tbuckley/cabot-search huggingface dataset:
Dopamine D<sub>1</sub> receptor ligands: Where are we now and where are we going
Authors: Jing Zhang, Bing Xiong, Xuechu Zhen, Ao Zhang
Journal: Medicinal Research Reviews (2008)

Abstract The dopamine (DA) D 1 receptor is the most highly expressed DA receptor subtype among the DA receptor family. Although the first DA D 1 receptor selective ligand SCH‐23390 ( 1 ) was introduced more than two decades ago, clinically useful D 1 receptor selective ligands are rare. A renewed interest was ignited in the early 1990s by Nichols and Mailman who developed dihydrexidine ( 27a ), the first high affinity full efficacy agonist for the D 1 receptor. Since then, a number of D 1 receptor agonists with full intrinsic activity, including A‐86929 ( 31a ), dinapsoline ( 32a ), dinoxyline ( 34a ), and doxanthrine ( 35a ) were identified. These compounds all contain a conformationally rigid structure. However, the fate of such ligands for clinical use as treatments of Parkinson's disease and other related CNS disorders is not optimistic since the clinical trial with dihydrexidine ( 27a ) was not successful. Further investigations on other compounds which are currently in the discovery stage will be crucial for determining the future of the D 1 receptor agonists. © 2008 Wiley Periodicals, Inc. Med Res Rev, 29, No. 2, 272–294, 2009
Breastfeeding and Antiepileptic Drugs
Authors: Kimford J. Meador
Journal: JAMA (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 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
Dutch nurse jailed for seven murders has conviction quashed
Authors: T. Sheldon
Journal: BMJ (2010)

In one of the worst miscarriages of justice in Dutch history, the nurse Lucia de Berk has had her conviction on seven charges of murder and three of attempted murder of babies and elderly people in her care quashed.

Ms de Berk, 48, who spent six years of a life sentence in jail for her alleged crimes, always denied the charges. Last week the chairman of the public prosecution service, Harm Brouwer, personally apologised and acknowledged her innocence.

The case has parallels with that of Sally Clark, the mother convicted in the United Kingdom of murdering her two children. In that case the expert witness Roy Meadow declared that the chances of Mrs Clark’s babies having both died as a result of cot deaths was 73 million to one.

In the case of Ms de Berk the court was told by an expert witness that more children had died on her shifts than …
Application of cationic liposomes for delivery of nucleic acids
Authors: Gayong Shim, Mi-Gyeong Kim, Joo Yeon Park, Yu-Kyoung Oh
Journal: Asian Journal of Pharmaceutical Sciences (2013)

Nucleic acid-based bioactive substances have recently emerged as a new class of next-generation therapeutics, but their development has been limited by their relatively weak delivery into target cells. Cationic liposomes have been studied as a means to enhance the stability of nucleic acid therapeutics in the bloodstream and improve their cellular delivery. As nucleic acid therapeutics, siRNA and plasmid DNA have been extensively tested for delivery using cationic liposomes. This review discusses recent progress in the application of cationic liposomes for the delivery of nucleic acid therapeutics.
Endgame: Glybera Finally Recommended for Approval as the First Gene Therapy Drug in the European Union
Authors: Seppo Ylä-Herttuala
Journal: Molecular Therapy (2012)

In an Editorial published earlier this year in Molecular Therapy,1 I described the regulatory uncertainty surrounding the evaluation of Glybera (alipogene tiparvovec) by the European Medicines Agency (EMA). Glybera is an adeno-associated viral vector engineered to express lipoprotein lipase in the muscle for the treatment of lipoprotein lipase deficiency. As with a typical TV serial, its regulatory saga has now had four acts, leading recently to a final recommendation by the EMA to approve Glybera in the European Union.
Psychosomatic Aspects in Self-Help Groups Made Up of Medical Patients
Authors: Hellmuth Freyberger
Journal: Psychotherapy and Psychosomatics (1979)

We present the psychosomatic aspects in self-help groups containing medical patients on the example of the ostomy group. Following the demonstration of the psycho-dynamic group processes, the patients' psychological characteristics are described as well as the aims of this type of self-help group. The specific ostomy group activities concern the visitors' service and the group work. Finally, we describe the psychotherapeutic interventions of the psychosomaticist.
Lansoprazole-associated collagenous colitis: unique presentation, similar to ischemic colitis
Authors: H. Yusuke, T. Jun, M. Naotaka, T. Yuichi, E. Yutaka, I. Kazuaki
Journal: Endoscopy (2009)

Recently, there have been reports of lansoprazole-associated collagenous colitis manifesting some characteristic clinical findings: chronic diarrhea, typical endoscopic findings, pathological evidence of collagen bands, and rapid clinical improvement after discontinuation of lansoprazole. We have also often encountered patients taking lansoprazole presenting with chronic diarrhea and typical endoscopic findings. Although one published article has stated that linear ulcers and ulcer scars should be considered specific for lansoprazole-associated collagenous colitis, another has not mentioned endoscopic findings at all [1] [2]. However, severe ulcers rarely cause colonic perforation [3]. Here we present a patient with lansoprazole-associated collagenous colitis who presented a unique clinical picture, similar to that of ischemic colitis.
MAST Suits-Reply
Authors: Keith Kaback
Journal: JAMA (1985)

<h3>In Reply.—</h3> We acknowledge the studies of Harman et al and Kron et al<sup>1,2</sup>indicating that elevation of intra-abdominal pressure impairs renal function. Inflation of the abdominal portion of the MAST suit is likely to increase intra-abdominal pressure, but this does not necessarily create the same situation as that experienced by the patients of Kron et al,<sup>2</sup>in whom increased intra-abdominal pressure resulted from postoperative complications, such as bleeding. Animal studies of renal compromise from MAST inflation have yielded variable results. Several human studies have suggested that any renal compromise is not clinically significant. Begin et al<sup>3</sup>reported no cases of renal failure in 47 patients with MAST use. Wayne and MacDonald<sup>4</sup>found a renal failure rate in hypotensive patients treated with MAST of 1%, a rate comparable with that of other studies where MAST was not employed. Despite the infrequency of renal failure with MAST
Molecular Form of Theophylline Responsible for Positive Inotropic Activity
Authors: Harold F. Hardman
Journal: Circulation Research (1962)

A comparison of the responses of the dog heart-lung, cat papillary muscle and perfused turtle heart preparations to equimolar doses of theophylline and 8-chlorotheophylline indicates that theophylline is a considerably more potent cardiac inotropic agent. This difference in activity has been related to the ionization characteristics of the two drugs. Studies performed on the isolated turtle heart over a pH range of 7.5 to 9.5, in which the ratio of ionized to nonionized theophylline is varied greatly, indicate that positive inotropic activity is determined by the concentration of nonionized theophylline presented to the heart in the perfusion medium. Similar studies with caffeine, which does not ionize to any appreciable degree over this pH range and thus exists almost exclusively in the nonionized form, indicate that positive inotropic activity is also determined by the concentration of nonionized caffeine presented to the heart in the perfusion medium. No significant difference in the positive inotropic activity of these two agents is discernible when they are compared on the basis of equimolar doses of nonionized drug at pH 7.5 and 8.5. No correlation was observed between the concentration of theophylline anion or cation in the extracellular or intracellular aqueous phase and positive isotropic activity over a wide range of drug concentration in the perfused turtle heart. The positive inotropic activity of theophylline and caffeine is influenced by the pH of the perfusion medium when the pH of this solution is less than 7.5. 8-Chlorotheophylline has been shown to be a potent positive inotropic agent, equivalent to theophylline in pharmacological response, when the concentration of nonionized drug is only one-fifteenth that required for an equivalent response from theophylline. The thesis is presented that the nonionized form of theophylline is the active form of the drug at its final site of action as a positive inotropic agent in the perfused turtle heart. It is suggested that a similar conclusion for the activity of this drug in mammalian cardiac tissue should be considered on the basis of the results obtained in the turtle heart and the indirect evidence obtained in mammalian tissues.
Is enteral nutrition a primary therapy in cancer patients?
Authors: F Bozzetti
Journal: Gut (1994)

At present, there is limited evidence for the role of enteral nutrition as a primary therapy in cancer patients. Cachexia commonly occurs in patients with advanced cancer. A consensus view from a large number of studies suggests that cachexia cannot be fully reversed by vigorous enteral nutritional support. A review is included of the available data on the effects of enteral nutritional support on the common indices of nutritional state and on the final outcome of patients receiving enteral nutrition in conjunction with radiotherapy or chemotherapy, or both. The 9nutritional9 effects are probably limited because the duration of the nutritional support in most studies consists of a few weeks while malnutrition in the cancer patients often occurs over many months.
Effect of Antioxidants on Androgen-Induced AP-1 and NF- B DNA-Binding Activity in Prostate Carcinoma Cells
Authors: M. O. Ripple, W. F. Henry, S. R. Schwarze, G. Wilding, R. Weindruch
Journal: JNCI Journal of the National Cancer Institute (1999)

Previous studies have suggested that male hormones (androgens) and certain forms of oxygen (reactive oxygen species) are linked to the development of prostate cancer. We hypothesized that androgens contribute to prostate carcinogenesis by increasing oxidative stress. We further hypothesized that antioxidants reduce prostate cancer risk by modulating androgen effects on cellular processes.To test these hypotheses, we looked for 1) a change in the level of reactive oxygen species in the presence of androgens, 2) androgen-induced binding activity of transcriptional activators AP-1 and NF-kappaB, whose activities are known to be altered during cell proliferation, and 3) the effect of antioxidants on androgen-induced transcription factor binding.Physiologic concentrations (1 nM) of 5alpha-dihydrotestosterone or 1-10 nM R1881, a synthetic androgen, produced sustained elevation of AP-1 and NF-kappaB DNA-binding activity in LNCaP cells, an androgen-responsive human prostate carcinoma cell line. Androgen-independent DU145 cells (another human prostate carcinoma cell line) were unaffected by R1881 treatment. AP-1-binding activity increased 5 hours after 1 nM R1881 treatment; NF-kappaB DNA-binding activity increased after 36 hours. Both activities remained elevated for at least 120 hours. Nuclear AP-1 and NF-kappaB protein levels were not elevated. Antioxidant vitamins C plus E blocked both androgen-induced DNA-binding activity and production of reactive oxygen species.Physiologic concentrations of androgens induce production of reactive oxygen species and cause prolonged AP-1 and NF-kappaB DNA-binding activities, which are diminished by vitamins C and E.
Low-Dose Radioactive Endovascular Stents Prevent Smooth Muscle Cell Proliferation and Neointimal Hyperplasia in Rabbits
Authors: Christoph Hehrlein, Christina Gollan, Klaus Dönges, Jürgen Metz, Reimer Riessen, Peter Fehsenfeld, Eberhard von Hodenberg, Wolfgang Kübler
Journal: Circulation (1995)

Background Restenosis induced by smooth muscle cell (SMC) migration and proliferation and neointimal thickening limits the clinical success of balloon angioplasty and stent implantation. In this study, the long-term effect of endovascular irradiation via low-dose radioactive stents on neointima formation was compared with conventional stent implantation in a rabbit model. Methods and Results Palmaz-Schatz stents were made radioactive in a cyclotron. The stents had a very low activity (maximum, 35 μCi), and thus, manipulation did not require extensive radiation protection. One, 4, 12, and 52 weeks after the implantation of nonradioactive stents and radioactive stents in rabbit iliac arteries, neointimal thickening was analyzed by quantitative histomorphometry. Immunostaining for endothelial cell von Willebrand factor, macrophages, SMC α-actin, collagen type I, and proliferating cell nuclear antigen (PCNA) was performed to determine radiation-induced changes in the arterial wall. SMC proliferation was quantified by computer-assisted cell counting of PCNA-immunoreactive cells. Neointima formation was markedly suppressed by the implantation of radioactive stents in a dose-dependent fashion at all observed time points. At peak proliferative activity of SMCs 1 week after nonradioactive stent implantation, 30±2% of SMCs in the neointima were proliferating, compared with 0.5±0.1% of SMCs after implantation of stents with an initial activity of 35 μCi ( P &lt;.001). The neointima covering radioactive stents was characterized by decreased smooth muscle cellularity and increased extracellular matrix formation. Further, we observed a delayed endothelialization depending on the radiation dose. No difference in vascular thrombosis was found after nonradioactive and radioactive stent implantation. Conclusions The results of this study clearly indicate that low-dose radioactive endovascular stents potently inhibit SMC proliferation and neointimal hyperplasia in rabbits.
Childhood Asthma Risk
Authors: Joan Stephenson
Journal: JAMA (2007)

One-month-old infants whose throats are colonized by certain bacteria are at substantially increased risk for recurrent wheeze and asthma, according to a prospective longitudinal birth-cohort study by Danish researchers (Bisgaard H et al. N Engl J Med. 2007;357[15]:1487-1495).
Role of Ca2+ in secretagogue-stimulated breakdown of phosphatidylinositol in rat pancreatic islets.
Authors: K V Axen, U K Schubart, A D Blake, N Fleischer
Journal: Journal of Clinical Investigation (1983)

Breakdown of phosphatidylinositol (PI) has been shown to be increased during Ca2+-mediated stimulation of cellular responses in many systems and has been proposed to be involved in stimulus-secretion coupling. The effects on PI breakdown of insulin secretagogues that alter cellular Ca2+ or cyclic (c)AMP levels were investigated in perifused rat islets of Langerhans. Isolated islets were labeled with myo-[2-3H(N)]inositol and the efflux of 3H-labeled metabolites was monitored. Glucose (16.7 mM) greatly increased 3H release in a manner that paralleled the second phase of the insulin secretory response; by 60 min, the amount of [3H]PI in the islet decreased by 50%. Removal of Ca2+ from the perifusate or blockade of Ca2+ entry through the voltage-dependent channels by D600 (20 microM) abolished the glucose-induced increase in 3H efflux. Depolarization with 47 mM K+, which increases Ca2+ entry, stimulated protracted 3H and insulin release. Glucose-stimulated output of 3H was not prevented by epinephrine (1 microM) even though the insulin response was abolished. In contrast, 3H output was not affected by isobutylmethylxanthine (1 mM), known to raise cellular levels of cAMP, although insulin release was stimulated. These findings indicate that PI breakdown is not related to the exocytotic process since stimulation of insulin release and PI breakdown could be uncoupled, and that it is not associated with cAMP-mediated regulation of insulin release. PI breakdown in islets differs from the immediate, transient phenomenon reported in other systems in both its timing and requirement for Ca2+. It appears to result from the entry of Ca2+ and not to be the mechanism by which glucose initiates Ca2+ influx.
The Agnew Clinic
Authors: Richard L. Keenan
Journal: JAMA (1986)

<h3>To the Editor.—</h3> A small but important correction must be made in the otherwise delightful discussion by M. Therese Southgate, MD,<sup>1</sup>of Thomas Eakins' painting<i>The Agnew Clinic</i>, which appeared on the May 23/30, 1986,<i>JAMA</i>cover. While the anesthetist in the picture is correctly identified as a young house officer, and the anesthetic is undoubtedly ether, Dr Southgate errs in referring to the method as "open-drop." <i>The Agnew Clinic</i>accurately records an earlier and cruder method of etherization, which used a paper cone stuffed with cotton. Instead of being dripped in a continuous process, ether was poured into the cotton before the cone was placed over the face.<sup>2</sup>This one-shot method worked well in the era before asepsis, when surgery was short and superficial. Eakins has clearly depicted a white paper cone in the left hand of the anesthetist. In his earlier painting,<i>The Gross Clinic</i>, Eakins
HIGH FIELD MR CAROTID VESSEL WALL IMAGING: REPRODUCIBILITY OF FIVE DIFFERENT MR WEIGHTINGS
Authors: Eleanore S. Kroner, Jos J. Westenberg, Rob J. van der Geest, Joost Doornbos, Joanne D. Schuijf, Eline Kooi, Albert de Roos, Jeroen J. Bax, Hildo J. Lamb, Hans-Marc Siebelink
Journal: Journal of the American College of Cardiology (2011)
Percutaneous Transluminal Coronary Angioplasty in Octogenarians
Authors: Mohamed O. Jeroudi
Journal: Annals of Internal Medicine (1990)

Objective: To assess the safety and short- and long-term outcomes of percutaneous transluminal coronary angioplasty in octogenarians. Design: Retrospective chart review of clinical series. Setting: Referral-based university medical center. Patients: Consecutive series of 54 octogenarian patients (mean age, 82.4 years) who had percutaneous transluminal coronary angioplasty between March 1980 and December 1988. Of these patients, 91% presented with severe angina (Canadian Cardiovascular Society Class III or IV); 59% had unstable angina. Twenty-six patients (48%) had had a previous myocardial infarction and 15 (28%) had had previous coronary artery bypass surgery. Multivessel disease was present in 44 patients (81%). Follow-up ranged from 1 to 50 months (mean, 19 months). Intervention: Percutaneous transluminal coronary angioplasty. Measurements and Main Results: The angiographic success rate was 50 of 54 (93%; 95% CI, 81% to 98%) and the clinical success rate was 49 of 54 (91%; CI, 79% to 97%). Two patients had procedure-related myocardial infarction. Two patients died in the hospital, 1 from cardiac tamponade because of pacemaker perforation and 1 from cardiogenic shock after a myocardial infarction despite successful angioplasty. During the follow-up period 4 patients required bypass surgery, 2 had myocardial infarction, and 7 died (4 deaths were cardiac). Eleven patients (20%) had restenosis, 7 of whom were managed with repeat angioplasty, including 1 patient who had four procedures. At follow-up, 42 of 45 survivors (93%) were asymptomatic or had class II angina. The Kaplan-Meier survival for all patients, including those who died in the hospital, was 87% at 1 year and 80% at 3 years. Cumulative freedom from major cardiac events (death, myocardial infarction, or coronary bypass surgery) was 81% at 1 year and 78% at 3 years. Conclusions: Percutaneous transluminal coronary angioplasty can be done in octogenarians with a high rate of angiographic and clinical success, low complication rate, and a favorable long-term (3-year) outcome. As such, it is a treatment option in managing advanced coronary artery disease in this fragile group of patients.
A Doughnut Sign of a Hydatid Cyst of the Liver on F-18 FDG PET/CT
Authors: Hakan Demir, Metin Halac, Selda Yilmaz, Serkan Isgoren, Kerim Sonmezoglu, Ilhami Uslu
Journal: Clinical Nuclear Medicine (2008)

A 59-year-old man underwent a whole-body PET/CT scan to evaluate the metabolic activity of a nodule in the upper lobe of the left lung seen on CT. Slightly increased peripheral activity with a large hypometabolic region centrally, a so-called doughnut sign, was seen in the right lobe of the liver. After the diagnosis of a hydatid cyst of the liver, the patient underwent surgery. This case demonstrates a hydatid cyst that caused increased F-18 FDG uptake as a doughnut pattern.
Cellular Sensitivity to Tumors
Authors: John R. David
Journal: New England Journal of Medicine (1970)

For many years investigators have looked for an immune response to tumor antigens in the hope that this would provide the means for manipulating clinical states in which tumor growth threatens the host.1 The paper in this issue of the Journal by Fass, Herberman and Ziegler provides further evidence for a link between cellular immune responses and host control of malignant tumors, for the authors demonstrate that a delayed response to autologous tumor is related to the course of disease. They report that in 12 patients with Burkitt's lymphoma who were skin tested at the time of tumor excision, only . . .
Superior Pharyngeal Constrictor Activation in Obstructive Sleep Apnea
Authors: SAMUEL T. KUNA, JAMES S. SMICKLEY
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Respiratory-related superior pharyngeal constrictor (SPC) muscle activity was determined in 18 obstructive sleep apnea (OSA) patients during wakefulness and sleep. Hooked-wire electrodes were implanted into the SPC muscle via a nasopharyngoscope. During quiet breathing in wakefulness, phasic expiratory SPC-muscle activity was consistently present in six subjects and intermittently present in 12 subjects, particularly following a swallow. The SPC muscle showed two patterns of activation during spontaneous obstructive apneic episodes in non-rapid-eye-movement (NREM) sleep: (1) activation during airway reopening, with or without waning phasic or tonic activation in the first half of the ensuing apnea (n = 13); and (2) absence of activation during apneas or arousals (n = 5). Activation on airway reopening following spontaneous apneas usually occurred on inspiration. When the apneic episodes were eliminated by application of nasal continuous positive airway pressure (CPAP), SPC-muscle activity was absent in NREM sleep in 16 subjects, but phasic expiratory activity persisted in two subjects. Sudden withdrawal of nasal CPAP in NREM sleep induced airway closure without a change in SPC-muscle activity. Arousal prior to or immediately after reapplication of nasal CPAP was associated with SPC-muscle activation during inspiration or expiration, and airway reopening. The results in OSA subjects indicate that SPC-muscle activation is similar to that of pharyngeal dilator muscles during spontaneous and induced apneas, and is not necessary to induce upper-airway closure during NREM sleep in OSA subjects.