tbuckley/cabot-search huggingface dataset:
Pulmonary Tuberculosis in Harvard Medical Students
Authors: Henry P. Brean, Lewis W. Kane
Journal: New England Journal of Medicine (1946)

DESPITE the marked fall in recent years in the morbidity and mortality due to pulmonary tuberculosis and despite advances in its early diagnosis and treatment, tuberculous infection of the lung remains the most serious medical problem that confronts the medical student. Although for more than a century European clinicians had been aware of an apparent high incidence of pulmonary tuberculosis among medical students, it was not until 1930 that Steidl1 called to the attention of American clinicians the fact that a similar high incidence was being overlooked in American medical schools. Stimulated by Steidl's report, Hetherington and his co-workers2 conducted . . .
The Effects of Biosynthetic Human Proinsulin on Carbohydrate Metabolism in Non-Insulin-Dependent Diabetes Mellitus
Authors: Harry S. Glauber, Robert R. Henry, Penny Wallace, Bruce H. Frank, John A. Galloway, Robert M. Cohen, Jerrold M. Olefsky
Journal: New England Journal of Medicine (1987)

We compared the glucose-lowering effect of proinsulin, the precursor molecule of insulin, with that of insulin itself. In patients with non-insulin-dependent diabetes mellitus (NIDDM) in whom proinsulin (0.2 U per kilogram of body weight) was subcutaneously injected at 9 a.m., fasting glucose levels (247 +/- 22 mg per deciliter [+/- SEM]) became normal within six hours and elevated rates of hepatic glucose output were lowered. The response to regular insulin (0.2 U per kilogram) was of similar magnitude but faster. Glucose clearance was stimulated less by proinsulin, reflecting its preferential action in suppressing glucose output. Hypoglycemia occurred in five of nine insulin-treated patients, but in only one of nine proinsulin-treated patients. After proinsulin injection at bedtime (30.5 +/- 4 U), serum proinsulin concentrations reached a peak by five hours and declined gradually thereafter. Fasting hepatic glucose output became normal, and euglycemia was sustained without overnight hypoglycemia. Proinsulin reduced plasma glucose more effectively than an equal unit dosage of NPH insulin, but since higher doses of NPH insulin were not used, no conclusions could be drawn about the relative desirability of these preparations for clinical use. We conclude that subcutaneously injected proinsulin has prolonged pharmacokinetics in plasma and can normalize plasma glucose in NIDDM characterized by severe hyperglycemia; as compared with the hypoglycemic effects of regular insulin, those of proinsulin are mostly due to suppression of hepatic glucose output, with little stimulation of glucose disposal and less hypoglycemia; and proinsulin may have a role in the treatment of NIDDM.
S108 Effect of baseline FVC on decline in lung function with nintedanib in patients with IPF: results from the INPULSIS® trials
Authors: M Kolb, T Kimura, S Stowasser, C Hallmann, L Richeldi
Journal: Thorax (2015)

<h3>Introduction</h3> The two replicate, randomised, placebo-controlled, 52-week Phase III INPULSIS® trials assessed the efficacy and safety of nintedanib 150 mg twice daily (bid) in patients with idiopathic pulmonary fibrosis (IPF). Patients with forced vital capacity (FVC) ≥50% predicted were included. The primary endpoint, the annual rate of decline in FVC, was significantly reduced in the nintedanib group compared with placebo in both trials, consistent with a slowing of disease progression. Key secondary endpoints were time to first acute exacerbation and change from baseline in St. George’s Respiratory Questionnaire total score, both over 52 weeks. In a pre-specified subgroup analysis of patients with baseline FVC ≤70% versus &gt;70% predicted, the treatment effect of nintedanib on decline in FVC was consistent in both subgroups. <h3>Methods</h3> A <i>post-hoc</i> subgroup analysis of patients with baseline FVC &gt;90% versus ≤90% predicted was undertaken using pooled data from the INPULSIS® trials to investigate whether patients with marginally impaired FVC receive the same benefit from nintedanib. <h3>Results</h3> 274 patients (nintedanib 166, placebo 108) had baseline FVC &gt;90% predicted and 787 patients (nintedanib 472, placebo 315) had baseline FVC ≤90% predicted. There was no significant treatment-by-subgroup interaction for the primary endpoint (p = 0.5300); in patients with baseline FVC &gt;90% predicted, the adjusted annual rate of decline in FVC was -91.5 mL/year with nintedanib and -224.6 mL/year with placebo (difference: 133.1 mL/year [95% CI: 68.0, 198.2]) while in patients with baseline FVC ≤90% predicted, it was -121.5 mL/year with nintedanib and -223.6 mL/year with placebo (difference: 102.1 mL/year [95% CI: 61.9, 142.3]). Consistent results were observed for changes from baseline in FVC over time (Figure 1). No significant treatment-by-subgroup interaction was observed for the key secondary endpoints. The frequency of adverse events and serious adverse events was comparable between the treatment arms of each subgroup. <h3>Conclusion</h3> In a subgroup analysis of pooled data from the INPULSIS® trials, nintedanib 150 mg bid slowed the decline in lung function in patients with IPF independent of degree of lung function impairment at baseline, suggesting that patients with marginally impaired FVC also benefit from treatment with nintedanib.
Otitis Media in Children
Authors: Stephen Berman
Journal: New England Journal of Medicine (1995)

The frequency of otitis media is one of a number of factors causing physicians to seek out the most cost-effective clinical strategies for managing the condition. It is estimated that, by the time they reach two years of age, all the children in the United States currently under that age will have had a total of 9.3 million episodes of acute otitis media,1 and that approximately 17 percent of children have three or more episodes during a six-month period.2 Frequent episodes of otitis disrupt child-care arrangements and work schedules and generate parental anxiety and stress. The annual cost of the . . .
Tumor progression and mortality associated with administration of erythropoiesis stimulating agents (ESAs) to cancer patients: Is toxicity due to ESAs or elevated hemoglobin (Hgb) levels
Authors: A. Kuykendal, C. L. Bennett, J. M. McKoy, S. Boyle, D. P. West, B. J. Edwards, D. M. Courtney, A. O. Sartor, S. Y. Lai, M. Henke
Journal: Journal of Clinical Oncology (2008)

11115 Background: In 1993, ESAs were approved to treat chemotherapy-associated anemia. Since 2006, ESA manufacturers disseminated alerts identifying mortality/tumor concerns with ESAs (epoetin, darbepoetin) among persons with cancer. Controversy exists over whether toxicity results from Hb levels>12 or ESA effects on Epo receptors (EpoR). Methods: Basic science studies (MeSH terms “EpoR” and “Cancer”, n=293) were reviewed. Any trial that assessed the presence or absence of EpoR or the response of malignant cells to ESAs was included. Clinical studies (n=1881) that evaluated mortality in ESA vs. placebo in chemotherapy- associated anemia were reviewed. Non-randomized studies were excluded. Results: 52 basic science studies were included (see Table). Meta-analyses of clinical studies from 1989–2008 (n=54 trials; 13,470 patients) evaluating ESAs vs. placebo in chemotherapy- associated anemia identified increased mortality (HR = 1.10; 95% CI, 1.02,1.21: p=0.014). These trials included several cell types and primarily targeted Hb>12 g/dl. Conclusion: ESA and cancer toxicity may result from a direct effect of ESAs. Basic science findings demonstrate increased virulence of a variety of cell lines in response to ESA exposure that is related to the presence and downstream effect of EpoR in cancer cell lines. Clinical findings demonstrate increased mortality with ESA exposure in numerous clinical settings. *Presence of downstream proteins activated by EpoR Cancer Cell Line # of studies EpoR Presence (%) Downstream Effects* (%) Progression in Response to ESAs (%) No Progression in Response to ESAs(%) Breast 9 67 44 33 33 Neuro-blastoma 6 83 33 33 50 Lymphoma 2 50 50 0 100 Ovary 6 83 67 83 17 Lung 2 100 50 50 Renal 3 67 33 33 Head and Neck 5 100 40 40 Cervix 6 100 67 67 Melanoma 4 100 75 75 Prostate 2 100 50 50 Endometrium 2 100 50 50 Glioma 3 100 67 100 Gastric 2 100 50 50 No significant financial relationships to disclose.
Listeriosis and Milk
Authors: Michael Barza
Journal: New England Journal of Medicine (1985)

The life cycle of Listeria monocytogenes seems to be inextricably intertwined with the monocyte. The species name was inspired by the curious ability of the organism to cause a monocytosis in the blood of infected laboratory animals. In 1929, Nyfeldt reported the first isolation from a human being, a boy with infectious mononucleosis, and three years later he described similar isolates from 3 of 10 patients with infectious mononucleosis. Although we now recognize that monocytosis is an uncommon manifestation of human listeriosis and that infectious mononucleosis is caused by the Epstein–Barr virus, the link between L. monocytogenes and the monocyte . . .
Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes Complicated by Severe Hypoglycemia
Authors: Bernhard J. Hering, William R. Clarke, Nancy D. Bridges, Thomas L. Eggerman, Rodolfo Alejandro, Melena D. Bellin, Kathryn Chaloner, Christine W. Czarniecki, Julia S. Goldstein, Lawrence G. Hunsicker, Dixon B. Kaufman, Olle Korsgren, Christian P. Larsen, Xunrong Luo, James F. Markmann, Ali Naji, Jose Oberholzer, Andrew M. Posselt, Michael R. Rickels, Camillo Ricordi, Mark A. Robien, Peter A. Senior, A.M. James Shapiro, Peter G. Stock, Nicole A. Turgeon
Journal: Diabetes Care (2016)

Impaired awareness of hypoglycemia (IAH) and severe hypoglycemic events (SHEs) cause substantial morbidity and mortality in patients with type 1 diabetes (T1D). Current therapies are effective in preventing SHEs in 50-80% of patients with IAH and SHEs, leaving a substantial number of patients at risk. We evaluated the effectiveness and safety of a standardized human pancreatic islet product in subjects in whom IAH and SHEs persisted despite medical treatment.This multicenter, single-arm, phase 3 study of the investigational product purified human pancreatic islets (PHPI) was conducted at eight centers in North America. Forty-eight adults with T1D for >5 years, absent stimulated C-peptide, and documented IAH and SHEs despite expert care were enrolled. Each received immunosuppression and one or more transplants of PHPI, manufactured on-site under good manufacturing practice conditions using a common batch record and standardized lot release criteria and test methods. The primary end point was the achievement of HbA1c <7.0% (53 mmol/mol) at day 365 and freedom from SHEs from day 28 to day 365 after the first transplant.The primary end point was successfully met by 87.5% of subjects at 1 year and by 71% at 2 years. The median HbA1c level was 5.6% (38 mmol/mol) at both 1 and 2 years. Hypoglycemia awareness was restored, with highly significant improvements in Clarke and HYPO scores (P > 0.0001). No study-related deaths or disabilities occurred. Five of the enrollees (10.4%) experienced bleeds requiring transfusions (corresponding to 5 of 75 procedures), and two enrollees (4.1%) had infections attributed to immunosuppression. Glomerular filtration rate decreased significantly on immunosuppression, and donor-specific antibodies developed in two patients.Transplanted PHPI provided glycemic control, restoration of hypoglycemia awareness, and protection from SHEs in subjects with intractable IAH and SHEs. Safety events occurred related to the infusion procedure and immunosuppression, including bleeding and decreased renal function. Islet transplantation should be considered for patients with T1D and IAH in whom other, less invasive current treatments have been ineffective in preventing SHEs.
The Cruveilhier-Baumgarten Syndrome
Authors: Alexander Blain, Muir Clapper
Journal: New England Journal of Medicine (1945)

INFREQUENTLY a venous hum or bruit occurs in the dilated collateral venous channels that may develop in portal obstruction. In 1942, Armstrong et al.1 reviewed the 53 published cases of this phenomenon and added 2 cases of their own. Actually, 5 of the cases — including 1 of Armstrong's—showed persistence of a patent umbilical vein without portal obstruction. Since the review of Armstrong, several additional cases of portal obstruction associated with a venous hum heard over the dilated collateral veins have been reported, mainly by English and French authors.Historical ConsiderationsPégot2 , 3 in 1833 observed a patient who had dilated . . .
Fulminant Central Nervous System Nocardiosis in a Patient Treated With Alemtuzumab for Relapsing-Remitting Multiple Sclerosis
Authors: Horst Penkert, Claire Delbridge, Nina Wantia, Benedikt Wiestler, Thomas Korn
Journal: JAMA Neurology (2016)

A woman in her late 40s w ith relapsing-remitting m u l t i p l e s c l e r o s i s ( M S ) w a s a d m itt e d b e c a u s e o f reduced ambulation and personality change in the previous 3 weeks.Her diagnosis of MS was made in 2007, and she was initially t re ate d w it h i nte r fe ro n beta-1a and switched to natalizumab because of ongoing disease activity.After 80 infusions, natalizumab was discontinued because of repeated relapses and seroconversion to positivity for JC virus.Her first cycle of alemtuzumab was given in February 2015 (Expanded Disability Status Sc ale score of 4.5), 18 weeks after the cessation of natalizumab treatment.Her medical history was remarkable for hypothyroidism, rec urrent infec tions, and an anorectic disorder (body mass index [calculated as weight in kilograms divided by height in meters squared] on admission, 14).On admission in June 2015, she had a tetraspastic syndrome and was wheelchair-bound.Her temperature was 37.2°C and her white blood cell count was 9100/μL (to convert to ×10 9 /L, multiply by 0.001) with an essentially depleted mononuclear fraction (Table ).Cerebrospinal fluid analysis showed 2 leukoc ytes per mic roliter.M a g n e t i c r e s o n a n c e i m a g i n g s h o w e d m u l t i p l e ring-enhancing lesions (Figure).Despite broad screening, no infectious agent was identified in the patient's blood or cerebrospinal fluid (including Toxoplasma gondii, mycobacterial species, Pneumocystis jiroveci, fungi, or human immunodeficiency virus), and a search for infectious foc i in the systemic compartment remained inconclusive.Because the patient's condition deteriorated within 2 days despite broad-spectrum antibiotic treatment, an intracranial biopsy specimen was obtained.Culture of intracranial abscess material resulted in identification of Nocardia farcinica (Figure).The patient's antibiotic treatment was revised to imipenem, co-trimoxazole, and amikacin plus dexamethasone.She required transient noradrenaline infusion and was mechanically ventilated for 10 days before she improved and could be discharged for rehabilitation.On follow-up, she was ambulatory, her peripheral blood mononuclear cell count had partly recovered (Table ), and number and size of Nocardia-associated intracerebral lesions were markedly reduced on the magnetic resonance image (Figure).Her intravenous antibiotic therapy was stopped after 8 weeks of treatment and oral administration of co-trimoxazole and amoxicillin-clavulanic acid was continued to maintain remission.
Rapid Immunization with Poliomyelitis Vaccine
Authors: Samuel Baron, Eugene V. Barnett, Beatrice L. Burch, John M. Lynch, Wilfred R. Ehrmantraut
Journal: New England Journal of Medicine (1959)

OLIOMYELITIS vaccine has been shown to be effective in the prevention of paralytic poliomyelitis when administered in 3 1-ml. doses over three months, as in the 1954 field trial,1 or currently in 3 doses over seven months.2 Under certain circumstances it would be desirable to provide such immunity rapidly for persons who have not completed a 3-dose immunization schedule.It is the purpose of this paper to record the rapid production of antibodies in persons given a single injection of 10 ml. of poliomyelitis vaccine produced in 1958.Materials and MethodsThree groups were used in the study. The first . . .
Congenital Hereditary Hematuria
Authors: Gertrud C. Reyersbach, Allan M. Butler
Journal: New England Journal of Medicine (1954)

THE purpose of this paper is to emphasize a congenital hereditary syndrome characterized primarily by hematuria and often accompanied by nerve deafness. It is important that this condition be distinguished from acute or chronic glomerulonephritis because of its different etiology, course and prognosis.Review of LiteratureIn 1901 Attlee1 described a family in which the father died of uremia at thirty years of age and 3 daughters were observed at five, four and two years of age to have recurrent attacks of gross hematuria associated with malaise and pyrexia. In the intervals between attacks the children appeared to be healthy, . . .
Intergroup ALFA/GOELAMS randomized phase II trial of lirilumab anti-KIR monoclonal antibody (IPH2102/BMS986015) as maintenance treatment in elderly patients with acute myeloid leukemia (EFFIKIR trial).
Authors: Norbert Vey, Hervé Dombret, Norbert Ifrah, Arnaud Pigneux, Claude Gardin, Marc E. Buyse, Pascale Andre, Anne Tirouvanziam-Martin, Robert Albert Zerbib, Renaud Buffet, Marcel Rozencweig
Journal: Journal of Clinical Oncology (2013)

TPS3117^ Background: Inhibitory killer immunoglobulin-like receptors (KIR) negatively regulate natural killer (NK) cell–mediated killing of HLA class I–expressing tumors. Lack of KIR-HLA class I interactions has been associated with potent NK cell-mediated antitumor efficacy and increased survival in patients with acute myeloid leukemia (AML) upon haploidentical stem cell transplantation from KIR-mismatched donors(Ruggeri, Blood 2007). Anti-KIR antibody treatment resulted in long-term survival in SCID mice inoculated with lethal autologous AML cells (Romagne, Blood 2009). Lirilumab is a second generation fully human monoclonal antibody targeting the major inhibitory KIR on NK cells. The objectives of this study are to determine if maintenance therapy with lirilumab can improve leukemia-free survival (LFS) of elderly patients in first complete remission (CR1) of AML and to assess two dose schedules leading to either intermittent or continuous KIR occupancy. Methods: EFFIKIR is a randomized double-blind 3-arm placebo controlled trial of lirilumab in elderly patients in CR1 of AML. Patients aged 60 to 80 in CR1 of AML following standard induction and consolidation programs are randomly allocated to receive placebo or lirilumab given at either 0.1 mg/kg q 12 weeks or 1 mg/kg q 4 weeks according to a minimization algorithm adjusting for center, primary vs. secondary AML, no. of consolidation cycles (1 vs. 2) and cytogenetics (intermediate vs. high risk). Patients are to receive up to 2 yrs of therapy. ECOG performance status of 0-1, adequate hematologic, liver and renal function, and recovery from toxicities of prior chemotherapies are required. Patients are excluded if they are eligible for bone marrow transplantation and if the time interval since last consolidation exceeds 3 mos. The primary endpoint is LFS based on independent central review. The trial will accrue 50 patients in each arm and is powered (80%) to detect an improvement in LFS with a hazard ratio of 0.60 and a one-sided alpha of 0.05. Each dose schedule will be compared to placebo using a Hochberg procedure. The first patient was randomized on 12/11/2012. Clinical trial information: NCT01687387.
Understanding Atomic Interactions to Achieve Well-being
Authors: Juan M. Pascual
Journal: JAMA Neurology (2016)

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P175 Use of a Virtual Clinic to Improve the Lung Cancer Patient Journey
Authors: A Nanapragasam, N Maddock, A McIver, C Smyth, MJ Walshaw
Journal: Thorax (2015)

<h3></h3> In 2014 with our primary care colleagues we introduced a ‘Straight to CT’ system for out-patients with a radiological or clinical suspicion of lung cancer. The CT was done on behalf of primary care, and only patients who had a CT suspicious of lung cancer, were automatically taken by the lung cancer team. Such scans are reviewed by a cancer clinician, who makes a provisional next best test plan, and this empowers a telephone clerking by a highly specialised lung cancer nurse. The assessment and plan are documented, and the GP receives a same day fax. We now report our results for the calendar year. <h3>Results</h3> 293 patients with suspicious scans were contacted through our virtual clinic, and of these 241 (82%) were triaged to the most appropriate next test as day cases (69 (29%) bronchoscopy, 50 (21%) EBUS, 69 (29%) PET scan, 26 (11%) CT biopsy, 4 (1%) FNA, 17 (7%) pleural aspiration, 6 (2%) bronchoscopy and pleural aspiration). At these attendances, patients were reviewed by medical staff and the CNS who undertook the telephone assessment, and any relevant other assessments performed. Of the remainder, 38 (13%) were triaged to a clinic for assessment, 2 (6%) were admitted, and 2 (6%) referred back to their GP for best supportive care. Using this service we have been successful in targeting cancer resources onto patients subsequently diagnosed with lung cancer (79%), we have improved our mean time to diagnosis to 19 days, with a histological rate of 89%. Our 62 day breach rate is 6%. The new process also provides a 42% cost saving for primary care. <h3>Conclusions</h3> We have shown that the use of a virtual clinic can target and speed up the diagnostic pathway for patients with lung cancer. It also makes more efficient use of scarce NHS resources, by ensuring that patients only attend the hospital for necessary investigations. We recommend the use of this innovative service to other clinicians charged with managing this common and distressing disease.