tbuckley/cabot-search huggingface dataset:
Isolation of Two Lines of Transplantable, Ethionine-Induced Rat Hepatomas of High and Low Catalase Activity From a Primary Tumor
Authors: Miloslav Rechcigl, Jr., Herschel Sidransky
Journal: JNCI Journal of the National Cancer Institute (1962)

Transplantation of a primary ethionine-induced hepatoma in OM/N rats gave rise to two lines of hepatomas, one (HC) with extremely high catalase activity, sometimes exceeding that of the normal liver, and the second (LC) with a low enzymatic activity. The difference in the catalase levels of the two lines persisted for over 10 transplant generations. Histologically no differences were observed in tissues from all transplanted tumors of both the high and the low catalase lines. The growth characteristics of the tumors indicated that the low catalase line grew more rapidly than the high catalase line. Enzyme assays for lactic dehydrogenase, glutamic-oxalacetic transaminase, acid and alkaline ribonuclease, arginase, amylase, tryptophan pyrrolase, uricase, D-amino acid oxidase, glucose-6-phosphatase, choline oxidase, and aldolase did not show significant differences between the low and the high catalase lines of the hepatomas. Similarly no apparent differences were found in the nitrogen, fat, water, glycogen, ribonucleic acid, and deoxyribonucleic acid contents of the two tumor lines.
Case 40-2005
Authors: Meredith August, Paul A. Caruso, William C. Faquin
Journal: New England Journal of Medicine (2005)

An 18-year-old man reported gradual painless swelling of the left mandible that had occurred over one month. An examination showed enlargement of the left mandible, with normal dentition. Imaging studies revealed a large, cystic lesion in the ramus and body of the left mandible. A diagnostic and therapeutic procedure were performed.
Dose-dense docetaxel, carboplatinum and trastuzumab (ddTCH) as neoadjuvant therapy for human epidermal receptor 2 (HER2) positive breast cancer
Authors: H. S. Han, P. Doliny, M. Blaya, S. Gluck, J. Slingerland, O. Silva, C. Welsh, J. Hurley
Journal: Journal of Clinical Oncology (2007)

11003 Background: Docetaxel, cisplatin, and trastuzumab given every 21 days in Her 2-postitive breast cancer demonstrates a pathologic complete response (pCR) rate of 23%. Decreasing the interval between doses of chemotherapy has lead to improvement in survival in the adjuvant setting. In one study dose dense chemotherapy improved response only in patients whose tumors overexpressed her-2. We conducted a phase II trial to evaluate the efficacy and safety of neoadjuvant dose-dense TCH for HER 2-positive breast cancer. Methods: Patients with T2–4 N0–3 M0 HER-2 positive (by FISH) breast cancers were eligible. Neoadjuvant therapy consisted of carboplatinum (AUC 6) Day 1,15,29,43, docetaxel (75mg/m2) Day 1,15,29, 43 and weekly trastuzumab for 10 weeks 4mg/kg Day 1 then 2mg/kg Day 8,15,22,29,36,43,50,57,64, Pegfilgastrim Day 2,16,30,44. The primary end point was the rate of pCR. Results: Twenty patients are evaluable for response. The median age was 51.5 years (range 29–73). Mean tumor size was 5.6 cm. Patients had stage IIA (30%), IIB (15%), IIIA (45%), IIIB (5%), and IIIC (5%). Estrogen receptors were positive in 36% of tumors. No grade 4 or 5 toxicity occurred. The most frequent toxicity was hand-foot syndrome (Grade I 15%, Grade II 10%, Grade III 15%). Neutropenia occurred in 5 patients (Grade II 10%, Grade III 15%) There were no episodes of febrile neutropenia or hospitalizations. Grade I cardiotoxicity was seen in 30%. The rate of pCR was 40% in the breast and 35% in both breast and axilla. 16/20 patients (80%) had pathologically negative lymph nodes. Conclusions: Changing the scheduling of TCH from every 21 days to every 14 days improves the pCR rate from 23 to 40%. The regimen was well tolerated. No significant financial relationships to disclose.
The Long-Term Outcome of Pituitary Irradiation after Unsuccessful Transsphenoidal Surgery in Cushing's Disease
Authors: Javier Estrada, Mauro Boronat, Mercedes Mielgo, Rosa Magallón, Isabel Millán, Santiágo Díez, Tomás Lucas, Balbino Barceló
Journal: New England Journal of Medicine (1997)

Irradiation of the pituitary is widely considered the most appropriate treatment for patients with Cushing's disease in whom transsphenoidal microsurgery has been unsuccessful. However, there is little information about the long-term efficacy of this treatment.We used external pituitary radiation to treat 30 adult patients with persistent or recurrent Cushing's disease after unsuccessful transsphenoidal surgery. The mean (+/-SD) dose of radiation was 50+/-1 Gy. Pituitary and adrenal function was assessed every six months after radiation therapy. Remission was defined as the regression of symptoms and signs of Cushing's syndrome, normal urinary cortisol excretion, and a low plasma cortisol concentration in the morning after the administration of 1 mg of dexamethasone at midnight.Twenty-five patients (83 percent) had remissions during a median follow-up of 42 months (range, 18 to 114). The remissions began 6 to 60 months after radiation therapy, but in most cases (22 patients) remission occurred during the first 2 years. None of the 25 patients had a relapse of Cushing's disease after remission was achieved. There was no relation between the response to radiotherapy and sex, age, urinary cortisol excretion before radiotherapy, the interval between surgery and radiotherapy, whether a pituitary adenoma was found by pathological examination, or tumor size. Seventeen patients had a deficiency of growth hormone after radiation therapy, 10 had a deficiency of gonadotropins, 4 had a deficiency of thyrotropin, and 1 had a deficiency of corticotropin.Pituitary irradiation is an effective and well-tolerated treatment for patients with Cushing's disease in whom transsphenoidal surgery is unsuccessful.
Preliminary Note: Identity of a Herpesvirus Antigen From Burkitt Lymphoma of Man and the Lucké Adenocarcinoma of Frogs
Authors: M A Fink, G S King, M Mizell
Journal: JNCI Journal of the National Cancer Institute (1968)

Herpesviruses isolated from a Burkitt lymphoma cell line and from the Lucké adenocarcinoma of a frog have at least one antigen in common, as shown by immunodiffusion tests using both viruses as antigen and the serum from Burkitt lymphoma patients and Vermont field frogs as antibody.
Helsinki Heart Study: Primary-Prevention Trial with Gemfibrozil in Middle-Aged Men with Dyslipidemia
Authors: M. Heikki Frick, Olli Elo, Kauko Haapa, Olli P. Heinonen, Pertti Heinsalmi, Pekka Helo, Jussi K. Huttunen, Pertti Kaitaniemi, Pekka Koskinen, Vesa Manninen, Hanna Mäenpää, Marjatta Mälkönen, Matti Mänttäri, Seppo Norola, Amos Pasternack, Jarmo Pikkarainen, Matti Romo, Tom Sjöblom, Esko A. Nikkilä
Journal: New England Journal of Medicine (1987)

In a randomized, double-blind five-year trial, we tested the efficacy of simultaneously elevating serum levels of high-density lipoprotein (HDL) cholesterol and lowering levels of non-HDL cholesterol with gemfibrozil in reducing the risk of coronary heart disease in 4081 asymptomatic middle-aged men (40 to 55 years of age) with primary dyslipidemia (non-HDL cholesterol ≥200 per deciliter [5.2 mmol per liter] in two consecutive pretreatment measurements). One group (2051 men) received 600 mg of gemfibrozil twice daily, and the other (2030 men) received placebo. Gemfibrozil caused a marked increase in HDL cholesterol and persistent reductions in serum levels of total, lowdensity lipoprotein (LDL), and non-HDL cholesterol and triglycerides. There were minimal changes in serum lipid levels in the placebo group. The cumulative rate of cardiac end points at five years was 27.3 per 1000 in the gemfibrozil group and 41.4 per 1000 in the placebo group — a reduction of 34.0 percent in the incidence of coronary heart disease (95 percent confidence interval, 8.2 to 52.6; P<0.02; two-tailed test). The decline in incidence in the gemfibrozil group became evident in the second year and continued throughout the study. There was no difference between the groups in the total death rate, nor did the treatment influence the cancer rates. The results are in accord with two previous trials with different pharmacologic agents and indicate that modification of lipoprotein levels with gemfibrozil reduces the incidence of coronary heart disease in men with dyslipidemia. (N Engl J Med 1987; 317:1237–45.)
Is There a Need for Axillary Dissection in Breast Cancer?
Authors: Jason P. Wilson, David Mattson, Stephen B. Edge
Journal: Journal of the National Comprehensive Cancer Network (2011)

The involvement of axillary nodes remains a significant prognostic factor in breast cancer. However, management has changed from complete surgical staging to sentinel lymph node biopsies. Although little controversy exists regarding patients with negative sentinel lymph node biopsies, some remains regarding what to do with patients with small volume of axillary disease. This article focuses on the examination of recent evidence in management of the axilla. It focuses on both the prognostic and therapeutic information gleaned from isolated tumor cells and micrometastatic disease and on the use of completion axillary lymph node dissections or axillary radiation in preventing regional recurrence.
Effects of Mitral-Valve Replacement on the Pulmonary Vascular Dynamics of Patients with Pulmonary Hypertension
Authors: Eugene Braunwald, Nina S. Braunwald, John Ross, Andrew G. Morrow
Journal: New England Journal of Medicine (1965)

THE development of an elevation of the pulmonary vascular resistance is a common complication of severe mitral-valve disease, and this abnormality has been attributed to a combination of obliterative changes in the pulmonary vascular bed and pulmonary vasoconstriction.1 2 3 In many patients the elevation of pulmonary vascular resistance is extreme and constitutes the major hemodynamic burden faced by the right ventricle.4 Under these circumstances the secondary changes in the pulmonary vascular bed become primarily responsible for many of the clinical findings, including ventricular failure. In view of these considerations determination of the extent to which these abnormalities in the pulmonary circulation . . .
A phase I study of EC0225 administered weeks 1 and 2 of a 4-week cycle.
Authors: S. Sharma, E. A. Sausville, P. LoRusso, N. J. Vogelzang, W. E. Samlowski, J. Carter, K. Forman, S. Bever, R. A. Messmann
Journal: Journal of Clinical Oncology (2010)

3082 Background: The folate receptor (FR) is expressed on many human tumors (e.g., ovarian, NSCLC, etc.) where it functions as a high-affinity receptor for folic acid. The FR is minimally expressed in normal tissue, making it a logical target for anticancer therapy. Indeed, the relevance of FR as a molecular target for antitumor agents was discussed in detail at the 2008 ASCO Annual Meeting. Folic acid can be used as a carrier molecule to deliver covalently-linked therapeutic and diagnostic moieties to the FR and EC0225 is a conjugate of folic acid coupled to mitomycin-C and desacetyl vinblastine hydrazide (DAVLBH). The EC0225 conjugate is a high-affinity ligand for the folate receptor (FR). This phase I study assessed the safety of escalating intravenous bolus doses of EC0225. Methods: Eligible patients with adequate performance status and organ function that had previously failed standard therapy were treated with EC0225 on days 1, 3, 5 (week 1) and 8, 10, 12 (week 2) of a 28-day cycle. Patients in the final cohort received drug on days 1, 3, 5 and 15, 17, 19 of a 28-day schedule. Endpoints included identification of the maximally-tolerated dose (MTD), the toxicity profile and any evidence of antitumor effect. Results: As of DEC 2009, 63 patients had received EC0225 at doses of 0.38, 0.8, 1.1, 1.5, 2.3, 3.1 and 3.9 mg (flat dose) and at 2.3 and 2.88 mg/m2; (where n =10, 8, 4, 14, 4, 5, 4, 7 and 7, respectively). EC0225 was generally well tolerated at dose levels ≤ 2.3 mg/m2. The most frequent treatment-related adverse events (all grades) included anemia (25%), constipation (17%), leukopenia (12%) and fatigue (10%). Grade 3 hypotension and Grade 4 neutropenia occurred in 1 patient each at the highest dose tested (2.88 mg/m2) defining the MTD at 2.3 mg/m2. Longer-term disease stabilization (≥ 4 months) occurred in patients with colorectal (4, 6 mo.), breast (4 mo.) and prostate cancer (10 mo.) and in patients with leiomyosarcoma (4 mo.) and mesothelioma (4 mo.). Traditional MMC- related pulmonary toxicities were not identified in this study. Conclusions: EC0225, a conjugate of folate, mitomycin-C and DAVLBH may be administered safely as a 2.3 mg/m2 intravenous bolus dose on days 1, 3, 5 and 8, 10, 12 of a 28-day schedule. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Endocyte Endocyte
Maximum tolerated dose–Results of a phase I trial of paclitaxel and cisplatin with radiation therapy in carcinoma of the cervix
Authors: E. Prasad
Journal: Journal of Clinical Oncology (2008)

13537 Background: Cisplatin based chemotherapy is the standard treatment for locally advanced carcinoma of the cervix. Recent studies have shown better response rates with treatment using newer combination chemotherapy regimens administered along with radiation therapy. The present study is a Phase I study, to establish the Maximal Tolerated Dose (MTD) of paclitaxel in combination with cisplatin as a radio sensitizer in the treatment of Carcinoma of the cervix and to analyze the toxicity profile of the combination regimen. Materials and Methods: 21 newly diagnosed patients with squamous cell carcinoma of the cervix stage (FIGO) I B to III B with good performance status (ECOG 0, 1) and with normal hepatic and renal parameters, were included in a Phase I trial to undergo concurrent chemoradiation with weekly paclitaxel and cisplatin. All eligible cohorts received external beam radiation therapy (50 Gy) given by conventional 4 field box technique. Concurrent chemotherapy was with weekly cisplatin (30 mg/m2) and an escalating dose level (according to the modified Fibonacci series) of weekly paclitaxel starting at 10 mg/m2 up to 50 mg/m2. This was followed by a single application of LDR brachytherapy. The maximum tolerated dose (MTD) of weekly paclitaxel was determined as 40 mg/m2. The dose limiting toxicity of this combination in our patients as occurred at a dose of 50 mg/m2 weekly paclitaxel, was grade 3 proctitis and vaginitis. Conclusion: In this Phase I trial of concurrent chemo radiation with weekly Paclitaxel at increasing doses and cisplatin (30 mg/m2) in patients with carcinoma of the cervix, the Maximum Tolerated Dose (MTD) was identified as paclitaxel (40 mg/m2). This combination was feasible, with an acceptable toxicity profile. This can be the recommended dose level in designing phase II studies. No significant financial relationships to disclose.
The Corneal Arcus
Authors: David G. Cogan
Journal: New England Journal of Medicine (1974)

The opacity of the peripheral cornea that all persons acquire to some degree in middle life, and occasionally earlier, should be telling us something. The relevant literature in the medical and ophthalmologic periodicals has led to controversial conclusions, possibly because informed and appropriate questions have not always been asked.Histologically and biochemically, arcus corneae — we avoid the term arcus senilis — consists of deposited lipids having a composition similar to that in serum. There is no underlying tissue degeneration nor reactive histiocytosis. Defatted sections, prepared for routine microscopical examination, show normal corneal structure with, ordinarily, no evidence of arcus. . . .
Increase in Human Cases of Tularemia — Colorado, Nebraska, South Dakota, and Wyoming, January–September 2015
Authors: Caitlin Pedati, Jennifer House, Jessica Hancock-Allen, Leah Colton, Katie Bryan, Dustin Ortbahn, Lon Kightlinger, Kiersten Kugeler, Jeannine Petersen, Paul Mead, Tom Safranek, Bryan Buss
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

Tularemia is a rare, often serious disease caused by a gram-negative coccobacillus, Francisella tularensis, which infects humans and animals in the Northern Hemisphere. Approximately 125 cases have been reported annually in the United States during the last two decades. As of September 30, a total of 100 tularemia cases were reported in 2015 among residents of Colorado (n = 43), Nebraska (n = 21), South Dakota (n = 20), and Wyoming (n = 16) (Figure). This represents a substantial increase in the annual mean number of four (975% increase), seven (200%), seven (186%) and two (70%) cases, respectively, reported in each state during 2004-2014.
Effect of Mode of Delivery in Nulliparous Women on Neonatal Intracranial Injury
Authors: Dena Towner, Mary Ames Castro, Elaine Eby-Wilkens, William M. Gilbert
Journal: New England Journal of Medicine (1999)

Infants delivered by vacuum extraction or other operative techniques may be more likely to sustain major injuries than those delivered spontaneously, but the extent of the risk is unknown.
Oncology Drug Review Process
Authors: Ann T. Farrell, Richard Pazdur
Journal: Journal of the National Comprehensive Cancer Network (2003)

The U.S. Food and Drug Administration facilitates the development of drugs intended to treat cancer and other serious or life-threatening diseases. This article describes the new drug application (NDA) process, endpoints used in oncologic trials, and recent initiatives to expedite the review of drugs used to treat serious and life-threatening diseases. The Food and Drug Administration can grant either regular or accelerated marketing approval for oncology drugs. Regular approval is based on endpoints demonstrating that the drug provides a clinical benefit, such as longer life, enhanced quality of life, or a favorable effect on an established surrogate for longer or better life, such as long-term complete responses. Accelerated approval is based on a surrogate endpoint that is less well established but is reasonably likely to predict a longer or better life and can be granted for drugs that are intended to treat a serious or life-threatening illness and that provide meaningful therapeutic benefit to patients over existing therapies. The Agency classifies an NDA as either a priority or a standard application. Drugs that receive priority review are agents that appear to represent significant improvements over existing therapies. A priority NDA is reviewed by the Agency within 6 months; a standard review is accomplished within 10 months. The Agency communicates with sponsors throughout the drug development process, suggesting appropriate trial designs and meaningful endpoints.
Case 31-2001
Authors: Daniel T. Baran, Gary St.A. Letts
Journal: New England Journal of Medicine (2001)

Presentation of CaseA 70-year-old woman was admitted to the hospital because of dyspnea and multiple cutaneous ulcers.The patient had a history of long-standing type 2 diabetes mellitus as well as an old myocardial infarct and a remote history of triple coronary-artery bypass surgery; she also had paroxysmal atrial fibrillation, congestive heart failure, peripheral vascular disease, and end-stage renal disease, which was being treated by peritoneal dialysis. Anticoagulation with warfarin was started six months before admission; the dosage of the drug had not changed recently.Twenty days before admission, the patient was admitted to another hospital because of areas . . .
Virus of Avian Myeloblastosis (BAI Strain A). XXIV. Nucleotide Composition of the Pentosenucleic Acid and Comparison with Strain R (Erythroblastosis)&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R. A. Bonar, Robert H. Purcell, Dorothy Beard, J. W. Beard
Journal: JNCI Journal of the National Cancer Institute (1963)

Analyses were made of the nucleotide composition of the pentosenucleic acids of the BAI strain A (myeloblastosis) and strain R (erythroblastosis) avian tumor viruses purified from the blood plasma of birds with myeloblastosis and erythroblastosis, respectively. The BAI strain A differed from strain R especially in the content of guanylic acid. There was a still greater difference between these agents and the Rous virus from tissue culture studied by other investigators. The nucleotide composition of strains BAI A, R, and Rous obtained from these sources differed greatly from the analogous constitution of myeloblasts and other avian cells as well as that of Rous virus preparation from solid tissue tumors. Concentrates from normal chicken plasma did not contain pentosenucleic acid in amounts sufficient to detract from the results with the BAI A and R strains. The findings suggest real differences between these avian tumor virus strains in biochemical constitution.
Case 51-1992
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, R.P. Cambria, D.C. Brewster
Journal: New England Journal of Medicine (1992)

Presentation of CaseA 78-year-old woman was admitted to the hospital because of recurrent bouts of gastrointestinal bleeding.The patient had a 30-year history of numerous vascular operations for atherosclerotic disease, which began with an aortoiliac endarterectomy with an iliac-vein patch angioplasty. Recurrent symptoms led to placement of an aortobifemoral-bypass graft. Late occlusion of the left limb of the graft required a right iliac-to-left-femoral crossover transpubic graft and subsequently a left axillobifemoral bypass procedure. Two years before admission the aortic valve was replaced with a St. Jude prosthesis, accompanied by a coronary-artery bypass, and a left carotid endarterectomy was performed. . . .
Use of Inhaled Corticosteroids and the Risk of Cataracts
Authors: Robert G. Cumming, Paul Mitchell, Stephen R. Leeder
Journal: New England Journal of Medicine (1997)

The use of systemic corticosteroids is a risk factor for the development of posterior subcapsular cataracts, but the association between inhaled corticosteroids and cataracts is uncertain.We conducted a population-based, cross-sectional study of vision and common eye diseases in an urban area of the Blue Mountains, near Sydney, Australia. We recruited 3654 people 49 to 97 years of age; the participation rate was 82 percent. We collected information by questionnaire on potential risk factors for cataracts, including the current or prior use of inhaled corticosteroids (beclomethasone or budesonide). Photographs of the subjects' lenses were graded, without information on the subjects, to determine the presence and severity of cortical, nuclear, and posterior subcapsular cataracts.Three hundred seventy subjects reported using inhaled corticosteroids, 164 currently and 206 previously. Among these subjects, after adjustment for age and sex, there was a higher prevalence of nuclear cataracts (relative prevalence, 1.5; 95 percent confidence interval, 1.2 to 1.9) and posterior subcapsular cataracts (relative prevalence, 1.9; 95 percent confidence interval, 1.3 to 2.8) than among the subjects with no inhaled-corticosteroid use, but the prevalence of cortical cataracts was not significantly higher (relative prevalence, 1.1; 95 percent confidence interval, 0.9 to 1.3). Higher cumulative lifetime doses of beclomethasone were associated with higher risks of posterior subcapsular cataracts (P for trend <0.001); the highest prevalence (27 percent) was found in subjects whose lifetime dose was over 2000 mg (relative prevalence, 5.5). Adjusting for the use of systemic corticosteroids and other potential confounders had little effect on the magnitude of the associations. The associations with posterior subcapsular cataracts, but not those with nuclear cataracts, were less marked when the analyses were restricted to subjects who had never used systemic corticosteroids.The use of inhaled corticosteroids is associated with the development of posterior subcapsular and nuclear cataracts.