 291: 592–597, 1974)
Splenectomy in Hemolytic Anemia
Authors: Paul R. McCurdy, Charles E. Rath, Kenneth McCoy
Journal: New England Journal of Medicine (1958)

SPLENECTOMY has been employed for many years in the treatment of hemolytic anemia. Although striking improvement can be expected in certain types of hemolytic anemia — particularly hereditary spherocytosis — results of splenectomy in other types have generally been unpredictable. The observations of Jandl et al.1 on body-surface scanning after the injection of red cells tagged with radioactive chromate (Cr51) suggested that this technic might be helpful in predicting the results of splenectomy.The present report is concerned with the evaluation of this procedure in 50 patients, including 10 in whom splenectomy was done.Material and MethodsPatients were . . .
Case 22-2013
Authors: Sook-Bin Woo, John H. Stone, Stefan Kraft
Journal: New England Journal of Medicine (2013)

A 51-year-old woman presented with a history of recurrent epistaxis and oral ulcers that were transiently responsive to glucocorticoids. Examination revealed erosions of the mucous membranes of the tongue, soft palate, and buccal mucosa. A diagnostic procedure was performed.
Controversies in Management: Psychological consequences are unclear
Authors: T. Marteau
Journal: BMJ (1994)

Advances in genetics enable testing for a growing number of conditions. But simply being able to do a test is not sufficient justification for introducing a screening programme. There are several criteria for deciding whether to start a screening programme, including severity of the condition, accuracy of the test, acceptability of the test and any consequent treatment, and cost.1 For population based screening programmes in which the intervention is the offer of termination of affected pregnancies, acceptability to patients is critically important. In addition, decisions about implementing a screening programme need to consider its contribution to a population's health needs.

Acceptability of a screening programme can be assessed by both its uptake and its impact on individuals.

Assessing demand as opposed to health professionals' enthusiasm for a screening test is difficult, but crucial. Whether people accept the offer of carrier screening for cystic fibrosis depends in part on how it is offered. While over 70%, and in one study 95%, will have the test if it is offered immediately, only 25% will make a return visit for such a test.2 This raises the question of how strongly people want the test.3

Among the few carrier couples who have been detected through population …
Cellulitis Due to Botfly Larvae
Authors: Rachel L. Chin
Journal: New England Journal of Medicine (1997)

To the Editor: Ridker and colleagues (April 3 issue) 1 have provided important new information that will be useful in assessing the risk of cardiovascular events and in optimizing prophylaxis.Both Ridker et al. and Maseri, in his editorial, 2 speculate that the antiinflammatory effects of aspirin may be important in reducing the risk of myocardial infarction when the level of C-reactive protein is high.It seems unlikely that the antiinflammatory effects of aspirin have an important role, since these effects are minuscule and short-lived at the dosage used in the study by Ridker et al. (325 mg every other day).Were these effects of aspirin indeed important, higher doses would be expected to confer a greater cardioprotective effect.I am not aware of any controlled study that has demonstrated a greater effect with higher doses.An alternative possibility is that an elevated level of C-reactive protein is associated with increased coagulability (local or systemic, or both) and that the cardioprotective effects of aspirin are proportional to the magnitude of this increase in coagulability.
Further Cases of Valvular Heart Disease Associated with Fenfluramine–Phentermine
Authors: David J. Graham, Lanh Green
Journal: New England Journal of Medicine (1997)

To the Editor: In this issue of the Journal is a report of 24 cases of valvular heart disease in women treated with a combination of fenfluramine and phentermine.1 On the basis of prepublication notification of this finding, the Food and Drug Administration issued a Public Health Advisory on July 8 in which it requested that other cases be reported. We now describe an additional 28 patients from the United States with similar disease. Excluded from this series were a handful of reports describing isolated tricuspid insufficiency in the presence of primary pulmonary hypertension or isolated mitral-valve prolapse. The reports . . .
Adoptive Transfer of CD8<sup>+</sup> T Cells Generated from Induced Pluripotent Stem Cells Triggers Regressions of Large Tumors Along with Immunological Memory
Authors: Hidehito Saito, Keisuke Okita, Alfred E Chang, Fumito Ito
Journal: Cancer Research (2016)

Current approaches to adoptive T-cell therapy are limited by the difficulty of obtaining sufficient numbers of T cells against targeted antigens with useful in vivo characteristics. Theoretically, this limitation could be overcome by using induced pluripotent stem cells (iPSC) that could provide an unlimited source of autologous T cells. However, the therapeutic efficacy of iPSC-derived regenerated T cells remains to be demonstrated. Here, we report the first successful reprogramming of T-cell receptor (TCR) transgenic CD8(+) T cells into pluripotency. As part of the work, we established a syngeneic mouse model for evaluating in vitro and in vivo antitumor reactivity of regenerated T cells from iPSCs bearing a rearranged TCR of known antigen specificity. Stably TCR retained T-cell-derived iPSCs differentiated into CD4(+)CD8(+) T cells that expressed CD3 and the desired TCR in vitro Stimulation of iPSC-derived CD4(+)CD8(+) T cells with the cognate antigen in the presence of IL7 and IL15 followed by expansion with IL2, IL7, and IL15 generated large numbers of less-differentiated CD8(+) T cells with antigen-specific potent cytokine production and cytolytic capacity. Furthermore, adoptively transferred iPSC-derived CD8(+) T cells escaped immune rejection, mediated effective regression of large tumors, improved survival, and established antigen-specific immunological memory. Our findings illustrate the translational potential of iPSCs to provide an unlimited number of phenotypically defined, functional, and expandable autologous antigen-specific T cells with the characteristics needed to enable in vivo effectiveness. Cancer Res; 76(12); 3473-83. ©2016 AACR.
MRI findings and return to play in football: a prospective analysis of 255 hamstring injuries in the UEFA Elite Club Injury Study
Authors: Jan Ekstrand, Justin C Lee, Jeremiah C Healy
Journal: British Journal of Sports Medicine (2016)

The present study evaluated whether the MRI parameters of hamstring injuries in male professional football players correlate with time to return to play (RTP).46 elite European football teams were followed prospectively for hamstring injuries between 2007 and 2014. Club medical staff recorded individual player exposure and time-loss after hamstring injury. MRI parameters were evaluated by two independent radiologists and correlated with the RTP data.A total of 255 grade 1 and 2 injuries were evaluated in this study. RTP was longer for grade 2 than grade 1 injuries (24±13, 95% CI 21 to 26 days vs 18±15, 95% CI 16 to 20 days; mean difference: 6, 95% CI 2 to 9 days, p=0.004, d=0.39). 84% of injuries affected the biceps femoris (BF) muscle, whereas 12% and 4% affected the semimembranosus (SM) and semitendinosus (ST), respectively. No difference in lay-off time was found for injuries to the three different muscles (BF 20±15 days, SM 18±11 days, ST 23±14 days; p=0.83). The recurrence rate was higher for BF injuries than for SM and ST injuries combined (18% vs 2%, p=0.009). The size of the oedema weakly correlated with time to RTP (r(2)=6-12%). No correlation was found between location of injury and time to RTP. The majority of the intramuscular injuries affected the MT junction (56% in grade 1 and 2 injuries), but no difference in lay-off time was found between the different types of injuries.The radiological grade and size of the oedema correlate with time to RTP for both, grade 1 and 2 injuries. No correlations were found between time to RTP and the location and type of injury.
Efficacy of Liver Transplantation in Patients with Primary Biliary Cirrhosis
Authors: Bernd H. Markus, E. Rolland Dickson, Patricia M. Grambsch, Thomas R. Fleming, Vincenzo Mazzaferro, Goran Bo G. Klintmalm, Russell H. Wiesner, David H. Van Thiel, Thomas E. Starzl
Journal: New England Journal of Medicine (1989)

No controlled trials have been performed to assess the efficacy of liver transplantation. Because of the marked improvement in survival after liver transplantation since 1981, random assignment of patients to a control group not undergoing transplantation is considered clinically inappropriate. To assess the efficacy of liver transplantation in patients with primary biliary cirrhosis, we compared survival in 161 patients with this diagnosis who had undergone a liver transplantation with survival in patients with the same diagnosis who had been treated conservatively. The comparison was performed with use of a recently developed statistical technique, the Mayo model. All patients had undergone liver transplantation between March 1980 and June 1987 and were followed for a median of 25 months. Three months after liver transplantation, the Kaplan–Meier survival probabilities in the recipients were substantially higher than the Mayo-model "simulated-control" survival probabilities (P<0.001). At two years, the Kaplan–Meier survival probability was 0.74, whereas the mean Mayo-model survival probability was 0.31. The patients who were at low risk according to the Mayo model had the best probability of survival after liver transplantation; however, patients at all risk levels who had undergone liver transplantation had higher probabilities of survival than those who had not. We conclude that liver transplantation is an efficacious treatment in patients with advanced primary biliary cirrhosis. (N Engl J Med 1989; 320:1709–13.)