tbuckley/cabot-search huggingface dataset:
Case 27-1963
Authors: W. Davies Sohier, Benjamin Castleman
Journal: New England Journal of Medicine (1963)

Presentation of CaseA sixty-six-year-old widow was referred to the hospital because of weakness and cough.During the year before entry the patient was weak and fatigued easily, and mental deterioration occurred. Three weeks before admission to the hospital coryza and a cough productive of greenish-yellow sputum developed; there was no hemoptysis, chill, fever or chest pain. One week before entry she complained of nausea, anorexia and a "foul odor to cigarettes," and later in the day she fell, without losing consciousness. On admission to another hospital moist rales were audible at both lung bases, and the spleen was palpable; . . .
Inhibition of Renal Phosphate Transport by a Tumor Product in a Patient with Oncogenic Osteomalacia
Authors: Qiang Cai, Stephen F. Hodgson, Pai C. Kao, Vanda A. Lennon, George G. Klee, Alan R. Zinsmiester, Rajiv Kumar
Journal: New England Journal of Medicine (1994)

In tumor-induced osteomalacia, a rare syndrome characterized by hypophosphatemia, hyperphosphaturia, low plasma 1,25-dihydroxyvitamin D concentrations, and osteomalacia,1–5 all biochemical and pathological abnormalities disappear when the tumor is removed. Tumors associated with this syndrome are thought to secrete a substance that inhibits the renal tubular reabsorption of phosphate,1–5 but whether this factor interacts directly with renal tubular cells is not known. We investigated the ability of medium in which sclerosing hemangioma cells from a patient with oncogenic osteomalacia were cultured to alter sodium-dependent phosphate transport in opossum-kidney epithelial cells. We found that the medium inhibited phosphate transport, without increasing . . .
Randomized study of pazopanib + lapatinib vs. lapatinib alone in patients with HER2-positive advanced or metastatic breast cancer
Authors: D. Slamon, H. L. Gomez, F. F. Kabbinavar, O. Amit, M. Richie, L. Pandite, V. Goodman
Journal: Journal of Clinical Oncology (2008)

1016 Background: Preclinical evidence indicates a direct molecular link between HER2 amplification and up-regulation of VEGF in HER2+ breast cancer. Concurrent over-expression of HER2 and VEGF is associated with a poorer clinical outcome than over-expression of either alone. Together these data provide the rationale for clinical translation of simultaneous blockade of both pathways. Pazopanib (P) is an oral angiogenesis inhibitor targeting VEGFR, PDGFR, and c-kit. Lapatinib (L) is an oral tyrosine kinase inhibitor of EGFR (ErbB1) and HER2 (ErbB2). This study (VEG20007) evaluates the efficacy and safety of dual pathway inhibition in patients (pts) with HER2+ adv/met breast cancer. Methods: Eligible pts received no prior chemotherapy or HER2-directed therapy for adv/met disease and had measurable disease per RECIST. Pts were randomized to receive P 400 mg/d + L 1,000 mg/d or L alone (1,500 mg/d) for 12 weeks. Following disease assessment at week (wk) 12, pts with an objective response could continue on study treatment following re-consent; those with stable disease could continue only where trastuzumab was unavailable. The primary endpoint was progressive disease rate (PDR) at wk 12 in HER2 FISH+ pts. A pre-specified interim analysis (IA) was performed when 62 of 140 pts reached wk 12. Results: 32 PL and 30 L pts were included in the IA (73% stage IV, 27% stage III). Pts in the PL arm had a shorter time since initial diagnosis (227 vs. 380 days); baseline characteristics were otherwise well balanced. Efficacy data (by independent review) at wk 12 were available in 69% (PL) and 77% (L) of pts: PDR was 19% (PL) vs. 27% (L); response rate was 44% (PL) vs. 30% (L). Reduction in target lesions occurred in 73% (PL) vs. 43% (L) of pts. The most common adverse events (PL vs. L) were diarrhea (63 vs. 57%), rash (22 vs. 20%) and nausea (22 vs. 17%). AST (63 vs. 33%) and bilirubin (39 vs. 21%) increases were more common on PL. Asymptomatic decline in left ventricular ejection fraction led to discontinuation of 1 pt on PL. Conclusions: This is the first phase II trial to evaluate the combination of 2 oral targeted agents in first-line HER2+ adv/met breast cancer. Preliminary data demonstrate the activity and tolerability of PL. The final analysis will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech BioOncology, GlaxoSmithKline GlaxoSmithKline
Real-world treatment patterns of previously treated advanced gastric and gastroesophageal junction adenocarcinoma (GC) in the United Kingdom (UK).
Authors: Astra M. Liepa, Jacqueline Brown, Bela Bapat, James A. Kaye
Journal: Journal of Clinical Oncology (2015)

184 Background: With no licensed therapies for previously treated advanced GC, little is known on how patients (pts) are managed after 1st-line chemotherapy (CTx) has failed. We present real-world data on characteristics, treatments, and resource utilization (RU) for such pts in the UK. Methods: Physicians who treat pts with advanced GC completed a web-based chart review detailing clinical and RU data for 3-4 de-identified pts each. Eligible pts were ≥18 years old, diagnosed Jan 2007-Mar 2012 with advanced GC, received 1st-line fluoropyrimidine+platinum, and had ≥3 months of follow-up after 1st-line discontinuation (DC). Data were summarized descriptively. Results: From Jun to Jul 2013, 58 physicians provided data for 200 pts. Pts’ mean age was 61 years; 69.5% were male. At advanced stage diagnosis, ECOG performance status (PS) was 21% 0, 72.5% 1, and 6.5% 2. The most common 1st-line regimens were capecitabine (cape)+oxaliplatin+epirubicin (epi) (34%), cape+cisplatin+epi (20.5%) and 5-FU+cisplatin+epi (13%). The most common reasons for 1st-line DC were completion of planned regimen (63%) and disease progression (24%). ECOG PS at 1st-line DC was 5% 0, 57.5% 1, 32% 2, 5.5% 3. 28.5% received 2nd-line, and 79% of these had PS 0/1 at start of 2nd-line. 21 unique 2nd-line regimens were reported; most common were docetaxel (28%), paclitaxel (11%), trastuzumab (9%), cape (7%) and irinotecan (7%). Among pts who received 2nd-line, 5% received 3rd-line. (See table.) The most common contributing reasons for hospitalization were palliative care and disease progression. Conclusions: In our study sample of advanced GC, the minority of pts received subsequent CTx after 1st-line CTx. There was considerable variation in 2nd-line regimens, although primarily monotherapy. Pts who received 2nd-line CTx had numerically similar or lower rates of supportive care. [Table: see text]
Efficacy of Intravitreal Foscarnet in a Patient with AIDS
Authors: Ronni M. Lieberman, Juan Orellana, R. Christine Melton
Journal: New England Journal of Medicine (1994)

To the Editor: Cytomegalovirus retinitis is a leading cause of morbidity in patients with AIDS. Although it is optimally treated systemically with either ganciclovir or foscarnet, intraocular therapy is becoming increasingly popular. We report here the response of a patient to intravitreal foscarnet without concomitant systemic therapy. The patient, a 59-year-old Hispanic man with AIDS, was given a diagnosis of cytomegalovirus retinitis of the left eye in November 1992 (Figure 1A). He was treated systemically with ganciclovir as induction therapy and then in maintenance doses. On June 14, 1993, the patient had a visual acuity of 20/200 in the left . . .
Abstract IA24: Science of surviving cancer: Lessons learned from our cancer survivors
Authors: Smita Bhatia
Journal: Cancer Research (2016)

Abstract The 5-year overall survival rate for childhood cancer now exceeds 80%. As a result of this improvement in survival, the number of childhood cancer survivors now exceeds 375,000. The increasing number of long-term survivors is attended by a growing awareness that many will develop health conditions as a direct or an indirect consequence of their cancer therapy. While some of these conditions occur during therapy and persist well after the therapy has been completed (such as steroid-induced osteonecrosis, or alkylating agent /radiation-induced hypogonadism), many outcomes are not evident until 10-20 years later, such as subsequent malignant neoplasms (SMNs) and anthracycline-related late onset congestive heart failure (CHF). Individuals exposed to radiation and chemotherapy are vulnerable to long-lasting organ toxicity. While clear and unambiguous associations exist between therapeutic exposures and specific complications, considerable inter-individual variability is observed in the risk of developing an outcome for any given exposure. Genetic predisposition and especially its interaction with therapeutic exposures can potentially exacerbate the toxic effect of treatment on normal tissues and organ systems, and can possibly explain the inter-individual variability. Thus, it becomes imperative to understand the individual variability in: i) the internal dose of the therapeutic agent; ii) the biologically effective dose; iii) the alterations in structure or function of the tissue or organ; and iv) the consequent development of preclinical disease, in order to understand the pathogenesis of therapy-related complications, and also develop a better idea of the individual susceptibility. Over the past decade, there have been several reports describing the role of genetic susceptibility in anthracycline-related CHF, in chemotherapy-related leukemia, radiation-related solid SMNs, and corticosteroid-related osteonecrosis. These studies have varied in their investigative approach – from a candidate gene investigation to a genome-wide association study. Understanding the etiology and pathogenetic pathways that lead to the morbidity is critical to developing targeted prevention and intervention strategies, optimizing risk-based health care of cancer survivors, thus minimizing chronic morbidities and improving quality of life. Citation Format: Smita Bhatia. Science of surviving cancer: Lessons learned from our cancer survivors. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr IA24.
Epicutaneous but Not Oral Immunotherapy Leads to Sustainable GATA-3 Hypermethylation and Foxp3 Hypomethylation in Peanut Sensitized Mice
Authors: Jorg Tost, Lucie Mondoulet, Emilie Puteaux, Florence Busato, Mélanie Ligouis, Véronique Dhelft, Camille Plaquet, Christophe Dupont, Pierre-Henri Benhamou
Journal: Journal of Allergy and Clinical Immunology (2016)
Case 42-1971
Authors: Richard C. Cabot, Benjamin Castleman, Betty U. McNeely, Robert E. Paul, Austin L. Vickery
Journal: New England Journal of Medicine (1971)

Presentation of CaseA 74-year-old woman was admitted to the hospital because of abdominal distress.She had been well until 13 years previously, when cutaneous lesions developed on the chest. Physical examination disclosed no other abnormality; biopsy of one of the lesions revealed lymphoma cutis. Radiation therapy was administered to the thoracic lesions and to purplish cutaneous plaques that developed subsequently on the face and the upper dorsal area. Six years before entry splenomegaly was found, although the patient remained asymptomatic; the platelet count was 150,000. One year later Paget's disease of the right nipple was detected. X-ray films of . . .
Pharmacokinetics (PK) of arsenic trioxide in cancer patients (pts) with renal dysfunction: Preliminary results
Authors: S. Remick, C. Sweeney, C. Takimoto, D. Douer, A. Bernareggi
Journal: Journal of Clinical Oncology (2004)

2018 Background: Trisenox (arsenic trioxide- ATO) is approved for treatment of relapsed/refractory acute promyelocytic leukemia. This study was designed to determine the PK of ATO in adult cancer pts with renal dysfunction and to evaluate its safety. Methods: 14 pts (median age 66 yrs, 29–85) in 4 renal function (RF) groups (normal- CLCR >80 mL/min; mild dysfunction: 50–80; moderate: 30–49; severe: <30) received IV ATO 0.15 mg/kg/d twice weekly for 4 wks, followed by 2 weeks without drug. Pts were treated for 2 six-week cycles. Arsenious acid (AsIII), arsenic acid (AsV), monomethyl arsonic acid (MMA), and dimethylarsinic acid (DMA) concentrations in plasma and urine were determined by validated methods based on anion exchange HPLC combined with ICPMS. Results: AsIII was rapidly distributed throughout the body (Table). MMA and DMA concentrations reached maximum values 24 hr after ATO. Urinary excretion of all As-containing species accounted for 27% of the dose (days 1–3). No significant correlations were found between AsIII PK parameters and RF, expressed by the CLCR value, except for urinary excretion, which was linearly correlated with CLCR (p<0.01). Exposure to inactive metabolites MMA and DMA inversely correlated with RF (p<0.05). After repeated dosing, plasma concentrations and excretion of methylated metabolites in urine were greater than those observed after the 1st administration, suggesting accumulation. The only severe drug-related toxicity was 1 grade 3 hyperglycemia. Conclusions: Renal excretion does not appear to be the main elimination route for AsIII, which is extensively metabolized to MMA and DMA. Systemic exposure of patients to AsIII, the active species, appears unaffected by RF, even in pts with severe dysfunction. Some accumulation of slowly eliminated metabolites MMA and DMA occurs on repeated dosing. ATO is well-tolerated at this dose in this pt population. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cell Therapeutics, Inc. Cell Therapeutics, Inc. Cell Therapeutics, Inc. Cell Therapeutics, Inc.
P62 A comparison of the relative effects of exposure on FEV1 and FVC in occupational COPD
Authors: JG Macfarlane, SC Stenton
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> A wide range of occupational exposures to dusts and fumes are known to cause COPD. Little is known about the underlying pathophysiology as few studies have measured gas transfer or included CT scans. It is not known whether the relative degree of small airway disease and emphysema is similar to that seen with smoking or varies by causative agents. The modifying effect on lung function of pneumonoconiosis, that is a feature of several accepted or possible causes of occupational COPD, is also uncertain. <h3>Methods</h3> We have reviewed papers investigating exposure-response relationships for FEV<sub>1</sub> and FVC to a range of occupational dusts and fumes. We examined the ratio of the slopes of the regression equations relating exposure to FEV<sub>1</sub> and FVC for the occupational exposures and for cigarette smoking. <h3>Results</h3> We identified 15 papers dealing with exposure to coal mine dust (5 papers), silica-containing dusts (8 papers) and other dusts (2 papers). The relative effects of exposure on FEV<sub>1</sub> and FVC are shown in Figure 1, together with the relative effects of smoking on FEV<sub>1</sub> and FVC obtained from the same papers. It should be noted that as FEV<sub>1</sub> is lower than FVC, an equal reduction in FEV<sub>1</sub> and FVC with exposure (ratio = 1) still leads to airflow obstruction. Cigarette smoking had an effect on FEV<sub>1</sub> that was approximately twice the effect on FVC. Coal mine dust was associated with a similar ratio of effect though with greater variability. Studies on silica-containing dusts had a more equal effect on FEV<sub>1</sub> and FVC. That was also the case for the two studies of non-silica containing dusts (carbon black and potash mining). <h3>Conclusions</h3> COPD associated with exposure to silica-containing dusts appears to be associated with a more restrictive abnormality than COPD associated with cigarette smoking and coal dust, possibly because of a modifying effect of associated lung fibrosis.
Peritoneal Transport of Antibiotics in Man
Authors: Leroy Shear, James H. Shinaberger, Kevin G. Barry
Journal: New England Journal of Medicine (1965)

PATIENTS undergoing peritoneal dialysis frequently require antibiotic therapy for intraperitoneal and systemic infections. Since information concerning transperitoneal movement of antibiotics is limited, drug dosage and route of administration in such patients are usually chosen empirically. Insufficient data are available to determine if antibiotic dosage should be supplemented by intraperitoneal therapy or increased because of removal of antibiotic in dialysate.The present study was undertaken to measure intraperitoneal concentrations of methicillin and tetracycline after systemic administration and conversely to determine serum concentrations of methicillin after intraperitoneal administration.Materials and MethodsPatients with chronic renal disease and azotemia requiring peritoneal dialysis were . . .
Physiologic Effects of Increasing Hemoglobin Concentration in Left-to-Right Shunting in Infants with Ventricular Septal Defects
Authors: George Lister, William E. Hellenbrand, Charles S. Kleinman, Norman S. Talner
Journal: New England Journal of Medicine (1982)

We studied the acute effects of increasing hemoglobin concentration and hematocrit on the pulmonary and systemic circulations of nine infants with large left-to-right shunts. After isovolemic exchange transfusion, which was designed to raise hemoglobin but keep blood volume constant, a consistent rise in systemic and pulmonary vascular resistances occurred. This rise was comparable to those previously found in isolated circulations showing a linear relation between hematocrit and loge of the vascular resistance. These changes in resistance were accompanied by decreases in systemic and pulmonary blood flow and a marked decline in left-to-right shunt. Despite the decrease in systemic blood flow, there was no decline in systemic oxygen transport, and there may have been a marginal decrease in left ventricular stroke work. These observations help explain why the newborn with a large ventricular septal defect and a high hemoglobin concentration does not have clinical signs of a large left-to-right shunt, and also suggest that the postnatal decline in hematocrit has a substantial role in the normal fall in pulmonary vascular resistance after birth. (N Engl J Med. 1982; 306:502–6.)
The study of the relationship between Notch signal transduction pathway and polycomb protein Bmi1 in colorectal caner cells
Authors: H. Zhang, Y. Ye, F. Xu, J. Zhou, S. Wang
Journal: Journal of Clinical Oncology (2007)

14501 Background: As is known the polycomb group protein BMI1 has been shown to support normal stem cell proliferation via its putative stem cell factor function. However, the potential molecular mechanism of BMI1 act as a cancer stem cell factor may also promote cancer development is unclear. In this study we demonstrated for the first time that Notch signal transduction pathway regulating expression of Bmi1 in colorecta caner cells and investigate the Notch1 mRNA and Bmi1 mRNA level in human colorectal cancer samples and their correlation with clinicopathological parameters of colorectal cancer. Methods and Results: We assessed Notch1 and Bmi1 mRNA in 50 cases of colorectal cancer and adjacent normal tissue by RT-PCR. The immunohistochemistry was used to determine the expression of ICN and in the 50 tissues of colorectal cancer and normal mucosa. Bmi1 SW480 cells were treated with DAPT (g-secretase inhibitor) at different times. MTT assay and flow cytometry were used to measure the proliferation and apoptosis of SW480 cells. The expression of ICN, Bmi1 were measured by western blot. Notch1 and Bmi1 mRNA level were increased in colorectal cancer compared with adjacent normal mucosa (P&lt;0.05), the median values were 1.97-fold, 1.88-fold, respectively. It was found that overexpression of Notch1 and Bmi1 was related to differentiation and lymph nodes metastasis in colorectal cancer (P&lt;0.05). The correlation between Notch1 and Bmi1 mRNA level, ICN and Bmi1 protein level are significant at the 0.01 level. Treating SW480 with DAPT, resulted in significant growth inhibition, apoptosis induction and downregulation of ICN and Bmi1. Conclusion: Our results show that overexpression of Notch1 and Bmi1 may play a critical role in the development of colorectal cancer. Notch1 signal transduction pathway regulating expression of Bmi1 in colorectal cancer cells.Blockade of Notch1 signal pathway can inhibit proliferation and accelerate apoptosis of colorectal cancer. [Key words] Colorectal cancer; BMI1; Signal transducers and activators of transcription3; Western blotting No significant financial relationships to disclose.
A Population-Based Study of the Risk of Recurrence of Birth Defects
Authors: Rolv Terje Lie, Allen J. Wilcox, Rolv Skjaerven
Journal: New England Journal of Medicine (1994)

Certain birth defects are known to recur in families, but most estimates of the risk of recurrence have come from clinic-based studies. In this study we estimated the risk of recurrent birth defects using a population-based registry.The study was based on the records of the first and second infants delivered by 371,933 women from 1967 through 1989. The records are maintained by the Medical Birth Registry of Norway. For the 9192 women whose first infant had a birth defect, we determined the relative risk of similar and dissimilar defects in the second infant. The reference population was women whose first infant had no defect.Among first infants, 2.5 percent had a birth defect. The mothers of affected first infants were 2.4 times as likely as other women to have second infants with any registered defect. This increased risk was due primarily to an increased (7.6 times higher) risk of the same defect in the second infant as in the first (95 percent confidence interval, 6.5 to 8.8) and secondarily to a slightly increased (1.5 times higher) risk of a different defect in the second infant (95 percent confidence interval, 1.3 to 1.7). Among the women who lived in the same municipality during both pregnancies, the relative risk of having a second infant with the same defect was 11.6, as compared with 5.1 among the women who moved to another municipality after the birth of their first infant (P < 0.001).Among women whose first infant has a birth defect, the risk of the same defect in the second infant is substantially increased and the risk of a different defect in the second infant is slightly increased. Environment plays a strong part in repeated defects.
Assessing borderline personality disorder with self-report, clinical interview, or semistructured interview
Authors: S W Hurt, S E Hyler, A Frances, J F Clarkin, R Brent
Journal: American Journal of Psychiatry (1984)

The authors compared three methods of assessing borderline personality disorders. Test-retest reliability for the self-report Personality Diagnostic Questionnaire was adequate and compared favorably with the interrater reliability of the DSM-III-oriented clinical interview and the semistructured research interview. The overall prevalence of personality disorders scored on the questionnaire was similar to that generated by the clinical interview. The specificity and sensitivity of the questionnaire for the diagnosis of borderline personality disorder were slightly higher than 60%, which suggests that it may be a useful and economical instrument for identifying patients with borderline personality disorder.
199P: Which is the most common malignancy that profits from the lung metastasectomy? Ten years experience
Authors: F. Caushi, D. Xhemalaj, I. Skenduli, H. Hafizi, Z. Pupla, A. Hatibi, E. Shima, E. Selenica, J. Gjerazi, B. Gega
Journal: Journal of Thoracic Oncology (2016)