tbuckley/cabot-search huggingface dataset:
Biochemical Characterization of Patients With In-Frame or Out-of-Frame<i>DMD</i>Deletions Pertinent to Exon 44 or 45 Skipping
Authors: Karen Anthony, Virginia Arechavala-Gomeza, Valeria Ricotti, Silvia Torelli, Lucy Feng, Narinder Janghra, Giorgio Tasca, Michela Guglieri, Rita Barresi, Annarita Armaroli, Alessandra Ferlini, Katherine Bushby, Volker Straub, Enzo Ricci, Caroline Sewry, Jennifer Morgan, Francesco Muntoni
Journal: JAMA Neurology (2013)

In Duchenne muscular dystrophy (DMD), the reading frame of an out-of-frame DMD deletion can be repaired by antisense oligonucleotide (AO)-mediated exon skipping. This creates a shorter dystrophin protein, similar to those expressed in the milder Becker muscular dystrophy (BMD). The skipping of some exons may be more efficacious than others. Patients with exon 44 or 45 skippable deletions (AOs in clinical development) have a less predictable phenotype than those skippable for exon 51, a group in advanced clinical trials. A way to predict the potential of AOs is the study of patients with BMD who have deletions that naturally mimic those that would be achieved by exon skipping.To quantify dystrophin messenger RNA (mRNA) and protein expression in patients with DMD deletions treatable by, or mimicking, exon 44 or 45 skipping.Retrospective study of nondystrophic controls (n = 2), patients with DMD (n = 5), patients with intermediate muscular dystrophy (n = 3), and patients with BMD (n = 13) at 4 university-based academic centers and pediatric hospitals. Biochemical analysis of existing muscle biopsies was correlated with the severity of the skeletal muscle phenotype.Dystrophin mRNA and protein expression.Patients with DMD who have out-of-frame deletions skippable for exon 44 or 45 had an elevated number of revertant and trace dystrophin expression (approximately 19% of control, using quantitative immunohistochemistry) with 4 of 9 patients presenting with an intermediate muscular dystrophy phenotype (3 patients) or a BMD-like phenotype (1 patient). Corresponding in-frame deletions presented with predominantly mild BMD phenotypes and lower dystrophin levels (approximately 42% of control) than patients with BMD modeling exon 51 skipping (approximately 80% of control). All 12 patients with in-frame deletions had a stable transcript compared with 2 of 9 patients with out-of-frame deletions (who had intermediate muscular dystrophy and BMD phenotypes).Exon 44 or 45 skipping will likely yield lower levels of dystrophin than exon 51 skipping, although the resulting protein is functional enough to often maintain a mild BMD phenotype. Dystrophin transcript stability is an important indicator of dystrophin expression, and transcript instability in DMD compared with BMD should be explored as a potential biomarker of response to AOs. This study is beneficial for the planning, execution, and analysis of clinical trials for exon 44 and 45 skipping.
Tertiary hyperparathyroidism with adenoma formation after renal transplantation.
Authors: K Y Ahmed, Z Varghese, M J Lange, D A Lawrence, J F Moorhead
Journal: BMJ (1978)

Emphysematous gastritis is a rare and frequently fatal condition caused by invasion of gas-forming bacteria into the gastric wall. There have only been a handful of reported cases in the paediatric population, and none of these have evidence of candidal infection or mucormycosis. Patients typically present with abdominal pain, vomiting, malaena and haematemesis. Risk factors for emphysematous gastritis are those that interfere with the natural barriers to infection in the stomach. Diagnosis is made on the basis of typical appearances on abdominal CT. Treatment is generally conservative with surgery reserved for failed medical management or later complications. Antimicrobial cover should be broad with a low threshold for antifungals. It is important to look for predisposing factors for this condition, perhaps including an assessment of the patient9s immunocompetency. We present a 16-year-old boy with global developmental delay who presented with this condition associated with candidal infection.
B-Lymphocyte Malignancy
Authors: Chester A. Alper
Journal: New England Journal of Medicine (1973)

The division of the lymphoid system into two major functionally distinct kinds of cells has increased immensely understanding not only of normal immunity but also of neoplasia affecting these cells. It is now abundantly clear that certain lymphocytes are conditioned by the thymus (hence their designation as T-cells) and acquire the ability to mediate delayed hypersensitivity and the rejection of foreign transplanted tissue. T-lymphocytes have a major role in the body's defense against viruses, fungi and certain bacteria such as tubercle and brucella bacilli. They elaborate such lymphokines as chemotactic factors, migration inhibition factor and a mitogenic factor. Thymus-independent lymphocytes, . . .
A requiem for the cholecystokinin provocation test?
Authors: A Smythe, A W Majeed, M Fitzhenry, A G Johnson
Journal: Gut (1998)

Background —The cholecystokinin provocation test (CCKPT) has been claimed to predict a better symptomatic result after cholecystectomy in patients with acalculous biliary pain. Aims —To examine the predictive value of the CCKPT for symptom relief after cholecystectomy in both CCKPT positive and negative patients. Patients and methods —Fifty eight patients with acalculous biliary pain underwent CCKPT with serial ultrasound gall bladder volumetry. CCKPT positive patients were offered cholecystectomy; negative patients were reassessed and were offered a cholecystectomy if symptoms persisted. Six months after cholecystectomy, the CCKPT was repeated. Results —Of 32 CCKPT positive patients, 27 underwent cholecystectomy and of these, 18 (67%) became symptom-free. Postoperatively, 20 of 25 patients converted to CCKPT negative but five remained CCKPT positive and were symptomatic. Of the 26 CCKPT negative patients, nine became symptom-free without cholecystectomy; six of 14 (42.8%) patients undergoing cholecystectomy became asymptomatic and remained CCKPT negative. Cholecystectomy seemed to reduce symptoms in both groups, but there was no significant difference in the symptomatic outcome between preoperative CCKPT positive and negative patients. Conclusions —In this study, cholecystokinin provocation testing did not predict symptomatic benefit from cholecystectomy and we suggest it should no longer be used in the evaluation of patients with acalculous biliary pain.
Current Concepts of the Genesis of Heart Sounds
Authors: Jonathan Abrams
Journal: JAMA (1978)

<h3>THIRD HEART SOUND</h3> The S3 (ventricular gallop) occurs in early diastole, 130 to 180 msec after A2, and coincides with the end of rapid filling of the left ventricle (LV). Ultrasonic studies have shown that the S3 occurs just as the LV septum and posterior free wall reach their greatest diastolic excursion; presumably, accelerating and decelerating forces are maximal at this time. The sound itself thus represents vibrations of LV structures and blood mass as the rapid inflow of left atrial blood is checked by the limits of LV diastolic expansion. <h3>Implications of an Audible S3</h3> The presence of an audible S3 is normal in children and young adults. For unclear reasons, the S3 is rarely a normal finding in persons more than 30 to 35 years of age. It has been recognized for many years that the presence of a S3 in an adult generally has ominous implications. An
Management of Severe Hyperthermia with Chlorpromazine and Refrigeration
Authors: Robert M. Jesati
Journal: New England Journal of Medicine (1956)

CONSIDERABLE interest has recently centered around the use of chlorpromazine in medicine. Many of the properties of this drug have been studied, and its use in clinical practice in this country in such conditions as the management of vomiting, hiccups, mental and emotional disturbances, intractable pain and alcoholism has frequently been discussed in the literature. Undoubtedly, the possibilities of chlorpromazine have not been exhausted, and it bids fair to achieve dramatic results in other major applications. In France its surgical indications have been particularly emphasized, for under the name of "artificial hibernation" Laborit and Huguenard1 , 2 introduced it as an antishock . . .
Ban on smoking in public places “disproportionate to the problem”
Authors: Zosia Kmietowicz
Journal: BMJ (2006)

New legislation that bans smoking in public places in England, which is due to reach the final stages of voting in the House of Lords later this month, is unjustified and an over-reaction to the scientific evidence on passive smoking, says a House of Lords report.

The impact of passive smoking in public places is a relatively minor problem compared with passive smoking in the home, says the House of Lords' economic affairs …
Modeling Tumor Dynamics and Overall Survival in Advanced Non–Small-Cell Lung Cancer Treated with Erlotinib
Authors: Ahmed Abbas Suleiman, Sebastian Frechen, Matthias Scheffler, Thomas Zander, Deniz Kahraman, Carsten Kobe, Jürgen Wolf, Lucia Nogova, Uwe Fuhr
Journal: Journal of Thoracic Oncology (2014)
Malpractice—An Iceberg?
Authors: Jere W. Lord
Journal: JAMA (1975)

To the Editor.—  In recent weeks, in New York as well as elsewhere in the Union, the specter of economic disaster due to exorbitant rises in malpractice premiums, coupled with the possibility of nonavailability of insurance coverage at all, represents that part of the iceberg that is visible above water. It is clear that under such conditions, young physicians, particularly those in the surgical specialties, will not be able to open an office. Similarly, senior physicians will be hard put to continue in practice. Hospital-based physicians will be in jeopardy when deficit-ridden hospitals are forced to pay huge sums for coverage of their doctors.  At the heart of the problem is the war between malpractice lawyers and the medical profession. In the United Kingdom and also in Canada, the annual cost to the physician is approximately $50 for malpractice coverage. The difference between physicians in those countries and in ours
TUTORIAL: A USEFUL WAY TO TEACH PSYCHIATRY TO SENIOR MEDICAL STUDENTS
Authors: PETER E. SIFNEOS
Journal: American Journal of Psychiatry (1962)

The psychiatry course as given to senior Harvard Medical School students at the Massachusetts General Hospital has been briefly described, with special emphasis placed on the use of intensive individual tutorial. The tutor-student relationship is dynamic. It has education as its main goal and involves a transference counter-transference that must be recognized early by the tutor, handled with subtlety, and resolved successfully by the end of one month in order to facilitate learning. It also offers both the tutor and the student a unique opportunity for learning. The tutor must be careful, however, that tutorial should not devolve into psychotherapy. Thus, from our staff experience and student ratings, tutorial is considered a most useful way to teach psychiatry to senior medical students.
LEFT VENTRICULAR EJECTION FRACTION FROM GATED SPECT THALLIUM IMAGING: COMPARISON WITH RNA AND CONTRAST VENTRICULOGRAPHY
Authors: T. D. Payne, J. J. Pippin, C. J. Branstetter, A. D. Ross, S. M. Devers, C. M. Carr, S. J. Durham
Journal: Clinical Nuclear Medicine (1996)

Payne, T.; Pippin, J. J.; Branstetter, C. J.; Ross, A. D.; Devers, S. M.; Carr, C. M.; Durham, S. J. Author Information
Laser-assisted angioplasty of inferior vena caval obstructions: What’s good for the artery is good for the vein
Authors: Lawrence I. Deckelbaum
Journal: Hepatology (1989)

Three cases of hepatic inferior vena cava (IVC) obstruction (two segmental and one membranous) associated with Budd-Chiari syndrome were successfully treated with percutaneous transluminal angioplasty (PTA) with use of an Nd-YAG (neodymium-yttrium, aluminum, garnet) laser. The occluded portions were canalized by advancing a ceramic-capped delivery system and delivering intermittent laser emissions. The canal was widened by simultaneous inflation of three or four Gruentzig balloon catheters. In two of the three cases, this procedure was done after unsuccessful canalization of the occluded portions by conventional means. Postoperatively, all patients showed disappearance of Budd-Chiari syndrome. One patient also showed marked regression of a huge intraluminal thrombus. There were no serious complications during and after the procedures. Use of the Nd-YAG laser seems to be of value in PTA for the treatment of hepatic IVC obstructions as well as in treatment of arteriosclerotic lesions.
THE INFLUENCE OF CORTISONE ON EXPERIMENTAL VIRAL INFECTION
Authors: Michael W. Rytel, Edwin D. Kilbourne
Journal: The Journal of Experimental Medicine (1966)

The administration, of 5.0 mg of cortisone 6 to 24 hr prior to the intravenous injection of mice with NDV was associated with a marked reduction in the interferon response as measured in serum and spleen. Reduced concentrations of interferon following cortisone pretreatment were demonstrable from 6 to 16 hr following injection of virus.
Inhaled or Reduced-Dose Intravenous Pentamidine for<i>Pneumocystis carinii</i>Pneumonia
Authors: JOHN E. CONTE
Journal: Annals of Internal Medicine (1987)

Study Objective: To evaluate inhaled or reduced-dose intravenous pentamidine for the treatment of patients with mild Pneumocystis carinii pneumonia. Design: Open, nonrandomized pilot study; measurement of pentamidine concentrations in plasma and bronchoalveolar lavage fluid. Patients: Of 22 men with mild P. carinii pneumonia (Po2 ≥ 55 mm Hg), 15 (9 in the inhaled group and 6 in the intravenous group) received treatment for their first episode and 7 for a repeat episode. Interventions: Pentamidine isethionate, 4 mg/kg body weight by inhalation, or 3 mg/kg intravenously, was given once daily, as long as clinically indicated. Measurements and Main Results: Of the 13 patients in the inhaled group, 9 had a satisfactory response; and of the 10 in the reduced-dose intravenous group, 9 had a satisfactory response. Major adverse reactions occurred in two patients in each group. Three patients in the inhaled group appeared to have had early relapses. Bronchoalveolar lavage fluid concentrations of pentamidine ranged between 16.8 ± 7.3 ng/mL and 149.7 ± 38.2 ng/mL in the inhaled group and 3.4 ± 0.2 ng/mL and 10.9 ng/mL in the intravenous group. Conclusions: Inhaled or reduced-dose intravenous pentamidine may be an effective and less toxic therapy for mild P. carinii pneumonia. These regimens are not recommended for general use until larger controlled trials are conducted.
CORONARY VASOSPASM OF COLLATERAL VESSEL INDUCED BY SEROTONIN SYNDROME MIMICKING ANTERIOR MYOCARDIAL INFARCTION
Authors: Takeshi Nishi, Junya Harada, Kazumasa Sugimoto, Yo Iwata, Takashi Nakayama, Fujimoto Yoshihide, Yoshio Kobayashi
Journal: Journal of the American College of Cardiology (2014)
Measuring Compliance-Reply
Authors: Joyce A. Cramer
Journal: JAMA (1989)

<h3>In Reply.—</h3> Mr Hoar has expressed concern about medication compliance in geriatric and retarded populations that were not addressed in our study. We observed medication-taking practices in adult patients with epilepsy (aged 18 through 68 years) of borderline to superior intelligence (IQ, 76 to 124) to assess compliance in a broad range of relatively normally functioning persons. Use by low-functioning patients is feasible, but has not been evaluated. The cost for Medication Event Monitoring Systems bottle rental ($7 per month) and a report ($56) is in the range of cost for a laboratory drug serum concentration test. As explained in the article, the Medication Event Monitoring Systems device counts "presumptive" doses. Indeed, this prototype device does not verify pill swallowing. The software developed by the Aprex Corporation (Fremont, Calif) to analyze Medication Event Monitoring Systems bottle data can filter excess, sequential openings. In addition, calendar plots showing missed doses and
Giant Brunneroma of the Duodenum
Authors: C Bästlein, R Decking, C Voeth, R Ottenjann
Journal: Endoscopy (1988)

A case of giant hyperplasia of Brunner's glands in the duodenum is reported. Recurrent vomiting due to stenosis of the duodenum was the leading symptom. Endoscopy, ultrasound and histological examination were employed as complementary methods to establish the diagnosis. The 5 × 7 cm large tumor was surgically excised. Brunneromas are always benign and their incidence is about 0.08 % in upper GI-tract endoscopy.
Are Intravenous Corticosteroids Required in Status Asthmaticus?
Authors: David Ratto
Journal: JAMA (1988)

Seventy-seven patients with status asthmaticus were prospectively studied to compare oral with intravenous methylprednisolone. Patients were given methylprednisolone, either 160 or 320 mg orally or 500 or 1000 mg intravenously, daily in equally divided doses. They were randomly assigned to either group on a daily sequential basis. Spirometry was performed within one hour of the initial dose of steroids. The mean presenting forced expiratory volume in 1 s was 26% of the predicted value. Spirometry was then repeated every six hours for the first 24 hours and then every eight to 12 hours until discharge or 72 hours, whichever occurred first. There were no significant differences in the incidence of respiratory failure, forced expiratory volume in 1 s, days of hospitalization, rate of improvement in pulmonary function, or side effects. No patient who went into respiratory failure did so more than three hours after receiving the initial dose of steroids. We conclude that oral methylprednisolone is safe and effective in the treatment of status asthmaticus. (<i>JAMA</i>1988;260:527-529)
Peroxisome proliferator-activated receptor ?/? activation inhibits hypertrophy in neonatal rat cardiomyocytes
Authors: A PLANAVILA, R RODRIGUEZCALVO, M JOVE, L MICHALIK, W WAHLI, J LAGUNA, M VAZQUEZCARRERA
Journal: Cardiovascular Research (2004)

Objective: Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is the predominant PPAR subtype in cardiac cells and plays a prominent role in the regulation of cardiac lipid metabolism. However, the role of PPARβ/δ activators in cardiac hypertrophy is not yet known.
Disulfiram Hypersensitivity Hepatitis
Authors: Emmet B. Keeffe
Journal: JAMA (1974)

DISULFIRAM is widely used as adjunctive therapy in the outpatient treatment of chronic alcoholism. Except for the disulfiram-alcohol reaction, disulfiram alone appears to be well tolerated by man. In a compilation by Ayerst Laboratories (New York) of more than 160 reports from the literature of 1948 to 1971, and in a personal search of the English literature, no reference to hepatic toxicity could be found. The following case, therefore, is reported because it included two episodes of acute hepatitis that were temporally related to the administration of disulfiram. <h3>Report of a Case</h3> A 44-year-old white salesman was transferred from the White City domiciliary to the Portland Veterans Administration Hospital for evaluation of a rising level of serum glutamic oxaloacetic transaminase (SGOT) and two recent episodes of hepatitis that occurred after the administration of disulfiram. From November 1971 to March 1972 he was hospitalized at the Palo Alto Veterans Administration Hospital
Induction of humoral and cell-mediated anti-human immunodeficiency virus (HIV) responses in HIV sero-negative volunteers by immunization with recombinant gp160.
Authors: J A Kovacs, M B Vasudevachari, M Easter, R T Davey, J Falloon, M A Polis, J A Metcalf, N Salzman, M Baseler, G E Smith
Journal: Journal of Clinical Investigation (1993)

Development of an effective vaccine for prevention of infection with HIV would provide an important mechanism for controlling the AIDS epidemic. In the current study, the first clinical trial of a candidate HIV-1 vaccine initiated in the United States, the safety and immunogenicity of escalating doses (10-1,280 micrograms) of recombinant gp160 (rgp160), were evaluated in 138 HIV-negative volunteers. Maximal antibody responses, as evaluated by ELISA, were seen after immunization with three doses of 1,280 micrograms rgp160. Responses to some specific epitopes of HIV gp160, including the second conserved domain and the CD4 binding site, were seen more frequently than after natural infection. Neutralizing antibodies to the homologous HIV strain, but not heterologous strains, were induced by this regimen. Blastogenic responses to rgp160 were seen in most volunteers receiving at least two doses of > or = 20 micrograms. These envelope-specific T cell responses were also seen against heterologous strains of HIV. No major adverse reactions were seen after immunization. Thus, rgp160 is a safe and immunogenic candidate HIV vaccine; further studies are needed to determine if it will provide any clinical benefit in preventing HIV infection.
PI3K p110δ uniquely promotes gain-of-function Shp2-induced GM-CSF hypersensitivity in a model of JMML
Authors: Charles B Goodwin, Xing Jun Li, Raghuveer S. Mali, Gordon Chan, Michelle Kang, Ziyue Liu, Bart Vanhaesebroeck, Benjamin G. Neel, Mignon L. Loh, Brian J. Lannutti, Reuben Kapur, Rebecca J. Chan
Journal: Blood (2014)
Should coronary arteries with less than 60% diameter stenosis be treated by angioplasty?
Authors: T Ischinger, A R Gruentzig, J Hollman, S King, J Douglas, B Meier, J Bradford, R Tankersley
Journal: Circulation (1983)

We evaluated all patients receiving percutaneous transluminal coronary angioplasty (PTCA) in the past year for mild stenosis (60% or less diameter narrowing, n = 64, group 1) and compared them with a random sample of 330 patients with greater than 60% stenosis (n = 66, group 2) treated during the same year. The degree of coronary stenosis before PTCA was 52 +/- 7% (mean +/- SD) in group 1 and 79 +/- 11% in group 2. The primary success rate was 90% (58 of 64 patients) in group 1 vs 86% (57 of 66 patients) in group 2. The incidence of complications requiring coronary surgery after PTCA failed was similar in both groups (3 of 64 in group 1, 4 of 66 in group 2), but there were four occurrences of myocardial infarction in group 1 and none in group 2 (p less than .05). Recurrence of stenosis was judged on the basis of objective data, 76% of which were angiographic data, in 97% of the patients with primary success. At a mean interval of 5 months with a mean follow-up period of 7 months, 17 of 58 patients (29%) with primary success in group 1 and 24 of 57 patients (42%) in group 2 developed restenosis. In group 1, restenosis was markedly more severe (73 +/- 15%) than initial stenosis (p less than .005), which was not the case in group 2. In conclusion, PTCA in mild stenosis has favorable primary and long-term results, yet carries the risk of myocardial infarction and emergency operation and may, in some cases, even accelerate the disease process.
ANTI-B1 MONOCLONAL ANTIBODY AND COMPLEMENT TREATMENT IN AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR RELAPSED B-CELL NON-HODGKIN'S LYMPHOMA
Authors: LeeM. Nadler, Leslie Botnick, Robert Finberg, GeorgeP. Canellos, Tak Takvorian, RobertC. Bast, Samuel Hellman, StuartF. Schlossman
Journal: The Lancet (1984)