tbuckley/cabot-search huggingface dataset:
Pharmacotherapy for the Treatment of Choroidal Neovascularization Due to Age-Related Macular Degeneration
Authors: Gary D. Novack
Journal: The Annual Review of Pharmacology and Toxicology (2007)

Age-related macular degeneration (AMD) is a progressive, degenerative disease of the macula that threatens central vision. It initially occurs in a "dry" form, and can progress to choroidal neovascularization (CNV) or geographic atrophy. It is the leading cause of blindness among European-descended people older than 65 years, with a prevalence of 1.5%. The treatment of CNV in developed nations in 2007 is substantially different than it was in 1997. Focal, photocoagulating, laser therapy was replaced by intravenous verteporfin and then by intravitreal pegaptanib, which is now being replaced by intravitreal ranibizumab and off-label use of bevacizumab. Other than a ranibizumab versus verteporfin trial, there are no published comparative studies of the three approved pharmacological treatments for CNV. Although frequent intravitreal injections are accepted as a current standard of care, their use is still far from ideal. Thus, there is an opportunity for improving therapy of CNV with respect to mechanism-targeted treatments, efficacy, and route of administration.
Cardiac Pacemakers and Cellular Telephones
Authors: Marc Roelke, Alan D. Bernstein
Journal: New England Journal of Medicine (1997)

The earliest cardiac pacemakers did not sense spontaneous beats, and their metronomic “asynchronous” stimuli competed with patients' intrinsic heart rhythms (if any were present). Later, “demand” or “inhibitory” pacemakers could sense spontaneous depolarizations and synchronize with them. This averted competition with the patient's intrinsic rhythm but created the potential for inappropriate inhibition of stimuli during single-chamber pacing when extraneous electromagnetic interference was mistaken for spontaneous cardiac depolarization. With the advent of dual-chamber pacing, extraneous electromagnetic interference sensed in the atrium could trigger inappropriate stimuli in the ventricle, producing palpitations or even inducing ventricular tachycardia. Extraneous electromagnetic interference has long been . . .
The effects of topical alpha-hydroxyacids on the normal skin barrier of hairless mice
Authors: T-H. Kim, E.H. Choi, Y.C. Kang, S.H. Lee, S.K. Ahn
Journal: British Journal of Dermatology (2001)

Background α‐hydroxyacids (AHA), such as glycolic acid and lactic acid, have recently been used in cosmetic and dermatological formulations. However, the mechanisms of action of these substances have not been well documented. Objectives This study was done to investigate the effects of AHA on the skin barrier of hairless mice and to clarify the contribution of AHA to the formation and secretion of the lamellar bodies (LB), which are known to be the critical structure for barrier function in the epidermis. Methods 5% Lactic acid and 5% glycolic acid were applied to normal skin of the mice daily for 14 days. Results Changes in transepidermal water loss (TEWL), capacitance and electron microscopic findings of the epidermis of hairless mice were compared with those in which only the vehicle was applied. Conclusions There were no significant differences in TEWL, capacitance or epidermal thickness between the epidermis of the mice to which AHA or vehicle only had been applied. On electron micrographs, the normal epidermis to which AHA had been applied showed an increase in the number and secretion of LB and a decrease in the number of stratum corneum (SC) layers in comparison with the epidermis to which the vehicle only had been applied. The lipid layers of the SC intercellular spaces and calcium gradient in both the epidermis with application of AHA and that with vehicle only were normal. These results suggest that AHA, in low concentration (5%), may improve the skin barrier in hairless mice by inducing enhanced desquamation, and by increasing the number and secretion of LB without increasing TEWL.
Sugar Intolerance in Malnourished Infants and Children
Authors: R. K. Chandra, R. R. Pawa, O. P. Ghai
Journal: BMJ (1968)

Of 100 malnourished Indian infants and children 50 showed a stool pH below 6. Carbohydrate-loading tests demonstrated intolerance to lactose in 39, to sucrose in 25, and to maltose in 15. D-Xylose absorption was reduced in 16. Steatorrhoea was detected in 7 of 18 children tested. Nutritional recovery reversed the abnormalities in all except four, in whom a primary enzymic deficiency was considered on the basis of persistent lactose intolerance and a positive family history.
Formation of 7α- and 7β-hydroxylated bile acid precursors from 27-hydroxycholesterol in human liver microsomes and mitochondria
Authors: Junichi Shoda, Anders Toll, Magnus Axelson, Fritz Pieper, Kjell Wikvall, Jan Sjövall
Journal: Hepatology (1993)

In a search for enzymes involved in the formation of bile acids from 27-hydroxycholesterol in humans, the metabolism of this and other side-chain oxygenated steroids was studied in human liver microsomes and mitochondria. The microsomal fraction contained enzyme(s) catalyzing 7α-hydroxylation of 27-hydroxycholesterol and 3β-hydroxy-5-cholestenoic acid, whereas the 7α-hydroxylation of cholesterol and 3β-hydroxy-5-cholenoic acid was low. Only small amounts of 7β-hydroxylated products were formed. Purification and subfractionation of microsomal protein yielded a fraction of cytochrome P-450, which required NADPH and NADPH-cytochrome P-450 reductase and catalyzed 7α-hydroxylation of the side-chain oxygenated 3β-hydroxy-δ 5 -C 27 -steroids but was inactive toward cholesterol. Added cholesterol did not inhibit the observed enzymatic activity. The results provide evidence that this enzyme is different from cholesterol 7α-hydroxylase. The mitochondrial fraction contained enzyme(s) that catalyzed an isocitrate-dependent 7α-hydroxylation of 3β-hydroxy-5-cholestenoic acid. The activity was much lower with 27-hydroxycholesterol. The mitochondrial fraction also catalyzed the oxidation of the 27-hydroxy group and contained a 3β-hydroxy-δ 5 -steroid dehydrogenase active on 7α-hydroxylated C 27 -steroids. The metabolic end product of the reactions catalyzed by these enzymes was 7α-hydroxy-3-oxo-4-cholestenoic acid. A considerable fraction of the 7α-hydroxy-δ 5 intermediates was also converted to the corresponding 7β-hydroxysteroids, probably by way of the 7-oxosteroids, suggesting the presence of an epimerizing enzyme in the mitochondrial fraction. This study shows that 7α-hydroxy-3-oxo-4-cholestenoic acid, which is believed to be an important precursor of chenodeoxycholic acid in human beings, can be formed from 27-hydroxycholesterol or 3β-hydroxy-5-cholestenoic acid by the action of 7α-hydroxylases present in the microsomal and mitochondrial fractions. These enzymes, found to be more active in humans and pigs than in rats and rabbits, can catalyze the formation of bile acids by way of pathways that bypass the microsomal cholesterol 7α-hydroxylase as the rate-limiting enzyme. (Hepatology 1993;17:395-403.)
Changing the Cause of Death
Authors: William A. Knaus
Journal: JAMA (1983)

"Patients don't die of their disease," William Osler once wrote, "they die of the physiologic abnormalities of their disease."<sup>1</sup>Advances in medical care now make it necessary to reexamine Osler's observation. In this issue ofThe Journal(p 1055), Hook and co-workers give us such an opportunity, by indicating that despite sophisticated physiological support in an intensive care unit, mortality rates for pneumococcal bacteremia have not changed since major review of the disease by Austrian and Gold nearly 20 years ago.<sup>7</sup> The article by Hook and colleagues is important for two reasons: (1) it provides an update on a long-recognized disease, and (2) it highlights a widely held misperception of the ability of a new therapy to save lives by correcting physiological abnormalities. What do we know about outcome from pneumococcal bacteremia? As Hook and colleagues point out, older patients, especially those with serious underlying health problems, such
What is the optimal pharmacological management of retained placenta?
Authors: J. M. N. Duffy, M. J. A. Wilson, K. S. Khan
Journal: BMJ (2014)

The third stage of labour is the period between childbirth and delivery of the placenta. It can be managed physiologically, with early cord clamping, cutting of the cord, and controlled cord traction, or it can be managed actively, with the addition of prophylactic oxytocics (oxytocin 10 IU intramuscularly). In the United Kingdom, the National Institute of Health and Care Excellence (NICE) defines the third stage of labour as prolonged if the placenta is retained after 30 minutes of active management or 60 minutes of physiological management.1 Retained placenta affects 0.1-3.3% of births, depending on the population studied.2 The incidence of retained placenta is rising because an increasing number of women with risk factors, including advancing maternal age and previous caesarean section, are giving birth.3 Retained placenta can result in severe maternal morbidity, including life threatening haemorrhage and sepsis.

Drugs, such as intraumbilical or intravenous oxytocin, are often used in the management of placental retention. Oxytocics cause myometrial contraction, which generates a shearing force that detaches the placenta from the uterine wall. However, after placental detachment, cervical constriction may trap the placenta within the uterus. Smooth muscle relaxants (such as glyceryl trinitrate) can release this entrapment and allow placental delivery. In practice, a variety of the drugs are used.

Despite active pharmacological management, if a retained placenta is not delivered, the placenta must be removed manually. This invasive surgical procedure physically removes the placenta from the uterine cavity and requires regional or general anaesthesia. The procedure can be complicated by haemorrhage, pain, infection, uterine inversion or perforation, and their …
ABC of spinal cord injury. At the accident.
Authors: A Swain, D Grundy, J Russell
Journal: BMJ (1985)

Spinal cord injury is a mortal condition and has been recognised as such .b^t-i-v.vr.$ ~since antiquity.In about 2500 BC, in the Edwin Smith papyrus, an unknown Egyptian physician accurately described the clinical features of traumatic ;TtIV'egiM, 4~wj~t etraplegia and revealed an awareness of the awful prognosis with the 8 w ¢ t W'A#|;+r AM chilling advice: "an ailment not to be treated."This view prevailed until the tpr ^;= n 4IsJ8.early years of this century.In the first world war 90% ofpatients suffering a spinal cord injury died within one year of wounding and only about 1%-1V -
The Measurement of Rate of Fat Absorption by External Body Counting
Authors: Donald Berkowitz, Joel Shapiro, Bernard Shapiro
Journal: JAMA (1964)

THE DETECTION and quantitation of steatorrhea is currently receiving much emphasis in clinical medicine. Although it is generally accepted that chemical stool analyses are the most accurate means to evaluate this condition, the more recently introduced isotopic fat procedures are easier to perform and give similar data provided that they are carried out in accordance with certain precise criteria.<sup>1-4</sup>However, both of these methods, chemical and radioactive, involve 48- to 72-hour fecal collections which impose serious limitations on their availability in many hospitals. The present report describes a new technique involving external body counting which obviates this difficulty and at the same time provides additional data including the rate of fat absorption. <h3>Method and Materials</h3> Without prior blocking of the thyroid gland, after an overnight fast, the patient receives a test meal containing approximately 100μc of triolein I<sup>131</sup>in 8 oz (236.6 ml) of a half-milk, half-cream mixture.
Review on Upper Digestive Surgery---Oesophagus, Stomach and Small Intestine
Authors: R C MASON
Journal: Gut (2001)

Review on Upper Digestive Surgery—Oesophagus, Stomach and Small Intestine . Edited by TV Taylor, A Watson, RCN Williamson (Pp 1112; illustrated; £180.00). Philadelphia: WB Saunders, 1999. ISBN 0702 014346.

This is a new comprehensive text covering upper gastrointestinal surgery other than HPB but also includes the small intestine which is a frequently forgotten part of the gastrointestinal tract coming as it does between the colorectal and upper gastrointestinal surgeons. It is an extremely comprehensive and inclusive textbook which is both its strength and in other senses its weakness. There is no real subject in the oesophagus, stomach, duodenum, and small bowel which is not covered to some degree within the text. In such a large text however the up to date nature of chapters varies with the bibliography, in some cases being up to the late 1990s but in others being really the …
Food companies ignore calorie count guidelines as attempts to tackle obesity crisis fail
Authors: H. Mooney
Journal: BMJ (2012)

The government’s attempt to tackle the national obesity crisis by asking food companies to commit to healthy eating pledges has been “inadequate” and lacks “real leadership,” with most major firms failing to join the scheme, the consumer watchdog Which? has warned.

It has found that major high street food outlets such as Costa Coffee, Pizza Express, and Garfunkels have failed to implement the government’s plan to reduce obesity by telling customers how much energy their products contain.

A number of food and drink producers and retailers have refused to join what the government had …
Should Benzodiazepines Be Replaced by Antidepressants in the Treatment of Anxiety Disorders? Fact or Fiction?
Authors: Karl Rickels
Journal: Psychotherapy and Psychosomatics (2013)

In this issue of Psychotherapy and Psychosomatics, Offidani et al. [1] address the important clinical question of the role of benzodiazepines (BZs) in the treatment of anxiety disorders and whether there exists evidence in the literature that the BZs should be replaced by the newer antidepressants (ADs).Experts today recommend the use of newer ADs as first-line treatments for anxiety disorders [2], replacing the BZs; yet what is the evidence for this recommendation? Prescribing patterns in US outpatients for mood and anxiety disorders in the year 2007 do not seem to support this recommendation [3]. For example, 136 million prescriptions were written for ADs and 85 million for BZs and the 10 most frequently prescribed medications for either an anxiety or depression diagnosis include 7 ADs and 3 BZs, alprazolam, lorazepam and diazepam (clonazepam was not included in this survey as its use was coded under 'convulsive disorders'). This 2007 prescribing pattern is very similar to the one reported by Stahl [4 ]for 2001.Controlled studies of BZs and ADs in anxiety disorders have been few and far apart as has been pointed out by Offidani et al. [1]. In fact, no evidence for the superiority of the newer ADs over BZs, both in terms of efficacy or safety, exists for either short-term or long-term treatment. BZ toxicity, adverse events, and withdrawal symptoms, not better efficacy, are usually cited in support of the use of ADs over BZs in anxiety disorders. Yet ADs are not better tolerated than BZs and they also cause withdrawal symptoms [5,6]. Therefore, gradual, not abrupt, taper is indicated after treatment with BZs and ADs [7,8], and a distinction between withdrawal symptoms and a return of anxiety, often a most difficult task, is critical for clinical management.A well-conducted comparison trial of a BZ and a newer AD simply does not exist, neither for acute nor chronic treatment. In fact, when in the late 1970s the National Institute of Mental Health (NIMH) made the decision to withdraw largely from supporting clinical trials of new drugs, turning new drug development over to industry, many clinically important trials, such as a comparison of BZs versus selective serotonin reuptake inhibitor ADs in anxiety disorders for example, were simply not done. It is therefore time that such comparison trials are conducted if possible under other sponsorship than that of the industry.
SPIRILLA ASSOCIATED WITH DISEASE OF THE FETAL MEMBRANES IN CATTLE (INFECTIOUS ABORTION)
Authors: Theobald Smith
Journal: The Journal of Experimental Medicine (1918)

Spirilla of identical morphological and cultural characters have been isolated in pure culture from the fetuses of fourteen cases of abortion. The condition of the fetus is much the same whether spirilla or the bacilli of abortion are present. This condition is probably due in both cases to interference with the placental circulation. The injurious action of the etiological factor when spirilla are present is limited to the fetal membranes, more particularly the chorion. Definite lesions of the fetus were not detected. The spirilla gain access to the digestive and respiratory organs of the fetus when the latter swallows the amniotic fluid. More rarely they are disseminated through the body, probably through the circulation. The spirilla will grow in certain culture media only under reduced oxygen tension, readily secured by sealing the ordinary culture tubes with sealing wax. Laboratory animals (mammals) are refractory. The precise relation of the spirillum to the pathologic process remains to be more definitely formulated. Since the spirillum was first isolated, twenty-seven cases have been found associated with Bacillus abortus and fourteen with the spirillum. In none was a mixed infection with both organisms detected. The spirillum has been isolated only from the second or succeeding pregnancies. Table I summarizes the data collected thus far. It gives by. number the male and shows that the spirillum is not associated with any one bull. The spirillum has been found in fetuses of various ages as shown in Column 3. The distribution of spirilla as shown by cultures is given, the sign + indicating pure cultures, the sign no growth. The guinea pig inoculations are shown to be uniformly negative as regards Bacillus abortus.
The "New Interpretation of Operative Principles"—A Pertinent Question.
Authors: Joseph Clements
Journal: JAMA (1898)

Kansas City, Mo., August, 1898. <h3>To the Editor:</h3> —What should be the attitude of the "science mind" in regard to discoveries and theories, revolutionary in their character and tendencies in medical science; in other words, the duty and obligation of the scientific physician in respect to "new interpretations of long-accepted basic principles in medical science now being promulgated? Unfortunately our wording of the subject is wordy; we trust our discussion of it will not be found mere words. It is said, history repeats itself. Up to the beginning of the fifteenth century the Ptolemaic system was the accepted astronomic science. All discoveries of new planets or fuller knowledge of known ones was adjusted to the recognized Ptolemaic plan of the earth as the central body. Many "hitches" in the workings of the scheme and anomalies arose here and there and again and again, but they were silently ignored or explained
LONG-TERM PRESERVATION OF BLOOD
Authors: Carl V. Moore
Journal: JAMA (1960)

Medical scientists and physicians interested in transfusion problems have worked hard to find ways of storing blood for months or years rather than for the current three or four weeks. Effective stockpiling of the large amounts of blood needed for the armed forces and the general population in the event of a nuclear attack would then become possible. Blood banks could accumulate rare types of blood and improve their ability to meet special demands, like those of open heart surgery. To date, only minor improvements have resulted from changes in the composition of solutions of anticoagulants and preservatives. Freezing of red blood cells, which has seemed the most promising attack, has been studied on a limited scale by many workers. The technical difficulties, however, are formidable: Formation of ice crystals during freezing and thawing must be avoided or cells will be damaged; glycerolization of erythrocytes has been found to prevent
Resuscitation of the newborn.
Authors: H B Valman
Journal: BMJ (1979)

Initial diagnosis of Rubinstein-Taybi syndrome was made in an infant with a prominent nose and broad thumbs and first toes. However, due to the presence of other anomalies such as low-set, malformed ears, anti-mongoloid slant of the eyes, colobomata of the iris, and cleft palate, cytogenetic studies were carried out and the diagnosis of trisomy 13 was confirmed. Since, occasionally, trisomy 13 syndrome may mimic the Rubinstein-Taybi syndrome, cytogenetic studies should be considered in all patients with clinical diagnosis of Rubinstein-Taybi syndrome.
Plasma levels of soluble E-selectin in patients with disseminated intravascular coagulation
Authors: Kenji Okajima, Mitsuhiro Uchiba, Kazunori Murakami, Hiroaki Okabe, Kiyoshi Takatsuki
Journal: American Journal of Hematology (1997)

The plasma level of soluble E-selectin (sE) reflects the activation of endothelial cells induced by cytokines such as tumor necrosis factor-α and interleukin-1 in vitro. These cytokines are important in the development of coagulation abnormalities in patients with sepsis. We compared the plasma levels of sE in patients with infections suspected of having disseminated intravascular coagulation (DIC) (n = 33) and in patients with underlying disorders other than infections, including solid tumors (n = 28), obstetric disorders (n = 13), hematologic malignancies (n = 13), and liver disease (n = 9), to clarify the involvement of cytokines in the development of coagulation abnormalities in patients with sepsis. Plasma levels of sE in patients with infection were significantly higher than in patients with the other underlying disorders. The plasma level of sE was also significantly higher in patients with infection with DIC (114.6 ± 77.9 ng/ml, n = 21) than in patients with infection without DIC (54.5 ± 53.1 ng/ml, n = 12, P < 0.02). There was no significant difference in sE level between patients with the other underlying disorders with and without DIC. The plasma level of sE was significantly correlated with the serum level of FDP(E) in patients with infection. The plasma level of sE was significantly higher in patients with infection with organ failure compared to patients without organ failure. There was no significant difference between patients with the other underlying disorders with and without organ failure. Plasma levels of tumor necrosis factor-α and interleukin-6 were detected in only 12.1% and 20.0% of patients with infections, respectively. These observations strongly suggest that plasma levels of sE reflect the activation of endothelial cells induced by cytokines, which may lead to DIC and organ failure in the presence of sepsis. Furthermore, determination of plasma level of sE may be useful for detecting the endothelial activation induced by cytokines in the pathologic conditions of sepsis, even when plasma levels of cytokines cannot be detected. Am. J. Hematol. 54:219–224, 1997 © 1997 Wiley-Liss, Inc.
Efficacy of adjunctive thrombolytic therapy in percutaneous transluminal coronary angioplasty
Authors: Paul T. Vaitkus, Warren K. Laskey
Journal: Journal of the American College of Cardiology (1994)

Adjunctive thrombolysis has net been shown to improve angioplasty success or complication rates in elective angioplasty or myocardial infarction und may be detrimental in unstable angina. Thrombolysis of chronically occluded vessels achieves recanalization at a rate comparable to conventional angioplasty and is associated with a high rate of complications and limited long-term patency. Thrombolysis administered for thrombus or acute occlusion complicating angioplasty usually achieves coronary artery patency but is unable to forestall complications in many cases. A benefit of thrombolysis in reducing restenosis has not been conclusively demonstrated.