tbuckley/cabot-search huggingface dataset:
AAV8-Mediated Hepatic Expression of Acid Sphingomyelinase Corrects the Metabolic Defect in the Visceral Organs of a Mouse Model of Niemann–Pick Disease
Authors: Christine M. Barbon, Robin J. Ziegler, Chester Li, Donna Armentano, Maribeth Cherry, Robert J. Desnick, Edward H. Schuchman, Seng H. Cheng
Journal: Molecular Therapy (2005)

Acid sphingomyelinase deficiency is a lysosomal storage disorder in which the defective lysosomal hydrolase fails to degrade sphingomyelin. The resulting accumulation of substrate in the lysosomes of histiocytic cells leads to hepatosplenomegaly and severe pulmonary inflammation. Administration of a recombinant AAV1 vector encoding human acid sphingomyelinase to acid sphingomyelinase knockout (ASMKO) mice effectively reduced the accumulated substrate in all of the affected visceral organs. However, more complete and rapid clearance of sphingomyelin was observed when an AAV8-based serotype vector was used in lieu of AAV1. Importantly, AAV8-mediated hepatic expression of higher and sustained levels of the enzyme also corrected the abnormal cellularity, cell differentials, and levels of the chemokine MIP-1alpha in the bronchoalveolar lavage fluids of the ASMKO mice. Treatment also reversed the morphological aberrations associated with the alveolar macrophages of ASMKO mice and restored their phagocytic activity. No antibodies to the expressed enzyme were detected when the viral vectors were used in conjunction with a transcription cassette harboring a liver-restricted enhancer/promoter. Together, these data support the continued development of AAV8-mediated hepatic gene transfer as an approach to treat the visceral manifestations observed in individuals with acid sphingomyelinase deficiency.
Success relies on winning hearts and minds
Authors: Donald Irvine
Journal: BMJ (2006)

Good Doctors, Safer Patients Reactions to the chief medical officer's reportLast week we reported on the background and the reactions to Liam Donaldson's report, Good Doctors, Safer Patients, which recommends broad changes to the regulation of the medical profession.This week, we hear from a variety of people and organisations affected by the proposals.
Reporting deaths to coroners.
Authors: S Leadbeatter, B Knight
Journal: BMJ (1993)

Cervical swabs for Chlamydia culture were collected from 638 unselected women attending a sexually transmitted diseases clinic with a fresh complaint. Chlamydia were isolated from 76 (12 per cent.) of the women. When the results were related to the patients9 diagnoses, Chlamydia were present in 44 per cent. of women with gonorrhoea and in 22 per cent. of women who were contacts of men with nonspecific urethritis (women who may be regarded as having non-specific genital infection). Chlamydia were uncommon in women with no evidence of genital infection. Significant correlations were found between the presence of Chlamydia and cervical erosion, cervical cytological inflammatory change, and absence of symptoms. Isolates were obtained more frequently from women with non-specific genital infection who were primary contacts than from women who were secondary contacts. These findings support the concept that Chlamydia are pathogens in the genital tract and are sexually transmitted.
Beefy Red Plaques in the Perianal Region
Authors: Mario Mitkov, Jason Pimentel, Alison Bruce
Journal: JAMA Dermatology (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
A behavior-analytic developmental model is better
Authors: Gary Novak, Martha Peláez
Journal: Behavioral and Brain Sciences (2002)

Behaviorists accept, but go beyond, Williams' notion that there is an evolutionary origin to some unlearned pain behaviors. A behavior-analytic developmental model is a better fit for explaining the totality of pain behaviors. This model focuses on respondent-operant interactions and views much pain behavior as “mands” (i.e., demands). Behaviorally based explanations from the crying and social referencing literature support this model.
Report on the Sanitary Condition of the Labouring Population of Great Britain
Authors: A. S. MacNalty
Journal: BMJ (1965)

the end of each.References are scarce, and annotated fully in the text for convenience.This work will be an invaluable reference manual for those studying congenital heart disease, especially cardiologists, radiologists, cardiac surgeons, and pathologists, all of whom will have every cause to be grateful to the authors for their exceptionally fine effort.
Letter: Variation in intravenous infusion rates.
Authors: D M Chaput de Saintonge, J Dixon, M S Newman
Journal: BMJ (1974)

1/10-1/1,000.Such reactions are abolished if the serum is preheated for 1-hours at 56°C prior to injection.These findings are in contrast to those of Dr. Bryant and his colleagues in that these workers were unable to show attachment of IgE at two and four hours after sensitization.However, they do agree with the findings of other workers who have been able to sensitize chopped human and monkey lung and human skin passively in vitro by ex- posure to IgE antibody for a short time.Our results indicate that human IgE attaches rapidly to macaaue monkey skin and elicits a P.C.A. reaction at two, four, and 24 hours; these reactions being abolished if the serum is heated for 1 hours at 56°C.Most importantly, they emphasize the im- portance of using "clean" experimental monkeys with a known history.-Weare, etc.,
B 663 (LAMPREN) IN MYCOBACTERIAL INFECTIONS
Authors: J.H.S Pettit
Journal: British Journal of Dermatology (1969)

Journal Article B 663 (LAMPREN) IN MYCOBACTERIAL INFECTIONS Get access J.H.S Pettit J.H.S Pettit Room 303, China Insurance Building, 174 Jalan Tuanku Abdul Rahman, Kuala Lumpur Malaysia Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 81, Issue 10, 1 October 1969, Pages 794–795, https://doi.org/10.1111/j.1365-2133.1969.tb15944.x Published: 01 October 1969
Skull Closure by Acrylic Plates
Authors: E. A. Turner, G. Foster
Journal: BMJ (1949)

Dangerous Symptoms after Injections ofHeroin (Diamorphine)It is thought that two recent experiences of the dangers of heroin should be added to the available information.CASE 1 A woman aged 40 spent a fatiguing day in town with her daughter.She travelled 230 miles by rail, dined on the train.did not fancy the meal, and reached home very tired.Next day she vomited repeatedly, diarrhoea developed, and by evening she appeared to be seriously ill.She sent for X.Y.Z., who had known her well for twenty-five years.He found her pale and rather limp.Her pulse was rapid, the systolic pressure 115 mm.Hg, and the breathing shallow and rapid.She stated repeatedly that she felt very ill.There was no rise of temperature nor any signs in abdomen or chest.He decided to give a morphine sedative to check the vomiting and diarrhoea, and chose heroin, as it is said to be less liable than morphine to cause nausea.In three or four previous cases he had injected 1/6 gr.(11 mg.) of heroin with little apparent effect.He therefore took two tablets of this dose, specially prepared for injection, dissolved them in water, and injected them subcutaneously.He waited (fortunately) to see the patient comfortable, and was at first gratified to note that her distress diminished; she was soothed and felt sleepy; she remarked drowsily, " It's coming over me."Then, 10 to 15 minutes after the injection, almost suddenly, she became deeply unconscious and unrousable.Inspirations became rapidly shallower, with longer and longer intervals; there was deep cyanosis, with complete muscular relaxation and an imperceptible pulse.The pupils were very small-not quite pin-point.X.Y.Z.reversed his therapeutics.He injected nikethamide 0.5 g., removed the pillows, raised the foot of the bed, sent a very urgent message for another doctor, and began artificial respiration.I arrived in ten minutes.By then respiration had entirely ceased, there were no reflexes, and the extremities were cooling.The only hopeful sign was
Intralesional Adalimumab for the Treatment of Refractory Balanitis Xerotica Obliterans
Authors: Elie B. Lowenstein, Joshua A. Zeichner
Journal: JAMA Dermatology (2013)

Balanitis xerotica obliterans (BXO) is a form of lichen sclerosus (LS) that affects the penis. This autoimmune inflammatory disorder can lead to significant morbidity because of scarring and urinary and sexual discomfort.
A Comparison of Allografting with Autografting for Newly Diagnosed Myeloma
Authors: Benedetto Bruno, Marcello Rotta, Francesca Patriarca, Nicola Mordini, Bernardino Allione, Fabrizio Carnevale-Schianca, Luisa Giaccone, Roberto Sorasio, Paola Omedè, Ileana Baldi, Sara Bringhen, Massimo Massaia, Massimo Aglietta, Alessandro Levis, Andrea Gallamini, Renato Fanin, Antonio Palumbo, Rainer Storb, Giovannino Ciccone, Mario Boccadoro
Journal: New England Journal of Medicine (2007)

In this trial of the treatment of newly diagnosed multiple myeloma, we compared a protocol that entailed a hematopoietic stem-cell autograft followed by an allograft from an HLA-identical sibling with a protocol of tandem autografts.We enrolled 162 consecutive patients with newly diagnosed myeloma who were 65 years of age or younger and who had at least one sibling. All patients were initially treated with vincristine, doxorubicin, and dexamethasone, followed by melphalan and autologous stem-cell rescue. Patients with an HLA-identical sibling then received nonmyeloablative total-body irradiation and stem cells from the sibling. Patients without an HLA-identical sibling received two consecutive myeloablative doses of melphalan, each of which was followed by autologous stem-cell rescue. The primary end points were overall survival and event-free survival.After a median follow-up of 45 months (range, 21 to 90), the median overall survival and event-free survival were longer in the 80 patients with HLA-identical siblings than in the 82 patients without HLA-identical siblings (80 months vs. 54 months, P=0.01; and 35 months vs. 29 months, P=0.02, respectively). Among patients who completed their assigned treatment protocols, treatment-related mortality did not differ significantly between the double-autologous-transplant group (46 patients) and the autograft-allograft group (58 patients, P=0.09), but disease-related mortality was significantly higher in the double-autologous-transplant group (43% vs. 7%, P<0.001). The cumulative incidence rates of grades II, III, and IV graft-versus-host disease (GVHD) combined and of grade IV GVHD in the autograft-allograft group were 43% and 4%, respectively. Overall, 21 of 58 patients (36%) were in complete remission after a median follow-up of 38 months (range, 10 to 72) after allografting. Of the 46 patients who received two autografts, 25 (54%) died.Among patients with newly diagnosed myeloma, survival in recipients of a hematopoietic stem-cell autograft followed by a stem-cell allograft from an HLA-identical sibling is superior to that in recipients of tandem stem-cell autografts. (ClinicalTrials.gov number, NCT00415987 [ClinicalTrials.gov].).
Abstract P5-03-02: Expression of RANK and RANK ligand (RANKL) in breast carcinoma and distinct breast epithelial cells from BRCA1 mutation carriers
Authors: GJ Lindeman, JE Visvader, F Vaillant, GB Mann, R Soriano, D Branstetter, WC Dougall
Journal: Cancer Research (2013)

Abstract Background: Breast tumors in BRCA1 mutation carriers likely arise from luminal progenitor (LP) cells, previously shown to exhibit aberrant growth properties. Oophorectomy, and possibly tamoxifen, reduce breast cancer risk in BRCA1 carriers, potentially via inhibition of paracrine mediated signaling to stem/progenitor cells. RANKL is a major paracrine effector of progesterone's mitogenic action in mammary epithelium via its receptor RANK, and has a role in ovarian hormone-dependent activation of stem cells. Here we assessed RANK and RANKL expression in breast tumors and normal breast epithelial subtypes from women with mutations of BRCA1 (mBRCA1) or BRCA2 (mBRCA2). Methods: RANK and RANKL expression in breast cancer or normal breast tissue samples with mBRCA1, mBRCA2 or wildtype (WT) BRCA1/2 were analyzed in formalin fixed paraffin embedded (FFPE) sections by IHC. kConFab and The Royal Melbourne Hospital Tissue Bank provided the samples used in this analysis; these samples were obtained with relevant IRB approval. RANK expression on normal breast epithelial cells was measured by flow cytometry. Antibodies against human RANK (N-1H8, N-2B10; Amgen) and RANKL (M366; Amgen) were used in both assays. Incidence of IHC staining was scored as a positive IHC signal of any intensity. The overall expression was generated using the H scoring method which is calculated as the staining intensity of the tumor (0-3) multiplied by the percentage of positively staining cells. Results: Breast tumors from women with mBRCA1 had a higher incidence of RANK expression (68/162; 42%) compared with mBRCA2 (17/113; 15%) or WT (34/314; 11%) and higher overall H score (21.3) compared with mBRCA2 (8.0) or WT (3.4); RANKL expression did not vary greatly between groups: mBRCA1 (13/135; 10%), mBRCA2 (5/114; 4%), WT (23/212; 11%). In normal breast tissue, LP (Lin−EpCAM+CD49f+) and basal/stem cells (Lin−EpCAM−CD49fhi) expressed RANK on their surface. Similar expression patterns were seen in these epithelial subtypes from each BRCA1/2 genotype. Stromal cells (Lin−EpCAM−CD49f−) had minimal RANK expression. Conclusions: RANK expression intensity and incidence scores are both enriched approximately 4-fold in breast tumors from BRCA1 carriers compared with other genotypes. Also, RANK is normally expressed in breast LP cells as well as the basal/stem cell containing population. Ongoing studies will assess functional regulation of LP or mammary stem cell activity by RANKL and determine if the RANKL/RANK signaling pathway affects the aberrant growth characteristics of these cells from BRCA1 mutation carriers. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-03-02.
Relationship Between Spectral Components of Cardiovascular Variabilities and Direct Measures of Muscle Sympathetic Nerve Activity in Humans
Authors: Massimo Pagani, Nicola Montano, Alberto Porta, Alberto Malliani, Francois M. Abboud, Clay Birkett, Virend K. Somers
Journal: Circulation (1997)

Spectral analysis of RR interval and systolic arterial pressure variabilities may provide indirect markers of the balance between sympathetic and vagal cardiovascular control.We examined the relationship between power spectral measurements of variabilities in RR interval, systolic arterial pressure, and muscle sympathetic nerve activity (MSNA) obtained by microneurography over a range of blood pressures. In eight healthy human volunteers, MSNA, RR interval, intra-arterial pressure, and respiration were measured during blood pressure reductions induced by nitroprusside and during blood pressure increases induced by phenylephrine. Both low-frequency (LF; 0.10 +/- 0.01 Hz) and high-frequency (HF; 0.23 +/- 0.01 Hz) components were detected in MSNA variability. Increasing levels of MSNA were associated with a shift of the spectral power toward its LF component. Decreasing levels of MSNA were associated with a shift of MSNA spectral power toward the HF component. Over the range of pressure changes, the LF component of MSNA variability was positively and tightly correlated with LF components of RR interval (in normalized units; P < 10(-6)) and of systolic arterial pressure variability (both in millimeters of mercury squared and normalized units; P < 5 x 10(-5) and P < 5 x 10(-6), respectively). The HF component of MSNA variability was positively and tightly correlated with the HF component (in normalized units) of RR-interval variability (P < 3 x 10(-4)) and of systolic arterial pressure variability (P < .01).During sympathetic activation in normal humans, there is a predominance in the LF oscillation of blood pressure, RR interval, and sympathetic nerve activity. During sympathetic inhibition, the HF component of cardiovascular variability predominates. This relationship is best seen when power spectral components are normalized for total power. Synchronous changes in the LF and HF rhythms of both RR interval and MSNA during different levels of sympathetic drive are suggestive of common central mechanisms governing both parasympathetic and sympathetic cardiovascular modulation.
Plans for the Centennial Celebration of The Journal of the American Medical Association
Authors: George D. Lundberg
Journal: JAMA (1982)

On July 14, 1883, the first issue of The Journal of the American Medical Association was published in Chicago under the founding editorship of Nathan S. Davis, MD, whose portrait graces the cover of this week's issue. We now begin the 100th year of consecutive publication ofThe Journal. The progress that has occurred in medical science and practice in this century is astonishing. The state of accelerating acceleration of current change is so obvious to many of us today that it blunts the impact of just how much has occurred in this past 100 years.  We intend to observe this centennial during a period of two years. The first phase is initiated today with the cover, the cover story (p 147), this editorial, and the initial offering of Lester King, MD (p 217), who will provide a series of essays, to appear monthly, under the general heading MEDICINE IN
Ethanol-induced hyperlacticacidemia: inhibition of lactate utilization
Authors: Robert A. Kreisberg, W. Crawford Owen, Alan M. Siegal
Journal: Journal of Clinical Investigation (1971)

The effects of oral ethanol administration on blood glucose and lactate concentrations, lactate inflow and outflow rates, and lactate incorporation into glucose were investigated in eight human volunteers. Lactate incorporation into glucose, lactate turnover, and lactate inflow and outflow rates were determined during an 8 hr constant infusion of 100 muCi of lactate-U-(14)C. Ethanol was administered by mouth at hourly intervals, 60 ml of bonded whiskey initially and 30 ml/hr thereafter. Blood lactate concentrations increased precipitously after the administration of ethanol, reached a plateau within 120-180 min, and remained constant thereafter despite the continued administration of ethanol. Before ethanol, the lactate turnover rate was 0.76 mmoles/kg per hr +/-0.05 (SEM) and lactate inflow and outflow rates were closely balanced. During the administration of ethanol, the lactate inflow rate was unchanged, but the lactate outflow rate was significantly inhibited, decreasing to 50% of the inflow rate. Despite the continued administration of ethanol, equilibrium between lactate inflow and outflow was restored within 120-180 min and coincided temporally with establishment of a constant blood lactate concentration. Lactate oxidation was unaltered by ethanol, but lactate incorporation into glucose was significantly inhibited. Lactate incorporation into glucose was reduced within 30 min of the administration of ethanol, and nadir values were reached within 120-180 min. Lactate incorporation into glucose remained constant thereafter at rates that were only 30% of those observed in the absence of ethanol. The results of these studies indicate that ethanol-induced hyperlacticacidemia is due to decreased lactate disposal rather than increased lactate production.
Myocardial Function and Left Ventricular Volumes in Acquired Valvular Insufficiency
Authors: GRAHAM A. H. MILLER, JOHN W. KIRKLIN, H. J. C. SWAN
Journal: Circulation (1965)

The effect of valvular insufficiency on left ventricular volumes was studied by an angiographic method in 37 patients. Ejection of the additional volume load imposed by valvular insufficiency was achieved by an increase in end-diastolic volume and not by increasing the proportion of end-diastolic volume ejected. Of the 37 patients, 16 (43 per cent) had a significant reduction in the fraction of end-diastolic volume ejected per beat. These patients performed significantly less stroke work from a given end-diastolic fiber length (end-diastolic volume) than did the others and evidence is presented that they had impaired myocardial function. An index of myocardial contractility is derived which relates stroke work to end-diastolic volume. The magnitude of left ventricular volumes is determined in part by the severity of the volume load but a further increase in volume without necessarily a further increase in ejection occurs in those patients with impaired myocardial function. Valvular insufficiency is quantitated from the difference between left ventricular ejection volume determined angiographically and forward stroke volume determined from indicator-dilution curves. The results show good agreement with subsequent surgical findings in the 15 patients who underwent operation.
The conductivity of ERCP guide wires during direct contact with current source
Authors: P. Young, P. Darwin
Journal: Endoscopy (2008)

During wire-guided ampullectomy, the snare often directly contacts the guidewire ([Fig. 1]) [1] [2] [3] [4]. It is therefore important to know how much current the guide wire conducts. No published study in the English literature addresses this issue.
Treatment of Gonorrhea
Authors: Vladas Kaupas
Journal: JAMA (1970)

To the Editor.—  Janet B. Hardy et al in their paper Failure of Penicillin in a Newborn with Congenital Syphilis ( 212 :1345-1349, 1970) state that: She was also [in addition to pregnancy] found to have an acute gonococcal infection, subsequently confirmed by culture, and received immediate treatment with benzathine penicillin G, 2.4 million units given intramuscularly. The authors later comment that the type and dose of penicillin administered is generally accepted as curative for syphilis in early stages. However, it is evident from their article that the patient was seen in a prenatal clinic with gonorrhea and that the treatment was not intended for syphilis, but for gonorrhea. An article coming from a reputable institution might mislead some readers into believing that benzathine penicillin G is also an accepted agent in treating gonorrhea. Unfortunately this is not the case. The National Communicable Disease Center, Venereal Disease Branch, Atlanta, recommends the