tbuckley/cabot-search huggingface dataset:
Drug for irritable bowel syndrome taken off the market
Authors: F. Charatan
Journal: BMJ (2000)

Alosetron hydrochloride (Lotronex), a prescription drug manufactured by GlaxoWellcome, and used to treat irritable bowel syndrome in women, has been withdrawn after reports of serious complications.

The US Food and Drug Administration (FDA) said that it had reviewed a total of 70 cases of serious adverse events, including 49 cases of ischaemic colitis and 21 cases of severe constipation. Of the 70 cases, 34 resulted in admission to hospital without surgery, 10 resulted in surgical procedures, and three resulted in death. The …
Plaster-of-Paris Bandages.
Authors: N. B. Bacon
Journal: JAMA (1903)

Toledo, Ohio, May 8, 1903. <h3>To the Editor:</h3> —It is not generally known that the late Dr. Hezekiah P. Mead of Morrisville, Madison County, N. Y., who died last year, was the first to discover the practicability of applying the plaster-of-paris bandage to the treatment of fractures and other displacements in which it is so universally used by the profession throughout the land. This was early in the year 1860. With an utter lack of any thirst for notoriety, and content with his mere contribution to the profession and to the good of humanity, he gracefully allowed the name of another skilled and more prominent surgeon of the time to be credited with this valuable discovery. Through intimate association and personal knowledge of the facts at the period named, I have felt it incumbent on me to call attention to the above fact, in justice to a man of consummate
Consequences of Intestinal Resection
Authors: Fred Kern
Journal: New England Journal of Medicine (1969)

The pace of progress in understanding the events of digestion and absorption in the intestine appears to be accelerating. This progress is evident in recent clarification of some of the differences between proximal and distal small intestine. One of these differences is in the activity of the intestinal mucosa toward bile acids. The proximal small intestine and colon absorb only a small amount of bile acids, and that only by the mechanism of passive diffusion. The distal small intestine, by contrast, possesses an active transport mechanism for absorption of bile acids and absorbs them avidly. Since bile acids facilitate lipid . . .
Caffeine and Incident Hypertension in Women
Authors: Johanna M. Geleijnse
Journal: JAMA (2006)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Dose Selection, Pharmacokinetics, and Pharmacodynamics of BRAF Inhibitor Dabrafenib (GSK2118436)
Authors: Gerald S. Falchook, Georgina V. Long, Razelle Kurzrock, Kevin B. Kim, H.-Tobias Arkenau, Michael P. Brown, Omid Hamid, Jeffrey R. Infante, Michael Millward, Anna Pavlick, Melvin T. Chin, Steven J. O'Day, Samuel C. Blackman, C. Martin Curtis, Peter Lebowitz, Bo Ma, Daniele Ouellet, Richard F. Kefford
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Dabrafenib is a selective, potent ATP-competitive inhibitor of the BRAFV600-mutant kinase that has demonstrated efficacy in clinical trials. We report the rationale for dose selection in the first-in-human study of dabrafenib, including pharmacokinetics, tissue pharmacodynamics, 2[18F]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) pharmacodynamics, and dose–response relationship. Experimental Design: Dabrafenib was administered orally once, twice (BID), or three times daily (TID). Selected dose cohorts were expanded to collect adequate data on safety, pharmacokinetics, or pharmacodynamics. A recommended phase II dose (RP2D) was chosen based on safety, pharmacokinetic, pharmacodynamic, and response data. Results: One hundred and eighty-four patients were enrolled and treated with doses ranging from 12 mg once daily to 300 mg BID in 10 cohorts. Pharmacokinetic assessment of dabrafenib demonstrated a less-than-dose-proportional increase in exposure after repeat dosing above 150 mg BID. Similar to parent drug concentrations, exposure for all metabolites demonstrated less-than-dose-proportional increases. Predicted target inhibition of pERK (&amp;gt;80%) was achieved at 150 mg BID, with a similar magnitude of inhibition at higher doses in BRAFV600 mutation melanoma biopsy samples. Although there was large variability between patients, FDG uptake decreased with higher daily doses in patients with BRAFV600 mutation–positive melanoma. A favorable activity and tolerability profile was demonstrated at 150 mg BID. There was no improvement with TID dosing compared with BID dosing, based on FDG-PET and tumor response analyses in patients with melanoma. Conclusion: The RP2D of dabrafenib was determined to be 150 mg BID after considering multiple factors, including pharmacokinetics, tissue pharmacodynamics, FDG-PET pharmacodynamics, and the dose–response relationship. A maximum tolerated dose for dabrafenib was not determined. Clin Cancer Res; 20(17); 4449–58. ©2014 AACR.
A CASE OF RAYNAUD'S DISEASE.
Authors: WM. F. BATMAN
Journal: JAMA (1894)

anees is taken from the notes of Dr. Baker, who per¬ formed the autopsy, and to it I append his description of the microscopic appearances of the tumor and its métastases :The abdomen contained about four quarts of bile- stained serous fluid, having a specific gravity of 1021.The intestines were everywhere firmly matted to¬ gether and distorted, especially near the pelvis.About midway of the descending colon, after much trouble in freeing it from old adhesions, was found the site of an intestinal resection.Below it was a
Tertiary lymphoid organs in infection and autoimmunity
Authors: Katrijn Neyt, Frédéric Perros, Corine H. GeurtsvanKessel, Hamida Hammad, Bart N. Lambrecht
Journal: Trends in Immunology (2012)

The lymph nodes (LNs) and spleen have an optimal structure that allows the interaction between T cells, B cells and antigen-presenting dendritic cells (DCs) on a matrix made up by stromal cells. Such a highly organized structure can also be formed in tertiary lymphoid organs (TLOs) at sites of infection or chronic immune stimulation. This review focuses on the molecular mechanisms of TLO formation and maintenance, the controversies surrounding the nature of the inducing events, and the functions of these structures in infection, transplantation and autoimmunity.
Abstract 4652: Identification and validation of a novel nine-gene signature predicting clinical outcome in malignant melanoma
Authors: Georg Brunner, Achim Heinecke, Martina Reitz, Andrea Lippold, Carola Berking, Ludwig Suter, Jens Atzpodien
Journal: Cancer Research (2010)

Abstract Incidence of malignant melanoma is rapidly increasing - with a doubling rate of 10-20 years. Conventional histopathological and clinical staging (based on Breslow tumor thickness, lymph node status, and ulceration) is largely inadequate for predicting clinical outcome of malignant melanoma. On the other hand, molecular prognostic markers are not yet available. Here, we identified a nine-gene signature which is closely associated with overall survival of melanoma patients. To identify prognostic genes we correlated gene expression profiles of 136 primary melanomas with patient overall survival using Cox regression analysis: Initially, a comparative analysis of 20 high-risk vs. 20 low-risk primary melanomas with a clinical follow-up of more than 20 years (training cohort) was performed using whole-genome DNA microarray analysis and yielded 92 prognostically relevant candidate genes. Technical and statistical validation using TaqMan Array real-time RT-PCR and correlation of gene expression with patient overall survival reduced candidate gene number to 11. Expression of these 11 genes was further analyzed in an extended group of 91 primary melanomas (study cohort), yielding a nine-gene signature with prognostic significance. This novel prognostic melanoma gene signature was successfully validated using an independent set of 45 primary melanomas (validation cohort). A risk score, based on the expression of the nine genes of the signature (KRT9, SPINK7/ECG2, KBTBD10, DCD, HES6, COL6A6, PIP, SCGB1D2, SCGB2A2), or any subgroup thereof, predicted patient overall survival in the study cohort (p = 0.0004, hazard ratio 3.83), independently of conventional AJCC 2002 staging. When combining gene expression score and AJCC staging, approximately two thirds (29/45, 64%) of patients with AJCC intermediate prognosis (i.e. stages IIA, IIB, and IIIA) were reclassified into good prognosis, exhibiting a long-term overall survival probability of 95%. Misclassification rate of all patients classified into good prognosis (low-risk gene score combined with AJCC stages I IIA/B, or IIIA) was very low at 4.6% and 6.25% in the training and validation cohorts, respectively. The prognostic value of this novel signature-based risk score is its ability to identify patients at low risk, not identified by AJCC staging. This re-classification may allow these patients to stay treatment-free while experiencing excellent long-term survival. The remaining patients are risk patients and are in need of adjuvant therapies. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4652.
HYPODERMIC DIGITALIS PREPARATIONS
Authors: HAROLD E. B. PARDEE
Journal: JAMA (1925)

The intravenous administration of digitalis preparations has been recommended because of certain advantages claimed for this method of giving the drug. It has been considered that: The digitalis effects would be produced more quickly because the time needed for absorption from the gastro-intestinal tract would be eliminated. The digitalis effects would be more certain, because of avoiding the variable absorption from the gastro-intestinal tract. Because of these things, a smaller dose would be needed to obtain effects. In the course of using these products in the treatment of patients with cardiac decompensation, it became plain to me that the manufacturers' claims as to potency, and particularly their recommendations as to dosage, were far from correct. It has never been properly demonstrated that any of these supposed advantages of the intravenous use of digitalis are actual facts, and so it seemed advisable to investigate the activity of these preparations. It seemed
PERFORATING WOUNDS OF THE EYEBALL AND SYMPATHETIC INFLAMMATION.
Authors: H. GRADLE
Journal: JAMA (1902)

Penetrating wounds of the eyeball constitute a fair share of ophthalmic practice. Where mechanical industries expose workmen to accidents, these injuries may represent nearly 5 per cent, of eye patients. Injuries of this kind are always so serious that the surgeon necessarily feels a grave responsibility until the healing is complete. Every penetrating wound is to be considered from three aspects, viz.: 1, the mechanical consequences; 2, the presence or absence of a foreign body, and 3, the question of infection. <h3>THE MECHANICAL CONSEQUENCES.</h3> Eye injuries are peculiar in their immediate results, for nowhere else in the body are so many separate tissues of distinctive individuality crowded into so small a space. A wound which perforates the cornea allows the aqueous humor to escape at once, whereby the anterior chamber becomes emptied. The edges of a small and linear wound will adhere sufficiently to allow a refilling within hours, or
Modulation of immunodominant sites in influenza hemagglutinin compromise antigenic variation and select receptor-binding variant viruses.
Authors: F Temoltzin-Palacios, D B Thomas
Journal: The Journal of Experimental Medicine (1994)

The regions of antigenic variation in influenza hemagglutinin (HA) are located on surface-accessible regions in the three-dimensional structure of the HA1 monomer. The aim of this study was to establish whether a novel variant virus, IMUT4, in which we had mutated specific amino acid residues (HA1 63, 144, 158, and 193) in these regions, previously shown to be immunodominant for CBA/Ca mice, would either (a) establish holes in the antibody (ab) repertoire or (b) preclude further antigenic variation in IMUT4. CBA/Ca mice were able to mount a neutralizing ab response to IMUT4 infection and molecular recognition sites were established by sequencing of the HA genes of monoclonal antibody (mAb)-selected laboratory variants of wild-type X31 virus (HA1 131, 145, 155, and 196). However, each of these mAbs failed to select further antigenic variants of IMUT4, in ovo, but rather a receptor binding mutant (HA1 190 Glu-->Asp; 226 Leu-->Gln) that was still recognized by the selecting mAb, specific for HA1 155 of X31 virus. The facility for antigenic variation in influenza would appear to be compromised, therefore, by targeted mutation of immunodominant sites, as initially proposed by S. Fazekas de St. Groth (Fazekas de St. Groth, S. 1977. Antigenic, adaptive and adsorptive variants of the influenza haemagglutinin. In Topics in Infectious Diseases. Vol. 3. R.G. Laver, H. Bachmayer, and R. Weil, editors. Springer-Verlag, Vienna. 25-48.). It is interesting to note that recent isolates of the H3 subtype, (e.g., A/Beijing/92) obtained between 1991 and 1993, contain the same substitutions at HA1 190 and 226, which may indicate similar constraints to immune evasion and the relevance of our findings to antigenic variation in the human population.
TREATMENT OF BILHARZIASIS BY ANTIMONY TARTRATE
Authors: F. O. Lasbrey, R. B. Coleman
Journal: BMJ (1924)

A Applicat ons.Discharge.Relapses. 1 26 Abscess of right iliacfossa None Evacuation and eusol 1; 2 years-None Well.oxygen 2 2. 13 Plastie peritonitis and obstruction Botl lungs Oxygen 5 1 year Two Mach impeoved.sl irh Ily-3 22 Abseess-from seventh right rib None Oxygen 4 11 yearls Noae Well. 4 17 Abscess in.neck from gland NoneL Aspiralion 2; oxygen 4; Ii years Note Well. 5 4 Absc-ss of left ihiae fossa, Nona Oxy-gen 2 2 yc ar3 None Well.6 18 Tuberculous elbow with abscess No Aspiration 1; cxygen 1 2 yeers Hroke dwn aftonce.'1 25 Iseas abscess in thigh None Oxygenl 6 14 yars BrolVe down after sixth . .~~~~~~~~~~~~~applic-ation,. 8 33 Peritonitis with effusion-Advanced pul-Oxygen. 1 Died w.thin few 3ays nionary from oener&izcd tubereulotis.§ 9.Ab cess from frfth-and six%l ribs.
An Address on the Behaviour of Fluid in the Chest and the Treatment of Empyema: With Special Reference to the Value, as an Operation, of Removal of Rib
Authors: J. F. Goodhart
Journal: BMJ (1887)

<h3>Objective</h3> To evaluate the utility of a novel discharge tool adapted for heart failure (HF) on patient experience. <h3>Design</h3> Semistructured interviews assessed the utility of a novel discharge tool adapted for HF; patient-oriented discharge summary (PODS-HF) at 72 hours and 30 days after leaving hospital. Interviews were recorded and transcribed verbatim. Three investigators used directed content analysis to determine themes and subthemes from the narrative data. <h3>Setting</h3> The cardiology ward of an urban academic institution in Canada. <h3>Participants</h3> 13 patients and caregivers completed 24 interviews. Eligible patients were &gt;18 years and admitted with a diagnosis of HF. <h3>Results</h3> Analysis revealed six interconnected themes: (1) Utility of discharge instructions: how patients perceive and use written and verbal instructions. Patients receiving PODS-HF identified value in the patient-centred summarised content. (2) Adherence: strategies used by patients to enhance adherence to medications, diet and lifestyle changes. PODS-HF provides a strong visual reminder, particularly early postdischarge. (3) Adaptation: how patients incorporate changes into ‘new norms’. This was more evident by 30 days, and those using PODS-HF had less unscheduled visits and readmissions. (4) Relationships with healthcare providers: patients’ perceptions of the roles of family physicians and specialists in follow-up care. (5) Role of family and caregivers: the pivotal role of caregivers in supporting adherence and adaptation. (6) Follow-up phone calls: the utility of follow-up calls, particularly early after discharge as a means of providing clarification, reassurance and education. <h3>Conclusion</h3> PODS-HF is a useful tool that increases patients’ confidence to self-manage and facilitates adherence by providing relevant written information to reference after discharge.
Frequency analysis of autoreactive T‐helper 1 and 2 cells in bullous pemphigoid and pemphigus vulgaris by enzyme‐linked immunospot assay
Authors: R. Eming, L. Büdinger, R. Riechers, O. Christensen, H. Bohlen, R. Kalish, M. Hertl
Journal: British Journal of Dermatology (2000)

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are autoimmune bullous skin diseases mediated by autoantibodies against adhesion molecules of the skin. Previous studies have identified autoreactive T cells in patients with BP and PV, which may be critical in providing B-cell help for autoantibody production.To evaluate the frequency of autoreactive T-helper (Th) 1 and Th2 cells in patients with BP (n = 7) or PV (n = 1) and in healthy controls (n = 11).In an enzyme-linked immunospot (ELISPOT) assay, microtitre plates were coated with antihuman interleukin (IL)-5 IgG or antihuman interferon (IFN)-gamma IgG prior to culturing human peripheral blood lymphocytes (PBL) with BP180 or desmoglein (Dsg) 3 proteins for 7 days. Cytokine-producing autoreactive T cells were visualized as spot-forming units.One BP patient with extensive blisters had 5.1 +/- 1.5 (mean +/- SD) BP180-reactive Th1 cells and 2.9 +/- 1.5 Th2 cells per 105 PBL. In contrast, PBL from six BP patients in remission or on immunosuppressive therapy did not form IFN-gamma- or IL-5-producing spots per </= 5 x 105 PBL. The patient with oral PV had 4.7 +/- 2.4 Th1 cells and 3.0 +/- 0.4 Th2 cells per 105 PBL and a vigorous PBL response to Dsg3. In addition, three of 10 controls had BP180-reactive Th1 (2.7-13.8 per 105 PBL) and Th2 (0.3-1.8 per 105 PBL) cells and one control had 9.0 +/- 0.7 Th1 cells and 1.1 +/- 0.8 Th2 cells per 105 PBL, with reactivity to Dsg3. ELISPOT reactivity correlated with 3H-thymidine incorporation in six of seven patients and controls with autoreactive T-cell responses.The ELISPOT assay seems to be promising for the quantitative and qualitative analysis of autoreactive T-cell responses in BP and PV.
Residual sleep-disordered breathing during autotitrating continuous positive airway pressure therapy
Authors: Angela L. Denotti, Keith K.H. Wong, George C. Dungan, John W. Gilholme, Nathaniel S. Marshall, Ronald R. Grunstein
Journal: European Respiratory Journal (2011)

Obstructive sleep apnoea (OSA) is often treated with autotitrating continuous positive airway pressure (autoCPAP) devices. Clinical and bench tests of these devices have suggested performance limitations. These studies do not indicate whether this is a failure to detect or a failure to respond to airway obstruction. In this randomised, crossover trial, 34 patients with moderate-to-severe OSA underwent polysomnography on two laboratory visits. The autoCPAP device was randomly set to a fixed subtherapeutic pressure (detection assessment) or autotitrating mode (response assessment). Airflow was measured both from the autoCPAP (autoCPAP flow) and directly from the nasal mask, and recorded on polysomnography. Apnoea/hypopnoea indices (AHIs) measured at the two sites and from the autoCPAP download report were compared. Regarding detection, the AHI measured from the nasal mask showed good agreement with the autoCPAP flow AHI, but agreement was lower with the autoCPAP report AHI. In autotitrating mode, there was significant misclassification of those with and without OSA (AHI ≥10 events·h −1 ) on the autoCPAP report. Regarding response, residual OSA (AHI ≥10 events·h −1 ) was still evident in 24% of patients during autotitration. In some patients, autoCPAP fails to detect and/or respond to sleep apnoea. Clinicians should consider limitations of each device and use caution when using autoCPAP report statistics to verify effective treatment.
Sib-pair analysis detects elevated Lp(a) levels and large variation of Lp(a) concentration in subjects with familial defective ApoB.
Authors: Y Y van der Hoek, A Lingenhel, H G Kraft, J C Defesche, J J Kastelein, G Utermann
Journal: Journal of Clinical Investigation (1997)

Whether or not Lp(a) plasma levels are affected by the apoB R3500Q mutation, which causes Familial Defective apoB (FDB), is still a matter of debate. We have analyzed 300 family members of 13 unrelated Dutch index patients for the apoB mutation and the apolipoprotein(a) [apo(a)] genotype. Total cholesterol, LDL-cholesterol, and lipoprotein(a) [Lp(a)] concentrations were determined in 85 FDB heterozygotes and 106 non-FDB relatives. Mean LDL levels were significantly elevated in FDB subjects compared to non-FDB relatives (P < 0.001). Median Lp(a) levels were not different between FDB subjects and their non-FDB relatives. In contrast, sib-pair analysis demonstrated a significant effect of the FDB status on Lp(a) levels. In sib pairs identical by descent for apo(a) alleles but discordant for the FDB mutation (n = 11) each sib with FDB had a higher Lp(a) level than the corresponding non-FDB sib. Further, all possible sib pairs (n = 105) were grouped into three categories according to the absence/presence of the apoB R3500Q mutation in one or both subjects of a sib pair. The variability of differences in Lp(a) levels within the sib pairs increased with the number (0, 1, and 2) of FDB subjects present in the sib pair. This suggests that the FDB status increases Lp(a) level and variability, and that apoB may be a variability gene for Lp(a) levels in plasma.
THE BISULPHITE BINDING POWER OF THE BLOOD IN HEALTH AND IN DISEASE, WITH SPECIAL REFERENCE TO VITAMIN B1 DEFICIENCY 1
Authors: F. H. L. Taylor, Soma Weiss, Robert W. Wilkins
Journal: Journal of Clinical Investigation (1937)

There is increasing evidence that the biological function of vitamin B1 is concerned with oxi- dative processes in the living organism.In stud- ies of oxygen utilization by manometric methods, Peters and his coworkers (1, 2) have shown that there is increased oxygen uptake by deficient brain and kidney tissues in vitro following the addition of vitamin B1.In the same laboratory Thompson and Johnson (3, 4) found increased amounts of carbonyl compounds in the blood of B1 avitamin- otic pigeons and rats.Clinical confirmation has recently been given these experimental findings by Platt and Lu (5), who reported marked increases in the carbonyl compounds in the blood of patients with acute beriberi in the Orient.These authors measured the carbonyl com- pounds by means of the bisulphite binding power of the blood.Pyruvic acid has received most at-