tbuckley/cabot-search huggingface dataset:
Case of Hypertrophy of the Parotid Gland
Authors: A. Duke
Journal: BMJ (1842)

HYPERTROPHY OF PAROTID.-SOLARASPHYXIA.may exist, and occasional tonics and stimdLlants, are the appropriate remedies in these cases, andIl enerally in time effect a cure.We know very little of the pathology of this disease, and we therefore suppose it to have something to do with the great syinpathetic iierve, and the ganglionic system connected therewithl; but about all these matters I must confess to you that we kniow very little, and therefore it is that I have very little to say to you about it.
Inhalation of sidestream cigarette smoke accelerates development of arteriosclerotic plaques.
Authors: A Penn, C A Snyder
Journal: Circulation (1993)

BACKGROUND Environmental tobacco smoke has been blamed for approximately 40,000 excess deaths from heart disease annually in the United States. As yet, no pathophysiological process that could be responsible for these deaths has been identified. Environmental tobacco smoke is composed mainly of aged and diluted sidestream smoke but also contains 15% to 20% exhaled mainstream smoke. Carcinogens, including nitrosamines and polynuclear aromatic hydrocarbons, are present in mainstream smoke and sidestream smoke. Carcinogen levels in sidestream smoke, unlike those in mainstream smoke, are not reduced in filtered cigarettes. The US Environmental Protection Agency has designated environmental tobacco smoke as a human (class A) carcinogen. In cockerels, subtumorigenic doses of polynuclear aromatic hydrocarbons carcinogens accelerate aortic arteriosclerotic plaque development. METHODS AND RESULTS To determine whether sidestream smoke inhalation affects arteriosclerotic plaque development, we exposed cockerels to sidestream smoke (n = 30) or to filtered air (n = 12) in inhalation chambers for 6 hours per day, 5 days a week from 6 to 22 weeks of age (0.4% of projected lifespan). Chamber levels of carbon monoxide, total suspended particulates, and nicotine were measured regularly during the exposures. The abdominal aorta from each cockerel was cut into 10 segments, and the plaque index (mean plaque cross-sectional area [mm2]/mean luminal circumference [mm] x 100) was calculated for each segment. There were no differences in plaque incidence or distribution between sidestream smoke-exposed and control cockerels; however, plaque indexes were significantly greater for sidestream smoke-exposed than control cockerels in all segments. CONCLUSIONS Thus, relatively brief exposures to sidestream smoke early in life are sufficient to enhance arteriosclerotic plaque development.
p-Bromindione: A New, Potent, Long-Acting Oral Anticoagulant Drug
Authors: Arthur J. Seaman
Journal: JAMA (1961)

P-BROMINDIONE is a potent, long-acting, inandione-derived, oral anticoagulant medication (Fig. 1). This report details our experience with the American synthesized product, Halinone. The identical chemical compound has been synthesized and evaluated clinically in Italy, 1-4 where it is known under the chemical name 2(4 bromophenyl)-1,3-indandione.  Materials and Methods  Fifty-eight patients have received this medication for a combined total of over 10,000 patient days. In many instances treatment is continuing. The longest periods of continuous administration to any individual patients are slightly in excess of one and one-half years. All patients had or have thromboembolic disease as the indication for their short-term therapeutic or long-term prophylactic anticoagulant use.  The laboratory monitoring of therapeutic response was carried out at appropriate intervals, using the prothrombin and proconvertin (P and P) method of Owren and Aas. 5 The target for optimum anticoagulant effect was 20% P and P activity, with values ranging between
Molecular basis of factor VIII inhibition by human antibodies. Antibodies that bind to the factor VIII light chain prevent the interaction of factor VIII with phospholipid.
Authors: M Arai, D Scandella, L W Hoyer
Journal: Journal of Clinical Investigation (1989)

Most antibodies to factor VIII have recently been shown to react with discrete regions of the factor VIII light chain (within the C2 domain) and/or the factor VIII heavy chain (within the amino-terminal segment of the A2 domain). The mechanism by which these antibodies, usually designated "factor VIII inhibitors," interfere with factor VIII function has been examined by determining their effect on factor VIII binding to a phospholipid. Factor VIII-phosphatidylserine binding was prevented by all seven factor VIII inhibitors that had strong factor VIII light chain reactivity and reduced by two inhibitors with weak anti-light chain reactivity. None of four inhibitors with heavy chain reactivity prevented factor VIII-phosphatidylserine interaction, though a partial reduction (less than 50%) was noted for the intact IgG preparations. However, when Fab' fragments were substituted, no detectable reduction in factor VIII-phosphatidylserine binding was noted for the anti-heavy chain inhibitors and complete inhibition was retained by the anti-light chain inhibitors. These data suggest that a subset of factor VIII inhibitors, those that bind to light chain determinants, inactivate factor VIII by preventing its effective interaction with phospholipid.
55 FUTILITY RULES IN TELAPREVIR COMBINATION TREATMENT
Authors: I.M. Jacobson, D.J. Bartels, L. Gritz, T.L. Kieffer, S. De Meyer, F. Tomaka, L. Bengtsson, D. Luo, B.S. Adiwijaya, R.S. Kauffman, G. Picchio, N. Adda
Journal: Journal of Hepatology (2012)
Radiographic Artifacts: Their Cause and Control
Authors: David H. Baker
Journal: JAMA (1984)

This short, well-structured, amply illustrated, clear text, detailing the myriad factors that can adversely affect a radiograph, was a pleasure to read. It obviously is not new material; however, bringing it all together in one place provides a great service for the radiological community. It rightly points out how vital attention to quality control is in a modern high-technology field. Not the least of that importance is related to the cost of repeat roentgenograms, necessitated by someone's lack of attention to quality assurance. The author mentions in the introductory paragraphs that several sets of circumstances or single circumstances may produce problems on a roentgenogram that can be very similar. He demonstrates that phenomenon well in subsequent chapters. Further emphasis in the text might have been helpful. One wonders whether the author plans to, or perhaps already is, developing an algorithm, as a separate entity, giving the nonsophisticate a path to
Hepatitis GB Virus C in Patients on Hemodialysis
Authors: X. de Lamballerie, R.N. Charrel, B. Dussol
Journal: New England Journal of Medicine (1996)

To the Editor: A new group of Flaviviridae viruses — hepatitis GB virus C (HGBV-C)1 and hepatitis G virus (HGV)2 — has recently been described. Patients infected with these viruses have persistent ...
Book Review Cardiac Arrest Simulation Program By J. Michael Dean. Diskette with manual, 80 pp. System needed: Apple IIe, Apple II Plus, or Apple II with Applesoft on a firmware card; 48K RAM; one drive; black-and-white or color monitor. Rockville, Md., Aspen Systems, 1984. $225.
Authors: Babu V. Koka
Journal: New England Journal of Medicine (1984)
Articulating the Elephant Man: Joseph Merrick and His Interpretors
Authors: Burton E. Einspruch
Journal: JAMA (1993)

Victorian England was captivated by the curious. Great collections of plants, fossils, and animals were amassed privately and for museums. Less savory was a fascination with physical oddities. Individuals and items from the far-flung empire were brought to the major cities for study, and, sadly, even ridicule. Joseph Merrick was one of the "oddities" who populated the freak shows of that day. Ascending to the English throne in 1837, Queen Victoria ushered in an era of development and unparalleled prosperity. Yet, it was an era not particularly known for charity. In their book<i>Articulating the Elephant Man</i>, Peter Graham and Fritz Oehlschlaeger, both professors of English at Virginia Polytechnic Institute and State University, aim as one of their main purposes to "examine, in a chronological and critical way, how the phenomenon labeled 'the Elephant Man' has been constructed and reconstructed—how Joseph Merrick has been transformed from a suffering individual to
Overcoming the Cystic Fibrosis Sputum Barrier to Leading Adeno-associated Virus Gene Therapy Vectors
Authors: Benjamin S Schuster, Anthony J Kim, Joshua C Kays, Mia M Kanzawa, William B Guggino, Michael P Boyle, Steven M Rowe, Nicholas Muzyczka, Jung Soo Suk, Justin Hanes
Journal: Molecular Therapy (2014)

Gene therapy has not yet improved cystic fibrosis (CF) patient lung function in human trials, despite promising preclinical studies. In the human CF lung, inhaled gene vectors must penetrate the viscoelastic secretions coating the airways to reach target cells in the underlying epithelium. We investigated whether CF sputum acts as a barrier to leading adeno-associated virus (AAV) gene vectors, including AAV2, the only serotype tested in CF clinical trials, and AAV1, a leading candidate for future trials. Using multiple particle tracking, we found that sputum strongly impeded diffusion of AAV, regardless of serotype, by adhesive interactions and steric obstruction. Approximately 50% of AAV vectors diffused >1,000-fold more slowly in sputum than in water, with large patient-to-patient variation. We thus tested two strategies to improve AAV diffusion in sputum. We showed that an AAV2 mutant engineered to have reduced heparin binding diffused twice as fast as AAV2 on average, presumably because of reduced adhesion to sputum. We also discovered that the mucolytic N-acetylcysteine could markedly enhance AAV diffusion by altering the sputum microstructure. These studies underscore that sputum is a major barrier to CF gene delivery, and offer strategies for increasing AAV penetration through sputum to improve clinical outcomes.
A Humoral Component of the Natriuretic Mechanism in Sustained Blood Volume Expansion
Authors: Harald Sonnenberg, Anthony T. Veress, James W. Pearce
Journal: Journal of Clinical Investigation (1972)

A natriuretic and diuretic response to whole blood infusion in the rat, exaggerated and sustained by intravenous reinfusion of excreted urine, was shown to be associated with increased glomerular filtration and reduced tubular reabsorption. Cross-circulation of animals so responding (donor rats) with isovolemic recipients led to a modest natriuretic and diuretic response in the latter, not accounted for by altered physical composition of the blood nor by observed changes in filtration rate or arterial blood pressure. The recipient natriuresis was unchanged when nephrectomized donors were used and it occurred in experiments in which donor urine was simultaneously replaced by intravenously infused Ringer-Locke solution; the natriuretic property of the cross-circulating blood could therefore not have been due to reinfusion of urinary constituents, nor to accumulation of metabolites, nor to a factor of renal origin. A recipient natriuresis was also observed when the expanded and urine reinfused donor had been acutely adrenalectomized, ruling out an altered secretion of adrenal cortical or medullary hormones as a principal cause of this natriuresis; the data, however, do not exclude participation of reduced aldosterone secretion in the normal effector mechanism. In control experiments in which whole blood was exchanged for donor blood, a small delayed natriuresis did occur in the recipient; this could be completely prevented by administration of aldosterone. In similar exchange experiments with adrenalectomized donors, a small natriuresis developed in the recipient before blood administration but declined afterwards. These minor natriuretic effects probably resulted from altered mineralocorticoid content of the cross-circulating blood due to factors other than blood volume change. The larger natriuretic response seen in all recipients when the donor was volume expanded must have been due largely to a humoral natriuretic factor of other than renal or adrenal origin.
ABC of Emergency Radiology: Maxillofacial Radiographs
Authors: D W Hodgkinson, R E Lloyd, P A Driscoll, D A Nicholson
Journal: BMJ (1994)

This article deals with the problems facing non-specialist doctors requesting emergency radiographs of facial bones. An appropriate history and clinical examination will lead to suspicion of maxillofacial trauma and other pathology. We describe a systematic approach to requesting and interpreting maxillofacial views.

Knowledge of the normal anatomy and radiological appearance of the skull is essential to interpreting radiographs of the face (see article on skull, 4 December,pp 1476-81).

The face can be divided into three areas: the upper third - area above the superior orbital margin; the middle third - area between the superior orbital margin above and the occlusal plane below; and the lower third - the lower jaw (mandible). Standard radiographic investigation of the face is describe with reference to these three areas.



FIG 1 
Lateral radiograph with line drawing showing radiological anatomy.



The mechanism of injury is an important aid to identifying the specific injury and any possible associated injuries. It can help decide which type of film to request and the urgency of the request. Isolated injuries to the maxillofacial skeleton commonly result from an assault. More severe injuries occur after high energy transfer (for example, road traffic accidents) and may be associated with injuries to the head, neck, chest, and other body regions.

Good quality, carefully positioned radiographs are required. This can be difficult to achieve in patients presenting to the emergency department (because of multiple injuries or alcohol intoxication). Poor quality and incorrectly positioned films must not be accepted. Radiology of a clinically suspected maxillofacial injury can often be delayed until the patient is more cooperative or good quality films can be taken.

The standard radiographic projections are listed below. Each projection provides only a limited amount of information and several views are therefore required to assess an injury fully. The clinical findings should be used …
Randomized controlled open-label trial of four treatment regimens for pemphigus vulgaris
Authors: Cheyda Chams-Davatchi, Nafiseh Esmaili, Maryam Daneshpazhooh, Mahin Valikhani, Kamran Balighi, Zahra Hallaji, Masoumeh Barzegari, Maryam Akhyani, S. Zahra Ghodsi, Hassan Seirafi, Mohammad-Javad Tabrizi Nazemi, Hossein Mortazavi, Mostafa Mirshams-Shahshahani
Journal: Journal of the American Academy of Dermatology (2007)
Methotrimeprazine in the Treatment of Labor Pain
Authors: Thomas J. DeKornfeld, John W. Pearson, Louis Lasagna
Journal: New England Journal of Medicine (1964)

METHOTRIMEPRAZINE, an interesting analgesic agent1 is, chemically, a phenothiazine and thus unrelated to the known potent analgesics. It also seems devoid of addiction liability in monkey2 and man3 and is less of a respiratory depressant, in equianalgesic doses, than morphine.4 The present study was undertaken to investigate the analgesic performance and side-action liability of this drug in a situation quite different from postoperative pain,1 comparing it with a standard narcotic analgesic (meperidine) and with a placebo. The results indicate a general similarity in the activity of meperidine and methotrimeprazine, with both compounds differing significantly from the placebo. The experimental design . . .
A Lifetime of Aldosterone Excess: Long-Term Consequences of Altered Regulation of Aldosterone Production for Cardiovascular Function
Authors: John M. C. Connell, Scott M. MacKenzie, E. Marie Freel, Robert Fraser, Eleanor Davies
Journal: Endocrine Reviews (2008)

Up to 15% of patients with essential hypertension have inappropriate regulation of aldosterone; although only a minority have distinct adrenal tumors, recent evidence shows that mineralocorticoid receptor activation contributes to the age-related blood pressure rise and illustrates the importance of aldosterone in determining cardiovascular risk. Aldosterone also has a major role in progression and outcome of ischemic heart disease. These data highlight the need to understand better the regulation of aldosterone synthesis and its action. Aldosterone effects are mediated mainly through classical nuclear receptors that alter gene transcription. In classic epithelial target tissues, signaling mechanisms are relatively well defined. However, aldosterone has major effects in nonepithelial tissues that include increased synthesis of proinflammatory molecules and reactive oxygen species; it remains unclear how these effects are controlled and how receptor specificity is maintained. Variation in aldosterone production reflects interaction of genetic and environmental factors. Although the environmental factors are well understood, the genetic control of aldosterone synthesis is still the subject of debate. Aldosterone synthase (encoded by the CYP11B2 gene) controls conversion of deoxycorticosterone to aldosterone. Polymorphic variation in CYP11B2 is associated with increased risk of hypertension, but the molecular mechanism that accounts for this is not known. Altered 11β-hydroxylase efficiency (conversion of deoxycortisol to cortisol) as a consequence of variation in the neighboring gene (CYP11B1) may be important in contributing to altered control of aldosterone synthesis, so that the risk of hypertension may reflect a digenic effect, a concept that is discussed further. There is evidence that a long-term increase in aldosterone production from early life is determined by an interaction of genetic and environmental factors, leading to the eventual phenotypes of aldosterone-associated hypertension and cardiovascular damage in middle age and beyond. The importance of aldosterone has generated interest in its therapeutic modulation. Disadvantages associated with spironolactone (altered libido, gynecomastia) have led to a search for alternative mineralocorticoid receptor antagonists. Of these, eplerenone has been shown to reduce cardiovascular risk after myocardial infarction. The benefits and disadvantages of this therapeutic approach are discussed.
Percutaneous endoscopic gastrostomy feeding.
Authors: A. H. Chapman
Journal: BMJ (1992)

ing (including fine bore tube feeding) have been well documented,5 but nasogastric feeding remains an essential part of nutritional support.Percutaneous endoscopic gastrostomy is a major technical advance in obtaining access for nutritional support, and though its safety is well.established, it is still an invasive procedure and not suitable for all.What has not been well established, and which neither Park and colleagues or Forgacs and colleagues addressed, is the indication for nutritional support in patients with disabling neurological conditions.Research and training in nutritional support are needed to define and outline the risks and benefits of nutritional intervention in such patients.Percutaneous endoscopic gastrostomy feeding is an advance for those who require long term tube feeding, and we would not have con- sidered randomising patients who had already had four weeks of nasogastric tube feeding.We do not see percutaneous endoscopic gastrostomy feeding as a panacea for all, nor will its use "prevent the degrading spectacle of elderly, under- nourished patients with their hands bandaged to the side of the bed."2Let clinicians decide whether nutritional support is appropriate and then institute appropriate treatment using well proved techno- logical advances such as percutaneous endoscopic gastrostomy.
An assessment of the cord blood:maternal blood methylmercury ratio: implications for risk assessment.
Authors: Alan H Stern, Andrew E Smith
Journal: Environmental Health Perspectives (2003)

In the current U.S. Environmental Protection Agency reference dose (RfD) for methylmercury, the one-compartment pharmacokinetic model is used to convert fetal cord blood mercury (Hg) concentration to a maternal intake dose. This requires a ratio relating cord blood Hg concentration to maternal blood Hg concentration. No formal analysis of either the central tendency or variability of this ratio has been done. This variability contributes to the overall variability in the dose estimate. A ratio of 1.0 is implicitly used in the model, but an uncertainty factor adjustment is applied to the central tendency estimate of dose to address variability in that estimate. Thus, incorporation of the cord:maternal ratio and its variability into the estimate of intake dose could result in a significant change in the value of the RfD. We analyzed studies providing data on the cord:maternal blood Hg ratio and conducted a Monte Carlo-based meta-analysis of 10 studies meeting all inclusion criteria to generate a comprehensive estimate of the central tendency and variability of the ratio. This analysis results in a recommended central tendency estimate of 1.7, a coefficient of variation of 0.56, and a 95th percentile of 3.4. By analogy to the impact of the similar hair:blood Hg ratio on the overall variability in the dose estimate, incorporation of the cord:maternal ratio may support a 3-fold uncertainty factor adjustment to the central tendency estimate of dose to account for pharmacokinetic variability. Whether the information generated in this analysis is sufficient to warrant a revision to the RfD will depend on the outcome of a comprehensive reanalysis of the entire one-compartment model. We are currently engaged in such an analysis.
A CASE OF OPIUM-POISONING
Authors: E. B. CLAYBROOK
Journal: JAMA (1910)

The following case is reported, because the man was in such profound stupor, and seemingly in such a dangerous condition, and yet responded so promptly to the treatment instituted, as to give no trouble or uneasiness to those in attendance. <h3>History.—</h3> J. W. S. was admitted to Allegheny Hospital on June 30, 1910, with no history except that he was taken from a train on the way from a near-by town, in profound coma. There happened to be in the hospital a patient from the same town, who knew the man, and said that he was a painter subject to painter's colic and a hard drinker. <h3>Examination.—</h3> The man was in profound coma, pupils pinpoint, pulse soft and regular, respiration three to the minute, temperature normal, urine normal. The diagnosis of opiumpoisoning was made. <h3>Treatment and Result.—</h3> The stomach was washed out, and the bladder emptied. Supra-orbital pressure and castigation