tbuckley/cabot-search huggingface dataset:
Risks and Benefits of Insulin-like Growth Factor
Authors: Saul Malozowski
Journal: Annals of Internal Medicine (1994)

Letters1 October 1994Risks and Benefits of Insulin-like Growth FactorSaul Malozowski, MD, PhD and Bruce Stadel, MD, MPHSaul Malozowski, MD, PhDSearch for more papers by this author and Bruce Stadel, MD, MPHSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-121-7-199410010-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Bondy and colleagues [1] provided an excellent review of available knowledge regarding insulin-like growth factor (IGF). I report additional information concerning IGF-I adverse drug experience reports received by the Food and Drug Administration (FDA) in the last 5 years.Syncopal reactions in the absence of hypoglycemia were reported in 11 patients. Nine received IGF-I intravenously at doses of 100 µg/kg of body weight as a bolus or by infusions that exceeded 24 µg/kg per hour, whereas another patient received 18 µg/kg per hour. One patient received IGF-I subcutaneously. Two patients had concomitant seizure-like activity with tonic muscle ...References1. Bondy CA, Underwood LE, Clemmons DR, Guler HP, Bach MA, Skarulis M. Clinical uses of insulin-like growth factor I. Ann Intern Med. 1994; 120:593-601. Google Scholar2. Usala AL, Madigan T, Burguera B, Sinha MK, Caro JF, Cunningham P, et al. Brief report: Treatment of insulin-resistant ketoacidosis with insulin-like growth factor I in an adolescent with insulin diabetes. N Engl J Med. 1992; 327:853-7. Google Scholar3. Malozowski S, Tanner LA, Wysowski D, Fleming GA. Growth hormone, insulin-like growth factor I, and benign intracranial hypertension (Letter). N Engl J Med. 1993; 329:665-6. Google Scholar4. Malozowski S. Gynecomastia (Letter). N Engl J Med. 1993; 329:209. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByMecasermin rinfabate: rhIGF-I/rhIGFBP-3 complex: iPLEX ™Musculoskeletal Effects of the Recombinant Human IGF-I/IGF Binding Protein-3 Complex in Osteoporotic Patients with Proximal Femoral Fracture: A Double-Blind, Placebo-Controlled Pilot StudyInsulin-Like Growth Factors 1 October 1994Volume 121, Issue 7Page: 549-550KeywordsFood and Drug AdministrationGrowth hormoneHypoglycemiaInsulin-like growth factorsNecrosisParalysisPeptide hormonesPhosphatesProteinsSyncope Issue Published: 1 October 1994 CopyrightCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Somatostatin analogue scintigraphy in Merkel cell tumours
Authors: B.K. Durani, A. Klein, M. Henze, U. Haberkorn, W. Hartschuh
Journal: British Journal of Dermatology (2003)

Merkel cell tumours are rare neoplasms of the skin with frequent regional and distant metastases. Scintigraphy with the radiolabelled somatostatin analogue octreotide is a possible method for in vivo localization of the primary tumour and its metastases.To estimate the diagnostic value of indium (111) -octreotide scintigraphy (Octreoscan in detecting metastases.Scans of 11 patients with Merkel cell carcinoma were evaluated, in whom scintigraphy was performed in addition to the conventional investigations, chest X-ray, ultrasonography and computed tomography (CT).In four cases metastases were found both by scintigraphy and by conventional methods; two investigations showed a suspicious accumulation of radioactivity on scintigraphy that could not be confirmed by CT and clinical progression. In three cases CT-verified metastases were not found by scintigraphy. Two patients were found to be tumour free, i.e. free of metastases by scintigraphy and conventional methods, indicating true-negative results.These data confirm that scintigraphy with the radiolabelled somatostatin analogue octreotide is not clinically helpful in detecting metastases from Merkel cell carcinoma. In this relatively small sample the method generated false-positive or false-negative results in five of 11 cases.
Lung Deposition and Clearance of Inhaled <sup>99m</sup>Tc-Heparin in Healthy Volunteers
Authors: KAREN E. BENDSTRUP, CAROLE B. CHAMBERS, JENS I. JENSEN, MICHAEL T. NEWHOUSE
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The purpose of this study was to quantify the lower respiratory tract (LRT) dose delivered by a single nebulization of 99mtechnetium-labeled sodium heparin as well as its airway distribution, and kinetics of aerosol clearance, since inhaled heparin may be useful in the treatment of asthma. Fifteen healthy subjects (5 male, 10 female) inhaled heparin from a jet nebulizer loaded with 90,000 IU of 99mTc-heparin, driving flow rate 10 L/min. Lung scintigrams and blood samples were taken immediately and at several time points up to 24 h after inhalation. 15 ± 3% (mean ± SD) (mean 13,300 IU) of the heparin nebulizer charge reached the mouth, and 8 ± 2% (mean 7,000 IU) was found in the LRT. Jet nebulizer residual was 48 ± 6% (mean 43,000 IU), 32 ± 4% (mean 29,000) was found on exhalation filters, and 5 ± 2% in the tubing. 99mTc-heparin was distributed uniformly in the lungs, and clearance was biphasic. 39 ± 8% of the LRT dose of 99mTc-heparin remained in the lungs 24 h after inhalation. 10.00 ± 3.40% (687 ± 310 IU) of the LRT dose or 0.76 ± 0.35% of the nebulizer charge was found in the blood. Peak concentration in the blood was found 61 ± 25 min after conclusion of inhalation, which took 15 min. We conclude that a small but significant fraction of nebulized heparin reaches the LRT. The inhaled heparin distributes uniformly in the lungs from which it clears slowly, making it suitable for local administration without induction of measurable changes in coagulation assays. Administration of the present single dose of heparin thus appears to be safe. Bendstrup KE, Chambers CB, Jensen JI, Newhouse MT. Lung deposition and clearance of inhaled 99mTc-heparin in healthy volunteers.
REEDUCATION IN APHASIA
Authors: CHARLES G. STIVERS
Journal: JAMA (1923)

Aphasia is defined as a loss of or modification of the ability to change concepts into words in spite of the integrity of the speech machinery. It is also a loss of the ability to understand the audible word in spite of the fact that hearing ability may be present. There is often inability to speak spontaneously or to use words. Reading, writing and writing from dictation are involved. Copying may be impossible. Motor aphasia is the failure to express ideas. Sensory aphasia is the failure to receive impressions and transmute them first into ideas and then express them. <h3>REPORT OF CASE</h3><h3>History.</h3> —C. J. K., a man, aged 36, a plumber, married, with one son, was struck on the left side of the head by the propeller of an aeroplane wind machine that he was starting, Nov. 5. 1919. A concave area extending from the middle line of the
Evidence that vitamin D3 promotes mast cell–dependent reduction of chronic UVB-induced skin pathology in mice
Authors: Lisa Biggs, Chunping Yu, Boris Fedoric, Angel F. Lopez, Stephen J. Galli, Michele A. Grimbaldeston
Journal: The Journal of Experimental Medicine (2010)

Mast cell production of interleukin-10 (IL-10) can limit the skin pathology induced by chronic low-dose ultraviolet (UV)-B irradiation. Although the mechanism that promotes mast cell IL-10 production in this setting is unknown, exposure of the skin to UVB irradiation induces increased production of the immune modifying agent 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3). We now show that 1α,25(OH)2D3 can up-regulate IL-10 mRNA expression and induce IL-10 secretion in mouse mast cells in vitro. To investigate the roles of 1α,25(OH)2D3 and mast cell vitamin D receptor (VDR) expression in chronically UVB-irradiated skin in vivo, we engrafted the skin of genetically mast cell–deficient WBB6F1-KitW/W-v mice with bone marrow–derived cultured mast cells derived from C57BL/6 wild-type or VDR−/− mice. Optimal mast cell–dependent suppression of the inflammation, local production of proinflammatory cytokines, epidermal hyperplasia, and epidermal ulceration associated with chronic UVB irradiation of the skin in KitW/W-v mice required expression of VDR by the adoptively transferred mast cells. Our findings suggest that 1α,25(OH)2D3/VDR-dependent induction of IL-10 production by cutaneous mast cells can contribute to the mast cell’s ability to suppress inflammation and skin pathology at sites of chronic UVB irradiation.
Immunochemical analysis of the released Leu-2 (T8) molecule.
Authors: J Fujimoto, S J Stewart, R Levy
Journal: The Journal of Experimental Medicine (1984)

We recently have found that the human T cell antigen Leu-2 was specifically released from Leu-2-bearing cells. The preliminary study showed that the released Leu-2 (RLeu-2) from HPB-ALL cells was composed of a single polypeptide chain of 27,000 molecular weight (mol wt), which was smaller than the subunit of the homodimeric molecule found on the cell surface. In the present study, RLeu-2 was further characterized and compared with cellular Leu-2 (CLeu-2). Metabolically radiolabeled Leu-2 was released from HPB-ALL cells and this released Leu-2 molecule had a mol wt of 27,000. Cell surface radioiodinated HPB-ALL cells were found to release radioactive Leu-2 molecules and this antigen also had the same mol wt of 27,000. In both experiments, the CLeu-2 was reconfirmed to be composed of a 33,000-mol wt subunit under reducing conditions. These experiments establish that the 27,000-mol wt single polypeptide chain of Leu-2 released from the cell is derived directly from the homodimeric Leu-2 molecule on the cell surface, presumably by a specific proteolytic cleavage. Two-dimensional gel analysis showed that CLeu-2 exhibited extensive charge heterogeneity with predominantly basic isoelectric points, whereas RLeu-2 was a group of more acidic proteins with less charge heterogeneity. Although CLeu-2 and RLeu-2 showed several different immunochemical characteristics, the homology between these two antigens was confirmed by the following results: CLeu-2 and RLeu-2 were found to share at least three different antigenic determinants, Leu-2a and Leu-2b, and those which were detected by a polyvalent rabbit antiserum. Significant similarities between CLeu-2 and RLeu-2 were demonstrated by peptide mapping analysis of these antigens. Therefore, RLeu-2 appears to be the specific, physiological product of the CLeu-2 protein.
Meta-Analyses of Randomized Controlled Trials
Authors: Henry S. Sacks, Jayne Berrier, Dinah Reitman, V.A. Ancona-Berk, Thomas C. Chalmers
Journal: New England Journal of Medicine (1987)

Abstract A new type of research, termed meta-analysis, attempts to analyze and combine the results of previous reports. We found 86 meta-analyses of reports of randomized controlled trials in the English-language literature. We evaluated the quality of these meta-analyses, using a scoring method that considered 23 items in six major areas — study design, combinability, control of bias, statistical analysis, sensitivity analysis, and application of results. Only 24 meta-analyses (28 percent) addressed all six areas, 31 (36 percent) addressed five, 25 (29 percent) addressed four, 5 (6 percent) addressed three, and 1 (1 percent) addressed two. Of the 23 individual items, between 1 and 14 were addressed satisfactorily (mean ±SD, 7.7±2.7). We conclude that an urgent need exists for improved methods in literature searching, quality evaluation of trials, and synthesizing of the results. (N Engl J Med 1987; 316:450–5.)
Neurological deficits, back pain tied to endometriosis
Authors: Catherine Macek
Journal: JAMA (1983)

Endometriosis usually is suspected early in the differential diagnosis of moderate to severe pelvic area pain in premenopausal women. But it also should be considered as a possible cause of low-back and lower-extremity pain as well as of certain neurological deficits, according to physicians at the University of California, Davis, Medical Center.  Few physicians are aware of this association, and prolonged delays in diagnosis and treatment are common in these patients, says James S. Lieberman, MD, professor of neurology and chair of the Department of Physical Medicine and Rehabilitation at Davis. Lieberman presented findings in three such cases at the American Academy of Physical Medicine and Rehabilitation meeting in Houston.  Right foot drop developed in a 28-year-old patient prior to menses each month and remitted 48 hours afterward. At the same time, the patient had decreased sensation to pinprick in the area of the sciatic nerve. At midcycle, however, she
Lectures ON THE SYMPATHETIC INNERVATION OF STRIATED MUSCLE: LECTURE II.--Part II. THE FUNCTIONS OF THE TWO GROUPS OF MUSCLE FIBRES: EXPERIMENTAL EVIDENCE
Authors: J. I. Hunter
Journal: BMJ (1925)

BRITISNI lhave triedl to shlowhlow far the coli)licatioiis due to mialpresentations anid misfits, to ante-pa rtuim lhalieorrliage and convulsions, witlh consequent interference ini Iaboiur, may be greatly lessenied.
Diagnosis and Treatment of Heart Failure Due to Left Ventricular Dysfunction
Authors: Ila V. Mehra
Journal: JAMA (1994)

<h3>To the Editor.</h3> —We would like to commend Dr Gaasch<sup>1</sup>for his excellent review on heart failure due to systolic and diastolic dysfunction. However, he recommends that symptomatic diastolic dysfunction be treated with β-adrenergic blockers or calcium channel blockers (CCBs). While we generally agree with this recommendation, we believe that further clarification is warranted. In the article, the statement was made that "negative chronotropic agents that slow the heart rate are the preferred therapeutic agents" and we fully support this recommendation. However, in Table 2 and in the explanation of the table, the blanket statement is made that β-blockers or CCBs should be used to treat symptomatic left ventricular dysfunction with normal ejection fraction (diastolic dysfunction).<sup>1</sup> In diastolic dysfunction, there is impaired filling and reduced diastolic relaxation of the left ventricle due to increased stiffness.<sup>2</sup>Tachycardia can cause increased diastolic wall tension and may worsen diastolic heart
Diagnosis and immunotherapy of mould allergy
Authors: H.‐J. Malling, R. Djurup
Journal: Allergy (1988)

The IgG subclass response was evaulated by a sensitive allergen‐ and subclass‐specific solid phase immunoradiometric assay during a 1‐year placebo‐controlled, double‐blind study of immunotherapy with Cladosporium herbamm in 22 adult asthmatics. The IgG response was mainly restricted to subclasses 1 and 4 but a few patients were IgG 2 and IgG 3 responders. An intense and early IgG 1 response was observed during the first clusters of injection followed by a levelling down of the titer. The IgG 4 response had a later onset and showed slowly increasing levels during the 12 months of immunotherapy. The graded clinical efficacy estimated by symptom‐medication score was significantly correlated to the preseasonal IgG 1 value, with high values indicating a deleterious response of immunotherapy (deterioration of disease activity). Likewise, the fold increase of IgG 1 and IgG 4 after two clusters of immunotherapy (i.e. after 4 weeks) was significantly related to the clinical outcome, Little or no increase of IgG 1 and IgG 4 was associated with improvement, i.e. decrease in symptom‐medication score. The magnitude of the IgG 1 response during the dose‐increase phase was directly correlated to the number of systemic side effects. No relation of IgG 1 , IgG 4 or IgG 4 /IgG 1 ratio to changes in the IgE‐mediated parameters (skin prick test, bronchial challenge and circulating specific IgE) was observed. Our data, which are based on few patients and only one allergen system, do not support the hypothesis of IgG acting as blocking antibody being the immunologic mechanism of immunotherapy. The association between high IgG4 values and a deleterious efficacy of immunotherapy might be caused by IgG4 acting as sensitizing antibodies. This explanation, however, is opposed by the lack of relation to systemic side effects.
Laennec's legacy
Authors: A. K Demetriades
Journal: Journal of the Royal Society of Medicine (2004)

Where Laennec was a true pioneer was in correlating clinical signs with pathology. In the first edition of his treatise on mediate auscultation (1819) he analysed the physical signs of percussion and auscultation and substantiated them with their pathologo-anatomical relevance; and, in the second (1823) he provided a complete description of pathology, diagnosis and treatment. Writing about three early Welsh followers of Laennec (March 2004 JRSM1), Dr Morris acknowledges that Williams, Davies and Lucas were among many foreigners who came under the French doctor's influence. In England these included Heberden, Fothergill and the ‘great men’ of Guy's Hospital—Richard Bright, Thomas Addison and Thomas Hodgkin—who fostered the attitudes that were to make Britain a leader in clinical medicine. Reference must also be made to the Irish connection—John Cheyne, Abraham Colles, Robert Adams and John Corrigan from the great Dublin School, and the two leaders Robert Graves and William Stokes. Laennec's teaching had an immediate impact in Britain by the influential work of such physicians. Graves and Stokes, both graduates of Edinburgh and subsequently professors in Dublin, collaborated in a new system of clinical instruction. Stokes in 1825 published a small treatise on the stethoscope inspired by Laennec.2

The modern practice of a complete clinical examination derives from nineteenth century methods such as auscultation and percussion. In today's world of imaging techniques and other technologies, it is a challenge for teachers to decide which of the old techniques are worthy of preservation.
Government postpones decision on future funding model for social care
Authors: I. Torjesen
Journal: BMJ (2012)

Health secretary Andrew Lansley has agreed with the Dilnot review’s recommendations for reforming funding of social care but has refused to commit to implementing them . 

On 11 July the government set out its proposals for reforming social care in its white paper, Caring for our future: reforming care and support,1 the draft Care and Support Bill,2 and a progress report on funding reform.3

Last year a government commissioned review of potential funding models, chaired by economist Andrew Dilnot, recommended that the threshold of assets an individual might have before they can access state support for social care should be raised from £23 250 (€29 500; $35 900) to £100 000. The review also said that the amount any individual has to pay towards their own care costs during their lifetime should be capped.4

The review proposed a cap of between £25 000 and £50 000, with £35 000 recommended as an “appropriate and fair figure” after which they would be eligible for full state support. Dilnot estimated that a £35 000 cap would cost the government about £1.7bn a year and said the current system was “confusing, unfair, and unsustainable,” did not enable people to plan for their future care needs, and forced many older people to sell their …
Lactate transport in mammalian ventricle. General properties and relation to K+ fluxes.
Authors: R C Shieh, J I Goldhaber, J S Stuart, J N Weiss
Journal: Circulation Research (1994)

Net cellular L-lactate efflux associated with accelerated anaerobic glycolysis has been implicated as a potential cause of the marked cellular K+ loss contributing to lethal cardiac arrhythmias in ischemic heart and to impaired function of fatigued skeletal muscle. To examine the mechanisms of transsarcolemmal L-lactate movement in the heart, isolated guinea pig ventricular myocytes were loaded with the fluorescent H+ or K+ indicators, carboxy SNARF-1 or PBFI, respectively, under whole-cell patch-clamp conditions. With H+ as the only permeable monovalent cation, a rapid increase in extracellular L-lactate concentration ([L-]o) from 0 to 30 mmol/L at constant pHo (7.35) caused an intracellular acidification averaging 0.18 +/- 0.02 pH units in 60 seconds (n = 7), reflecting L-lactate influx in association with H+ influx (or OH- efflux). Under voltage-clamp conditions, no significant electrogenic current was associated with H(+)-coupled L-lactate influx, and membrane potential (-75 to +75 mV) had no effect on the degree of acidification produced by 30 mmol/L [L-]o, indicating that L-lactate influx was predominantly nonelectrogenic. Acidification in response to increased [L-]o was saturable (Km, approximately 5 mmol/L), partially stereospecific for L-lactate over D-lactate, and inhibited by 55 +/- 7% and 82 +/- 7% by the monocarboxylate carrier inhibitors alpha-cyano-4-hydroxycinnamate and mersalyl acid, respectively, consistent with a carrier-mediated transport mechanism. Extracellular K+ inhibited H(+)-coupled L-lactate influx by 36 +/- 2%, suggesting that K+ either inhibited or substituted for H+ in cotransport with L-lactate. However, in myocytes loaded with PBFI, no significant increase in [K+]i was detected during exposure to 30 mmol/L [L-]o, suggesting that only a minor component, if any, of L-lactate influx was cotransported or codiffused with K+.
PD5-2-3: Translating research into routine clinical practice: image-guided lung stereotactic radiation therapy for unresectable patients with early stage lung cancer
Authors: Andrea Bezjak, Kevin Franks, Tom Purdie, Shannon Pearson, Anthony Brade, John Cho, Gabrielle Kane, Alex Sun, Payne David, Jean-Pierre Bissonnette
Journal: Journal of Thoracic Oncology (2007)
Changing Maternal Mortality in Massachusetts
Authors: John Figgis Jewett
Journal: New England Journal of Medicine (1957)

THE purpose of this address is threefold. In the first place, a review of past changes in maternal mortality in Massachusetts, both remote and recent, will show that they are surprisingly pertinent and should prevent us from losing sight of our objectives or from resting on our laurels. Secondly, a somewhat detailed scrutiny of the present will be made. Finally, a future course of action will be plotted for changing the maternal mortality rate still further through use of statistics, however fallible these may be.The PastA remote but reliable record of maternal mortality in the past is shown . . .