tbuckley/cabot-search huggingface dataset:
Phase I trial of ipilimumab (IPI) alone and in combination with radiotherapy (XRT) in patients with metastatic castration resistant prostate cancer (mCRPC)
Authors: T. M. Beer, S. F. Slovin, C. S. Higano, S. Tejwani, T. B. Dorff, E. Stankevich, I. Lowy
Journal: Journal of Clinical Oncology (2008)

5004 Background: IPI is a fully human, anti-CTLA 4 monoclonal antibody capable of enhancing anti-tumor immunity. In preclinical models, XRT results in tumor antigen release and enhances anti-tumor activity of CTLA-4 blockade. Methods: Pts with mCRPC and ECOG PS of 0–1 were treated with escalating doses of IPI every 3 weeks X 4 doses in cohorts of 6 pts at dose levels of 3, 5, and 10 mg/kg. After the 10 mg/kg cohort was completed, a protocol amendment added single fraction XRT prior to IPI starting at the 3 mg/kg dose level. The primary endpoint was safety. Imaging was repeated every 3 months and serum PSA was monitored monthly. Results: Between 1/2006 and 12/2007, 8, 6, and 6 pts were treated at the 3, 5, and 10 mg/kg dose levels respectively; 6 pts were then treated in the first XRT cohort for a total of 26 pts. 19 pts experienced 29 immune-related adverse events (irAEs) including diarrhea/colitis (14), rash (9), hepatitis (4), endocrinopathy (2). irAEs were ≥ Grade 3 in 9 pts: GI (6), hepatitis (2), and rash (1) and were generally responsive to immunosuppression. One pt died of opportunistic infections (OI) after 3 months of immunosuppression for colitis; this prompted inclusion of OI prophylaxis within the treatment algorithms. Another pt continues (1yr+) on immunosuppression to suppress colitis. Six pts (23%, 95% CI: 9–44%), all with irAEs, had a confirmed >50% PSA decline (median duration 140d, range 49 to 269+; median time to PSA decline 84d, range 41 to 147). 1 of 7 pts with measurable disease had a PR in nodal metastases and the prostate and achieved an undetectable PSA after treatment with 10 mg/kg IPI. Measurable disease response and PSA decline are both ongoing for 185+, 269+ d, respectively. Conclusions: The irAEs seen in this trial are similar in type to those seen in melanoma trials with IPI. Antitumor activity appears associated with irAEs. Both irAEs and PSA declines were seen across dose levels. Addition of XRT to 3 mg/kg appears feasible, and evaluation of radiation with 10 mg/kg of IPI is underway. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Medarex, Inc. Medarex, Inc. Medarex, Inc.
The Organization of Medical Care -- Lessons from the Medicare End Stage Renal Disease Program
Authors: Norman G. Levinsky
Journal: New England Journal of Medicine (1993)

National attention is currently focused on the organization of medical care in the United States. Competing groups with different ideas about reorganizing health care advance views based on socioeconomic hypotheses and evaluations of health care systems in other countries. The participants in the debate about the reorganization of U.S. health care have taken little notice of the experience with existing health care systems organized by our government. The Medicare program that provides treatment for patients with end-stage renal disease (ESRD) is 20 years old; recently, it has been the subject of extensive review and analysis1. Over the past 20 . . .
The Genesis and Spread of a Hospital Staphylococcal Epidemic on an Adult Medical Ward
Authors: R. A. Vogel, Y. J. Trotter, J. H. Shinaberger, J. E. McCroan
Journal: New England Journal of Medicine (1959)

THE current epidemiology of hospital staphylococcal infection deals primarily with outbreaks in pediatric, maternity and surgical units.1 2 3 4 5 6 7 8 These outbreaks, as shown by bacteriophage typing, are usually due to antibiotic-resistant Type "80/81" strains of staphylococci. Many modes of epidemic spread have been described, but most attention has been given to contaminated fomites and nasal carriers. Recent reports by Barber and Dutton9 and Caswell et al.10 have shown that severe epidemics can occur on adult medical wards, through patient crossinfection. The following study describes an outbreak of 63 infections caused by a single strain of a coagulase-positive Staphylococcus aureus originating on the . . .
Neonatal Herpes Simplex Virus Infection in Relation to Asymptomatic Maternal Infection at the Time of Labor
Authors: Zane A. Brown, Jacqueline Benedetti, Rhoda Ashley, Sandra Burchett, Stacy Selke, Sylvia Berry, Louis A. Vontver, Lawrence Corey
Journal: New England Journal of Medicine (1991)

To define the risk factors associated with neonatal acquisition of herpes simplex virus (HSV) infection, we prospectively obtained HSV cultures from the cervix and external genitalia of 15,923 pregnant women in early labor who were without symptoms or signs of genital HSV infection. Follow-up of the women with positive cultures for HSV and their HSV-exposed infants included serologic tests and serial cultures for HSV.
Effects of Reducing or Discontinuing Inhaled Budesonide in Patients with Mild Asthma
Authors: Tari Haahtela, Markku Jarvinen, Tuomo Kava, Kirsti Kiviranta, Sirkka Koskinen, Kaarina Lehtonen, Kurt Nikander, Tore Persson, Olof Selroos, Anssi Sovijarvi, Brita Stenius-Aarniala, Thore Svahn, Ritva Tammivaara, Lauri A. Laitinen
Journal: New England Journal of Medicine (1994)

In a previous study, we found that two years of treatment with an inhaled corticosteroid, budesonide, was more effective than treatment with an inhaled β2-agonist, terbutaline, in patients with newly diagnosed, generally mild asthma. We continued this study for a third year to investigate whether the steroid dose could be reduced or discontinued and what effect crossover of patients from β2-agonist therapy to corticosteroid therapy would have.
ErbB2/Her2 ectodomain shedding is regulated by a membrane-associated metalloprotease
Authors: Kendall D. Carey, Debra L. Dugger, Ralph H. Schwall, Mark X. Sliwkowski
Journal: Cancer Research (2005)

3695  The inappropriate activation or overexpression of members of the epidermal growth factor family of receptors (ErbB) is associated with the development and severity of many cancers, particularly breast cancer. The extracellular domain of ErbB2 is released by proteolytic cleavage in both breast cancer tissue culture cell lines and in patients with metastatic breast cancer where its serum levels correlate with increased metastasis and decreased survival. However, the enzyme responsible for ErbB2 ectodomain shedding is unknown. To better understand the role of ErbB2 shedding and its role in regulating ErbB signaling, we have used a tumor xenograft model system derived from MMTV-ErbB2 transgenic animals. Using a bioinformatics and biochemical approach, we have identified a candidate ErbB2 sheddase, MT2-MMP, a member of the membrane-associated matrix metalloprotease family. Purified MT2-MMP cleaves ErbB2 near the juxtamembrane domain in vitro and a catalytically dead mutant of MT2-MMP co-immunoprecipitates ErbB2 from transfected cell lysates. However, MT1-MMP, a structurally related metalloprotease, does not cleave or interact with ErbB2. Downregulating MT2-MMP protein levels by RNA interference reduces ErbB2 ectodomain shedding in cultured breast cancer cell lines and reduces cell growth. Overexpression of MT2-MMP, or a soluble form of the protease, augments ErbB2 receptor shedding. The product of receptor shedding, a truncated form of the ErbB2 receptor, is constitutively phosphorylated and heterodimerizes with EGFR and ErbB3 in a ligand-dependent manner. These observations suggest a novel role of MT2-MMP in regulating ErbB2 receptor signaling.
P116 Impact of bariatric surgery on OSAS: a 4-year experience
Authors: V Palissery, S Kumar, D Ghosh, M O’Kane, MW Elliott
Journal: Thorax (2015)

<h3>Background</h3> Obstructive Sleep Apnoea Syndrome (OSAS) is common in morbidly obese patients. Previous studies indicate bariatric surgery reduces the severity of OSAS but may not cure it. We explored the impact bariatric surgery on patients who were commenced on CPAP prior to surgery. <h3>Methods</h3> All morbidly obese patients who underwent bariatric surgery at our institution, between June 2010 and May 2014 who underwent sleep study (SS) or oximetry prior to bariatric surgery were included. The primary end point was cure (oximetry off CPAP showing either ODI less than 5 or ODI 5–15 with ESS &lt;10 and no other symptoms of SDB) from OSAS. Secondary end points were weight loss achieved, improvement in OSAS and improvement in ESS. All data were obtained from electronic bariatric surgery and sleep service databases. <h3>Results</h3> 184 patients underwent bariatric surgery. 97 (52.7%) had SS or oximetry prior to surgery. (Figure 1) Mean ODI was 25 (95% CI 19–30) and ESS 12 (95% CI 10–13). Out of 46 patients considered for CPAP, 45 continued using CPAP peri-operatively, one discontinued after failed trial. 20 (43.4%) patients were considered cured from OSAS by 12–24 months. 17 (36.9%) patients became asymptomatic and returned CPAP were considered to be cured clinically but not had SS post surgery. At 12 months post bariatric surgery, there were significant (P &lt; 0.0001) reductions in various parameters; means of difference in ODI 34, ESS 10 and BMI 17.8. <h3>Discussion and conclusion</h3> In contrast to the meta-analysis (Greenburg <i>et al</i>. 2009) in which 62% had residual disease in our cohort 80% had clinical cure and they had a lower post-op ODI (7.1) in spite of comparable weight loss. Even though our patients had similar pre-op BMI but the mean pre-op ODI was less than most reported studies the reason for which is not clear but might be responsible for a much higher cure rate. <h3>Reference</h3> 1 Greenburg DL, Lettieri CJ, Eliasson AH. Effects of surgical weight loss on measures of obstructive sleep apnea: a meta-analysis. <i>Am J Med</i> 2009;<b>122</b>:535–42
Spur-Cell Anemia
Authors: Jeanne Allen Smith, Edmund T. Lonergan, Kenneth Sterling
Journal: New England Journal of Medicine (1964)

THE syndrome in the case presented below has been designated "spur-cell anemia" because of the curious projections from the surfaces of the red blood cells. These bizarre erythrocytes were associated with intense hemolytic anemia in a young man with hepatic cirrhosis.Case ReportA 29-year-old male wire splicer of German descent entered the Bronx Veterans Administration Hospital with jaundice of 10 months' duration. For about 10 years he had a heavy alcohol intake and had increased his consumption in the months before the illness. Because of gradual icterus and abdominal swelling for 1 month he had entered another hospital, where . . .
Sarcoidosis in Siblings
Authors: Morgan Y. Swirsky, Robert M. Lowman
Journal: New England Journal of Medicine (1955)

SARCOIDOSIS, a granulomatous process of unknown etiology with a tendency to affect the reticuloendothelial tissues of all organs, running a chronic, usually mild and relapsing course, can produce many confusing symptoms and clinical manifestations. Excellent reviews of the early literature concerning the disease have already been published. There have been more recent contributions by Gravesen,1 Longcope and Freiman2 and Freiman.3 Over the course of years, diverse sources have recorded numerous observations from which the composite picture of sarcoidosis has eventually developed.Although there is considerable controversy over the possible tuberculous or nontuberculous origin of sarcoidosis we do not intend to . . .
Miliary Tuberculosis Developing during Pregnancy
Authors: Robert H. Goodwin, Maurice D. Kenler
Journal: New England Journal of Medicine (1952)

Miliary tuberculosis is uncommon in adults. Its occurrence complicating pregnancy is an especially rare finding. The case to be presented is of unusual interest because only one other case of miliary tuberculosis developing during pregnancy has been reported1 and because the infant survived and at twelve months of age is known to be in excellent health. The mother died on her twelfth post-partum day.Miliary tuberculosis is frequently observed below the age of two years. Despite antibiotics, the mortality has continued high. Miliary tuberculosis complicated by meningitis has shown an even higher mortality rate.In 1938 a review of the . . .
Case 12-2003
Authors: Atul Malhotra, Victorine V. Muse, Eugene J. Mark
Journal: New England Journal of Medicine (2003)

Presentation of CaseAn 82-year-old man was admitted to the hospital because of dyspnea and peripheral edema.The patient had a long history of hypertension, diabetes mellitus, and depression with mild dementia. He had smoked heavily until 30 years before admission and had chronic obstructive pulmonary disease. Fifteen months before the current admission, he was admitted to another hospital because of substernal pain, dyspnea, and sustained ventricular tachycardia. The rhythm did not respond to the administration of adenosine, metoprolol, diltiazem, or lidocaine, but electrical cardioversion restored a normal rhythm. The results of laboratory tests are shown in Table 1.First Admission . . .
BCG in Finland: changing from a universal to a selected programme
Authors: E PI Salo
Journal: Eurosurveillance (2006)

In Finland, all newborns are currently offered BCG vaccination, and the national coverage is over 98%. The annual incidence of tuberculosis is low, at 6.6/100 000 in 2004 and has been steadily declining in recent years. Finland differs from the other Nordic countries in that the majority of cases are detected in people aged 65 and over in the indigenous population, and only a smaller proportion (12%) detected in immigrants. The high incidence of TB and MDR TB in neighbouring countries has raised concern, but no increase in TB detected in Finnish-born citizens has been seen. A decision has been made to change from mass BCG vaccination to targeting risk groups.
Rat Hepatomas: Chemotherapy With Lycurim and Pyrazofurin&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: M S Lui, R C Jackson, R J Harkrader, G Weber
Journal: JNCI Journal of the National Cancer Institute (1982)

Hepatoma 8999 was sensitive to Lycurim [1,4-di-(methylsulfonyloxy-ethylamino)-1,4-dideoxy-ms-erythritol] with a mean lethal dose (LD50) of 8.1 × 10−8M for a 6-hour treatment in vitro. The drug dose lethal to 10% of the rats with Lycurim (10 mg/kg) injected ip 12 times into hepatoma 8999-bearing BUF rats at 10-day intervals provided a mean increase in life-span (ILS) of 156%. The more rapidly growing, less differentiated hepatoma 3924A was tenfold less sensitive to Lycurim in vitro, and three treatments in vivo (10 mg/kg given every 8 days) gave an ILS of only 18% in ACI/N rats. Because hepatoma 8999 had a high adenosine kinase activity, the effect of Pyrazofurin (PF; 3-β-d-ribofuranosyl-4-hydroxypyrazole-5-carboxamide) was examined in vitro: The LD50 was 8.5 × 10−8M in a 6-hour exposure. In hepatoma 3924A, with a fifteenfold lower adenosine kinase, the LDso was 22-fold higher. Three treatments with PF (4 mg/kg given every 2 days) in hepatoma 8999 caused an 18% ILS and no host toxicity, bu. in hepatoma 3924A no significant ILS was observed. Lycurim combined with PF (0.05 μM each) in hepatoma 8999 cells in vitro provided synergistic kill, but Lycurim and PF (0.3 and 1 μM, respectively) in hepatoma 3924A cells yielded summation. When 10 rats with hepatoma 8999 were treated 15 times with the optimal dose of Lycurim (7.5 mg/ kg every 10½ days), 1-year survivors numbered 7. Alternate doses of Lycurim (7.5 mg/kg) and PF (3 mg/kg) at 5-day intervals for 4 months to 10 rats gave an ILS of 152% with eight 1-year survivors and no host toxicity.
Abstract 296: Targeting Macrophage Subsets Attenuates Cardiac Remodeling and Dysfunction Following Experimental Myocarditis in Rat
Authors: Shunit Rinkevich-Shop, Tamar Ben-Mordechai, David Kain, Micha S. Feinberg, Natalie Landa-Rouben, Jonathan Leor
Journal: Circulation Research (2013)

Introduction: The mechanism of myocarditis is complex and poorly understood. Monocytes and macrophages comprise the majority of infiltrates in myocarditis. Hypothesis: We aimed to test the hypothesis that macrophage subsets have a key role in the pathogenesis and progression of myocarditis, and that targeting macrophages would modulate disease progression and outcome. Methods and Results: Experimental autoimmune myocarditis (EAM) was induced in 67 male Lewis rats. Of them, 27 were sacrificed at different time points to assess M1 and M2- macrophage subsets by flow cytometry. The remaining rats were randomized either to early macrophage depletion (from day 8-14 after EAM induction), by intravenous injections of clodronate-liposomes (CL), or late depletion (from day 15-35 after induction of EAM), or PBS-liposome injections (control). Left ventricula (LV) remodeling and function were assessed by echocardiography; before induction of EAM, before CL treatment, and 35 days after induction of EAM. Macrophages in the heart peaked at 21 days after induction of EAM (25±7%,p=0.0008).The number of M1 macrophages in the heart was highest at 14 days after EAM induction (16.3±2%), while M2 macrophages peaked at day 21 (15.5±2.7%,p=0.003). Early macrophage depletion (8-14d) decreased LV diastolic dimension and volume by 5.3±3.9% and 10.4±8% (p=0.04). Late macrophage depletion (15-35d) increased LV wall thickness and decreased LV systolic dimension and volume by 10.2±4% and 21±8% (p=0.03). Furthermore, late macrophage depletion increased LV ejection fraction and fractional shortening by 14.6±6% (p=0.01) and 22±10% (p=0.02) 35 days after EAM. Conclusions: Our study describes, for the first time, the kinetics of M1 and M2 macrophages in ocarditis and shows that macrophages contribute to the progression of adverse remodeling and dysfunction. Thus, targeting macrophages could be a new therapeutic strategy to improve cardiac remodeling and function in myocarditis.
Latent Herpes Simplex Virus in Human Trigeminal Ganglia
Authors: K D Croen, J M Ostrove, L J Dragovic, J E Smialek, S E Straus
Journal: New England Journal of Medicine (1987)

We used in situ hybridization to study the expression of herpes simplex virus type 1 genes during latent infections of human sensory ganglia. Trigeminal ganglia were recovered at autopsy from 24 subjects with no evidence of an active herpetic infection. These ganglia were hybridized to 35S-labeled single-stranded RNA probes spanning 72 percent of the herpes simplex genome. In the ganglia of 16 subjects, 0.2 to 4.3 percent of the neuronal cells contained abundant nuclear signals for viral RNA. Ganglia from three patients with low or undetectable levels of antibodies to herpes simplex type 1 lacked viral RNA signals, whereas the ganglia from all of six patients with elevated antibody titers showed viral RNA signals. Transcription was detected only from the region of the viral genome containing a gene that encodes an immediate early protein known as the infected-cell protein number zero (ICP0). However, normal ("sense") transcripts of this gene, which are prominent in an acute infection, were not detected. In contrast, a novel transcript was found overlapping with, but opposite in direction to, the ICP0 transcript (and was therefore "anti-sense"). Although this transcript has been only partially characterized, we believe that it may have a role in maintaining the latency of herpes simplex virus.
Analysis of late infections after human bone marrow transplantation: role of genotypic nonidentity between marrow donor and recipient and of nonspecific suppressor cells in patients with chronic graft-versus-host disease
Authors: K Atkinson, V Farewell, R Storb, MS Tsoi, KM Sullivan, RP Witherspoon, A Fefer, R Clift, B Goodell, ED Thomas
Journal: Blood (1982)
Ethacrynic Acid in Acute Pulmonary Edema
Authors: Stuart L. Fine, Robert I. Levy
Journal: New England Journal of Medicine (1965)

DIURETICS are frequently used as part of the therapeutic regimen in the management of patients in acute pulmonary edema. The decreased cardiac output and reduced glomerular filtration rate of patients in acute pulmonary edema often result in a disappointing diuretic response, even with the most potent diuretics currently available. The delay of four to six hours in the onset of action of the mercurial diuretics reduces their effectiveness in altering the immediate course of acute pulmonary edema. There is a need, then, for a potent diuretic agent with a rapid onset of action that would promote an effective diuresis within . . .
Her-2/Neu over expression in patients with breast cancer and early central nervous system (CNS) relaps
Authors: H. Zafar, B. Pollock, I.-T. Yeh, W. Knight
Journal: Journal of Clinical Oncology (2004)

707 Background: CNS metastasis is diagnosed in approximately 15% of patients with breast cancer (BC). The prevalence of Her-2/neu over expression in BC is approximately thirty percent. Over one third of the women treated with trastuzamab for metastatic disease develop CNS metastasis. There is a suspicion that Her-2/neu positive cells may have a predilection for the CNS. We conducted a historic cohort analysis of patients who developed CNS relapse in order to determine if there is a relationship between Her-2/neu over expression and time to relapse. Methods: Between January 1997 and May 2003, 63 patients were identified with a diagnosis of BC who had received cranial radiation for CNS metastasis. Her-2/neu and six putative prognostic factors (Age, Race, Stage, Estrogen Receptor[ER], Progesterone Receptor [PR]), and Histologic grade) were assessed. Her-2/neu was considered positive if it was 3+ by immunohistochemistry (IHC) or gene amplification by florescent in situ hybridization (FISH). Time to CNS relapse was measured from the day of diagnosis to the first evidence of CNS disease by magnetic resonance imaging or computerized tomography. Univariate analysis using a general linear modeling approach was performed to determine the association between the time to failure and Her-2/Neu as well as other prognostic factors. Results: There was no association between Her-2/Neu and time to relapse (p=0.68). Age, race and tumor grade were not associated with early relapse. However both ER negativity and stage were highly associated with early CNS relapse (p=0.0048 and p=0.0005 respectively). The prevalence of Her-2/Neu positive BC was the same as previously reported in other series. Conclusion: Her-2/Neu over expression does not appear to be associated with early CNS relapse. ER negativity and higher stage of disease are significantly related to time to CNS relapse and may justify increased surveillance for occult metastasis. No significant financial relationships to disclose.
Hearing Impairment Among Noise-Exposed Workers — United States, 2003–2012
Authors: Elizabeth A. Masterson, P. Timothy Bushnell, Christa L. Themann, Thais C. Morata
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

Hearing loss is the third most common chronic physical condition in the United States, and is more prevalent than diabetes or cancer (1). Occupational hearing loss, primarily caused by high noise exposure, is the most common U.S. work-related illness (2). Approximately 22 million U.S. workers are exposed to hazardous occupational noise (3). CDC compared the prevalence of hearing impairment within nine U.S. industry sectors using 1,413,789 noise-exposed worker audiograms from CDC's National Institute for Occupational Safety and Health (NIOSH) Occupational Hearing Loss Surveillance Project (4). CDC estimated the prevalence at six hearing impairment levels, measured in the better ear, and the impact on quality of life expressed as annual disability-adjusted life years (DALYs), as defined by the 2013 Global Burden of Disease (GBD) Study (5). The mining sector had the highest prevalence of workers with any hearing impairment, and with moderate or worse impairment, followed by the construction and manufacturing sectors. Hearing loss prevention, and early detection and intervention to avoid additional hearing loss, are critical to preserve worker quality of life.