tbuckley/cabot-search huggingface dataset:
Oral Administration of Penicillin
Authors: Sidney Ross, Frederic G. Burke, Sidney Olansky
Journal: New England Journal of Medicine (1947)

THE role of penicillin administered by mouth has been reported on by several investigators,1 2 3 4 5 6 and the conclusion seems warranted that if the drug is given in sufficiently large doses, cures may be expected in susceptible infections. The optimal dose, as well as the necessity of preliminary or concurrent neutralization of the gastric acidity to avoid the inactivating influence of hydrochloric acid in the stomach when penicillin is administered orally, has been the subject of some controversy in the recent literature.2 3 4 , 7 To evaluate the latter point, penicillin blood levels were determined in a control group of over 600 subjects, plain calcium . . .
Pharyngeal collapsibility during sleep is elevated in insulin-resistant females with morbid obesity
Authors: Oscar L. Llanos, Panagis Galiatsatos, Edmarie Guzmán-Vélez, Susheel P. Patil, Philip L. Smith, Thomas Magnuson, Michael Schweitzer, Kimberley Steele, Vsevolod Y. Polotsky, Alan R. Schwartz
Journal: European Respiratory Journal (2016)

Insulin resistance is associated with sleep apnoea, leading us to hypothesise that it is also associated with elevations in pharyngeal collapsibility, even in the absence of sleep apnoea. 90 bariatric patients were characterised for sleep apnoea, pharyngeal collapsibility and insulin resistance. Patients with a respiratory disturbance index (RDI) &gt;10 events·h −1 , diabetes mellitus, tonsillar hypertrophy and pulmonary disease were excluded. The remaining 14 females underwent collapsibility measurements (passive critical pressure, P crit p ) during non-rapid eye movement sleep. The homeostasis model assessment (HOMA) index, a measure of insulin resistance, was derived from measurements of fasting glucose and insulin levels, and compared to P crit p . Groups with high P crit p compared to low P crit p did not differ in age, body mass index or RDI. HOMA and insulin were elevated in the high P crit p group compared to the low P crit p group (p&lt;0.02). P crit p correlated with HOMA (Spearman's ρ=0.565, 95% CI 0.104–0.862; p=0.035) and insulin (Spearman's ρ=0.609 95% CI 0.196–0.835; p=0.021). Obese insulin-resistant subjects without frank diabetes or sleep apnoea demonstrate preclinical elevations in pharyngeal collapsibility, which may increase their susceptibility to sleep apnoea. Our findings suggest that insulin resistance could play a significant role in sleep apnoea pathogenesis by generating requisite elevations in pharyngeal collapsibility.
Phase I study of ABT-414 mono- or combination therapy with temozolomide (TMZ) in recurrent glioblastoma (GBM).
Authors: Hui K. Gan, Kyriakos P. Papadopoulos, Lisa Fichtel, Andrew B. Lassman, Ryan Merrell, Martin J. Van Den Bent, Priya Kumthekar, Andrew M. Scott, Michelle Pedersen, Erica J. Gomez, Judee S. Fischer, William Ames, Hao Xiong, Ho-Jin Lee, Wijith Munasinghe, Lisa Roberts-Rapp, Peter Ansell, Kyle D. Holen, Rose Lai, David A. Reardon
Journal: Journal of Clinical Oncology (2015)

2016 Background: GBM remains almost universally fatal and new therapies are needed. The epidermal growth factor receptor (EGFR) is a key oncogenic target. ABT-414, an antibody-drug conjugate with a toxic payload (monomethylauristatin F) targeted to activated EGFR, showed efficacy in preclinical models. We report the data of patients (pts) with recurrent GBM (Arms B + C) from an ongoing phase 1, open-label, 3-arm study (NCT01800695). Methods: Eligible pts ( ≥ 18 years) had recurrent supratentorial GBM and KPS ≥ 70. ABT-414 was given i.v. every 2 weeks combined with TMZ re-challenge (150–200 mg/m2 days 1–5 q28; Arm B) or as monotherapy (Arm C). ABT-414 doses were escalated using a modified continual reassessment method. Primary objectives were safety, maximum tolerated dose (MTD), and recommended phase 2 dose (RP2D) of ABT-414; secondary objectives included antitumor activity. Results: As of Jan 2015, accrual included 18 pts in Arm B treated in 4 dose groups (0.5, 1.0, 1.25, 1.5 mg/kg) and 28 pts in Arm C treated at 1.25 mg/kg. Median age was 51/57 years (Arms B/C), 50%/50% were male, 56%/75% had KPS ≥ 80, and 11/7 pts had amplified EGFR. Treatment-emergent adverse events (AEs) occurring in ≥ 25% of pts either in Arm B or C were blurred vision (n = 11/15), fatigue (n = 6/10), foreign body sensation in the eyes (n = 8/5), photophobia (n = 5/7), nausea (n = 9/2), constipation (n = 5/1), and GGT increase (n = 5/1). Grade 3/4 AEs in ≥ 10% of Arm B or C pts were keratitis (n = 1/3), GGT increase (n = 3/0), fatigue (n = 2/0), and thrombocytopenia (n = 2/0). Dose-limiting toxicities in Arm B were corneal deposits and GGT increase (n = 1 each); none occurred in Arm C during dose escalation. ABT-414 MTD was 1.5 mg/kg in Arm B and 1.25 mg/kg in Arm C; RP2D is 1.25 mg/kg for both arms. Best objective responses were complete response (CR) in 1 pt and partial responses (PR) in 4 pts in Arm B, and 1 CR and 1 PR in Arm C. EGFR amplification was found in all pts with confirmed responses. Confirmed responses were durable, ranging from 5–16 months. Conclusions: The ABT-414 RP2D is 1.25 mg/kg for monotherapy or combined with TMZ. The unique ABT-414 safety profile included ocular AEs. ABT-414 appears to have antitumor activity in recurrent GBM pts, particularly those with amplified EGFR. Clinical trial information: NCT01800695.
Reduced Allergen-Induced Nasal Congestion and Leukotriene Synthesis with an Orally Active 5-Lipoxygenase Inhibitor
Authors: Howard R. Knapp
Journal: New England Journal of Medicine (1990)

The clinical importance of leukotrienes in human allergy has not been defined, in part because there have been no selective 5-lipoxygenase inhibitors that have been effective and safe for use in humans. To address the hypothesis that stimulated leukotriene synthesis causes symptoms of immediate-hypersensitivity reactions in vivo, I investigated the effects of a new 5-lipoxygenase inhibitor, A-64077, on provoked allergic nasal symptoms and mediator release in a double-blind, randomized, placebo-controlled study. Eight subjects with allergic rhinitis underwent nasal challenge on two occasions after an oral dose of 800 mg of A-64077 or an identical-appearing placebo.
Case 27-1993
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Jorge F. Tapia, James M. Schumacher
Journal: New England Journal of Medicine (1993)

Case Records of the Massachusetts General Hospital from The New England Journal of Medicine — Case 27-1993 — A 32-Year-Old Man with the Sudden Onset of a Right-Sided Headache and Left Hemiplagia and Hemianesthesia
ACTH and Cortisone in the Treatment of Keloids
Authors: Francesco Ronchese, Arthur B. Kern
Journal: New England Journal of Medicine (1954)

THE treatment of keloids, particularly old and large ones, has often been unsatisfactory. With the demonstration in recent years of the connective-tissue-inhibiting effect of ACTH and cortisone in laboratory animals and in human beings a trial in the management of keloids appeared justified.We began their use in the first case of our series in December, 1951. A review of the literature shortly thereafter revealed two reports, both published in November, 1951, concerning the use of these steroid hormones in the treatment of keloids. The patient of Poison, Pattee and Woolhouse1 was given cortisone intramuscularly in a dosage of 200 . . .
Quality of breast cancer care in NCCN centers as assessed by the ASCO/NCCN quality measures: Overall performance and reasons for nonconcordance
Authors: M. E. Hughes, R. Ottesen, J. C. Niland, S. B. Edge, R. L. Theriault, J. Wilson, D. W. Blayney, Y. Wong, J. C. Weeks
Journal: Journal of Clinical Oncology (2009)

6506 Background: To assess the quality of breast cancer care in the National Comprehensive Cancer Network (NCCN), we compared practice against the ASCO/NCCN quality measures (QM). Methods: Using the NCCN Outcomes Database, we studied the care of women with newly diagnosed stage I-III breast cancer treated at 8 NCCN centers in 2003–6 to determine the proportion whose care was consistent with the 3 QMs (tamoxifen or anastrozole within 1 year of diagnosis for HR+ &gt;1 cm tumors [HT]; post- lumpectomy radiation within 1 year of diagnosis for women &lt;70 yo [RT]; and chemotherapy within 120 days of diagnosis of HR- &gt;1 cm tumors for women &lt;70 yo). Based on chart review, reasons for non-concordant care were classified as: 1) treatment recommended, but declined; 2) MD recommended against treatment; 3) non-recommended treatment administered; or 4) system problem (referral to the relevant specialist not documented or specialist not seen, delayed treatment initiation, or no relevant documentation in the chart). Results: 5,175 women were analyzable on at least one QM. Overall, treatment was consistent with the QM for 6,628/7,265 (91%) of the unique patient-recommendation pairs. Non-concordant care was received by 11% of patients eligible for the HT QM, 5% for the RT QM, and 13% for the chemotherapy QM. The reasons for non-concordance are shown in the table. Conclusions: Overall, breast cancer care in the NCCN is highly concordant with the ASCO/NCCN quality measures. System problems rather than patient refusal or physician recommendations account for the majority of care that deviates from the QM recommendations. This suggests that quality improvement targeting systems rather than physicians would be especially efficient and effective. [Table: see text] No significant financial relationships to disclose.
Overdose of Metoprolol Treated with Enoximone
Authors: Marius M. Hoeper, Klaus H.W. Boeker
Journal: New England Journal of Medicine (1996)

The image submitted by Gregory and Davis is a computed tomographic (CT) scan showing angioedema of the small intestine due to lisinopril.It would have been interesting, as well as clinically relevant, if the authors had included amylase or lipase values as well as an image of the pancreas, since lisinopril has been associated with acute pancreatitis. [1]2][3] The authors note that the patient presented with abdominal pain, nausea, vomiting, and distention, which are consistent with the presence of acute pancreatitis.ACE inhibitors have recently been implicated as a potential cause of acute pancreatitis, with reports of cases associated with lisinopril, captopril, and enalapril. 1, 2Cases of lisinopril-associated pancreatitis have been reported to occur from two weeks to two years after therapy is begun. 1 A fatal case of acute pancreatitis associated with lisinopril was recently reported. 2 Angioedema of the upper aerodigestive tract is a wellknown adverse effect of ACE inhibitors and may be due to altered bradykinin metabolism. 1,4 Angioedema of pancreatic tissue may result in obstruction of the ductal system and lead to pancreatitis. 3,4 Clinicians should consider acute pancreatitis in any patient in whom abdominal pain develops who is taking lisinopril or another ACE inhibitor.
Increased Risk of Cancer in the Peutz–Jeghers Syndrome
Authors: Francis M. Giardiello, Stephen B. Welsh, Stanley R. Hamilton, G. Johan A. Offerhaus, Alan M. Gittelsohn, Susan V. Booker, Anne J. Krush, John H. Yardley, Gordon D. Luk
Journal: New England Journal of Medicine (1987)

The Peutz–Jeghers syndrome is an autosomal dominant hereditary disease characterized by hamartomatous polyps of the gastrointestinal tract and by mucocutaneous melanin deposits. The frequency of cancer in this syndrome has not been studied extensively. Therefore, we investigated 31 patients with the Peutz–Jeghers syndrome who were followed from 1973 to 1985. All cases of cancer were verified by histopathological review. Cancer developed in 15 of the 31 patients (48 percent) — gastrointestinal carcinomas in 4, nongastrointestinal carcinomas in 10, and multiple myeloma In 1. In addition, adenomatous polyps of the stomach and colon occurred in three other patients. The cancers were diagnosed when the patients were relatively young, but after the Peutz–Jeghers syndrome had been diagnosed (interval between diagnoses, 25±20 years; range, 1 to 64). According to relative-risk analysis, the observed development of cancer in the patients with the syndrome was 18 times greater than expected in the general population (P<0.0001). Our results suggest that patients with the Peutz–Jeghers syndrome have an increased risk for the development of cancer at gastrointestinal and nongastrointestinal sites. (N Engl J Med 1987; 316:1511–4.)
Long-Term Course of Neonatal Diabetes
Authors: Karl Ernst von Mühlendah, Heiner Herkenhoff
Journal: New England Journal of Medicine (1995)

Neonatal diabetes mellitus — defined here as hyperglycemia occurring within the first month of life that lasts for at least two weeks and requires insulin therapy — is a very rare form of the disease. Little is known about it, particularly with respect to its long-term course.
PTU-161 An opportunity missed in diagnosing coeliac disease: Abstract PTU-161 Table 1
Authors: S Subramaniam, A Joshi, K Besherdas
Journal: Gut (2015)

<h3>Introduction</h3> The prevalence of coeliac disease (CD) is around 1% in the UK. The ‘gold standard’ diagnosis of CD requires a distal duodenal (D2) biopsy when the patient is on a gluten containing diet and in most cases positive serology (eg tissue transglutaminase antibodies, tTG ab). CD is confirmed when histological criteria as set out in the Marsh classification [increased intraepithelial lymphocytosis, crypt hyperplasia, villous atrophy (VA)] are met. The diagnosis of CD may be delayed as it can present with a wide range of signs and symptoms including iron deficiency anaemia, weight loss, osteoporosis, neuropathy and vague abdominal symptoms. Many patients with vague abdominal symptoms undergo upper GI endoscopy (OGD), however, in the majority D2 biopsies to look for CD are not obtained. Endoscopic examination may reveal classical features of VA such as ‘scalloping’ of the duodenal mucosa but may also be normal. The aim of the study was to evaluate the range of duodenal endoscopic findings in patients with proven CD and VA on D2 biopsy. <h3>Method</h3> A single centre, retrospective analysis of patients with histologically proven CD (Marsh 3 classification) on D2 biopsies in a London district general hospital was performed. Data was obtained from the hospital’s histology database, endoscopy reporting software and electronic patient record system. Information on the patients’ demographics, symptoms, index endoscopy findings, histology and coeliac serology prior to a gluten free diet was scrutinised. <h3>Results</h3> 65 patients had a confirmed diagnosis of CD with VA. 6 patients were excluded from our analysis as endoscopy reports were unavailable. Of the remaining 59, there were 36 females and 29 males. Indications for endoscopy based on patients presenting symptoms were as follows: 18/59 for iron deficiency anaemia, 12/59 (abdominal pain/bloating), 11/59 (diarrhoea), 10/59 (asymptomatic but positive tTG ab), 6/59 (weight loss) and 2/59 for fatigue. tTG ab was positive in 50/59 patients, negative in 7 and not tested in 2. The Table 1below shows the endoscopy findings in these 59 patients with CD. <h3>Conclusion</h3> Over half of our CD patient cohort had normal endoscopic findings on diagnosis despite confirmed VA on D2 biopsies. 17% of patients were asymptomatic at diagnosis and 12% of patients were tTG ab negative. Given the wide ranging clinical presentation of CD and its overall prevalence, D2 biopsies should not be limited to patients presenting with classical symptoms as we may be missing the opportunity to diagnose this easily treatable condition. We recommend that all patients presenting to OGD for vague abdominal symptoms have duodenal biopsies to exclude CD. <h3>Disclosure of interest</h3> None Declared.
Inheritance of Immunogenicity and Metastatic Potential in Murine Cell Hybrids from the T-Lymphoma ESb08 and Normal Spleen Lymphocytes&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: L. Larizza, V. Schirrmacher
 5, M. Stöhr, E. Pflüger, R. Dzarlieva
Journal: JNCI Journal of the National Cancer Institute (1984)

T-lymphoma cells were fused with normal lymphoid cells to examine the segregation of tumorigenicity and metastatic capacity in the hybrids. In independent fusions the immunogenic ESb08 T-lymphoma line fused successfully with normal syngeneic spleen cells (from DBA/2 and CD1 mice) enriched either with T-cells or B-cells. Ten times fewer hybrids were obtained with B-cells compared to the number obtained with T-cells, and marker assays showed that both types of fusions preferentially generated T-T hybridomas. Some of the hybrids resembled their tumor parent in their ability to form primary and secondary tumors only in irradiated DBA/2 mice, whereas other hybrids lost the high ESb08 immunogenicity, were equally tumorigenic, and in some cases metastatic, in nonirradiated mice. DNA distributions of the original hybrid lines ranged from a hexaploid DNA content (expected for complete hybrids derived from a tetraploid line and normal diploid cells) to a tetraploid DNA content, confirming the reported chromosome instability of T-T hybrids. No correlation was noted between the initial DNA content and tumorigenicity, but in the case of complete hybrids, reduction in the ploidy levels always was observed in the cells of primary and metastatic lesions. One chromosomally stable and highly malignant hybrid (C2), which was analyzed for segregation of chromosomes and for drug-resistance markers, showed preferential loss of chromosomes from the normal T-cell fusion partner. The decreased immunogenicity of this hybrid could not be related to any detectable loss of chromosomes from the ESb08 tumor parent.
A Critique of the Methodology of Studies of Benign Breast Disease and Breast Cancer Risk
Authors: W Webber, N Boyd
Journal: JNCI Journal of the National Cancer Institute (1986)

After almost a century of research the relationship of benign breast disease to breast cancer risk is still controversial. The present investigation assessed this controversy by examining all published cohort studies that examined the risk of breast cancer in subjects with benign breast disease for their compliance with widely accepted standards for the conduct of etiologic research. Most of these studies describe the breast cancer incidence in women who have had breast biopsies. The 16 standards included a description of the population studied, a definition of benign breast disease, an account of follow-up, and a description of the analysis of risk. Of the 36 studies examined, 22 reported finding an increase in breast cancer risk in women with benign breast disease and all met more methodologic standards than the 11 studies reporting no increase in risk (3 studies reported no conclusions). In particular, none of the 11 "negative" studies calculated the number of cancers expected in the population studied, whereas all 22 "positive" studies did so. There is thus considerable statistical support from well-conducted studies for the view that benign breast disease is associated with an increase in breast cancer risk. By contrast, there is no credible support for the contrary view, which is often based on small studies in which no cancers were observed or on studies whose conclusions are not supported by an appropriate analysis of the data they contain.
Antibody Production to Aggregated Human γg-Globulin in Acquired Hypogammaglobulinemia
Authors: Christopher S. Henney, Elliot F. Ellis
Journal: New England Journal of Medicine (1968)

A patient with acquired hypogammaglobulinemia, who suffered "anaphylactic shock" after intramuscular administration of commercially prepared human γG-globulin (HGG), was found on gel diffusion analysis to have precipitating antibody specific for the aggregated form of HGG. The antibody was principally of the γG-globulin type, and could be differentiated from classic rheumatoid factor by a number of hemagglutination technics. Unlike rheumatoid factor, the antibody failed to agglutinate sheep red cells sensitized with rabbit γG-globulin antibody, nor would it agglutinate latex particles coated with native HGG. The antibody readily agglutinated human A cells coated with homologous human γG-globulin antibody, however, and also agglutinated latex particles coated with aggregated HGG. Because of the specificity of this antibody, its coincident appearance and its increase after a period of considerable γ-globulin "immunization," it is postulated that its occurrence resulted from the administration of γG-globulin aggregates present in the preparations used for therapy.
Familial Isolated Thyrotropin Deficiency with Cretinism
Authors: Kiyoshi Miyai, Mizuo Azukizawa, Yuichi Kumahara
Journal: New England Journal of Medicine (1971)

Abstract Two sisters with nongoitrous cretinism, offspring of a consanguineous marriage, were found to have isolated thyrotropin (TSH) deficiency. Growth hormone, ACTH and gonadotropin secretion we...
Steroid Therapy of Hypercalcemia and Renal Insufficiency in Sarcoidosis
Authors: R. W. Phillips, D. P. Fitzpatrick
Journal: New England Journal of Medicine (1956)

THE damaging effect on the kidney of uncontrolled hypercalcemia leading to nephrocalcinosis and renal insufficiency seems well established.1 2 3 One of the diseases with which hypercalcemia is at times associated is Boeck's sarcoid. Several articles in the past two years indicate that steroid therapy can correct this disturbance of mineral metabolism when it occurs in sarcoidosis.4 5 6 7 We wish to describe our experiences in the successful treatment of hypercalcemia in 2 patients with sarcoidosis and to point out subsequent improvement in renal function. The apparent uniform success of steroid therapy for hypercalcemia of this type deserves emphasis since its continuation unrecognized or . . .
Intracellular Released Payload Influences Potency and Bystander-Killing Effects of Antibody-Drug Conjugates in Preclinical Models
Authors: Fu Li, Kim K. Emmerton, Mechthild Jonas, Xinqun Zhang, Jamie B. Miyamoto, Jocelyn R. Setter, Nicole D. Nicholas, Nicole M. Okeley, Robert P. Lyon, Dennis R. Benjamin, Che-Leung Law
Journal: Cancer Research (2016)

Antibody-drug conjugates (ADC) comprise targeting antibodies armed with potent small-molecule payloads. ADCs demonstrate specific cell killing in clinic, but the basis of their antitumor activity is not fully understood. In this study, we investigated the degree to which payload release predicts ADC activity in vitro and in vivo ADCs were generated to target different receptors on the anaplastic large cell lymphoma line L-82, but delivered the same cytotoxic payload (monomethyl auristatin E, MMAE), and we found that the intracellular concentration of released MMAE correlated with in vitro ADC-mediated cytotoxicity independent of target expression or drug:antibody ratios. Intratumoral MMAE concentrations consistently correlated with the extent of tumor growth inhibition in tumor xenograft models. In addition, we developed a robust admixed tumor model consisting of CD30(+) and CD30(-) cancer cells to study how heterogeneity of target antigen expression, a phenomenon often observed in cancer specimens, affects the treatment response. CD30-targeting ADC delivering membrane permeable MMAE or pyrrolobenzodiazepine dimers demonstrated potent bystander killing of neighboring CD30(-) cells. In contrast, a less membrane permeable payload, MMAF, failed to mediate bystander killing in vivo, suggesting local diffusion and distribution of released payloads represents a potential mechanism of ADC-mediated bystander killing. Collectively, our findings establish that the biophysical properties and amount of released payloads are chief factors determining the overall ADC potency and bystander killing. Cancer Res; 76(9); 2710-9. ©2016 AACR.