tbuckley/cabot-search huggingface dataset:
Anaerobic Bacterial Endocarditis
Authors: Joel M. Felner, V. R. Dowell
Journal: New England Journal of Medicine (1970)

Clinical and bacteriologic data were analyzed for 33 patients with suspected endocarditis due to anaerobic bacteria. One hundred and thirty blood-culture specimens from these patients yielded bacteroides, fusobacterium, clostridium, propionibacterium and peptostreptococcus species. Sixty per cent of the patients in this series demonstrated embolic phenomena, whereas 48 per cent had pre-existing heart disease, a ratio lower than that of patients with endocarditis due to facultative bacteria. The oropharynx was the portal of entry for the anaerobes in 1/3 of the patients. Seven patients died; five had Bacteroides fragilis, one Bacteroides oralis, and one Propionibacterium acnes (Corynebacterium acnes). Loculated abscesses, polymicrobic infections and the absence of a bactericidal antibiotic for the treatment of B. fragilis endocarditis complicated therapy.
Risk of Local and Systemic Infection with Polyethylene Intravenous Catheters
Authors: Richard N. Collins, Peter A. Braun, Stephen H. Zinner, Edward H. Kass
Journal: New England Journal of Medicine (1968)

Abstract Risk of local and systemic infection associated with polyethylene intravenous catheters was determined in a prospective study of 213 catheterizations in 176 general medical and surgical patients. Catheters were used in approximately 80 per cent of all patients receiving fluids. Phlebitis occurred in 39 per cent of catheterizations but was not a reliable sign of local infection; cultures of less than half the catheters removed from phlebitic patients were positive at the time of removal. One third of all catheters were positive by culture at removal. Risk of local infection with pathogenic organisms increased with duration of use. Risk of catheter-induced bacteremia was 2 per cent in the study group, and such bacteremia was a major contributing cause of death in 1 per cent. Further studies to curtail or modify the use of intravenous catheters are indicated.
Neutrophil Actin Dysfunction and Abnormal Neutrophil Behavior
Authors: Laurence A. Boxer, E. Tessa Hedley-Whyte, Thomas P. Stossel
Journal: New England Journal of Medicine (1974)

An infant had recurrent bacterial infections but failed to produce pus. His neutrophils migrated slowly and ingested particles at 15 per cent of the rate of normal. The secretion of granule contents into phagosomes was 2.5 times greater than the control when corrected for the impaired ingestion. Because of the neutrophil abnormalities the role of actin was studied. As compared with normal, fewer microfilament-rich pseudopodia were visible in the patient's neutrophils. Heavy meromyosin bound to microfilaments in both normal and the patient's glycerinated neutrophils, indicating that the filaments were actin polymers. The patient's and normal neutrophils contained equal quantities (13.8 and 14.3 per cent) of actin protein. However, seven times less of the patient's actin sedimented after polymerizing treatment with potassium chloride. The association of a poorly polymerizable actin in extracts of neutrophils exhibiting abnormal locomotion, ingestion and degranulation is evidence for the participation of this protein in these functions. (N Engl J Med 291: 1093–1099, 1974)
Cytotoxic Autoantibodies to Beta Cells in the Serum of Patients with Insulin-Dependent Diabetes Mellitus
Authors: Michael J. Dobersen, Joshua E. Scharff, Fredda Ginsberg-Fellner, Abner Louis Notkins
Journal: New England Journal of Medicine (1980)

We studied serum from 36 patients with insulin-dependent diabetes mellitus (IDDM) for the capacity to lyse beta cells. Immunofluorescence revealed an islet-cell cytoplasmic antibody (ICA) in 20 patients with IDDM and an islet-cell-surface antibody (ICSA) in 23. Neither ICA nor ICSA was found in any of 21 normal controls or 15 patients with non-insulin-dependent diabetes. In the presence of complement. ICSA-positive serum caused significant lysis as measured by release of 51Cr (50.1 +/- 8.8 per cent) from cultured rat islet cells, but ICSA-negative serum did not (17.7 +/- 7.3 per cent) (P < 0.001). Proof that ICSA-positive serum was lytic for beta cells was obtained by a double-fluorescence technique that identified lysed cells by their capacity to take up ethidium bromide and beta cells by their staining with fluorescein-conjugated antibody to insulin. These findings suggest that cytotoxic ICSA contributes to the pathogenesis of IDDM, but the mere presence of ICSA does not appear to be sufficient to produce diabetes; family studies showed that one fourth of the serum samples from nondiabetic first-degree relatives of diabetic probands were ICSA-positive and cytotoxic for beta cells.
S126 Measuring ER protein mobility during ER fragmentation in alpha-1-antitrypsin deficiency
Authors: JA Dickens, A Ordonez, JE Chambers, DA Lomas, SJ Marciniak
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> Alpha-1-antitrypsin is a serine protease inhibitor produced in the liver that is responsible for the regulation of pulmonary inflammation. The commonest pathogenic gene mutation yields Z-alpha-1-antitrypsin, which has a propensity to self-associate into polymers that become entrapped within inclusions of endoplasmic reticulum (ER). This predisposes to the development of cirrhosis, while the resulting paucity of circulating alpha-1-antitrypsin leads to early-onset emphysema. It is unclear whether intracellular inclusions are physically or functionally connected to the main ER network in Z-alpha-1-antitrypsin expressing cells. In this study, we sought to clarify the behaviour of proteins within inclusion bodies to further our understanding of the consequences of Z-alpha-1-antitrypsin expression on cellular dysfunction. <h3>Methods</h3> We created YFP tagged wild-type and Z-alpha-1-antitrypsin constructs and expressed them in a cell model along with other fluorescently tagged proteins of interest. Using live-cell imaging including photobleaching techniques, we assessed the relative mobilities of alpha-1-antitrypsin and other ER resident proteins. We further assessed the nature of inter-inclusion protein trafficking by creating a permeabilised cell system in which the cytosol could be manipulated or removed. <h3>Results</h3> We have shown that inclusions are translationally active ER fragments in which polymerisation occurs. Using fluorescence recovery after photobleaching (FRAP), we observed that despite inclusions containing immobile polymeric alpha-1-antitrypsin, small ER resident proteins including the ER chaperone BiP are able to diffuse freely within them (Figure 1). We observed that inclusions are physically separated from the tubular ER network but despite this, cargo is transported between inclusions in a cytosol-dependent fashion that is dependent on vesicular trafficking components and may involve the ER-Golgi intermediate compartment (ERGIC). <h3>Conclusions</h3> We propose that protein movement between physically separated ER inclusions via ER-ERGIC recycling acts to minimise ER heterogeneity in Z-alpha-1-antitrypsin expressing cells. This may reduce the toxic effects of polymer accumulation via increased availability of, for example, ER chaperones within inclusions and is consistent with <i>in vivo</i> observations of a striking lack of toxicity in cells expressing Z-alpha-1-antitrypsin.
INTEGRATE: A randomized phase II double-blind placebo-controlled study of regorafenib in refractory advanced oesophagogastric cancer (AOGC)—A study by the Australasian Gastrointestinal Trials Group (AGITG), first results.
Authors: Nick Pavlakis, Katrin Marie Sjoquist, Eric Tsobanis, Andrew Martin, Yoon-Koo Kang, Yung-Jue Bang, Christopher J. O'Callaghan, Niall C. Tebbutt, Sun Young Rha, Jeeyun Lee, Jae Yong Cho, Lara Rachel Lipton, Margot J. Burnell, Thierry Alcindor, Andrew Strickland, Mark Wong, Jin Won Kim, John Simes, John Raymond Zalcberg, David Goldstein
Journal: Journal of Clinical Oncology (2015)

9 Background: Advanced Oesophago-Gastric Carcinoma (AOGC) has limited options following failure of first or second line chemotherapy (CT). Regorafenib (REG) is an oral multi-kinase inhibitor of kinases involved in angiogenesis, tumor microenvironment, and oncogenesis. This study examined whether REG has sufficient activity and safety for further evaluation. Methods: International (Australia &amp; New Zealand (ANZ), Korea, Canada (NCIC CTG)) randomised phase II trial with 2:1 randomisation and stratification by: (1) Lines of prior CT for advanced disease (1 vs. 2) and (2) Region. Eligible patients received best supportive care plus 160mg REG or matching PBO orally on days 1-21 each 28-day cycle until disease progression or prohibitive adverse events. Primary endpoint was progression free survival (PFS) in the REG arm, assuming median 8 weeks (wks) in PBO arm, aiming for 13.2 wks with REG to be of interest. Results: From Nov 2012 to Feb 2014, 152 patients were enrolled, 147 evaluable [pre-specified primary analysis population]: (REG n=97: PBO n=50); well matched for key baseline prognostic indicators; male:female (118:29); primary location: OG Junction (56), stomach (85); lines of prior therapy: 1 (63), 2 (84); ECOG 0 (62): 1 (85). Time on treatment: Median: 7.9 (REG) v 4 (PBO) wks. In the evaluable population median PFS was 11.1 wks (95% CI: 7.7 - 12.3) (REG) and 3.9 wks (95% CI: 3.7 - 4.0) (PBO), log-rank p &lt;0.0001; HR 0.41 (95% CI: 0.28 to 0.59). PFS results were maintained for secondary analysis including all randomized patients (n = 152). REG was well tolerated, with the spectrum of toxicity in keeping with previous reports. Conclusions: PFS was clearly significantly longer with REG than PBO, though PBO PFS was less than anticipated. The pre-specified exploratory comparisons provide compelling evidence that REG has sufficient activity with acceptable tolerability in refractory AOGC to warrant phase III evaluation. Mature OS results will be presented at the meeting. Clinical trial information: 12612000239864.
Case 4-1991
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely
Journal: New England Journal of Medicine (1991)

Presentation of Case An 18-year-old man was admitted to the hospital with pain in the right leg and a local mass after a subtotal resection of the mass performed elsewhere. The patient was known to have Morquio's syndrome. There was a history of an anterior subluxation of the second cervical vertebra upon the third cervical vertebra at the age of seven years, without neurologic sequelae; no evidence of instability was detected on repeated radiographic examinations. At the age of eight years bilateral proximal femoral osteotomies were performed. Two months later osteotomies were performed on both distal femurs in treatment of . . .
Case 3-1999
Authors: Daniel L. Menkes, Darryl E. Palmer-Toy, E Tessa Hedley-Whyte
Journal: New England Journal of Medicine (1999)

Presentation of CaseA 41-year-old woman was admitted to the hospital because of muscle weakness, painful paresthesias, and transient visual problems.The patient had been well until four months earlier, when a rash developed on her thighs, and lumbar pain radiated down the backs of both legs to the heels, followed by the development of tingling and numbness in the feet. About one month before admission, she began to have episodes of transient monocular blindness that involved either eye, but usually the right. The episodes began with sudden “black clouding” of the visual field, with “tunnel vision,” and subsided after . . .
Physical Conditioning Augments the Fibrinolytic Response to Venous Occlusion in Healthy Adults
Authors: R. Sanders Williams, Everett E. Logue, James L. Lewis, Thomas Barton, Nancy W. Stead, Andrew G. Wallace, Salvatore V. Pizzo
Journal: New England Journal of Medicine (1980)

The effects of a 10-week physical-conditioning program on fibrinolytic activity at rest and after stimulation by venous occlusion were studied in 69 healthy adults 25 to 69 years old. Physical conditioning was documented by treadmill performance, and fibrinolysis was measured with a newly developed radioenzymatic assay. Whereas fibrinolysis declined at rest from 16.2 +/- 1.3 to 11.4 +/- 0.8 units (mean +/- S.E.M.) (P = 0.0017), the increment in fibrinolysis produced by venous occlusion was increased from 21.7 +/- 2.9 to 33.8 +/- 4.7 units (P = 0.0037). This augmentation was most marked in women, persons with low initial levels of stimulated fibrinolysis, and persons with low initial physical fitness. We conclude that physical conditioning can enhance the augmentation of fibrinolytic activity that occurs in response to venous occlusion. Enhanced fibrinolysis in response to thrombotic stimuli could be an important mechanism in the beneficial effect of habitual physical activity on the risk of cardiovascular disease.
Epimacular Brachytherapy for Previously Treated Neovascular Age-Related Macular Degeneration (MERLOT)
Authors: Timothy L. Jackson, Riti Desai, Andrew Simpson, James E. Neffendorf, Robert Petrarca, Kelly Smith, Janet Wittes, Cornelius Lewis, Luke Membrey, Richard Haynes, Mark Costen, David H.W. Steel, Alyson Muldrew, Usha Chakravarthy
Journal: Ophthalmology (2016)

To assess the safety and efficacy of epimacular brachytherapy (EMB) for patients with chronic, active, neovascular age-related macular degeneration (AMD).Phase 3 randomized controlled trial.Patients (n = 363) with neovascular AMD already receiving intravitreal ranibizumab injections.Either pars plana vitrectomy with 24-gray EMB and ongoing pro re nata (PRN) ranibizumab (n = 224) or ongoing PRN ranibizumab monotherapy (n = 119).The coprimary outcomes, at 12 months, were the number of PRN ranibizumab injections and Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (VA). Secondary outcomes included the proportion of participants losing fewer than 15 ETDRS letters, angiographic total lesion size, choroidal neovascularization (CNV) size, and optical coherence tomography (OCT) foveal thickness. A predefined subgroup analysis tested the influence of baseline ocular characteristics on the response to EMB.The mean number of PRN ranibizumab injections was 4.8 in the EMB arm and 4.1 in the ranibizumab monotherapy arm (P = 0.068). The mean VA change was -4.8 letters in the EMB arm and -0.9 letters in the ranibizumab arm (95% confidence interval of difference between groups, -6.6 to -1.8 letters). The proportion of participants losing fewer than 15 letters was 84% in the EMB arm and 92% in the ranibizumab arm (P = 0.007). In the EMB arm, the mean total lesion size increased by 1.2 mm(2) versus 0.4 mm(2) in the ranibizumab arm (P = 0.27). The CNV size decreased by 0.5 mm(2) in the EMB arm and by 1.3 mm(2) in the ranibizumab arm (P = 0.27). The OCT foveal thickness decreased by 1.0 μm in the EMB arm and by 15.7 μm in the ranibizumab arm (P = 0.43). Most subgroups favored ranibizumab monotherapy, some significantly so. One participant showed retinal vascular abnormality attributed to radiation, but otherwise safety was acceptable.These results do not support the use of EMB for chronic, active, neovascular AMD. Safety is acceptable out to 12 months, but radiation retinopathy can occur later, so further follow-up is planned.
A Possible Autoimmune Basis for Addison's Disease in Three Siblings, One with Idiopathic Hypoparathyroidism, Pernicious Anemia and Superficial Moniliasis
Authors: Wellington Hung, Claude J. Migeon, Robert H. Parrott
Journal: New England Journal of Medicine (1963)

FAMILIAL Addison's disease is an uncommon entity. In 1959 Meakin, Nelson and Thorn1 reviewed the literature and found 5 cases of familial Addison's disease documented by steroid studies or autopsy findings,2 3 4 5 6 and reported another case. Since that time 4 additional cases fulfilling their criteria have been reported.7 8 9 10 The association of superficial moniliasis, idiopathic hypoparathyroidism and Addison's disease is even rarer, only 6 cases being found in the literature.11 12 13 14 15 The purpose of this report is to describe a family in which Addison's disease was present in 3 siblings, 1 of whom also had superficial moniliasis, idiopathic hypoparathyroidism and pernicious anemia. We . . .
Comparison of a High-Carbohydrate Diet with a High-Monounsaturated-Fat Diet in Patients with Non-Insulin-Dependent Diabetes Mellitus
Authors: Abhimanyu Garg, Andrea Bonanome, Scott M. Grundy, Zu-Jun Zhang, Roger H. Unger
Journal: New England Journal of Medicine (1988)

We compared a high-carbohydrate diet with a high-fat diet (specifically, a diet high in monounsaturated fatty acids) for effects on glycemic control and plasma lipoproteins in 10 patients with non-insulindependent diabetes mellitus (NIDDM) receiving insulin therapy. The patients were randomly assigned to receive first one diet and then the other, each for 28 days, in a metabolic ward. In the high-carbohydrate diet, 25 percent of the energy was in the form of fat and 60 percent in the form of carbohydrates (47 percent of the total energy was in the form of complex carbohydrates); the high-monounsaturated-fat diet was 50 percent fat (33 percent of the total energy in the form of monounsaturated fatty acids) and 35 percent carbohydrates. The two diets had the same amounts of simple carbohydrates and fiber. As compared with the high-carbohydrate diet, the highmonounsaturated-fat diet resulted in lower mean plasma glucose levels and reduced insulin requirements, lower levels of plasma triglycerides and very-low-density lipoprotein cholesterol (lower by 25 and 35 percent, respectively; P<0.01), and higher levels of high-density lipoprotein (HDL) cholesterol (higher by 13 percent; P<0.005). Levels of total cholesterol and low-density lipoprotein (LDL) cholesterol did not differ significantly in patients on the two diets. These preliminary results suggest that partial replacement of complex carbohydrates with monounsaturated fatty acids in the diets of patients with NIDDM does not increase the level of LDL cholesterol and may improve glycemic control and the levels of plasma triglycerides and HDL cholesterol. (N Engl J Med 1988; 319:829–34.)
The Relation between the Industrial Physician and the Family Doctor
Authors: Thomas L. Shipman
Journal: New England Journal of Medicine (1948)

DURING the decade from 1911 to 1920 all but a handful of states enacted workmen's compensation acts and thereby brought into being that peculiarly hybrid creature, the industrial physician. Back in those early days the propriety of entering such a low-born specialty was questionable, and there can be no doubt that a number of poorly qualified doctors entered this field. There were in addition, however, men of unquestioned ability and integrity, and as pioneers in a new and uncharted field they endured the scorn and insults of other doctors, and at the same time they evolved the fundamental knowledge and . . .
The Polymicrobial Origin of Intestinal Infections in Homosexual Men
Authors: Thomas C. Quinn, Walter E. Stamm, Steven E. Goodell, Emanuel Mkrtichian, Jacqueline Benedetti, Lawrence Corey, Michael D. Schuffler, King K. Holmes
Journal: New England Journal of Medicine (1983)

To determine the microbial cause and the clinical and pathologic correlates of anorectal and intestinal symptoms in homosexually active men, we performed comprehensive microbiologic studies, anoscopy, sigmoid-oscopy, and rectal biopsy in men examined in a clinic for sexually transmitted diseases. Enteric pathogens were found in 95 of 119 consecutive homosexual men with anorectal or intestinal symptoms and in 29 of 75 randomly selected homosexual men without such symptoms (P less than 0.001). The syndromes of proctitis, proctocolitis, and enteritis were differentiated on the basis of predominant symptoms and findings on anoscopy and sigmoidoscopy. Neisseria gonorrhoeae, herpes simplex virus, Chlamydia trachomatis (non-lymphogranuloma venereum serotypes), and Treponema pallidum were associated with 80 per cent of cases with symptomatic proctitis. Known causes of colitis, including Campylobacter jejuni, Campylobacter fetus fetus, Shigella flexneri, Chl. trachomatis (lymphogranuloma venereum serotypes), Entamoeba histolytica, and Clostridium difficile, were identified in 60 per cent of the cases of proctocolitis. Giardia lamblia was the only agent significantly correlated with enteritis. These data demonstrate that intestinal symptoms in homosexual men are attributable to a complex spectrum of microorganisms, but that careful clinical classification can serve as a guide to the selection of microbiologic studies and to a rational initial choice of therapy.
94P: First-line treatment with cisplatin plus etoposide for small cell lung cancer and large cell neuroendocrine carcinoma: Our center experience
Authors: G. Del Bene, A. Prelaj, J.R. Giron Berrios, L. De Filippis, A. Emiliani, A. Galletti, C. Ferrara, F. Longo
Journal: Journal of Thoracic Oncology (2016)
Case 45-1962
Authors: William C. Quinby, Austin L. Vickery
Journal: New England Journal of Medicine (1962)

Presentation of Case*A seventeen-year-old boy was admitted to the hospital because of abdominal pain.Three days before entry, soon after pushing an automobile, the patient experienced the onset of steady periumbilical pain and nausea. The pain increased in severity during the day, and vomiting began. A physician gave him meperidine (Demerol), which afforded temporary relief, but the pain recurred and persisted and was centered largely in the upper portion of the abdomen. On the following day the pain migrated to the right middle portion of the abdomen and left lower quadrant and then to the lower abdominal quadrants. The . . .
Corticotropin-Releasing Factor Stimulation Test
Authors: A N Elias, G Gwinup
Journal: New England Journal of Medicine (1984)

Abstract We investigated the effect of exogenous corticotropin-releasing factor on plasma levels of ACTH and Cortisol in 13 patients with ACTH-secreting pituitary adenomas (Cushing's disease) and in 9 patients with other forms of Cushing's syndrome. In all patients with Cushing's disease, ovine corticotropin-releasing factor, given intravenously as a bolus injection (1 μg per kilogram of body weight), caused a further increase in the already elevated levels of ACTH and cortisol. Successful transsphenoidal adenomectomy was followed as early as one week after surgery by normalization or near-normalization of the ACTH and cortisol responses to corticotropin-releasing factor. On the other hand, patients with the ectopic ACTH syndrome, who also had high basal plasma concentrations of ACTH and cortisol, had no ACTH or cortisol responses to corticotropin-releasing factor. This difference in responsiveness between these two patient groups cannot be explained on the basis of different metabolic clearance rates of ...
Sustainability of Phenotype and Suppressive Activities of Tregs after Discontinuation of Epit but Not of OIT or Slit in Peanut Sensitized Mice.
Authors: Vincent Dioszeghy, Lucie Mondoulet, Camille Plaquet, Emilie Puteaux, Mélanie Ligouis, Véronique Dhelft, Christophe Dupont, Pierre-Henri Benhamou
Journal: Journal of Allergy and Clinical Immunology (2016)
Case 22-1973
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Arnold N. Weinberg, Gerald Nash
Journal: New England Journal of Medicine (1973)

Presentation of CaseA 76-year-old woman was admitted to the hospital because of shaking chills.For 10 years she had experienced repeated respiratory-tract infections during the winter, characterized by a cough productive of small amounts of white sputum that persisted for approximately six weeks. Six months before entry there was the onset of fatigue, polyuria, polydipsia and apparent weight loss. One week before admission she again contracted a cough that was productive of moderate amounts of white sputum, accompanied by weakness, malaise and increased polyuria and polydipsia. Three days before entry she began to have repeated shaking chills, with dyspnea . . .