tbuckley/cabot-search huggingface dataset:
Functions of the Cystic Fibrosis Transmembrane Conductance Regulator Protein
Authors: Raymond D. Frizzell
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Cloning of the cystic fibrosis (CF) gene through genetic linkage analysis has led to new discoveries concerning the function of ion channels and disease mechanisms. Current understanding of CF indicates that epithelial cells from CF patients have reduced Cl− permeability, which impairs fluid and electrolyte secretion and results in luminal dehydration. There is also evidence that the cystic fibrosis transmembrane conductance regulator (CFTR) is the cyclic AMP-dependent ion channel whose activation is defective in CF cells. The CFTR is composed of 1480 amino acids that reveal a structural homology to a family of transport proteins termed the transport ATPases. The nucleotide-binding domains of CFTR are the locus of many disease-causing mutations; the common mutation in CFTR is deletion of a phenylalanine at position 508. In addition, CFTR contains a regulatory domain with consensus sites for phosphorylation by protein kinases. Reversible phosphorylation is a regulatory feature of the signal transduction pathway in which the CF defect lies. The phosphorylated channel requires the continuous presence of ATP, whether in the form of ATP binding or hydrolysis, to maintain channel activity. Channel activation requiring ATP can be inhibited by simultaneous presence of ADP, showing that this nucleotide diphosphate competes with ATP for activation. Studies of mutant CFTR expression indicate that at least two basic mechanisms are responsible for the CF phenotype, including CFTR protein dysfunction and inappropriate protein targeting. If mechanisms for bringing this partially functional protein to the plasma membrane can be found, the airway disease of the vast majority of patients with CF could be improved.
Epicardial activation and repolarization patterns in patients with right ventricular hypertrophy.
Authors: P S Chen, K M Moser, W P Dembitsky, W R Auger, P O Daily, C M Calisi, S W Jamieson, G K Feld
Journal: Circulation (1991)

To map global epicardial repolarization patterns and test the "SI" model of T wave generation, the patterns of epicardial activation and repolarization in patients with chronic pulmonary thromboembolism and right ventricular hypertrophy were studied by computerized mapping techniques and monophasic action potential (MAP) recording. The ventricular activation patterns were characterized by delayed right ventricular activation and the absence of normal early epicardial ventricular breakthrough in some cases. The repolarization patterns were characterized by nonuniform distribution of T wave morphologies. The T waves were predominantly positive over the left ventricular epicardium and negative or biphasic over the right ventricular epicardium. The activation-recovery (A-R) intervals were measured from the local activation to the maximal dV/dt of the upstroke of the T waves (Wyatt method). The difference between the A-R intervals and the MAP from onset of activation to 90% repolarization (MAP90) varies according to T wave morphology and could be as high as 96 msec with positive T waves, despite significant correlations (r = 0.56-0.90) between MAP90 and A-R intervals for each morphology. Better overall correlations were found if the minimal dV/dt on the downslope of the positive T waves was chosen to estimate the time of local repolarization (alternative method). Using this method, the mean A-R intervals were the same over the right and left ventricles. Cardiopulmonary bypass significantly prolonged the action potential duration equally at all parts of the epicardium. We conclude that in patients with right ventricular hypertrophy, the time of local repolarization can be estimated by our alternative method; the right ventricle completes activation and repolarization later than the left ventricle, and the distribution of T wave morphologies is nonuniform, with predominantly positive T waves observed over the left ventricle and negative or biphasic T waves observed over the right ventricle. These findings are compatible with the SI model of the generation of T waves.
PAIN FROM TUBERCULOUS LARYNGITIS RELIEVED BY COCAINIZATION OF THE NASAL (SPHENOPALATINE, MECKEL'S) GANGLION
Authors: L. K. Gundrum
Journal: JAMA (1924)

Since Sluder's report of neuralgic pains attributed to a diseased nasal ganglion, many have reported alleviation of symptoms such as glossodynia, cricodynia, otalgia, toothache, painful accommodation and headache, by treatment of this ganglion. I have been unable, however, to find the report of a case of painful tuberculous laryngitis relieved by such treatment. In two cases of this disease I cocainized the nasal ganglions, using the Sluder technic. <h3>REPORT OF CASES</h3><h3>Case 1.</h3> —P. L., a man, aged 35, Mexican, came to me, June 22, 1924, with hoarseness and severe laryngeal pain. April 1, he had had hoarseness and slight pain in the region of the larynx. The hoarseness gradually increased. At the time of examination, the patient could talk only in a whisper, and pain was present all the time. He was unable to swallow solids, and swallowed liquids only with difficulty. Laryngeal examination showed great swelling of the
Primary Myocardial Disease and Alcoholism
Authors: JOHN R. TOBIN, JOHN F. DRISCOLL, MANUEL T. LIM, GEORGE C. SUTTON, PAUL B. SZANTO, ROLF M. GUNNAR
Journal: Circulation (1967)

The course of primary myocardial disease (PMD) was observed in 39 alcoholics. After initial examination 3 years or more before this report, we classified the severity of each patient's illness as stage I, II, or III. Stage I patients had minimal symptoms and normal-sized hearts. Stage II patients had evidence of concentric left ventricular hypertrophy and clinical manifestations like those of hypertensive heart disease. Stage III patients had left, and frequently right, ventricular hypertrophy and dilatation associated with persistent congestive heart failure, and clinical manifestations typical of patients with PMD. Only the duration of congestive heart failure differed significantly between stages II and III. Eight patients had exploratory mediastinotomy and myocardial biopsy. Gross and microscopic findings supported the diagnosis of PMD and our classification of severity and revealed diffuse interstitial fibrosis. Fifteen patients have been observed for 3 or more years; 10 have died and 14 have disappeared. These studies emphasize alcoholism's importance in the genesis of this form of PMD. Correlations were positive between abstention from alcohol and waning of clinical severity, and between persistent drinking and waxing of clinical severity.
The Merit of Medical Discretion
Authors: Sidney H. Rosenberg
Journal: JAMA (1973)

To the Editor.—  Most medical students are admonished at some time during their schooling to use the utmost of discretion in discussing the quality of another physician's performance with a patient. After only one year in practice, I have been most distressed to find that such discretion is virtually absent in the general medical community. Physicians seem absurdly quick to jump to a conclusion that is critical of a colleague's performance, without even so much as finding out from an actual record precisely what transpired. That patients have a great capacity to misconstrue what is said to them and what is done for them in the course of receiving medical care is known to virtually everyone who has ever dealt with patients. Nevertheless, the same physician who would question a chest roentgenogram report by a very experienced radiologist, who would question an electrocardiogram reading by a very experienced cardiologist, or
A SIMPLE AND ACCURATE METHOD OF OUTLINING THE STOMACH.
Authors: WILHELM BECKER
Journal: JAMA (1902)

The determination of the outlines of the stomach has always been and always will be a matter of great interest to the gastro-enterologist. It is not necessary to name and describe the advantages and disadvantages of the various methods of outlining the size of the stomach, nor will space allow me to do this. During the last two years I have tried a simple and accurate method which has given me great satisfaction. By its employment I have determined the size of the stomachs of about three hundred patients of all varieties. A considerable number of these patients were free dispensary patients of the Milwaukee Medical College and I take this opportunity to extend my thanks to Prof. W. H. Nielson for generously placing the gastro-contingency of the college clinic at my disposal. The following is a short description of the method: The patient's stomach is washed out in the
Long-Term Restoration of Rod and Cone Vision by Single Dose rAAV-Mediated Gene Transfer to the Retina in a Canine Model of Childhood Blindness
Authors: Gregory M. Acland, Gustavo D. Aguirre, Jean Bennett, Tomas S. Aleman, Artur V. Cideciyan, Jeannette Bennicelli, Nadine S. Dejneka, Susan E. Pearce-Kelling, Albert M. Maguire, Krzysztof Palczewski, William W. Hauswirth, Samuel G. Jacobson
Journal: Molecular Therapy (2005)

The short- and long-term effects of gene therapy using AAV-mediated RPE65 transfer to canine retinal pigment epithelium were investigated in dogs affected with disease caused by RPE65 deficiency. Results with AAV 2/2, 2/1, and 2/5 vector pseudotypes, human or canine RPE65 cDNA, and constitutive or tissue-specific promoters were similar. Subretinally administered vectors restored retinal function in 23 of 26 eyes, but intravitreal injections consistently did not. Photoreceptoral and postreceptoral function in both rod and cone systems improved with therapy. In dogs followed electroretinographically for 3 years, responses remained stable. Biochemical analysis of retinal retinoids indicates that mutant dogs have no detectable 11-cis-retinal, but markedly elevated retinyl esters. Subretinal AAV-RPE65 treatment resulted in detectable 11-cis-retinal expression, limited to treated areas. RPE65 protein expression was limited to retinal pigment epithelium of treated areas. Subretinal AAV-RPE65 vector is well tolerated and does not elicit high antibody levels to the vector or the protein in ocular fluids or serum. In long-term studies, wild-type cDNA is expressed only in target cells. Successful, stable restoration of rod and cone photoreceptor function in these dogs has important implications for treatment of human patients affected with Leber congenital amaurosis caused by RPE65 mutations.
Variations in Patients' Compliance with Doctors' Orders.
Authors: Milton S. Davis
Journal: Annals of Internal Medicine (1965)

s1 November 1965Variations in Patients' Compliance with Doctors' Orders.Milton S. Davis, M.D.Milton S. Davis, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-63-5-911_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn a recent paper the author pointed out that while social scientists as well as physicians have manifested increased interest in the doctor-patient relationship over the past decade, little attention has been given to the identification of factors, along with the interaction between the doctor and the patient that may play a part in determining whether or not patients will follow their doctor's instructions.Accordingly, the specific aim of this study is to identify some of the major social, psychological, and physical factors that account for variations in ambulatory patients' compliance with the medical regimens established for them by their... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: New York, New York PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 November 1965Volume 63, Issue 5Page: 911-911KeywordsScientists Issue Published: 1 November 1965 PDF DownloadLoading ...
THE PREVENTION OF DIFFICULT LABOUR
Authors: W. H. Maidlow
Journal: BMJ (1906)

<h3>Abstract</h3> Neurons in the Middle Temporal area (MT) of the primate cerebral cortex respond to moving visual stimuli. The sensitivity of MT neurons to motion signals can be characterized by using random-dot stimuli, in which the strength of the motion signal is manipulated by adding different levels of noise (elements that move in random directions). In macaques, this has allowed the calculation of “neurometric” thresholds. We characterized the responses of MT neurons in sufentanil/nitrous oxide anesthetized marmoset monkeys, a species which has attracted considerable recent interest as an animal model for vision research. We found that MT neurons show a wide range of neurometric thresholds, and that the responses of the most sensitive neurons could account for the behavioral performance of macaques and humans. We also investigated factors that contributed to the wide range of observed thresholds. The difference in firing rate between responses to motion in the preferred and null directions was the most effective predictor of neurometric threshold, whereas the direction tuning bandwidth had no correlation with the threshold. We also showed that it is possible to obtain reliable estimates of neurometric thresholds using stimuli that were not highly optimized for each neuron, as is often necessary when recording from large populations of neurons with different receptive field concurrently, as was the case in this study. These results demonstrate that marmoset MT shows an essential physiological similarity to macaque MT, and suggest that its neurons are capable of representing motion signals that allow for comparable motion-in-noise judgments. <h3>New and Noteworthy</h3> We report the activity of neurons in marmoset MT in response to random-dot motion stimuli of varying coherence. The information carried by individual MT neurons was comparable to that of the macaque, and that the maximum firing rates were a strong predictor of sensitivity. Our study provides key information regarding the neural basis of motion perception in the marmoset, a small primate species that is becoming increasingly popular as an experimental model.
A NEW COUNTING CHAMBER FOR THE ENUMERATION OF BLOOD CORPUSCLES.
Authors: CHARLES E. SIMON
Journal: JAMA (1906)

Every worker in the clinical laboratory, no doubt, has felt that in the construction of the hemomytometric slide undue prominence is given to the ruling for the enumeration of the red corpuscles, while as a matter of fact the leucocyte count is made much more frequently than the red count. In teaching, also, the red lines prove confusing to the beginner, and the patience of the instructor is often severely taxed in explaining again and again the meaning of the various lines. To overcome these difficulties, which seem entirely unnecessary, I have had E. Leitz &amp; Co. construct a counting slide which is much simpler than any other with which I am acquainted. It will be found especially convenient in the enumeration of the leucocytes, but may also be utilized in counting the red cells. Its description and directions for use follow: <h3>DESCRIPTION.</h3> The instrument, as placed on the market,
Somatostatin blockade of acute and chronic stimuli of the endocrine pancreas and the consequences of this blockade on glucose homeostasis.
Authors: E W Chideckel, J Palmer, D J Koerker, J Ensinck, M B Davidson, C J Goodner
Journal: Journal of Clinical Investigation (1975)

The nature and extent of somatostatin-induced inhibition of pancreatic endocrine secretion were studied by administration of a number of stimuli of either glucagon or insulin to over night fasted baboons with and without an infusion of linear somatostatin. The stimuli for acute-phase insulin release were intravenous pulses of glucose, tolbutamide, isoproterenol, and secretin. When given 15 min after the start of a somatostatin infusion, these agents were essentially unable to stimulate insulin secretion. Chronic insulin secretion was stimulated by infusions of either glucose or glucagon. Within 10 min of the start of a super-imposed infusion of somatostatin, insulin levels fell to less than 40 percent of prestimulus control and remained suppressed for the duration of the somatostatin infusion. Stimulation of glucagon secretion by insulin-induced hypoglycemia was also blocked by somatostatin. Plasma glucose decreased during somatostatin infusions except when superimposed upon an infusion of glucagon. Somatostatin had no effect on glucose production in a rat liver slice preparation. We conclude: (a) Somatostatin is a potent and so far universally effective inhibitor of both acute and chronic phases of stimulated insulin and glucagon secretion (b) The inhibitory effect is quickly reversible and the pattern of recovery of secretion is appropriate to prevailing signals; (c) Present evidence suggests that the effect of somatostatin on blood glucose is mediated through its effect on blood glucagon; (d) In the overnight-fasted baboon both in the basal state and 45 min into a 4-mg/kg-min glucose infusion, a somatostatin-induced fall in serum insulin levels appears to be unable to prevent a decrease in hepatic glucose production.
Tobacco marketing: shackling the pied piper
Authors: G. Hastings, L. MacFadyen, M. Stead
Journal: BMJ (1997)

These are encouraging times for tobacco control. Both the British and the American governments are trying to curb the activities of the tobacco industry, and the European Union will probably now move against tobacco advertising across Europe. This is a good moment, therefore, to emphasise that our key concern should be not with advertising, or sponsorship, or indeed any individual element of the industry's promotional activity, but with the whole process of tobacco marketing.

As with the successful marketing of other consumer goods, tobacco marketing is based on careful research to provide a detailed understanding of customers, and this guides linked strategies in the four marketing areas of product development, distribution, pricing, and promotion. These strategies aim to build successful brands and thereby maximise the appeal of the industry's offerings.

Tobacco has two sorts of customer: starters, who are just trying out the habit and deciding whether to take it up, and committed users, who have been smoking for some time. Committed users are easier to please: they simply need access to their regular fix of nicotine.

Starters …
FROZEN SECTIONS PREPARED BY USE OF "DRY ICE"
Authors: Janvier W. Lindsay
Journal: JAMA (1931)

The value of frozen sections of pathologic tissue is being more and more emphasized and is becoming more generally recognized as the application of this form of examination is demonstrated in many of the large clinics and as it is familiarized by frequent and constant employment in one's own laboratory.  Modification of the technic with resulting simplification of the process and reduction of cost will, we believe, lead to even more extensive usefulness and remove some of the objections that doubtless occur to many laboratory men. A departure from the standard type of apparatus, with the purpose of eleminating some of the difficulties, is offered.  The special equipment, which may be readily attached to any microtome and which is shown in the accompanying illustration, consists of an ice chamber with a freezing plate, and a plunger with which the ice may be brought into contact with or released from the
Treatment of 150 cases of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments. Final report of a multicenter study.
Authors: E M Antman, T L Wenger, V P Butler, E Haber, T W Smith
Journal: Circulation (1990)

One hundred fifty patients with potentially life-threatening digitalis toxicity were treated with digoxin-specific antibody fragments (Fab) purified from immunoglobulin G produced in sheep. The dose of Fab fragments was equal to the amount of digoxin or digitoxin in the patient's body as estimated from medical histories or determinations of serum digoxin or digitoxin concentrations. The youngest patient received Fab fragments within several hours of birth, and the oldest patient was 94 years old. Seventy-five patients (50%) were receiving long-term digitalis therapy, 15 (10%) had taken a large overdose of digitalis accidentally, and 59 (39%) had ingested an overdose of digitalis with suicidal intent. The clinical response to Fab was unspecified in two cases, leaving 148 patients who could be evaluated. One hundred nineteen patients (80%) had resolution of all signs and symptoms of digitalis toxicity, 14 (10%) improved, and 15 (10%) showed no response. After termination of the Fab infusion, the median time to initial response was 19 minutes, and 75% of the patients had some evidence of a response by 60 minutes. There were only 14 patients with adverse events considered to possibly or probably have been caused by Fab; the most common events were rapid development of hypokalemia and exacerbation of congestive heart failure. No allergic reactions were identified in response to Fab treatment. Of patients who experienced cardiac arrest as a manifestation of digitalis toxicity, 54% survived hospitalization.(ABSTRACT TRUNCATED AT 250 WORDS)
Précis of<i>The Rational Imagination: How People Create Alternatives to Reality</i>
Authors: Ruth M. J. Byrne
Journal: Behavioral and Brain Sciences (2007)

The human imagination remains one of the last uncharted terrains of the mind. People often imagine how events might have turned out "if only" something had been different. The "fault lines" of reality, those aspects more readily changed, indicate that counterfactual thoughts are guided by the same principles as rational thoughts. In the past, rationality and imagination have been viewed as opposites. But research has shown that rational thought is more imaginative than cognitive scientists had supposed. In The Rational Imagination, I argue that imaginative thought is more rational than scientists have imagined. People exhibit remarkable similarities in the sorts of things they change in their mental representation of reality when they imagine how the facts could have turned out differently. For example, they tend to imagine alternatives to actions rather than inactions, events within their control rather than those beyond their control, and socially unacceptable events rather than acceptable ones. Their thoughts about how an event might have turned out differently lead them to judge that a strong causal relation exists between an antecedent event and the outcome, and their thoughts about how an event might have turned out the same lead them to judge that a weaker causal relation exists. In a simple temporal sequence, people tend to imagine alternatives to the most recent event. The central claim in the book is that counterfactual thoughts are organised along the same principles as rational thought. The idea that the counterfactual imagination is rational depends on three steps: (1) humans are capable of rational thought; (2) they make inferences by thinking about possibilities; and (3) their counterfactual thoughts rely on thinking about possibilities, just as rational thoughts do. The sorts of possibilities that people envisage explain the mutability of certain aspects of mental representations and the immutability of other aspects.
Confidentiality of personal health information used for research
Authors: Dipak Kalra, Renate Gertz, Peter Singleton, Hazel M Inskip
Journal: BMJ (2006)

[8-14C]Theophylline was infused into mice with an osmotic minipump. Theophylline and its metabolites were separated from urine, blood, and feces by high-performance liquid chromatography and the radioactivity was determined by liquid-scintillation counting. The strains examined were SJL, DBA/2, C57BL/6, A/J, C3H/HeJ, AKR, SWR, and BALB/c. The theophylline clearance ranged from 479 +/- 30 ml/kg/hr in the A/J strain to 845 +/- 58 ml/kg/hr in the SJL strain. The total clearance in the A/J strain was signficantly different (p &lt; 0.05) from that in the BALB/c, C57BL/6, and SJL strains. The metabolic pathway primarily responsible for this variation was the production of 1,3-dimethyluric acid.