tbuckley/cabot-search huggingface dataset:
THE ETIOLOGY OF DIPHTHERIA.Read in the Section of Practice of Medicine and Physiology, at the Forty-second Annual Meeting of the American Medical Association, held at Washington, D. C., May 5-8, 1891.
Authors: J. LEWIS SMITH
Journal: JAMA (1891)

No other infectious disease of childhood has been so much investigated in recent years as diphtheria. It has been the subject of full and accurate study by the most distinguished clinical instructors in both hemispheres, and numerous microscopic examinations and experiments with cultures of its specific principle have thrown light on its nature. Nevertheless, it has continued to extend and destroy its victims. It has encircled the globe, occurring with a heavy mortality in every country reached by commerce or travel. We read in medical journals of its prevalence, with the usual death rate, in Brazil, Algiers, and in distant Australia. It has occurred for ages in Eastern Asia, where it probably originated, and the complex prescriptions of the Chinese doctors, which have descended as an inheritance with little variation from their ancestors, and which are frequently employed by European residents of China, have lately been added to the literature
Does adding fibre to a low energy, high carbohydrate, low fat diet confer any benefit to the management of newly diagnosed overweight type II diabetics?
Authors: V A Beattie, C A Edwards, J P Hosker, D R Cullen, J D Ward, N W Read
Journal: BMJ (1988)

The effect of supplementing a low energy (roughly 5·0 MJ), high carbohydrate (180 g), low fat (roughly 25 g) diet with 10-15 g of either cereal fibre or guar gum was investigated in 24 newly diagnosed overweight non-insulin-dependent (type II) diabetics. The patients were divided into three treatment groups: one received a low fibre control diet throughout the study period of 20 weeks and the other received two supplements of cereal fibre and guar gum in a crossover manner. The nutrient content of the diets was kept constant throughout. Though patients taking the low fibre diet showed a smaller reduction in fasting plasma glucose concentrations over the first eight weeks than patients taking a high fibre diet, this difference was not evident at the end of 20 weeks; reductions in weight and glycated haemoglobin values were similar for each dietary regimen throughout the trial. There was little evidence that supplementing a low energy, high carbohydrate diet with fibre confers any therapeutic benefit to type II diabetics and no evidence that taking fibre as viscous polysaccharides is any more beneficial to overweight diabetics than taking a similar fibre supplement as cereal. On the contrary, guar gum caused more abdominal discomfort and flatulence than the other diets.
The use of thin layer chromatography in the separation of free porphyrins and porphyrin methyl esters
Authors: S.G SMITH
Journal: British Journal of Dermatology (1975)

Thin layer chromatographic techniques for the separation and subsequent quantification of free porphyrins, coproporphyrin isomers and the methyl esters of porphyrins are described including a 2-dimensional system. The relevant RFs for a wide range of porphyrins are given. These methods have been in use in Cardiff and Barcelona for a number of years and were used in the survey of cases described by Pinol et al. (1975) which resulted in the discovery of the new porphyria, hepato-erythrocytic porphyria.
Abstract S6-5: Primary results of BEATRICE, a randomized phase III trial evaluating adjuvant bevacizumab-containing therapy in triple-negative breast cancer
Authors: D Cameron, J Brown, R Dent, C Jackisch, J Mackey, X Pivot, G Steger, T Suter, M Toi, M Parmar, L Bubuteishvili-Pacaud, V Henschel, R Laeufle, R Bell
Journal: Cancer Research (2012)

Abstract Background: Bevacizumab (BEV), an anti-VEGF antibody, significantly enhanced progression-free survival in metastatic breast cancer (BC) (E2100, AVADO, RIBBON-1, RIBBON-2) and pathologic complete response rates in the neoadjuvant setting (GeparQuinto, NSABP B-40) when combined with chemotherapy (CT). The dependence of micro-metastases on angiogenesis [Holmgren 1995] suggests that patients might benefit from anti-angiogenic strategies applied in the adjuvant setting. The BEATRICE trial was designed to test this hypothesis in patients with triple-negative BC, who have a poor prognosis and lack targeted options for treatment. Methods: In this open-label randomized multinational phase III trial, patients with centrally confirmed triple-negative operable primary invasive BC (pT1a-pT3) were randomized 1:1 after definitive surgery to receive ≥4 cycles of either CT alone or the same CT + 1 year of BEV 5 mg/kg/wk equivalent. CT was anthracycline [anth] and/or taxane-based. Patients were stratified by nodal status (0 vs 1–3 vs ≥4 involved nodes), CT backbone (anth vs anth + taxane vs taxane), hormone receptor status (negative vs low), and surgery (breast-conserving vs mastectomy). The primary objective is to compare invasive disease-free survival (IDFS) [Hudis 2007] with adjuvant CT ± 1 year of BEV. Secondary outcome measures are overall survival (OS), breast cancer-free interval, disease-free survival (DFS), distant DFS, and safety (NCI CTCAE v3.0). The sample size was calculated to provide 80% power for a HR=0.75 at α=0.05 assuming 5-year IDFS of 72.0% with CT vs 78.2% with CT + BEV with 388 events. BEATRICE also includes evaluation of potential predictive and prognostic biomarkers. Results: Between Dec 2007 and Mar 2010, 2591 patients were randomized. At data cut-off (Feb 29, 2012), median follow-up was 32 months. The mean CT exposure was balanced between treatment arms. Median BEV duration was 11.7 months. BEV was associated with an increased incidence of grade ≥3 congestive heart failure/left ventricular dysfunction (3% vs &amp;lt;1% with CT), grade ≥3 hypertension (12% vs &amp;lt;1%), and treatment discontinuation (BEV and/or CT: 20% vs 2%) but no increase in the risk of fatal adverse events (0.3% vs 0.2%). No new safety signals were observed. Conclusion: There was no statistically significant improvement in IDFS with the addition of 1 year's BEV to adjuvant CT for triple-negative BC. Further follow-up is required to assess the impact of BEV on OS. The safety profile was consistent with previous reports in metastatic BC with a low incidence of fatal adverse events. Protocol-specified biomarker analyses are ongoing. Updated OS results are expected in 2013. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr S6-5.
Functional Hypothalamic Amenorrhea
Authors: Catherine M. Gordon
Journal: New England Journal of Medicine (2010)

A 16-year-old girl presents for evaluation of secondary amenorrhea. Her menarche was at the age of 12 years. Her last menstrual period was 6 months ago. She has lost 2.3 kg (5 lb) over the past 3 months and reports a 2-week history of unilateral foot pain. She typically runs 10 km (6 mi) per day, at least five times per week. Her body-mass index is 19. How should her case be evaluated and managed?
Doppler Ultrasound in Obstetrics
Authors: Ross E. Brown
Journal: JAMA (1971)

Since its first description in 1964, Doppler-principle ultrasound has been used for detection of fetal life, placental localization, and more recently detection of multiple pregnancies and fetal heart monitoring. Techniques and methods of interpretation as applied to 521 patients gave the following accuracy in each determined: detection of fetal life (single examination, 98.8%; double examination, 100%); placental localization for placenta praevia, 96%, and diagnosis of multiple pregnancies, 99.7%. Two limitations of these techniques are (1) the fetal heart is not heard prior to 10 to 12 weeks gestation, and (2) experience is the key factor in placental localization, and thus it must be carried out by only one or two well-trained individuals in each hospital unit. On the other hand, accuracy, safety, and simplicity of the Doppler-principle ultrasound techniques far outweigh the limitations.
Cystic Fibrosis Since 1938
Authors: Pamela B. Davis
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Cystic fibrosis (CF) was distinguished from celiac disease in 1938. Then, it was a pathologic diagnosis, life expectancy was approximately 6 months, and the autosomal recessive disease was believed to arise from abnormal mucus plugging exocrine ducts. Death often occurred from lung infection. Discovery of the sweat electrolyte defect in 1953 and standardization of the sweat test in 1959 allowed identification of milder cases, and CF was no longer considered only a disorder of mucus. In 1955, establishment of centers with programs of aggressive, comprehensive care initiated striking improvement in longevity. The pillars of care established then (attention to nutrition, airway clearance, treatment of lung infection) remain today. In 1983, chloride transport was identified as the basic physiologic CF defect, accompanied by increased sodium reabsorption. In 1980, we learned that inflammation contributes independently to lung disease and constitutes an independent therapeutic target. In 1989, the discovery of the CF gene demonstrated the basic defect to be in a cAMP-regulated chloride channel. This afforded new diagnostic tests, opportunities for research, and prospects for using the gene as therapy. Since then, substantial advances in basic and clinical research catalyzed therapeutic improvements: median survival age now exceeds 30 years. The Cystic Fibrosis Foundation center network provides not only opportunity to conduct clinical trials but also means to disseminate new therapies. In the future, treatments directed at the basic defect can be expected, with concomitant improvements in morbidity and mortality.
Proper Statistics for Clinical Studies
Authors: ROBERT S. HOLZMAN
Journal: Annals of Internal Medicine (1971)

Letters, Comments, and Corrections1 October 1971Proper Statistics for Clinical StudiesROBERT S. HOLZMAN, M.D.ROBERT S. HOLZMAN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-75-4-649_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: It has become a common practice, in the Annals and elsewhere, to describe the duration of a clinical study in patient-years (the sum of the number of years each patient was followed). Thus, if 3 patients were followed for 6 years and 12 for 1 year, we would have 30 patient-years of experience.The inflationary nature of this procedure is obvious in the example. More important, no adequate estimate of the usual duration of follow-up and its variability can be obtained from the number of patient-years. Dividing by the number of patients does give the mean duration,... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: ROBERT S. HOLZMAN, M.D.Affiliations: Infectious Disease and Immunology Division School of Medicine New York University Medical Center New York, N.Y. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 October 1971Volume 75, Issue 4Page: 649-649 ePublished: 1 December 2008 Issue Published: 1 October 1971 PDF downloadLoading ...
Committee calls for substantial investment in allergy services
Authors: Lynn Eaton
Journal: BMJ (2004)

The government needs to make a substantial investment in allergy services in the NHS in England, says the House of Commons health select committee in its latest report, which describes the current provision as “manifestly inequitable.”

“The current provision… owes nothing to the geographical spread of allergy in the population,” the report says. “Rather, it comprises those centres where specialist research in allergy has taken place, on the back of which clinical services have developed ad hoc.”

No comprehensive allergy service in England north of Manchester and west of Bournemouth currently exists, says the report. The committee calls for a minimum of one specialist allergy centre in …
A boy with a painful arm
Authors: D. A. Pettitt, P. McArthur
Journal: BMJ (2011)

A healthy 8 year old boy, with no history of surgery or medical conditions, presented to the accident and emergency department with severe pain in his right arm after falling off a four foot wall. He had a painful, tender, and swollen right elbow, which he was hesitant to move. The radial pulse was not palpable on examination. Radiography confirmed that he had a right supracondylar fracture of the humerus (Gartland type III, completely displaced). He was treated urgently by open reduction and internal fixation with K wires. After surgery, the radial pulse was still not palpable, although his fingers showed good capillary refill and pain was initially absent on extension. During the postoperative period, the arm became increasingly painful. The pain was “out of proportion” to the nature of the injury and required increasing doses of analgesia. The arm was also notably warm and swollen; palpation showed a tense forearm with extremely reduced capillary refill.



### 1 What is the most likely diagnosis?

#### Short answer

The most likely diagnosis is an acute compartment syndrome.

#### Long answer

A diagnosis of compartment syndrome is primarily based on signs of …
Langerhans cell histiocytosis in the elderly: A report of three cases
Authors: Catherine M. Stefanato, William K. Andersen, Eduardo Calonje, Frances A. Swain, Susanna Borghi, Luigi Massone, James V. Kowalski, Jag Bhawan
Journal: Journal of the American Academy of Dermatology (1998)

Langerhans cell histiocytosis is most common in children and is unusual in the elderly. We describe 3 cases of langerhans cell histiocytosis limited to the skin in elderly patients. Biopsy specimens showed a dermal infiltrate abutting the epidermis composed of atypical langerhans cells with abundant eosinophilic cytoplasm and a "kidney-shaped" nucleus. Immunoperoxidase stain CD1a was positive in all 3 cases and S-100 stain was positive in 2. Electron microscopy revealed Birbeck granules in the cytoplasm of the atypical langerhans cells in 2 cases. Langerhans cell histiocytosis with skin involvement has a chronic course with an overall good prognosis. However, cutaneous manifestations may precede systemic involvement by many years. (J Am Acad Dermatol 1998;39:375-8.)
Antitumor efficacy of cisplatin-loaded glycol chitosan nanoparticles in tumor-bearing mice
Authors: Jong-Ho Kim, Yoo-Shin Kim, Kyeongsoon Park, Seulki Lee, Hae Yun Nam, Kyung Hyun Min, Hyung Gon Jo, Jae Hyung Park, Kuiwon Choi, Seo Young Jeong, Rang-Woon Park, In-San Kim, Kwangmeyung Kim, Ick Chan Kwon
Journal: Journal of Controlled Release (2008)
Phosphorylation of cytosolic phospholipase A2 by IL-3 is associated with increased free arachidonic acid generation and leukotriene C4 release in human basophils
Authors: Katsushi Miura, Walter C. Hubbard, Donald W. MacGlashan
Journal: Journal of Allergy and Clinical Immunology (1998)

Background: Human basophils secrete leukotriene C4 (LTC4) in response to various stimuli, and a short treatment with IL-3 enhances LTC4 release, although IL-3 alone does not induce LTC4 release. However, the mechanism of this priming effect of IL-3 for LTC4 generation remains unknown in human basophils.Objective: This study was designed to explore the mechanisms by which short treatments with IL-3 enhance stimulated secretion of LTC4, with a focus on the activation of cytosolic phospholipase A2 (cPLA2).Methods: The phosphorylation state of cPLA2 in human basophils was examined by its shift in electrophoretic mobility as detected by Western blotting. Free arachidonic acid (AA) and LTC4 were measured by gas chromatography–negative ion chemical ionization mass spectrometry and LTC4-specific RIA, respectively.Result: Human basophils expressed cPLA2. IL-3, as well as the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate, caused a shift in the electrophoretic mobility of cPLA2, which indicated phosphorylation of cPLA2 and therefore its activation. Ionomycin at a concentration of 0.1 μg/mL was used to induce a modest elevation of cytosolic calcium response ([Ca2+]I), no apparent cPLA2 phosphorylation, and little free AA and LTC4 generation. Pretreatment with IL-3 (1 to 10 ng/mL) markedly enhanced ionomycin (0.1 μg/mL)-mediated AA and LTC4 generation. The concentration dependence of cPLA2 phosphorylation by IL-3 and its effects on free AA and LTC4 generation were similar. The selective PKC inhibitors, bis-indolylmaleimide II and Ro-31-8220 inhibited the phorbol 12-myristate 13-acetate–mediated cPLA2 electrophoretic mobility shift, but not the IL-3–mediated shift, suggesting that the IL-3 effect is PKC independent. Both the anaphylatoxin split product of the C component C5 (C5a) and f-Met-Leu-Phe induced PKC-independent cPLA2 phosphorylation with a similar time course most notable for the absence of observable changes in cPLA2 phosphorylation before 30 seconds. These results suggested an explanation for the absence of free AA generation by C5a. When [Ca2+]I was elevated in response to C5a, there was no phosphorylation of cPLA2, and by the time cPLA2 became phosphorylated, [Ca2+]I had returned to resting levels. Treatment with IL-3 preconditioned the cPLA2 by causing its phosphorylation so that the transient [Ca2+]I response, which followed stimulation by C5a, could induce the generation of free AA and LTC4.Conclusion: Taken together, these results suggest that the effect of IL-3 for free AA generation and LTC4 release might be due to induction of cPLA2 phosphorylation. The studies demonstrated a need for synchronous cPLA2 phosphorylation and elevations in [Ca2+]I. (J Allergy Clin Immunol 1998;102:512-20.)
Abstract 1258: Regulation of energy metabolism and protein synthesis by the Pim protein kinases
Authors: Marina Yu Zemskova, Zanna Beharry, Sandeep Mahajan, Andrew S. Kraft
Journal: Cancer Research (2011)

Abstract The serine/threonine Pim kinases are overexpressed in solid cancers and hematologic malignancies and promote cell growth and survival. Here, we find that a novel Pim kinase inhibitor, SMI-4a, or Pim-1 siRNA blocked mTORC1 activity by stimulating the phosphorylation, and thus activating the mTORC1 negative regulator AMP-dependent protein kinase (AMPK). Mouse embryonic fibroblasts (MEFs) deficient for all three Pim kinases (TKO MEFs) demonstrated activated AMPK driven by elevated ratios of AMP:ATP relative to wild type MEFs. Consistent with these findings, TKO MEFs were found to grow slowly in culture and have decreased rates of protein synthesis secondary to a diminished amount of 5′-cap dependent translation. Pim-3 expression alone in TKO MEFs was sufficient to reverse AMPK activation, increase protein synthesis, and drive MEF growth similar to wild type. Pim-3 expression was found to markedly increase the protein levels of both c-Myc and PGC-1α, enzymes capable of regulating glycolysis and mitochondrial biogenesis, which were diminished in TKO MEFs. These results demonstrate the Pim kinase -mediated control of energy metabolism through regulation of AMPK activity, and identify a new and important role for Pim-3 in modulating c-Myc and PGC-1α protein levels and cell growth. In prostate cancer cell lines we find that the Pim-3 protein kinase is elevated in those cells that are highly metastatic including PC3-LN4, ARCaPM and M12 when compared to PC-3, ARCaPE and p69 and the amount of Pim-3 correlates with c-Myc levels. Further experiments will be needed to determine whether the Pim-3 protein kinase expression regulates the metastatic potential of prostate cancer cells through control of energy metabolism and protein synthesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1258. doi:10.1158/1538-7445.AM2011-1258
Recent Advances in Clinical Neurophysiology: Functions of the Spinal Cord; Neurophysiological Investigations of Brain Diseases; EEG in Stress
Authors: R. L. Maulsby
Journal: JAMA (1968)

Atlas d'Électroencéphalographie Infantile, by Paul Laget and Roger Salbreux, 653 pp, 250 francs, $51, Paris: Masson et Cie, 1967. In spite of the clinical emphasis implied by the title (<i>Recent Advances in Clinical Neurophysiology</i>), the papers are heavily weighted towards experimental neurophysiology. The volume includes three symposia. The first reports morphological, electrophysiological, and pharmacological investigations of the spinal cord, principally in animals. The second is a somewhat heterogenous group of presentations broadly labeled, "Neurophysiological Investigations of Brain Diseases." Two minisymposia can be discerned within this chapter: dealing with EEG in relationship to cerebral blood flow and reports of microelectrode recordings in man. The third symposium, "EEG in Stress," serves to broaden one's concept of stress. The list includes such conditions and stimuli as high temperatures, low temperatures, high noise levels, sensory deprivations, copulation, hepatic coma, and others. It would be difficult to glean unifying concepts from this symposium. As isolated
In vivo hepatocyte MR imaging using lactose functionalized magnetoliposomes
Authors: Ashwini Ketkar-Atre, Tom Struys, Tom Dresselaers, Michael Hodenius, Inge Mannaerts, Yicheng Ni, Ivo Lambrichts, Leo A. Van Grunsven, Marcel De Cuyper, Uwe Himmelreich
Journal: Biomaterials (2013)
Abnormal First-Pass Flow Through the Azygos Vein From Valsalva Maneuver
Authors: LUBAN MRHAC, SAAD ZAKKO, HANAN AL SHAMSI
Journal: Clinical Nuclear Medicine (1996)

A 3-month-old boy had a dynamic renal study due to antenatally proven left hydronephrosis. After injection of Tc-99m ethylene-L—dicystein (EC) into a vein in the left foot, a double stripe of abdominal labeling appeared, indicating an abdominal venous anomaly. Two subsequent studies showed a normal inferior vena cava (IVC) and the finding is ascribed to passage of the bolus through the azygos and hemiazygos veins because of a Valsalva maneuver in a restless child. The exact route to the right atrium was not distinguishable in any picture. The"duplication" appeared again in a fourth study 13 months later. The same phenomenon has been observed in another patient since.
Sublingual immunotherapy in the treatment of adult allergic rhinitis patients
Authors: G. W. Canonica, G. Passalacqua
Journal: Allergy (2006)

Sublingual immunotherapy (SLIT) was accepted for clinical use by the medical community only 15 years after the first controlled trial published. The acceptance of SLIT has been driven by the evidence base of a large number of clinical trials confirming the efficacy and a recent meta-analysis study. Although SLIT is self-managed by the patient, this does not generate problems with compliance. The safety profile, assessed in clinical trials and postmarketing surveillance studies, is satisfactory with no reports of systemic adverse reactions. New data are available on the persisting, long-lasting effect of SLIT and on the association with the prevention of asthma in paediatric patients. However, there is only indirect evidence for such persistence and duration of effect in adult patients. Key priorities for further investigation are the mechanisms of action, the efficacy in asthma, the cost/effectiveness and the identification of those patients who will achieve the maximum benefit with SLIT.