tbuckley/cabot-search huggingface dataset:
Hyperphenylalaninemia Due to a Deficiency of Biopterin
Authors: Seymour Kaufman, Stanley Berlow, George K. Summer, Sheldon Milstien, Joseph D. Schulman, Sheldon Orloff, Stephen Spielberg, Siegfried Pueschel
Journal: New England Journal of Medicine (1978)

We studied the components of the hepatic phenylalanine hydroxylating system in a child with phenylketonuria who showed substantial neurologic impairment despite early dietary control of elevated blood phenylalanine levels. Phenylalanine hydroxylase, dihydropteridine reductase and dihydrofolate reductase activities were normal. In contrast the level of hydroxylation cofactor, tetrahydrobiopterin, in liver was only 10 per cent of normal. In addition to this hepatic deficiency, serum and urinary levels of biopterin-like compounds were low, and the serum biopterin did not increase in response to a phenylalanine load as it does in normal and phenylketonuric subjects. The phenylalanine hydroxylase activity in this child, as determined by an in vivo tritium-release assay, was 2.3 per cent of the normal value. These results indicate that the child suffers from a variant form of phenylketonuria--a deficiency of a functional phenylalanine hydroxylating system secondary to a defect in biosynthesis of biopterin.
NHS still failing to tackle alcohol misuse despite rise in admissions
Authors: R. Coombes
Journal: BMJ (2009)

Local health services are failing to tackle alcohol harm despite a sharp climb in related hospital admissions, MPs warned this week. Reducing Alcohol Harm , a report by the UK House of Commons public accounts committee, also found the government’s approach to the United Kingdom’s growing alcohol problem muddled and uncoordinated.

Alcohol misuse costs the NHS an estimated £2.7bn (€3.2bn; $4.5bn) a year. In 2006-7 there were some 811 000 alcohol related hospital admissions, representing a 71% rise in four years. However, primary care trusts are free to decide for themselves how much to spend on services to tackle alcohol harm. The report found that many trusts did not even know what they spent on such services, and throughout England there is little …
The Challenging Future of Medical Education
Authors: Carlos J. M. Martini
Journal: JAMA (1987)

The decade of the 1980s has brought serious and diverse challenges to medical education. All of these challenges are due to unprecedented changes in medical knowledge and practice. Many of the pressures for change are external to medicine itself, with an increase in public demand for selfdiscipline and accountability. Other pressures such as the increased number of medical students and medical schools in the 1970s, the long-term impact of which is now being felt, are due to health care policies that misfired. An overloaded system of graduate medical education and the commercialization and fragmentation of continuing medical education (CME) programs are also creating smoldering new fires that require innovative management approaches and solutions. In the following pages of this issue ofTHE JOURNAL, American Medical Association staff present data documenting some of these concerns. Perhaps the single most important challenge for medical education at this time is to develop approaches
Medications as a Potential Source of Exposure to Phthalates in the U.S. Population
Authors: Sonia Hernández-Díaz, Allen A. Mitchell, Katherine E. Kelley, Antonia M. Calafat, Russ Hauser
Journal: Environmental Health Perspectives (2008)

BackgroundWidespread human exposure to phthalates, some of which are developmental and reproductive toxicants in experimental animals, raises concerns about potential human health risks. Underappreciated sources of exposure include phthalates in the polymers coating some oral medications.ObjectiveThe objective of this study was to evaluate whether users of phthalate-containing medications have higher urinary concentrations of phthalate metabolites than do nonusers.MethodsWe used publically available files from the National Health and Nutrition Examination Survey for the years 1999–2004. For certain survey periods, participants were asked to recall use of prescription medication during the past 30 days, and for a subsample of individuals, the urinary concentrations of phthalate metabolites were measured. We a priori identified medications potentially containing phthalates as inactive ingredients and then compared the mean urinary concentration of phthalate metabolites between users and nonusers of those medications.Results:Of the 7,999 persons with information on urinary phthalate concentrations, 6 reported using mesalamine formulations, some of which may include dibutyl phthalate (DBP); the mean urinary concentration of monobutyl phthalate, the main DBP metabolite, among these mesalamine users was 50 times higher than the mean for nonusers (2,257 μg/L vs. 46 μg/L; p < 0.0001). Users of didanosine, omeprazole, and theophylline products, some of which may contain diethyl phthalate (DEP), had mean urinary concentrations of monoethyl phthalate, the main DEP metabolite, significantly higher than the mean for nonusers.ConclusionSelect medications might be a source of high exposure to some phthalates, one of which, DBP, shows adverse developmental and reproductive effects in laboratory animals. These results raise concern about potential human health risks, specifically among vulnerable segments of the general population and particularly pregnant women and children.
Pimp my slang
Authors: Paul W Keeley
Journal: BMJ (2007)

Objective To test whether standard information for patients using Crunchie and Aero chocolate bars to explain bone health and risk of fracture is robust.Design Observational study.Setting Domestic kitchen in rural west Wales.Participants 10 Crunchie bars and 10 Aero bars.Main outcome measure Fracture after falls from varying heights.Results Both Crunchie and Aero bars exhibited the same T and Z scores for bone density.Crunchie bars had a lower chocolate mass index than the Aero bars.Crunchie bars are more liable to fracture.Conclusions Using Crunchie and Aero chocolate bars to explain bone structure to patients may be visually attractive but oversimplifies the situation. IntroductIonIt is important that information provided to patients as part of their treatment should be comprehensive and accurate.Within our area of practice relating to osteoporosis and fragility fracture we have noticed a tendency to compare normal, healthy bone to the finely honeycombed structure of a Crunchie (Cadbury Trebor Bassett; Bournville, Birmingham) chocolate bar and to compare abnormal, osteoporotic bone to the coarser structure of an Aero (Nestle UK; York) bar (fig 1). 1 2 Although this explanation is readily appreciated by patients and clinicians it struck us that the comparison may not be completely valid as no work has been published on the fracture potential of each bar.This might mean that with best intentions we are advising patients to aspire to a bone structure that is actually more liable to fracture.To enable us to provide accurate data to our patients we studied the fracture risk for each chocolate bar. MethodsWe randomly purchased 20 chocolate bars (10 Crunchie and 10 Aero) from a reputable high street confectioner; the number of bars was limited by research funds and our rural environment.Each bar was measured to provide information on height
Truth Telling in Medicine
Authors: Mark Sheldon
Journal: JAMA (1982)

The viewpoints of L.J. Henderson, Sissela Bok, and Joseph Ellin on the nature and importance of truthfulness in the physician-patient relationship are examined in relation to various types of specific medical situations. While the theoretical models of Henderson and Ellin would more frequently justify deception by physicians for benevolent purposes, the author thinks that their approach may appear to work simply because many patients have been conditioned not to ask physicians confrontational questions.
A97: Endothelial Function in Children With a History of Henoch-Schonlein Purpura
Authors: Yonatan butbul Aviel, Lotem Dafna, Riva Brik, Giora Pilar
Journal: Arthritis & Rheumatology (2014)

Background/Purpose:

Few reports have focused on vascular endothelial function in children with Henoch-Schonlein purpura (HSP). The purpose of the present study was to assess the long term effect of HSP on endothelial function, in children and adolescents.



Methods:

Patients between 6–20 years old, who were diagnosed as having HSP according to ACR Criteria, were included in the study. All patients were followed by the rheumatologic clinic at Meyer children's hospital Israel. The time interval between diagnosis of HSP and endothelial study was at least 6 months.



Endothelial function evaluation was assessed by a noninvasive technology named peripheral arterial tonometry, using an ENDO_PAT device. The device measures blood flow in the limb, in response to arterial occlusion as an index of endothelial function, Reactive Hyperemic Index (RHI). Endothelial function was compared to known normal values of existing control group consisting of 23 healthy children and adolescents.



Results:

Nineteen children and adolescents (M:F 8/11) age (3.9 ± 13.5 years) with history of HSP were included in the study. Endothelial function was compared to that of a known control group comprising of 23 healthy children and adolescents of the same age group and M:F ratio.



There was no difference in RHI levels between the children with diagnosis of HSP and the control group (1.8 ± 0.7 vs. 1.9 ± 0.35 p = 0.7).



For patients with HSP we used multi variant regression models to evaluate relation between RHI and different variables the final model include smoking that have negative effect (β = (−1.042), P = 0.31) and, period of time from diagnosis to time of evaluation that have positive effect (β = 0.139, P = 0.003) (R2 = 0.476).



When we excluded two patients with exceptional level of RHI from the study a higher correlation was found between those variables and RHI (R2 = 0.76).



RHI levels were significantly higher in patients that endothelial function was measured more than 6 years after diagnosis of HSP compared to the rest of the group (1.98 ± 0.74 vs 1.38 ± 0.43 P = 0.037).



Conclusion:

These results suggest that HSP cause endothelial dysfunction that improves with time.



The influence of the endothelial dysfunction on the long term chances of developing atherosclerosis has still to be determined.
Sleep Deprivation and Performance of Residents
Authors: Bruce R. Pawel
Journal: JAMA (1989)

<h3>To the Editor. —</h3> In the recent article entitled "Sleep Deprivation and Resident Performance,"<sup>1</sup>the authors conclude that sleep deprivation associated with an every-other-night on-call schedule does not adversely affect patient care. However, the evidence presented in their article does not support that conclusion. In making the critical decision to define sleep deprivation by a cutoff point of less than 4 hours' uninterrupted sleep, the authors stated that this is what appears to be the minimum requirement for a beneficial effect on cognitive performance in studies of nonphysicians. If the thrust of their article is that sleep deprivation does not affect cognitive and motor performance of residents, the logical conclusion must be either that the authors' original definition of sleep deprivation is flawed or that physicians are somehow physiologically different from other human beings. Also, the use of the residents as their own controls is extremely questionable in a
IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis
Authors: Ken Sugimoto, Atsuhiro Ogawa, Emiko Mizoguchi, Yasuyo Shimomura, Akira Andoh, Atul K. Bhan, Richard S. Blumberg, Ramnik J. Xavier, Atsushi Mizoguchi
Journal: Journal of Clinical Investigation (2008)

Expression of IL-22 is induced in several human inflammatory conditions, including inflammatory bowel disease (IBD). Expression of the IL-22 receptor is restricted to innate immune cells; however, the role of IL-22 in colitis has not yet been defined. We developed what we believe to be a novel microinjection-based local gene-delivery system that is capable of targeting the inflamed intestine. Using this approach, we demonstrated a therapeutic potency for IL-22–mediated activation of the innate immune pathway in a mouse model of Th2-mediated colitis that induces disease with characteristics similar to that of IBD ulcerative colitis (UC). IL-22 gene delivery enhanced STAT3 activation specifically within colonic epithelial cells and induced both STAT3-dependent expression of mucus-associated molecules and restitution of mucus-producing goblet cells. Importantly, IL-22 gene delivery led to rapid amelioration of local intestinal inflammation. The amelioration of disease by IL-22 was mediated by enhanced mucus production. In addition, local gene delivery was used to inhibit IL-22 activity through overexpression of IL-22–binding protein. Treatment with IL-22–binding protein suppressed goblet cell restitution during the recovery phase of a dextran sulfate sodium–induced model of acute colitis. These data demonstrate what we believe to be a novel function for IL-22 in the intestine and suggest the potency of a local IL-22 gene–delivery system for treating UC.
Interleukin-10 expression and chemokine regulation during the evolution of murine type II collagen-induced arthritis.
Authors: T Kasama, R M Strieter, N W Lukacs, P M Lincoln, M D Burdick, S L Kunkel
Journal: Journal of Clinical Investigation (1995)

In the enclosed study we have examined the expression and contribution of specific chemokines, macrophage inflammatory protein 1 alpha (MIP-1 alpha) and macrophage inflammatory protein 2 (MIP-2), and interleukin 10 (IL-10) during the evolution of type II collagen-induced arthritis (CIA). Detectable levels of chemotactic cytokine protein for MIP-1 alpha and MIP-2 were first observed between days 32 and 36, after initial type II collagen challenge, while increases in IL-10 were found between days 36 and 44. CIA mice passively immunized with antibodies directed against either MIP-1 alpha or MIP-2 demonstrated a delay in the onset of arthritis and a reduction of the severity of arthritis. On the contrary, CIA mice receiving neutralizing anti-IL-10 antibodies demonstrated an acceleration of the onset and an increase in the severity of arthritis. Interestingly, anti-IL-10 treatment increased the expression of MIP-1 alpha and MIP-2, as well as increased myeloperoxidase (MPO) activity and leukocyte infiltration in the inflamed joints. These data suggest that MIP-1 alpha and MIP-2 play a crucial role in the initiation and maintenance, while IL-10 appears to play a regulatory role during the development of experimental arthritis.
Brendan Bethel Jacobs
Authors: F. Coutts
Journal: BMJ (2011)

Brendan Bethel Jacobs was a very special “old style” general practitioner, who gave total care and commitment to his patients. He was born in Dublin and spent his early childhood in China where his father was an engineer. Later he went to Oundle School when the family home was in France.

In the early 1950s at the Department of Human Ecology in Cambridge, where he met his wife, Jean, he made an epidemiological study of rheumatic complaints in East Anglia. He entered general practice during the exciting period of the start of the Royal College of General Practitioners and became a founder member of the college. In 1953 he joined a practice in Arnold, Nottingham, where he remained until his retirement, aged 69 years.

Early in his career he felt deficient in the diagnosis and treatment of emotional problems in general practice. In 1957, …
Biased expression of JH-proximal VH genes occurs in the newly generated repertoire of neonatal and adult mice.
Authors: B A Malynn, G D Yancopoulos, J E Barth, C A Bona, F W Alt
Journal: The Journal of Experimental Medicine (1990)

We have previously demonstrated a dramatic preference for utilization of the most JH-proximal VH gene segments in the newborn liver versus adult spleen. We now examine in detail the relative expression of different VH gene families throughout ontogeny and in immunodeficient mice to gain insight into factors that cause the shift in VH usage. We find that the relative expression of VH gene families remains constant and biased throughout fetal and neonatal liver development. In addition, the primary VH repertoire expressed in neonatal spleen displays a similarly biased, position-dependent VH repertoire. The pattern of VH gene expression begins to change at 5-7 d postnatally and reaches the adult randomized pattern at approximately 2 wk of age. We also find biased expression of JH-proximal VH gene families in adult bone marrow and in spleens of adult leaky scid mice, suggesting that the spontaneously generated repertoire of adult mice is similar to that observed in neonates. Together, these data suggest that a position-dependent repertoire is generated in differentiating pre-B cells at all stages of ontogeny, at least in part, as a result of preferential rearrangement of proximal VH gene segments. Therefore, mechanisms subsequent to V gene rearrangement, such as regulatory interactions and antigen selection, must play a major role in normalizing the repertoire.
Vegetarian Diets and Blood Pressure
Authors: Yoko Yokoyama, Kunihiro Nishimura, Neal D. Barnard, Misa Takegami, Makoto Watanabe, Akira Sekikawa, Tomonori Okamura, Yoshihiro Miyamoto
Journal: JAMA Internal Medicine (2014)

IMPORTANCE Previous studies have suggested an association between vegetarian diets and lower blood pressure (BP), but the relationship is not well established. OBJECTIVE To conduct a systematic review and meta-analysis of controlled clinical trials and observational studies that have examined the association between vegetarian diets and BP. DATA SOURCES MEDLINE and Web of Science were searched for articles published in English from 1946 to October 2013 and from 1900 to November 2013, respectively. STUDY SELECTION All studies met the inclusion criteria of the use of (1) participants older than 20 years, (2) vegetarian diets as an exposure or intervention, (3) mean difference in BP as an outcome, and (4) a controlled trial or observational study design. In addition, none met the exclusion criteria of (1) use of twin participants, (2) use of multiple interventions, (3) reporting only categorical BP data, or (4) reliance on case series or case reports. DATA EXTRACTION AND SYNTHESIS Data collected included study design, baseline characteristics of the study population, dietary data, and outcomes. The data were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES Net differences in systolic and diastolic BP associated with the consumption of vegetarian diets were assessed. RESULTS Of the 258 studies identified, 7 clinical trials and 32 observational studies met the inclusion criteria. In the 7 controlled trials (a total of 311 participants; mean age, 44.5 years), consumption of vegetarian diets was associated with a reduction in mean systolic BP (-4.8 mm Hg; 95% CI, -6.6 to -3.1; P < .001; I2 = 0; P = .45 for heterogeneity) and diastolic BP (-2.2 mm Hg; 95% CI, -3.5 to -1.0; P < .001; I2 = 0; P = .43 for heterogeneity) compared with the consumption of omnivorous diets. In the 32 observational studies (a total of 21,604 participants; mean age, 46.6 years), consumption of vegetarian diets was associated with lower mean systolic BP (-6.9 mm Hg; 95% CI, -9.1 to -4.7; P < .001; I2 = 91.4; P < .001 for heterogeneity) and diastolic BP (-4.7 mm Hg; 95% CI, -6.3 to -3.1; P < .001; I2 = 92.6; P < .001 for heterogeneity) compared with the consumption of omnivorous diets. CONCLUSIONS AND RELEVANCE Consumption of vegetarian diets is associated with lower BP. Such diets could be a useful nonpharmacologic means for reducing BP.
Single-center evaluation of the INNO-LiPA HBV genotyping, a reverse hybridization assay for the detection of HBV genotypes A–G
Authors: P. Halfon, H. Khiri, M. Bourliere, L. Celis, A. De Brauwer, K. De Nys, P. Segers, M. Van Brussel, E. Sablon
Journal: Journal of Hepatology (2003)
JFK—An Allonge
Authors: Charles S. Petty
Journal: JAMA (1993)

There is absolutely nothing like preaching to the choir. Those who would keep alive the controversy regarding the Kennedy-Connally shooting will neither read nor hear what they do not wish to believe. It is because I have not wished to be involved in a useless (and thankless) task that I have written nothing for publication regarding the Kennedy assassination. Lattimer's article,<sup>1</sup>closely following publication of the interviews with Humes, Boswell, and Finck,<sup>2,3</sup>has provided me with an engine to make some amplifying and other comments. See also pp 1507, 1525, 1540, and 1544. <h3>The Firearm</h3> The 6.5-mm, Mannlicher-Carcano firearm used was not a "rifle" and it was not "high-velocity" or "high-powered." The velocity of the bullets at the time they struck Kennedy cannot be precisely predicted. The muzzle velocity varies depending on a number of factors that cannot be absolutely determined. Also, the distance traveled by the bullets
The Effect of Tumor Location on Prognosis in Patients Treated with Radical Nephroureterectomy at Memorial Sloan-Kettering Cancer Center
Authors: Ricardo L. Favaretto, Shahrokh F. Shariat, Daher C. Chade, Guilherme Godoy, Ari Adamy, Matthew Kaag, Bernard H. Bochner, Jonathan Coleman, Guido Dalbagni
Journal: European Urology (2010)
Breast-feeding lauded by pediatricians
Authors: May Annexton
Journal: JAMA (1978)

Is mother's milk the optimum in human infant nutrition? Emphatically yes, according to a joint statement recently issued by the American Academy of Pediatrics (AAP) and the Canadian Paediatric Society (CPS). The two main advantages of breast-feeding, according to the statement, are the transmission of maternal immunity and the reinforcement of "bonding," which is considered necessary for the emotional nurturing of the infant. "There is increasing evidence that a newborn infant can acquire certain important elements of host resistance from breast milk while maturation of his own immune system is taking place. The human breast secretes antibodies to some intestinal microorganisms and this may help protect breast-fed infants from enteric infection," the joint statement declares. "Recent observation has established the presence of an enteromammary system by which enteric antigenstimulated mucosal plasma cells in the mother migrate to breast tissue where they secrete antibodies or are [themselves] secreted directly into breast