tbuckley/cabot-search huggingface dataset:
Maintenance of Alveolitis in Patients with Chronic Beryllium Disease by Beryllium-Specific Helper T Cells
Authors: Cesare Saltini, Karen Winestock, Martha Kirby, Paula Pinkston, Ronald G. Crystal
Journal: New England Journal of Medicine (1989)

Chronic beryllium disease is characterized by the accumulation of helper/inducer T cells, macrophages, and granulomas in the lungs. To evaluate the hypothesis that the proliferation of CD4+ (helper/inducer) T cells in the lungs of patients with this disorder is maintained by local activation of beryllium-specific T-cell clones, we studied T cells obtained from peripheral blood and by bronchoalveolar lavage in eight patients and five healthy controls. The proliferation of T cells in response to beryllium in vitro was confined to the CD4+ T cells from the patients and was dependent on the presentation of antigen in the presence of both major histocompatibility complex class II antigens and functional interleukin-2 receptors. T cells from the patients' lungs had a significantly greater response to beryllium than did T cells from their peripheral blood (stimulation index, 103 vs. 5; P less than 0.01). Lines and clones of cells developed from T cells from the patients' lungs showed dose-dependent proliferation in response to beryllium but did not respond to recall antigens or to other metals. Although all beryllium-specific T-cell clones were CD4+ and none were CD8+ (suppressor/cytotoxic), all beryllium-specific clones studied had different rearrangements of T-cell antigen receptors, suggesting that the response to beryllium involved T cells with diverse specificities for beryllium. We conclude that in patients with chronic beryllium disease, beryllium acts as a class II-restricted antigen, stimulating local proliferation and accumulation in the lung of beryllium-specific CD4+ (helper/inducer) T cells. Hence, chronic beryllium disease is a hypersensitivity disease in which beryllium is the specific antigen.
Neurotoxicity and Elevated Cerebrospinal-Fluid Methotrexate Concentration in Meningeal Leukemia
Authors: Werner A. Bleyer, James C. Drake, Bruce A. Chabner
Journal: New England Journal of Medicine (1973)

Cerebrospinal-fluid methotrexate concentration was measured in 25 patients receiving intrathecal therapy for prophylaxis or treatment of meningeal leukemia. In 20 patients with no manifestations of neurotoxicity, the mean antifolate value in the cerebrospinal fluid was 1.7 X 10–7 M two days after administration of 12 to 15 mg per square meter of intrathecal methotrexate, and declined thereafter with a half-life of 12 to 18 hours. Five patients with severe neurotoxicity had cerebrospinal-fluid methotrexate concentrations averaging 13.8 times higher than the mean, and these concentrations were consistently higher than the range of antifolate values in the asymptomatic patients. One patient with values 20 to 100 times greater than the mean in asymptomatic patients sustained a fatal myelopathy, and in another, with an apparent antifolate half-life of 48 hours, irreversible neurologic sequelae developed. These observations suggest that the neurotoxicity associated with intrathecal methotrexate may be secondary to prolonged exposure to excessive drug concentrations in the central nervous system. (N Engl J Med 289:770–773, 1973)
Sleeping in on pancreatic cancer pain: Schwann cell secreted IL-6 pushes snooze on the pain alarm
Authors: Patrick A Hughes
Journal: Gut (2016)

Pain is an essential signal of danger and provides motivation to seek treatment, facilitating early diagnosis of disease. Pancreatic cancer is particularly lethal and has a 5-year survival rate below 5%. This is mainly due to delayed perception of visceral pain resulting in late diagnosis, by which time the tumour has metastasised.1 This sobering statistic highlights the need for rapid detection and the importance of understanding pain mechanisms in pancreatic cancer. Patients with pancreatic cancer who report more intense pain have shorter survival times, indicating pain intensity is prognostic for disease progression.2 Further, neuropathies including pancreatic nerve damage, neuritis and cancer cell invasion are typical features of pancreatic cancer, and the degree of neuropathy correlates with the severity of pain highlighting the importance of cancer–nerve interactions.2 ,3 This marked neural plasticity is supported by peripheral glial cells (Schwann cells) which have immune cell-like functions and also high affinity for pancreatic cancer cells. Schwann cells initiate and mediate neural interactions with cancer cells, particularly in the early stages of pancreatic cancer. In this issue of Gut , Demir et al 4 undertook a comprehensive investigation of Schwann cell involvement in human and mouse pancreatic cancer which revealed that interleukin-6 (IL-6) secreted by activated Schwann cells inhibits pain signalling in the early stages of pancreatic cancer. This novel mechanism has dire implications, as inhibiting pain signalling would delay treatment seeking behaviour and therefore early detection of cancer.

Demir et al …
Unusual Manifestations Due to Involvement of Involuntary Muscle in Dystrophia Myotonica
Authors: Norman N. Kohn, James S. Faires, Theodore Rodman
Journal: New England Journal of Medicine (1964)

DYSTROPHIA myotonica (Steinert's disease) is an uncommon disorder usually characterized by symptoms referable to the voluntary muscles of the head, neck and extremities including difficulty with voluntary grasp release (myotonia). The diagnosis is readily made when other characteristic features of the syndrome are present, such as frontal baldness in men, cortical lenticular opacities, testicular atrophy, conspicuous atrophy of the sternocleidomastoids and muscles of the arms and legs and a characteristic facial expression. When these findings are not prominent, the diagnosis may readily be overlooked, particularly if the clinical picture is dominated by disturbances of involuntary rather than voluntary muscle.We . . .
SURG-11THE IMPACT OF PRE-OPERATIVE TUMOR FEATURES ON RESECTION AND SURVIVAL OUTCOMES IN GLIOBLASTOMA: A PHASE II FLUORESCENCE-GUIDED SURGERY STUDY
Authors: James S. Cordova, Saumya S. Gurbani, Chad A. Holder, Jeffrey J. Olson, Eduard Schreibmann, Ying Guo, Hui-Kuo G. Shu, Hyunsuk Shim, Costas G. Hadjipanayis
Journal: Neuro-Oncology (2015)

BACKGROUND: The survival benefit provided by   resection of glioblastoma (GBM) remains under debate. Part of this debate is likely due to the lack of reliable tools for pre- and post-surgical volumetric tumor measurement. In this study, we used a validated, semi-automated tumor segmentation tool to evaluate the relationship between pre-operative tumor morphology metrics, resection outcomes, and survival outcomes in a 5-aminolevulinic acid (5-ALA) fluorescence-guided surgery (FGS) trial. METHODS: Thirty-one patients from a prospective Phase II trial evaluating 5-ALA FGS for newly diagnosed GBM were assessed. Tumors were segmented pre-operatively using a semi-automated method to assess morphological features, such as surface area (SA), SA to volume ratio (SAVR), and percent necrosis (NV%), as well as post-operatively to evaluate extent-of-resection (EOR) and residual tumor volume (RTV). Multivariate analysis was performed using a general linear model to assess the effects of multiple covariates on RTV and to describe resectability in terms of pre-operative tumor features. The impact of morphological, clinical, and resection measures on progression-free survival (PFS) and overall survival (OS) were evaluated using univariate and multivariate Cox proportional hazard regression. RESULTS: Median EOR and RTV were 94.3% and 0.821 cm3, respectively. Pre-operative tumor volume, SA, SAVR, and NV% exhibited statistically-significant associations with RTV. In addition to age and O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, preoperative tumor SA, SAVR, NV%, and volume were shown to impact the likelihood of complete resection. Pre-operative SAVR and RTV were significantly associated with OS, even controlling for the known confounders of age, KPS, and MGMT methylation. CONCLUSIONS: This study supports claims that 5-ALA FGS is more effective than conventional microsurgery in decreasing tumor burden in GBM. Moreover, morphological indices describing tumor shape and composition may impact not only resection outcomes, but also patient survival, and should be considered in tumor resection studies.
Syphilitic Gummas in a Patient with Human Immunodeficiency Virus Infection
Authors: L C Roeske, P R Kennedy
Journal: New England Journal of Medicine (1996)

Figure 1. A 26-year-old woman who was positive for the human immunodeficiency virus presented with focal motor seizures, a CD4 cell count of 238 per cubic millimeter, a rapid plasma reagin titer of 1:32, and a positive test for serum treponemal IgG antibody. One year earlier, she had received a single dose of intramuscular penicillin (dose and rapid plasma reagin titer not known). On admission, gadolinium-enhanced T1-weighted magnetic resonance imaging showed multiple syphilitic cerebral gummas (Panels A and B). Studies of cerebrospinal fluid revealed a white-cell count of 20 per cubic millimeter (92 percent lymphocytes and 8 percent . . .
Renal-Stone Dissolution Via Percutaneous Nephrostomy
Authors: Stephen P. Dretler, Richard C. Pfister, Jeffrey H. Newhouse
Journal: New England Journal of Medicine (1979)

Recurrent renal stones associated with urinary infection were treated in eight kidneys in six patients by percutaneous nephrostomy and irrigation with hemiacidrin, a commercially available solution of organic acids and magnesium. The stones, presumably composed of triple phosphates (magnesium, ammonium and calcium phosphate), were completely dissolved in six kidneys; in two they were partially dissolved and subsequently recovered by other methods. No serious complications were encountered. The technic requires special precautions against perinephric and intravascular dissemination of infection, but it offers potentially effective therapy for certain kidney stones without the use of general anesthesia or operation. (N Engl J Med 300:341–343, 1979)
PTH-299 Significance of the lymph node count after neo-adjuvant treatment for rectal cancer: Abstract PTH-299 Table 1
Authors: MAS Khan, AR Hakeem, N Scott, I Botterill
Journal: Gut (2015)

<h3>Introduction</h3> Lymph node metastases is a significant prognostic indicator for disease recurrence in colorectal cancer (CRC) patients. The aim of this study was to assess the impact of short course radiotherapy (SCRT) and long course chemo-radiotherapy (CRT) on the number of lymph nodes retrieved for rectal cancer surgery and its ultimate outcome on disease recurrence. <h3>Method</h3> Data for patients who underwent surgery alone or received SCRT or CRT followed by surgery for resectable primary rectal cancer from January 2005 till December 2010 were analysed. The primary outcomes measured were the number of lymph nodes retrieved, their status and disease recurrence. Patients with metastatic disease and palliative resections were excluded. <h3>Results</h3> There were 434 patients. Of these 166 had surgery alone, 104 had short course radiotherapy and 164 had long course chemo-radiotherapy followed by surgical resection. The patients who received neo-adjuvant treatment were relatively younger. CRT decreased the retrieval of more than 12 lymph nodes, the median number of lymph nodes and the median number of metastatic lymph nodes as tabulated below (P &lt; 0.001). Stage III was less common in CRT group (26%) than surgery alone (32%) and SCRT group (44%). Despite this 33.5% patients in CRT group had local and systemic disease recurrence as compared to 16% in surgery alone and 24% in SCRT group. This was statistically significant in CRT vs. surgery alone group (P &lt; 0.001). Number of lymph nodes retrieved did not prove to be a significant prognostic indicator for disease free survival after CRT. <h3>Conclusion</h3> Low lymph node count after CRT for rectal cancer surgery reflects the sensitivity to neo-adjuvant treatment and does not signify inadequate resection. This is the lymph node metastases and not the number of lymph nodes retrieved that is the prognostic factor for disease free survival. <h3>Disclosure of interest</h3> None Declared.
A pilot study of modified neoadjuvant docetaxel/cisplatin/5-FU (TPF) to concomitant chemoradiotherapy (CT/RT) in locally advanced head and neck cancer (LAHNC): Preliminary results
Authors: D. Isla, J. Martínez-Trufero, S. Morales, A. Yubero, J. Lambea, I. Álvarez, E. Polo, M. A. Seguí, E. Pujol, P. Pastor
Journal: Journal of Clinical Oncology (2009)

6039 Background: Sequential treatment with induction CT followed by CT/RT is highly active and under study in ongoing randomized trials. We started a pilot phase II trial to explore the efficacy, toxicity profile and organ preservation of a modified neoadjuvant TPF to concurrent CT/RT in both resectable (R) and unresectable (UR) LAHNC. Methods: One hundred seventy patients(p) with stage III-IV, PS ECOG 0–2, were included to receive 3 cycles of docetaxel 75 mg/m 2 iv day(d) 1, cisplatin(P) 75 mg/m 2 iv d2 and 5-FU 750 mg/m 2 iv continuous infusion d2–5, every 3 weeks with prophylactic ciprofloxacin 500 mg twice daily from d6–15 of each cycle and granulocyte colony-stimulating factor as secondary or primary setting, followed by P 100 mg/m 2 iv d1, 22, 43 concomitant with RT (66–70 Gy, conventional fractionation). Neck dissection was planned for p with stage N2–3 after induction CT or salvage surgery for resectable p with persistent disease at the end of treatment. Results: Main p characteristics were: median age 58 years (39–77), male 89%, ECOG 0/1/2 47%/50.6%/2.4%, stage IV 62.7%, larynx/hipopharynx/oral cavity/oropharynx 45%/12%/17.3%/25.7% and R/UR 41.8%/58.2%. Median TPF/P cycles administered were 3/3. Neoadjuvant CT/total treatment overall response rate evaluation (R/UR): 70% (73%/68%)/86% (84%/88%). Neck dissection was performed in 16 p and salvage surgery in 6 p. Organ preservation was achieved in 90.8% of R p. Main G3–4 toxicity during TPF treatment was neutropenia 11.2%, febrile neutropenia 11.2%, mucositis 11.2%, and during CT/RT mucositis 16.5%, neutropenia 16.5%. Median time to progression was 19.5 m(R:15.6, UR:20.3), and median overall survival was not reached (R:not reached, UR:32.8). Conclusions: Preliminary results indicate that modified neoadjuvant TPF followed by CT/RT is an active and well tolerated regimen in LAHNC, with satisfactory organ preservation and survival. No significant financial relationships to disclose.
Effect of Chlorpromazine on Serum Growth-Hormone Concentration in Man
Authors: Lawrence Sherman, Sooseng Kim, Fred Benjamin, Howard D. Kolodny
Journal: New England Journal of Medicine (1971)

Chlorpromazine, a commonly used tranquilizer of the phenothiazine group, was administered orally to 15 subjects in doses of 25 mg four times a day for one week. Fasting serum growth-hormone concentrations and growth-hormone responses to insulin stimulation were measured before and after the treatment period. Definite suppressive effects were found: fasting levels were decreased in 10 of 15 patients. At one and two hours after intravenous insulin injection the levels were lower in 13 of 14, and 10 of 15 subjects, respectively. The decrease was statistically significant during fasting (p<0.05), at one hour (p<0.005) and at two hours (p<0.05). These results warrant appraisal of phenothiazine derivatives as therapeutic adjuncts in chronic hypersecretion of growth hormone.
Short-Term Group Therapy of Patients with Parkinson's Disease
Authors: Morris E. Chafetz, Norman Bernstein, William Sharpe, Robert S. Schwab
Journal: New England Journal of Medicine (1955)

IT has always been desirable to make special efforts to improve the reactions of patients to chronic illness. Since Pratt1 originated a classroom treatment for tuberculous patients in 1906, group therapy has been applied to many medical syndromes. Among these were the efforts of Chappell et al.2 to use group methods in regulating dietary regimens for patients with peptic ulcer. Buck3 tried to improve the adjustment of hypertensive patients, and Cholden4 worked with the blind. Harris,5 in 1939, reviewed the group work done up to that time, including data on group methods with undernourished children, diabetic patients, ante-partum and post-partum . . .
Anti–Interferon‐Inducible Protein 16 Antibodies Associate With Digital Gangrene in Patients With Scleroderma
Authors: Zsuzsanna H. McMahan, Ami A. Shah, Dhananjay Vaidya, Fredrick M. Wigley, Antony Rosen, Livia Casciola‐Rosen
Journal: Arthritis & Rheumatology (2015)

Objective To examine the association between anti–interferon‐inducible protein 16 (anti–IFI‐16) antibodies and clinical features of scleroderma. Methods Sera from a discovery sample of 94 patients with scleroderma and 47 healthy controls were assayed for anti–IFI‐16 antibodies by enzyme‐linked immunosorbent assay, and associations were examined using regression analyses. Since anti–IFI‐16 autoantibodies were found to be strongly associated with digital gangrene in the discovery sample, a subsequent case–control study (with subjects matched 1:1 on disease duration) was designed for further exploration. Cases were patients with scleroderma and digital gangrene, while controls were patients with scleroderma and Raynaud's phenomenon alone (n = 39 matched pairs). Nonparametric, unadjusted matched pairs analysis as well as univariate and multivariable conditional logistic regression analyses were performed. Results In the discovery sample, anti–IFI‐16 antibodies were more prevalent in patients with scleroderma than in healthy controls (18% versus 2%; P = 0.01). Patients with anti–IFI‐16 antibodies, compared to anti–IFI‐16 antibody–negative patients, were more likely to have limited scleroderma (77% versus 46%; P = 0.03), a longer disease duration (median 15.2 years [interquartile range 10.6–18.3] versus 6.0 years [interquartile range 3.4–13.8]; P &lt; 0.01), digital gangrene (24% versus 4%; P = 0.02), and a low diffusing capacity for carbon monoxide (DL co ) ( P &lt; 0.01). In the case–control study, 35 (45%) of 78 patients were anti–IFI‐16 antibody positive. Anti–IFI‐16 antibody levels were significantly higher in cases with digital gangrene than in matched controls ( P = 0.02). In analyses adjusted for age, cutaneous scleroderma subtype, smoking, and DL co , high anti–IFI‐16 antibody levels were associated with the presence of digital gangrene (adjusted odds ratio 2.3, 95% confidence interval 1.0–5.6, P = 0.05). The odds of having digital gangrene increased with higher anti–IFI‐16 antibody titers, in a dose‐dependent manner. Conclusion Anti–IFI‐16 antibodies are associated with digital gangrene in patients with scleroderma. Longitudinal prospective studies exploring anti–IFI‐16 antibodies as a disease biomarker, and biologic studies investigating the pathogenicity of these antibodies, are warranted.
TCTAP A-082 The Influence of the Diabetic Status on the Clinical Outcomes After Percutaneous Coronary Intervention in the Era of Drug Eluting Stent: 5-Year Follow-up Data from the Asan Multi-Vessel Registry
Authors: Min Soo Cho, Seung-Jung Park, Seong-Wook Park, Cheol Whan Lee, Young-Hak Kim, Seung-Whan Lee, Duk-Woo Park, Soo-Jin Kang, Jung-Min Ahn, Pil Hyung Lee, Se Hun Kang, Cheol Hyun Lee, Jae Seok Bae, Yu Na Kim, Sung Han Yoon, Do-Yoon Kang, Mineok Chang
Journal: Journal of the American College of Cardiology (2016)
Magnetic Surgical Instruments for Robotic Abdominal Surgery
Authors: Florence Leong, Nicolo Garbin, Christian Di Natali, Alireza Mohammadi, Dhan Thiruchelvam, Denny Oetomo, Pietro Valdastri
Journal: IEEE Reviews in Biomedical Engineering (2016)

This review looks at the implementation of magnetic-based approaches in surgical instruments for abdominal surgeries. As abdominal surgical techniques advance toward minimizing surgical trauma, surgical instruments are enhanced to support such an objective through the exploration of magnetic-based systems. With this design approach, surgical devices are given the capabilities to be fully inserted intraabdominally to achieve access to all abdominal quadrants, without the conventional rigid link connection with the external unit. The variety of intraabdominal surgical devices are anchored, guided, and actuated by external units, with power and torque transmitted across the abdominal wall through magnetic linkage. This addresses many constraints encountered by conventional laparoscopic tools, such as loss of triangulation, fulcrum effect, and loss/lack of dexterity for surgical tasks. Design requirements of clinical considerations to aid the successful development of magnetic surgical instruments, are also discussed.
Euthanasia — The Need for Procedural Safeguards
Authors: G I Benrubi
Journal: New England Journal of Medicine (1992)

ACTIVE euthanasia is the deliberate termination of a patient's life in order to prevent further suffering. In ethical discussions this has been seen as different from the withholding of life-sustaining treatment or the administration of a drug, such as morphine, that may hasten death but that has another primary purpose.Over the years, a large body of literature has been published for and against active euthanasia.1 2 3 4 5 6 The discussion turns on the tension between the ethical imperative to alleviate suffering, particularly in terminally ill patients who make a conscious decision to end their lives, and the proscription against participation by physicians . . .
A Further Study of the Kveim Reaction in Sarcoidosis and Tuberculosis
Authors: Harold L. Israel, Maurice Sones, Herman Beerman, Thomas Pastras
Journal: New England Journal of Medicine (1958)

IN our experience, the Kveim reaction has not been a reliable aid in the diagnosis of sarcoidosis.1 , 2 Nevertheless, enthusiastic reports concerning its specificity continue to appear. James and Thomson3 found the Kveim test positive in 12 of 16 patients with clinical evidence of sarcoidosis, and negative in 47 subjects with other diseases. Nelson and Schwimmer4 obtained positive results in 74 per cent of 53 patients with sarcoidosis; only 1 positive test was observed among 99 patients with tuberculosis, and no positive tests among 100 other control subjects.In an effort to duplicate these results, we have carried out another series . . .