tbuckley/cabot-search huggingface dataset:
The influence of antimalarial treatment on IL-1β, IL-6 and TNF-α mRNA expression on UVB-irradiated skin in systemic lupus erythematosus
Authors: A. Wozniacka, A. Lesiak, J. Boncela, K. Smolarczyk, D.P. McCauliffe, A. Sysa-Jedrzejowska
Journal: British Journal of Dermatology (2008)

Background There are very few data addressing the mechanisms of antimalarial treatment benefit locally within the skin of patients with lupus erythematosus, at the level of cytokine messenger RNA (mRNA) expression. Objectives The aim of this study was to evaluate whether 3 months of monotherapy with chloroquine influences the mRNA skin expression of interleukin (IL)‐1β, IL‐6 and tumour necrosis factor‐α (TNF‐α) in nonirradiated and locally ultraviolet B (UVB) irradiated nondiseased skin of patients with systemic lupus erythematosus (SLE). Patients/Methods Skin biopsies were collected from 14 patients with SLE 24 h after irradiation at one site and from an adjacent unirradiated site, before and after 3 months of chloroquine treatment. Messenger RNA levels for IL‐1β, IL‐6 and TNF‐α were determined by relative quantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR). Results There were no significant differences in the levels of mRNA cytokine expressions in the unirradiated sites before and after 3 months of chloroquine administration. In the irradiated sites, the expression of all three cytokine mRNA levels was significantly higher than in the unirradiated group, approximately 24 h after irradiation, before chloroquine treatment. Significantly lower expression of IL‐1β, IL‐6 and TNF‐α mRNAs was noted in irradiated skin samples after 3 months of chloroquine treatment. Conclusions These results demonstrate the local inhibitory effects of chloroquine on UVB‐induced upregulation in the mRNA expression of proinflammatory cytokines in irradiated skin of SLE patients, and provide further insight into the apparent immunomodulatory, anti‐inflammatory and photoprotective properties of chloroquine.
MODERN METHODS OF ELECTROSHOCK THERAPY
Authors: E. H. PARSONS, S. R. BANET, J. U. KEATING, G. H. LAWRENCE
Journal: American Journal of Psychiatry (1955)

We have attempted to present in a somewhat chronologic form the growth and development of what we have termed a modern form of the application of electroshock therapy. It is well established that electroshock therapy benefits some psychiatric syndromes. We believe that by applying techniques now available this therapy may be applied safely with minimal complications, at the same time retaining benefits observed in its original form of application as well as, perhaps, additional ones. We have approached our objective—retention of therapeutic efficacy with the diminution of complications—by a series of stages or steps which, in retrospect, indicate that we elected to follow certain courses of action instead of others. We fully agree with Kalinowsky that electroshock therapy is made complicated by use of additional masking or modifying agents. We recognize that our use of sodium pentothal anesthesia is such a masking and complicating agent but justify its use because of the ability of the type of electrical equipment used to overcome the effect of the pentothal anesthesia if it happens that the operator uses more of this substance than is necessary. The very form of equipment we use is that which would be used were we treating a patient for respiratory cessation as a result of pentothal poisoning. The utilization of electroshock therapy today implies concepts of objectives, neurophysiologic states, and avoidance of complications which formerly could be accepted as reasonable hazards. Pus, once regarded as laudable by surgeons, would now constitute malpractice. Similarly, "complications" of electroshock, as utilized originally, no longer find adequate defense in modern treatment. Judiciously applied to selected cases for particular purposes, electroshock has reached a state of therapeutic acceptance. Its application as a panacea for all psychiatric syndromes in a "routine" manner is injudicious and may be hazardous. Modern electroshock therapy implies the utilization of both technical skills and clinical acumen in making the treatment less hazardous than the disease. Electroshock is a valuable tool; it can be a dangerous weapon.
Visualization of the Spleen with Radiophosphate in Severe Combined Immunodeficiency Disease
Authors: M. CHARRON, L. ROSENTHALL
Journal: Clinical Nuclear Medicine (1988)

This is a case report of a 12-month-old male suffering from severe combined immunodeficiency disease who demonstrated an intense concentration of MDP in the spleen. The precise mechanism for this accretion is not known and remains speculative.
Regulation of<i>µ</i>-Opioid Receptors: Desensitization, Phosphorylation, Internalization, and Tolerance
Authors: John T. Williams, Susan L. Ingram, Graeme Henderson, Charles Chavkin, Mark von Zastrow, Stefan Schulz, Thomas Koch, Christopher J. Evans, MacDonald J. Christie
Journal: Pharmacological Reviews (2013)

Morphine and related <i>µ</i>-opioid receptor (MOR) agonists remain among the most effective drugs known for acute relief of severe pain. A major problem in treating painful conditions is that tolerance limits the long-term utility of opioid agonists. Considerable effort has been expended on developing an understanding of the molecular and cellular processes that underlie acute MOR signaling, short-term receptor regulation, and the progression of events that lead to tolerance for different MOR agonists. Although great progress has been made in the past decade, many points of contention and controversy cloud the realization of this progress. This review attempts to clarify some confusion by clearly defining terms, such as desensitization and tolerance, and addressing optimal pharmacological analyses for discerning relative importance of these cellular mechanisms. Cellular and molecular mechanisms regulating MOR function by phosphorylation relative to receptor desensitization and endocytosis are comprehensively reviewed, with an emphasis on agonist-biased regulation and areas where knowledge is lacking or controversial. The implications of these mechanisms for understanding the substantial contribution of MOR signaling to opioid tolerance are then considered in detail. While some functional MOR regulatory mechanisms contributing to tolerance are clearly understood, there are large gaps in understanding the molecular processes responsible for loss of MOR function after chronic exposure to opioids. Further elucidation of the cellular mechanisms that are regulated by opioids will be necessary for the successful development of MOR-based approaches to new pain therapeutics that limit the development of tolerance.
Abstract P2-16-11: Impact of adjuvant trastuzumab (T) with chemotherapy on breast cancer specific and cardiac outcomes in older women with small, node-negative HER2-positive breast cancer
Authors: KA Cadoo, PG Morris, S Patil, L Norton, CA Hudis, HL McArthur
Journal: Cancer Research (2013)

Abstract Introduction: For women with high risk early breast cancer that overexpresses HER2, the role of adjuvant T with chemotherapy is well established. Although the benefits of this approach in women with small, node negative tumors are less well defined, we previously published a retrospective sequential cohort study that suggested that T with chemotherapy is active in this setting. However there are few data about the safety and efficacy of adjuvant T in older women with small, node negative HER2+ breast cancer. Thus, this we conducted a retrospective study of breast cancer specific and cardiac outcomes for this subset. Methods: From our previously reported dataset, we identified women &amp;gt; 60y with &amp;lt;2 cm, node-negative HER2+ breast cancer. We identified a “no-T” cohort of 32 women diagnosed Jan ‘02 - May ‘05 and a “T” cohort of 39 patients diagnosed May ‘05 - Dec ‘08. Electronic medical records were reviewed to examine risk factors and incidence of cardiotoxicity as well as patient outcomes including distant disease-free survival (DDFS) and overall survival (OS). Results: Women in the two cohorts had similar baseline characteristics including cardiac risk factors (Table 1). There were no cardiac events in the no-T group. In the T group, 3 patients discontinued T due to a cardiac event: 1 with asymptomatic decline in ejection fraction (EF), 1 with atrial fibrillation and dyspnea, and 1 with symptomatic EF decline associated with myocardial infarct and valvular disease. Patients in both cohorts had excellent disease control at a median follow up of 9y and 6y for the no-T and T cohorts respectively. The 3y DDFS numerically favors the T cohort, the confidence intervals are broad and overlapping (Table 1). There were no detectable differences in OS between groups. In our previous report (not selected for age), DDFS at 3yrs was 95% (90-99) and 100% in the no-T (N = 106) and T (N = 155) cohorts respectively. Conclusion: In this small retrospective study, older women with small, node negative HER2+ breast cancers had excellent disease control and a low risk of cardiotoxicity. The possible benefits of T in this setting are consistent with prior reports uncontrolled for age. Table 1 No Trastuzumab N = 32 N (%)Trastuzumab N = 39 N (%)Tumor Size (cm), median (range)1.4 (0.1-2.0)1.3 (0.5-2.0)Multifocal Disease6 (19)4 (10)Grade 324 (75)33 (85)ER Positive20 (63)20 (51)Age, median (range)66 (60-85)65 (60-82)BMI, median (range)24.7 (18.2-34.2)27.3 (18.2-47.1)Chemotherapy16 (50)39 (100)Radiotherapy23 (72)25 (64)Hypercholesterolemia11 (34)18 (46)Hypertension12 (38)13 (33)3yr DDFS (95% CI)91% (74-97)97% (83-100)3yr OS (95% CI)97% (80-100)97% (83-100) Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-16-11.
Sudden Unexplained Nocturnal Deaths
Authors: Karl Speiser
Journal: JAMA (1985)

To the Editor.—  Sudden unexplained nocturnal deaths (SUND) among Southeast Asian males, as described in a CASE REPORT inThe Journal, 1 is known in Japan as pok-kuri disease and in the Philippines as bangungut . 2 In a recent pathological study of SUND from Japan, 3 fulminant deletion of myoglobin from myocardial fibers in multiple disseminated foci, with deposition of myoglobin in the interstitium, was found. It was speculated that the multiple necroses were due to functional spasm of main coronary branches in a state of vagotonia during sleep. The terminal event might be ventricular fibrillation caused by diffusion of potassium from necrotic sites. Another communication suggested that there may be congenital lesions of the conduction system in victims of SUND. 4   Because subjects prone to SUND are healthy men of younger age, screening of the East Asian (immigrant) population seems impossible. Awareness by relatives and prompt delivery of resuscitation
Administration of an aldose reductase inhibitor induces a decrease of collagen fluorescence in diabetic rats.
Authors: G Suárez, R Rajaram, K C Bhuyan, A L Oronsky, J A Goidl
Journal: Journal of Clinical Investigation (1988)

As a consequence of an increased flux through the sorbitol pathway fructose levels rise in various tissues in diabetes. Also, in vitro nonenzymatic fructosylation of protein induces the generation of fluorescence at a rate 10 times greater than glucosylation. The administration of sorbinil, an aldose reductase inhibitor known to lower tissue fructose concentration, to experimental diabetic rats led to a decrease in the fluorescence related to advanced Maillard products in their skin collagen. This effect is consistent with the in vivo occurrence of nonenzymatic fructosylation of collagen. A potential pathogenetic role for this posttranslational modification in diabetic complications should be considered.
Fatal Chloroquine Poisoning: Two More Cases
Authors: James R. Mason, Khurshid Khan, H. Leslie Frewing
Journal: JAMA (1964)

<h3>To the Editor:—</h3> Reports of patients with acute chloroquine poisoning have pointed out the rapid, sudden collapse with respiratory and cardiac arrest.<sup>1</sup>This letter describes two patients with similar collapse but with electrocardiographic evidence of persistent, though grossly abnormal, cardiac activity. <h3>Case 1.—</h3> A 3-year-old boy was first seen with the story that he had taken seven chloroquine phosphate tablets (a total of 1.75 gm) about a half hour previously. He was drowsy and complained of difficulty in seeing. His pulse was 120 beats per minute and there were a few rhonchi in the chest. A stomach tube was immediately passed in a futile attempt to remove part of what was a fatal dose. A small amount of mucus containing a few granules was aspirated. Within five minutes respirations stopped and the pulse and heartbeat could not be detected. Tracheal intubation with oxygen by bag compression and external cardiac
Molecular pathogenesis of mantle cell lymphoma
Authors: Pedro Jares, Dolors Colomer, Elias Campo
Journal: Journal of Clinical Investigation (2012)

Mantle cell lymphoma is a B cell malignancy in which constitutive dysregulation of cyclin D1 and the cell cycle, disruption of DNA damage response pathways, and activation of cell survival mechanisms contribute to oncogenesis. A small number of tumors lack cyclin D1 overexpression, suggesting that its dysregulation is always not required for tumor initiation. Some cases have hypermutated IGHV and stable karyotypes, a predominant nonnodal disease, and an indolent clinical evolution, which suggests that they may correspond to distinct subtypes of the disease. In this review, we discuss the molecular pathways that contribute to pathogenesis, and how improved understanding of these molecular mechanisms offers new perspectives for the treatment of patients.
Populations, Public Health, and the Law
Authors: Edward P. Richards
Journal: JAMA (2009)

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
Migrants' access to health care needs to be improved, conference is told
Authors: J. Hearn-Walker
Journal: BMJ (2009)

The “myth of health tourism” and a culture of suspicion surrounding asylum seekers are among the factors impeding access of migrants to primary and secondary health care, delegates at a conference in London on 21 March heard.

The aim of the annual conference of Medecins du Monde UK was to identify ways in which healthcare professionals can help make health care more accessible to migrants. This issue is becoming increasingly important, as it is estimated that over …
Abstract 2069: A novel berbamine derivative induces apoptosis of chemotherapy-resistant human osteosarcoma cells through activation of ROS/JNK signaling
Authors: Fan Yang, Sangkil Nam, Robin Zhao, Yan Tian, David Horne, Richard Jove
Journal: Cancer Research (2012)

Abstract Osteosarcoma is the most common primary bone tumor in children and adolescence. There is a critical need to find more potent drugs for patients with metastatic or recurrent disease. Berbamine (BBM) is a natural compound derived from the Berberis amurensis plants. BBM and its derivatives have been shown to have anti-tumor effects in several cancers. Here, we report that a new berbamine derivative, BBMD3 (5 µM), induces apoptosis of human osteosarcoma cells, which are resistant or insensitive to conventional chemotherapy including cisplatin, doxorubicin and methotrexate. BBMD3 inhibited cell viability and induced apoptosis of G292, KHOS and MG-63 human osteosarcoma cells in a time- and dose-dependent manner. BBMD3 activated caspase-3, and cleaved poly(ADP-ribose) polymerase (PARP). Caspase inhibitor (Z-VAD-FMK) could rescue tumor cells from the cytotoxic effects of BBMD3 on cell survival. Importantly, BBMD3 increased phosphorylation of c-Jun N-terminal kinase (JNK) in these tumor cells, resulting in activation of its substrates, c-Jun and c-Fos. Moreover, reactive oxygen species (ROS) scavenger, N-acetylcysteine (NAC), blocked the phosphorylation of JNK and c-Jun induced by BBMD3. However, Z-VAD-FMK treatment did not inhibit the induction of phosphorylated JNK and c-Jun by BBMD3, suggesting that phosphorylation of JNK and c-Jun occurred before activation of caspases. BBMD3 increased the expression of the pro-apototic gene Bad, associated with apoptosis induction. Finally, BBMD3 also decreased the expression of cyclin D1, a positive cell cycle regulator, which is correlated with growth suppression in osteosarcoma cells. Collectively, these findings indicate that BBMD3 is a potentially promising drug for the treatment of chemotherapy-resistant osteosarcomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2069. doi:1538-7445.AM2012-2069
What to cut
Authors: Tony Delamothe
Journal: BMJ (2009)

After the years of plenty the NHS will have to tighten its belt

In the first decade of the Labour government, spending on the NHS rose at an annual rate of 6.1%. This year and next it will rise at 5.5%, unless the current financial storm blows this commitment off course. From April 2011, spending will rise at 1%, if at all. This means that the NHS has two years to tighten its belt. I learnt all this at a recent health strategy summit organised by the Nuffield Foundation, which got me thinking about ways to save money. Here’s my top 10.

As Jo Ellins and colleagues pointed out in their recent article on the primary care market, “spare capacity and instability [in the NHS] may be necessary to create the conditions for choice and competition” ( BMJ 2009;338;b1127, doi:10.1136/bmj.b1127). The independent sector treatment centres, liberalisation of the primary care market, and the polyclinics mooted by the health minister Ara Darzi were intended to produce both. Yet patients’ appetite for choice is minimal, as last year’s joint report from the Healthcare …
Radiotherapy in the treatment of Hodgkin's disease.
Authors: A R Timothy, S B Sutcliffe, A G Stansfeld, P F Wrigley, A E Jones
Journal: BMJ (1978)

Eighty-seven untreated patients with localised Hodgkin's disease seen from 1969 to 1975 were treated by megavoltage radiotherapy. All were followed for at least 33 months. Thirty-three patients were staged clinically and 54 underwent more extensive investigation by lapaortomy and splenectomy. The projected five-year disease-free survival figures for patients staged surgically were 100% for the 17 with stage IA disease, 70% for the 19 with stage IIA disease, and 73% for the 15 with stage IIIA disease. These results were consistently better than those obtained in clinically staged patients. Five patients died, one of them without evidence of Hodgkin's disease. As irradiation seems to produce excellent disease-free survival in most patients who are staged accurately at diagnosis, caution should be exercised in the routine use of adjuvant chemotherapy until the full risks of such treatment are clear. Combined modality therapy may be appropriate for patients with unfavourable features at presentation.
Molecular fingerprinting of the podocyte reveals novel gene and protein regulatory networks
Authors: Melanie Boerries, Florian Grahammer, Sven Eiselein, Moritz Buck, Charlotte Meyer, Markus Goedel, Wibke Bechtel, Stefan Zschiedrich, Dietmar Pfeifer, Denis Laloë, Christelle Arrondel, Sara Gonçalves, Marcus Krüger, Scott J. Harvey, Hauke Busch, Joern Dengjel, Tobias B. Huber
Journal: Kidney International (2013)
Heat in Tumor Therapy-Reply
Authors: Harry H. Le Veen
Journal: JAMA (1976)

Electrocautery employs an electrically heated hot wire, which is seldom used in the United States. What is probably meant is electrocoagulation, which uses dampened sine waves of RF (radiofrequency) currents ranging from 0.5 to 1.5 MHz. Cutting currents have a plain sinewave configuration. The active electrode is a point source that generates heat on contact. In contrast, our technique included both dielectric and inductive heating of tissue in an entire region of the body containing the cancer—clearly different from electrocoagulation and electrocautery. Temperatures in the tumor reach 44 to 48 C during therapy. The temperatures in the center of the tumor may exceed these values. Although most tumors resorb, there seems to be a critical mass that can be absorbed for any vascular bed. Large tumors form necrotic masses that may require surgical intervention. The fractional destruction of tumors is unwise and contributes to spread and thermal resistance.
Effects of albumin-bilirubin complexes with syngeneic or allogeneic albumin on DNA and protein synthesis in liver and spleen of partially hepatectomized rats
Authors: Olga Yu Abakumova, Ludmila M. Fedorova, Andrey A. Popov, Vladimir S. Li, Susanna L. Arkhangelskaya, Galina I. Bachmanova
Journal: Journal of Hepatology (1994)
Mineralocorticoid Receptor Antagonism in Experimental Atherosclerosis
Authors: Sanjay Rajagopalan, Damon Duquaine, Steven King, Bertram Pitt, Paresh Patel
Journal: Circulation (2002)

Background — Aldosterone has been implicated in the effects of angiotensin II in the vasculature. We hypothesized that there is local expression of the mineralocorticoid receptor (MR) in the vasculature and that the use of a selective aldosterone receptor antagonist (SARA) improves endothelial function in early atherosclerosis. Methods and Results — New Zealand rabbits were placed on normal chow or 1% cholesterol diets, randomized to placebo or SARA (eplerenone, 50 mg/kg twice daily), and killed at the end of 6 weeks for various studies. In the hyperlipidemic (HL) chow group, there was a 2.3-fold increase in superoxide (O 2 ·− ) generation. SARA normalized O 2 · − generation in intact aortas and reduced NADH and NADPH oxidase activity to basal levels (0.31±0.04 and 0.27±0.02 in HL versus 0.16±0.05 and 0.07±0.02 in HL-SARA, respectively; P &lt;0.01 by ANOVA). This was associated with improvements in peak relaxations to the endothelial-dependent agonist acetylcholine (82±6% in HL-SARA versus 61±4 in HL; P &lt;0.01 by ANOVA; ED 50 6.8×10 −8 mol/L in HL-SARA and 1.2×10 −7 mol/L in HL; P =NS) to near-normal levels. Vessels from the HL group demonstrated hyperreactivity to angiotensin II that could not be corrected with SARA. Plasma aldosterone levels by radioimmunoassay demonstrated a 4- to 5-fold increase in response to SARA but no differences with lipid feeding. Real-time reverse transcriptase–polymerase chain reaction studies revealed expression of MR in the aorta of HL rabbits and those of controls. Conclusions — MR antagonism improves endothelial function and reduces O 2 ·− generation in diet-induced atherosclerosis. Targeting aldosterone by blocking its receptor has potential antiatherosclerotic effects.