tbuckley/cabot-search huggingface dataset:
1021. Suppression and Replacement Strategies for Rhodopsin-Linked Autosomal Dominant Retinitis Pigmentosa
Authors: Arpad Palfi, Mary O'Reilly, Sophia Millington-Ward, Marius Ader, Naomi Chadderton, Gearoid Tuohy, Anna-Sophia Kiang, Niamh McNally, Marian Humphries, Peter Humphries, Paul F. Kenna, G. Jane Farrar
Journal: Molecular Therapy (2006)

Top of pageAbstract
Retintis pigmentosa (RP) is a term used to describe a group of inherited retinopathies primarily involving photoreceptor cell loss. The clinical and genetic heterogeneity inherent in RP has been highlighted with over 35 disease genes now characterised (http://www.sph.uth.tmc.edu/retnet/home.htm). One of the first genes to be identified as causative of autosomal dominantly inherited RP (adRP) was the rhodopsin gene (RHO) which encodes the light sensitive pigment present in rod photoreceptor cells. Over 100 mutations have been characterised in this gene, highlighting the mutational heterogeneity present in adRP. Gene therapies targeting a disorder such as RHO-linked adRP will likely require suppression of the mutant allele causative of the disease pathology. For this reason, RNA interference (RNAi) has been explored as a means to provide potent suppression of the target RHO gene both in cell culture and organotypic culture, that is, in retinal explant tissue. A number of synthesised siRNAs have been found to elicit potent suppression of expression of RHO in HELA cells as assessed at the mRNA and protein levels. In addition, retinal explants from transgenic mice expressing a RHO gene, were electroporated with short hairpin RNA constructs (shRNAs) at post-natal day zero. Suppression of RHO expression was evaluated by quantitative real-time rt PCR 14 days subsequent to electroporation of shRNAs and notably potent suppression of the target gene was obtained in these retinal explants. Results from the study provide evidence that RNAi may be used as a means of suppressing expression of RHO in cell culture and in the target cell type for adRP, that is, photoreceptors. A therapeutic strategy for adRP, in addition to suppression of the mutant and wild-type RHO genes, will require a replacement element whereby a RHO gene capable of avoiding suppression is supplied. A transgenic mouse has been generated which expresses a wild-type human RHO protein from a cDNA modified at an siRNA target site, exploiting the degeneracy of the genetic code, to avoid suppression by RNAi. Retinal function and thickness as analysed using ERG and histology suggests that the modified human replacement RHO gene rescues the disease pathology in a knockout rho mouse model. This work demonstrates that the replacement element of the strategy works well in a transgenic animal.
Drug Use in Pregnancy: Mother and Child
Authors: Richard Fulroth
Journal: JAMA (1990)

The "crack cocaine" crisis has greatly increased the need for the health care practitioner to have an understanding of the identification and management of the substance-abusing mother and the approach to the follow-up of the drugexposed infant. The management of the substanceabusing mother includes evaluation of many factors: the complex interaction of drugs, including cigarettes and alcohol; often the lack of prenatal care; inadequate nutrition; mood disorders; and the possible involvement of sexually transmitted diseases. Care of a drugexposed infant requires diagnosis of the physical injury and sensitive follow-up techniques to monitor potential developmental delay.<i>Drug Use in Pregnancy: Mother and Child</i>introduces a comprehensive treatment model used at Northwestern University. Editor Ira Chasnoff, MD, has organized the 13 chapters around the Perinatal Services Project, a comprehensive treatment model for drug abuse during pregnancy. The 18 contributing authors describe the individual areas of risk, such as pharmacology, recognition, management, mother-infant
Five Years After To Err Is Human
Authors: Lucian L. Leape, Donald M. Berwick
Journal: JAMA (2005)

Five years ago, the Institute of Medicine (IOM) called for a national effort to make health care safe. Although progress since then has been slow, the IOM report truly "changed the conversation" to a focus on changing systems, stimulated a broad array of stakeholders to engage in patient safety, and motivated hospitals to adopt new safe practices. The pace of change is likely to accelerate, particularly in implementation of electronic health records, diffusion of safe practices, team training, and full disclosure to patients following injury. If directed toward hospitals that actually achieve high levels of safety, pay for performance could provide additional incentives. But improvement of the magnitude envisioned by the IOM requires a national commitment to strict, ambitious, quantitative, and well-tracked national goals. The Agency for Healthcare Research and Quality should bring together all stakeholders, including payers, to agree on a set of explicit and ambitious goals for patient safety to be reached by 2010.
Helical Computed Tomography of the Liver: Techniques, Applications and Pitfalls
Authors: P. C. Freeny
Journal: Endoscopy (1997)

Helical computed tomography (CT) of the liver has greatly improved both the accuracy and characterization of focal liver masses. This paper focuses on specific techniques for helical CT, including dual helical CT (acquisition of scans during both the arterial and portal venous phases of contrast enhancement), high-dose helical CT, delayed iodine CT, and helical CT angiography and portography. Techniques of generating three-dimensional helical CT angiograms from axial datasets are also discussed here. The clinical applications and results of these different techniques will also be discussed. In addition, helical CT produces or reveals some specific hepatic perfusion abnormalities that can lead to erroneous diagnoses; caveats for avoiding these pitfalls in interpretation are offered.
RUPTURE OF THE NORMAL SPLEEN IN PREGNANCY
Authors: E. C. Burnett, W. H. McMenemey
Journal: BMJ (1935)

I EDJIALORNALafter operation, whilst of those who had -to have the avertin supplemented 17 per cent.showed post-operative vomiting.Of the 700 cases only two had any post-operative respiratory trouble-one a bronchitis, which cleared up in two days, and one case of pneumonia, which ran a higl temperature for a few days and then got quite well.There were no deaths in the series due to the avertin.All the patients except two left the hospital alive.One of these had multiple brain abscesses, and died from this condition ten days later.The other was found at operation to have an extensive inoperable abdominal tumour, which caused her death from acute intestinal obstruction three weeks later.Only eighteen of the cases (2.5 per cent.),gave rise to any anxiety.Eight became pale during the operation without other signs of shock, five had shallow respiration, and four showed shock after operation.These all improved after coramine was injected.There was one case of acute haemorrhagic colitis, which cleared up and made a good recovery.The best mixture and dosage seem to be:Avertin: 0.175 to 0.2 gram per kg.body weight.Morphine: 1/40 to 1/10 grain according to age.Atropine: 1/180 grain to children under 10 years of age and 1 / 150 grain to those over 10 years.Novocain: Enough 1 per cent.solution locally to produce a field block (about 20 to 30 c.cm.).
Cerebral thrombosis in two patients with malabsorption syndrome treated with vitamin K.
Authors: J Florholmen, H Waldum, A Nordoy
Journal: BMJ (1980)

Cerebral thrombosis in two patients with malabsorption syndrome treated with vitamin K Thrombosis may be a complication in inflammatory bowel disease.1 2 We report the occurrence of cerebral arterial thrombosis in two patients with malabsorption syndromes due to coeliac disease treated with vita- min K.Case reports
In vivo lymphocyte-mediated myocardial injuries demonstrated by adoptive transfer of experimental autoimmune myocarditis.
Authors: M Kodama, Y Matsumoto, M Fujiwara
Journal: Circulation (1992)

BACKGROUND To elucidate the mechanisms of immune-related myocardial injuries, we examined whether autoimmune myocarditis was passively transferable by use of humoral or cellular factors. METHODS AND RESULTS Active myocarditis was elicited in Lewis rats by immunization with human cardiac myosin fraction in complete Freund's adjuvant. This experimental myocarditis was characterized by macroscopic features such as pericardial effusion, enlargement of the heart, and gray discoloration of the cardiac surface. Histologically, extensive myocardial necrosis and numerous inflammatory cell infiltrations were observed. Interestingly, multinucleated giant cells were frequently observed in the lesions. Transfer of the disease by the humoral factor was examined by use of fresh sera and immunoglobulin fraction of pooled sera from rats with severe myocarditis, and transfer by the cellular factor was tested by use of spleen cells and lymph node cells from the diseased rats. When naive Lewis rats were given 15.75 mg of immunoglobulin fraction, no particular change was observed in the hearts. Fresh sera also could not elicit myocarditis in recipient rats. In contrast, intravenous injection of spleen cells or lymph node cells that were cultured for 3 days in the presence of 1 microgram/ml of concanavalin A elicited severe myocarditis. The macroscopic and microscopic findings of passively transferred myocarditis are essentially the same as those found in actively induced myocarditis. Multinucleated giant cells were also observed in the lesions of transferred myocarditis. CONCLUSIONS This study demonstrates direct evidence for in vivo lymphocyte-mediated myocardial injuries.
Comparison of Oral Agents for Treatment of Pneumocystis carinii Pneumonia
Authors: Mark A. Perazella
Journal: Annals of Internal Medicine (1997)

Letters1 March 1997Comparison of Oral Agents for Treatment of Pneumocystis carinii PneumoniaMark A. Perazella, MDMark A. Perazella, MDYale University School of Medicine, New Haven, CT 06520Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-5-199703010-00011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Safrin and colleagues [1] provide a useful comparison of the efficacy and tolerability of three oral antibiotic regimens (trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine) used to treat Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Rash, nausea and vomiting, myelosuppression, and hepatotoxicity accounted for most of the toxic reactions associated with these regimens. Surprisingly, hyperkalemia occurred in only one of their patients, who was treated with either trimethoprim-sulfamethoxazole or dapsone-trimethoprim. This lack of hyperkalemia makes the results of this study clearly different from the results of previous studies done in patients with AIDS who received trimethoprim-containing ...References1. Safrin S, Finkelstein DM, Feinberg J, Frame P, Simpson G, Wu A, et al. Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS. A double-blind, randomized trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine. Ann Intern Med. 1996; 124:792-802. Google Scholar2. Medina I, Mills J, Leoung G, Hopewell PC, Lee B, Modin G, et al. Oral therapy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A controlled trial of trimethoprim-sulfamethoxazole versus trimethoprim-dapsone. N Engl J Med. 1990; 323:776-82. Google Scholar3. Velazquez H, Perazella MA, Wright FS, Ellison DH. Renal mechanism of trimethoprim-induced hyperkalemia. Ann Intern Med. 1993; 119:296-301. Google Scholar4. Alappan R, Perazella MA, Buller GK. Hyperkalemia in hospitalized patients treated with trimethoprim-sulfamethoxazole. Ann Intern Med. 1996; 124:316-20. Google Scholar Author, Article, and Disclosure InformationAffiliations: Yale University School of Medicine, New Haven, CT 06520 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByTrimethoprim-Induced Hyperkalaemia 1 March 1997Volume 126, Issue 5Page: 407KeywordsAIDSAntibioticsAttentionBlood plasmaBody weightNauseaPneumocystis carinii pneumoniaPotassiumRashesVomiting Issue Published: 1 March 1997 CopyrightCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Hypertrophy of the Caudate Lobe of the Liver Demonstrated with Single Photon Emission CT
Authors: KIKUO MACHIDA, SHIGERU FURUI, KOHKI YOSHIKAWA
Journal: Clinical Nuclear Medicine (1983)

A case of hypertrophy of the caudate lobe of the liver is reported in which transmission CT scanning strongly suggested the presence of a liver tumor. However, single photon emission CT using Tc-99m phytate showed that there was only caudate lobe enlargement with no evidence of a space-occupying lesion. The usefulness of single photon emission CT in such situations is discussed.
Evaluation of biplane color Doppler transesophageal echocardiography in 200 consecutive patients.
Authors: R Omoto, S Kyo, M Matsumura, P M Shah, H Adachi, Y Yokote, Y Kondo
Journal: Circulation (1992)

We developed the first biplane transesophageal echocardiography (TEE) probe with two orthogonal transducers, allowing synchronous side-by-side displays of the heart on a monitor TV, and compared its diagnostic value with that of conventional single-plane TEE using commercially available Doppler equipment in 200 consecutive patients intraoperatively, perioperatively, or on an outpatient basis.Insertion was easy, except in one patient with a mediastinal tumor, and no complications were encountered. Both transverse and longitudinal scans allowed correct identification of true and false lumina in all 30 aortic dissection examinations, but longitudinal scanning was slightly superior in detecting types I and III entry sites. Three entries that were not detected by transverse scanning (two of DeBakey type I and one of type III) were visualized by longitudinal scanning. Among 37 cases of mitral regurgitation (MR), longitudinal scans were significantly superior (p less than 0.05) in revealing multiple jets (nine compared with two with transverse scanning). Although both planes yielded almost identical mean values for the maximum jet areas, a difference of over 50% in jet area size on the two planes was observed in 19 cases. The measured jet areas showed significant correlation with the angiographic MR grading, especially for the larger of the biplane measurements (p less than 0.01), and different grades showed little overlap. Longitudinal images increased the acoustic window of the heart and aorta from the esophagus. Moreover, longitudinal scanning provided good visualization of both ventricular outflow tracts, the ascending aorta, main pulmonary artery, and superior vena cava.This modality greatly facilitates a three-dimensional comprehension of cardiovascular lesions and flow dynamics, especially in aortic dissection and MR, and its safety was demonstrated. Our data demonstrate the usefulness of this new technique in comparison with conventional single-plane TEE.
Efficacy of 8-methoxypsoralen vs. 5-methoxypsoralen plus ultraviolet A therapy in patients with mycosis fungoides
Authors: A. Wackernagel, A. Hofer, F. Legat, H. Kerl, P. Wolf
Journal: British Journal of Dermatology (2005)

Background Psoralen plus ultraviolet (UV) A (PUVA) is the standard treatment for early stage mycosis fungoides (MF). When 8‐methoxypsoralen (8‐MOP) is used in PUVA therapy, it often produces intolerance reactions such as nausea, vomiting and headache.
Russia to raise tax rate for unfiltered cigarettes by 30%
Authors: Andrew Osborn
Journal: BMJ (2004)

Russia, home to some of the world's cheapest cigarettes and most committed smokers, is to risk the wrath of the tobacco industry and raise cigarette taxes by up to 30%.

The excise increase has already been approved in a first reading in the country's Duma (lower house) and is expected to take effect on 1 January 2005.

For Russia the move is a radical step, but the traditionally smoker friendly country is starting from an extraordinarily low base.

Domestically produced unfiltered cigarettes, which are popular with many Russians on lower incomes, cost as …
Psychiatry 1982: The American Psychiatric Association Annual Review
Authors: Carl C. Bell
Journal: JAMA (1982)

Derived from the annual review program of the 1982 annual meeting of the American Psychiatric Association, this first<i>Annual Review</i>makes an important contribution to medical literature on psychiatry. For part 1, "The Psychiatric Aspects of Sexuality," Dr Virginia A. Sadock gathered a faculty that adequately reviews sexual anatomy and physiology; diagnostic complexities and treatment of psychosexual dysfunctions; the interface between medicine, surgery, and sexual dysfunction; and sexual behavior in the separated, divorced, widowed, and aged. In addition, excellent informative chapters are presented on gender-gender disturbance, incest, and rape. Dr Robert Cancero was the preceptor for part 2 and compiled an impressive faculty to produce a comprehensive, current, precise, educational exposition of "The Schizophrenic Disorders." Issues of the clinical picture and diagnosis of schizophrenia as well as the genetic, social, biochemical, and morphological factors involved in the etiology of the illness are reviewed. These chapters, along with chapters on treatment
Dengue, Complement and Shock
Authors: Peter A. Ward
Journal: New England Journal of Medicine (1973)

In the past few years it has become apparent that in human beings immunized with vaccines containing killed measles or respiratory syncytial virus "un-natural" antibody responses develop that sometimes become translated into serious immunopathologic consequences when these persons are later confronted with naturally occurring infective virus. Dengue infection in man seems to be the corresponding "experiment of nature." In this disease the complication of hemorrhagic fever with shock syndrome apparently only develops in those who already had at least one prior experience with dengue infection. Whereas protective immunity appears to be serotype-specific, antibodies cross-react with each of the four serotypes . . .
Dr. Priscilla White
Authors: Donald M. Barnett
Journal: New England Journal of Medicine (1975)

On April 1, 1975, the Joslin Auditorium was the scene of four outstanding presentations by Drs. Peter Forsham, Kenneth J. Ryan, Mary Ellen Avery and Miles Shore to celebrate the Golden Anniversary of Dr. Priscilla White's practice of medicine. Each speaker had known Dr. White as a resident or fellow, and all returned to examine their fields of expertise.*Dr. Elliott P. Joslin first recognized Dr. White's exceptional talents in 1922, when she was working in his laboratory at the New England Deaconess Hospital as a medical student. Two years later she returned at his request to practice with him . . .
Methods to identify and characterize developmental neurotoxicity for human health risk assessment. I: behavioral effects.
Authors: D A Cory-Slechta, K M Crofton, J A Foran, J F Ross, L P Sheets, B Weiss, B Mileson
Journal: Environmental Health Perspectives (2001)

Alterations in nervous system function after exposure to a developmental neurotoxicant may be identified and characterized using neurobehavioral methods. A number of methods can evaluate alterations in sensory, motor, and cognitive functions in laboratory animals exposed to toxicants during nervous system development. Fundamental issues underlying proper use and interpretation of these methods include a) consideration of the scientific goal in experimental design, b) selection of an appropriate animal model, c) expertise of the investigator, d) adequate statistical analysis, and e) proper data interpretation. Strengths and weaknesses of the assessment methods include sensitivity, selectivity, practicality, and variability. Research could improve current behavioral methods by providing a better understanding of the relationship between alterations in motor function and changes in the underlying structure of these systems. Research is also needed to develop simple and sensitive assays for use in screening assessments of sensory and cognitive function. Assessment methods are being developed to examine other nervous system functions, including social behavior, autonomic processes, and biologic rhythms. Social behaviors are modified by many classes of developmental neurotoxicants and hormonally active compounds that may act either through neuroendocrine mechanisms or by directly influencing brain morphology or neurochemistry. Autonomic and thermoregulatory functions have been the province of physiologists and neurobiologists rather than toxicologists, but this may change as developmental neurotoxicology progresses and toxicologists apply techniques developed by other disciplines to examine changes in function after toxicant exposure.
Mechanism of Action of OPC-8490 in Human Ventricular Myocardium
Authors: Amelia Focaccio, George Peeters, Matthew Movsesian, Robert Roden, Yutaka Eki, Judith Krall, Michael R. Bristow
Journal: Circulation (1996)

Background The quinolinone compounds OPC-8212 (vesnarinone), OPC-18790, and OPC-8490 are members of a family of unique positive inotropic compounds that have no positive chronotropic effects. In subjects with heart failure, the prototypic compound OPC-8212 may reduce morbidity and mortality at low doses but increase mortality at high doses. Methods and Results To further characterize the inotropic mechanism(s) of action of these compounds, we investigated the effects of OPC-8490, a water-soluble quinolinone, on the inotropic response, inhibition of phosphodiesterase (PDE), and action potential in human ventricular myocardial preparations. In isolated right ventricular trabeculae and membranes prepared from left ventricular myocardium, OPC-8490 produced dose-related positive inotropic effects, inhibited type III PDE activity, and prolonged action potential. Comparative experiments with other PDE inhibitors, sodium channel agonists, and potassium channel antagonists indicated that the positive inotropic effects are due to PDE inhibition, whereas the action potential effects of OPC-8490 are due to effects on ion channels. Conclusions We conclude that OPC-8490 produces selective positive inotropic effects because of type III PDE inhibition combined with ion channel effects, with the latter property inhibiting the positive chronotropic response usually associated with agents that increase intracellular cAMP concentrations.