tbuckley/cabot-search huggingface dataset:
Mechanism of tyrosinase inhibition by deoxyArbutin and its second-generation derivatives
Authors: S. Chawla, M.A. deLong, M.O. Visscher, R.R. Wickett, P. Manga, R.E. Boissy
Journal: British Journal of Dermatology (2008)

Disorders, such as age spots, melasma and hyperpigmentation at sites of actinic damage, emanate from the augmentation of an increased amount of epidermal melanin.The ineptness of current therapies in treating these conditions, as well as high cytotoxicity, mutagenicity, poor skin penetration and low stability of skin-depigmenting formulations led us to investigate new compounds that meet the medical requirements for depigmentation agents. We have shown previously that the tyrosinase inhibitor deoxyArbutin (dA) is a more effective and less toxic skin lightener than hydroquinone (HQ).The efficacy and reversibility of dA and its derivatives on inhibiting tyrosine hydroxylase and DOPAoxidase was assessed using standard assays.dA and its second-generation derivatives inhibit tyrosine hydroxylase and DOPAoxidase activities of tyrosinase dose dependently thereby inhibiting melanin synthesis in intact melanocytes, when used at concentrations that retain 95% cell viability in culture. This depigmenting effect was completely reversible when the compounds were removed. Tyrosinase inhibition was also observed in vitro when tested using human and purified mushroom tyrosinase, establishing that they are direct enzyme inhibitors. Lineweaver-Burk reciprocal plot analysis using mushroom tyrosinase illustrated that dA and its derivatives are more robust competitive inhibitors than HQ, when tyrosine is used as substrate.Thus, dA and its second-generation derivatives, which inhibit melanogenesis at safe concentrations by specifically acting on the tyrosinase enzyme at a post-translational level, are promising agents to ameliorate hyperpigmented lesions or lighten skin.
Transient Elevation of Serum Thyroid Hormone Concentration After Initiation of Replacement Therapy in Myxedema
Authors: MORRIS E. BROWN
Journal: Annals of Internal Medicine (1980)

Measurements of thyroid hormone concentrations in serum are commonly used to determine the proper dose of hormone replacement. We have noted that early in the course of thyroxine (T4) replacement in myxedema, serum T4 concentrations may be transiently elevated before reaching a lower "steady-state" level. This observation is illustrated in a study of six patients. Serum T4, free thyroxine index, and triiodothyronine (T3) rose to peak concentrations at 2 to 6 weeks, 35% to 120% above the values achieved 4 to 8 months later. Values were transiently in the thyrotoxic range in five of the six patients. This phenomenon is most likely due to a decrease in the metabolic clearance rate of the absorbed hormone associated with hypometabolism. Thus, serum T4 and T3 concentrations during the first 6 months of therapy do not reflect the optimal dose of T4 replacement on a long-term basis.
Comparative Effectiveness and Costs of Inpatient and Outpatient Detoxification of Patients with Mild-to-Moderate Alcohol Withdrawal Syndrome
Authors: Motoi Hayashida, Arthur I. Alterman, A. Thomas McLellan, Charles P. O'Brien, James J. Purtill, Joseph R. Volpicelli, Arnold H. Raphaelson, Charles P. Hall
Journal: New England Journal of Medicine (1989)

Abstract We compared the effectiveness, safety, and costs of outpatient (n = 87) and inpatient (n = 77) detoxification from alcohol in a randomized, prospective trial involving 164 male veterans of low socioeconomic status. The outpatients were evaluated medically and psychiatrically and then were prescribed decreasing doses of oxazepam on the basis of daily clinic visits. The inpatient program combined comprehensive psychiatric and medical evaluation, detoxification with oxazepam, and the initiation of rehabilitation treatment. The mean duration of treatment was significantly shorter for outpatients (6.5 days) than for inpatients (9.2 days). On the other hand, significantly more inpatients (95 percent) than outpatients (72 percent) completed detoxification. There were no serious medical complications in either group. Outcome evaluations completed at one and six months for 93 and 85 percent of the patients, respectively, showed substantial improvement in both groups at both follow-up periods. At one month there were fewer alcohol-related problems among inpatients and fewer medical problems among outpatients. However, no group differences were found at the six-month follow-up, nor were differences found in the subsequent use of other alcoholism-treatment services. Costs were substantially greater for inpatients ($3,319 to $3,665 per patient) than for outpatients ($175 to $388). We conclude that outpatient medical detoxification is an effective, safe, and low-cost treatment for patients with mild-to-moderate symptoms of alcohol withdrawal. (N Engl J Med 1989; 320:358–65.)
How Reliable Are Letters?
Authors: Arnold S. Relman
Journal: New England Journal of Medicine (1983)

Letters to the Editor arrive in our office at the rate of nearly 100 a week. They come from all over the world, and they deal with virtually every conceivable medically related subject. The majority concern articles or letters previously published in the Journal, but there are also opinions on an endless variety of other, unrelated topics. One kind of letter that seems to be more frequent of late is a report of new research findings. These brief scientific communications describe limited observations on one or two cases or preliminary experimental results of pilot studies. They often include a . . .
γ-Glutamyl-Cysteine Synthetase Deficiency
Authors: Patricia N. Konrad, Frederick Richards, William N. Valentine, Donald E. Paglia
Journal: New England Journal of Medicine (1972)

Abstract In some families with hemolytic anemia and a low level of reduced glutathione in erythrocytes, the disorder is associated with a deficiency of glutathione synthetase, the second of two enz...
EOSINOPHIL CATIONIC PROTEIN: A NEW BIOMARKER OF CORONARY ATHEROSCLEROSIS.
Authors: Giampaolo Niccoli, Giuseppe Ferrante, Nicola Cosentino, Micaela Conte, Andrea Silenzi, Flavia Belloni, Marcello Marino, Vito Sabato, Domenico Schiavino, Giampiero Patriarca, Luigi Marzio Biasucci, Filippo Crea
Journal: Journal of the American College of Cardiology (2010)
Genome-wide and fine-resolution association analysis of malaria in West Africa
Authors: Muminatou Jallow, Yik Ying Teo, Kerrin S Small, Kirk A Rockett, Panos Deloukas, Taane G Clark, Katja Kivinen, Kalifa A Bojang, David J Conway, Margaret Pinder, Giorgio Sirugo, Fatou Sisay-Joof, Stanley Usen, Sarah Auburn, Suzannah J Bumpstead, Susana Campino, Alison Coffey, Andrew Dunham, Andrew E Fry, Angela Green, Rhian Gwilliam, Sarah E Hunt, Michael Inouye, Anna E Jeffreys, Alieu Mendy, Aarno Palotie, Simon Potter, Jiannis Ragoussis, Jane Rogers, Kate Rowlands, Elilan Somaskantharajah, Pamela Whittaker, Claire Widden, Peter Donnelly, Bryan Howie, Jonathan Marchini, Andrew Morris, Miguel SanJoaquin, Eric Akum Achidi, Tsiri Agbenyega, Angela Allen, Olukemi Amodu, Patrick Corran, Abdoulaye Djimde, Amagana Dolo, Ogobara K Doumbo, Chris Drakeley, Sarah Dunstan, Jennifer Evans, Jeremy Farrar, Deepika Fernando, Tran Tinh Hien, Rolf D Horstmann, Muntaser Ibrahim, Nadira Karunaweera, Gilbert Kokwaro, Kwadwo A Koram, Martha Lemnge, Julie Makani, Kevin Marsh, Pascal Michon, David Modiano, Malcolm E Molyneux, Ivo Mueller, Michael Parker, Norbert Peshu, Christopher V Plowe, Odile Puijalon, John Reeder, Hugh Reyburn, Eleanor M Riley, Anavaj Sakuntabhai, Pratap Singhasivanon, Sodiomon Sirima, Adama Tall, Terrie E Taylor, Mahamadou Thera, Marita Troye-Blomberg, Thomas N Williams, Michael Wilson, Dominic P Kwiatkowski
Journal: Nature Genetics (2009)
Dynamic force microscopy imaging of plasmid DNA and viral RNA
Authors: Ferry Kienberger, Lilian T. Costa, Rong Zhu, Gerald Kada, Manuela Reithmayer, Lilia Chtcheglova, Christian Rankl, Ana B.F. Pacheco, Stefan Thalhammer, Vassili Pastushenko, Wolfgang M. Heckl, Dieter Blaas, Peter Hinterdorfer
Journal: Biomaterials (2007)
Harvesting Knowledge From Improvement
Authors: Donald M. Berwick
Journal: JAMA (1996)

Among the important gains in health care in this quarter-century has been the progress of disciplined statistical methods for clinical research. Thanks to leaders like Sir Richard Doll, J. N. Morris, Kerr White, Alvan Feinstein, Frederick Mosteller, Thomas Chalmers, David Sackett, and others, clinical investigators today use more sophisticated approaches to inference, and readers of their reports are more able to judge the soundness of experimental design. The randomized clinical trial (RCT) has emerged for good reason as the prince of designs, and we also understand better the proper use of case-control, cohort, and quasi-experimental studies. See also p 841. These new standards have reached the mainstream. Journal reviewers demand evidence of proper control and statistical analyses. Study sections attend carefully to details of proposed methods, like sample size calculations, randomization rules, and investigator blinding. Of the first 50 original scientific reports in the<i>New England Journal of Medicine</i>in
Conducting Clinical Research in Geriatric Populations
Authors: ANNE WILDER ZIMMER
Journal: Annals of Internal Medicine (1985)

Clinical research on geriatric populations requires adaptation of traditional methodologies, modification of expectations, and the development of new procedures. Some aspects of research methodology are unique to studies of geriatric populations. Experience in this relatively new area of geriatric research indicates that new partnerships between researchers and long-term care providers are needed. These new relationships require an understanding of the needs of geriatric populations and of the differences between providers of long-term care and of acute-care. Researchers must consider heterogeneity of the population, the probability of multiple diagnoses and treatments, subject attrition, and the possibility of invalid data. Such considerations require extra staff, more time, and increased funding as well as new thinking about study design and protocol implementation.
Haemolytic Anaemia Treated by A.C.T.H., Cortisone, and Splenectomy
Authors: J. D. Aitchison
Journal: BMJ (1953)

The average changes in weight of groups of industrial workers (male and female) in small firms and of housewives measured during the course of the Minis- try of Food's Body Weight Survey (1943 to 1949) have been compared with the calorie value of the food con- sumption recorded for urban working-class households in the Ministry's National Food Survey during the same years.. Body weights of adults fluctuated with the calorie values of the diet.There is evidence from various parts of the country of parallel changes in the growth rates of children.The bearing of these results on the desirable calorie levels of the national food supply is discussed.
A BACTERIAL TOXIN AS THE CAUSE OF RETINAL HEMORRHAGE
Authors: F. PARK LEWIS
Journal: JAMA (1918)

In the summer of 1917, a case of retinal hemorrhage came under my observation which illuminated the heretofore obscure etiology of this condition. It made definite that which, in such conditions before, had been vague. It determined causes which could be corrected, and it made precise, measures of treatment which before had been speculative. Its importance, therefore, would seem to warrant a brief report with the deductions to which it gives rise. It is briefly as follows: A woman in middle life had been having a series of recurrent hemorrhages in the retina for a period of eight months. During this time she had been under the advice and observation of an excellent internist and an ophthalmologist of international reputation. The treatment, therefore, might reasonably be accepted as fairly expressive of that which the best professional skill would approve. It consisted of elimination through the kidneys by saline cathartics and
Rituximab plus standard of care for treatment of primary immune thrombocytopenia: a systematic review and meta-analysis
Authors: Shaan Chugh, Saeed Darvish-Kazem, Wendy Lim, Mark A Crowther, Waleed Ghanima, Grace Wang, Nancy M Heddle, John G Kelton, Donald M Arnold
Journal: The Lancet Haematology (2015)
More NHS reorganisation is announced in Queen's speech
Authors: Zosia Kmietowicz
Journal: BMJ (2007)

The prime minister set out his priorities for the health service in the Queen's speech this week—with plans to legislate for a new quality control regulator and changes in the way doctors are regulated and in the rules concerning assisted reproduction and embryo research.

Gordon Brown used his first Queen's speech to announce the creation of a new regulator, whose aim will be “to ensure clean and safe services and high quality care.” 

The new body, to be known as the Care Quality Commission (or Ofcare for short), will take over the functions of the Healthcare Commission, the Commission for Social Care Inspection, and the Mental Health Act Commission. It will be set up under the …
Statement of Principles for Health Care Journalists
Authors: Gary Schwitzer
Journal: PLoS Medicine (2005)

Gatz's statement, "At least half of the explanation for individual differences in susceptibility to Alzheimer disease is genetic" [1], is, in my opinion, incorrect.As the one who led the team debating Ashford and Mortimer, whose 2002 article [2] supports this statement, at the 2001 conference on Alzheimer disease (AD) in Cincinnati ("Challenging Views of Alzheimer's Disease") [3], I think that the evidence that dietary and lifestyle factors explain the majority of the individual risk for AD in the US is very strong.My original paper in 1997 [4] found that total dietary fat and energy intake were the most important dietary risk factors, while fi sh and cereal intake were the most important risk reduction factors.These fi ndings have been generally confi rmed by Drs.Luchsinger and Morris and others.The reason I did my study was that the Honolulu Heart Study reported that Japanese American men in Hawaii had 2.5 times the risk of AD of native Japanese.African-Americans have about four times the risk of AD of native Nigerians.If genetics were the primary risk factor, those living in the US would have a risk of developing AD very similar to that of individuals living in their ancestral home.The reason this is not the case is that the American diet provides too much food, which is a particular problem for those genetically predisposed to AD.
Intravenous Procaine in Transfusion
Authors: G. S. W. Organe, C. F. Scurr
Journal: BMJ (1948)

Two Unusual Cases of Abdominal Extrauterine PregnancyTwo cases of abdominal extrauterine pregnancy are reported which were admitted to Mengo Hospital, Kampala, Uganda, within four months and present features worthy of record.CASE 1 The patient, a Muganda woman in the early twenties, had had a previous normal pregnancy.During antenatal observation the preg- nancy appeared normal, the foetal position was left occipito-anterior, the head above the brim of the pelvis, but a small hard mass low down on the right side of what was thought to be the enlarging uterus was noted and presumed to be a fibroid.On April 15, 1946, when apparently at term, the patient was admitted to hospital, having taken a native drug popularly believed to induce labour.This drug, we have observed, usually causes abdominal distension and tonic contractions of the uterus.She appeared to be very ill and in severe pain, with a rapid pulse rate.The abdomen was distended and the uterus felt very hard and was tender.The foetal position was anterior and the foetal heart rate 120 a minute.The head was above the brim and the cervix was not taken up.She was treated expectantly with morphine.The pain decreased, and on April 29 the head was found to have entered the pelvis and was well below the mass felt on the right side.After a month, during which tinme she complained persistently of pain, the physical signs were unaltered.A medical induction on June 1 was unsuccessful.At her own request, and as her condition was deteriorating, laparotomy was performed.At operation on June 5 the foetus was found lying free in an amniotic sac in the abdominal cavity.The presentation was cephalic in a completely occipito-anterior position.Some exertion was needed to disimpact the head from the pelvis.The child, slightly post- mature and weighing 8 lb. 2 oz.(3.66 kg.), was delivered alivg.The uterus was enlarged to the size of a 10-weeks pregnancy.Immediately after delivery there was a profuse haemorrhage from some detach- ment of the placenta, which was implanted on and received the majority of its blood supply from the ovarian pedicle and left Fallopian tube and was also adherent to the omentum and mesocolon.The haemorrhage was temporarily controlled by a piece of rubber tubing used as a tourniquet around the base of the placental attachment.As much of the placenta was removed as possible, but the membranes were left in situ.The abdomen was drained for 24 hours.The condition of mother and child was good next day, and they were discharged from hospital well some three weeks later.
Presynaptically Released Cbln1 Induces Dynamic Axonal Structural Changes by Interacting with GluD2 during Cerebellar Synapse Formation
Authors: Aya Ito-Ishida, Taisuke Miyazaki, Eriko Miura, Keiko Matsuda, Masahiko Watanabe, Michisuke Yuzaki, Shigeo Okabe
Journal: Neuron (2012)
ABC of poisoning. Eliminating poisons.
Authors: A Vale, T Meredith, B Buckley
Journal: BMJ (1984)

Most poisoned patients recover with little more than nursing care, though about 10% will need intensive support to maintain vital functions.Infewer than 5% ofcases, however, are methods to increase poison elimination either feasible or appropriate.Such techniques should as far as possible be undertaken only by those experienced in their use.Moreover, these methods are oflittle value in patients who have ingested drugs such as tricyclic antidepressants which are highly tissue bound.
Clinical significance of serum neuron‐specific enolase in patients with adult T‐cell leukemia
Authors: Hiroshi Fujiwara, Naomichi Arima, Hideo Ohtsubo, Tadashi Matsumoto, Toshimasa Kukita, Hideaki Kawada, Rie Imaizumi, Atsuo Ozaki, Kakushi Matsushita, Chuwa Tei
Journal: American Journal of Hematology (2002)

Abstract The present study examines the clinical significance of serum neuron‐specific enolase (NSE) in patients with adult T cell‐leukemia (ATL). Serum NSE values were measured using a radioimmunoassay in 35 patients (acute type, n = 15; lymphoma type, n = 10; chronic type, n = 10) and in 7 controls carrying T lymphotropic virus type‐1 (HTLV‐1). Serum NSE values &gt;10 ng/mL were detected in 9 of 15 patients with acute type (60%), 5 of 10 with lymphoma type (50%), and in one of 10 patients with chronic type (10%) ATL, but in none of the HTLV‐1 carriers. Contrary to previous findings demonstrating that 20% of patients with non‐Hodgkin's lymphoma (NHL) had positive serum NSE, the frequency of a high NSE value in patients with acute and lymphoma type ATL was much higher (60% and 50%, respectively). The serum NSE value positively correlated with serum thymidine kinase activity (TK) and serum soluble interleukin‐2 receptor (sIL‐2R) levels ( P &lt; 0.04 and P &lt; 0.01, respectively). Serum NSE values at the initial diagnosis were adversely related to overall survival time according to the log‐rank test ( P &lt; 0.02). Pathological examinations demonstrated that both patients with anaplastic large cell lymphoma type ATL had cytoplasmic NSE and CD30 markers on cell membranes. These findings suggest that serum NSE is partially produced by ATL cells and that ATL tumor cells seem preferentially produce NSE compared with other NHL cells. Serum NSE may be a novel marker of disease aggressiveness as well as a prognostic factor for ATL. Am. J. Hematol. 71:80–84, 2002. © 2002 Wiley‐Liss, Inc.
Serum Insulin, Obesity, and the Incidence of Type 2 Diabetes in Black and White Adults
Authors: Mercedes R. Carnethon, Latha P. Palaniappan, Cecil M. Burchfiel, Frederick L. Brancati, Stephen P. Fortmann
Journal: Diabetes Care (2002)

OBJECTIVE—In this study, we tested the hypothesis that fasting serum insulin is higher in nonobese black adults than in white adults and that high fasting insulin predicts type 2 diabetes equally well in both groups. RESEARCH DESIGN AND METHODS—At the baseline examination (1987–1989) of the Atherosclerosis Risk in Communities Study, fasting insulin and BMI were measured in 13,416 black and white men and women without diabetes. Participants were examined at years 3, 6, and 9 for incident diabetes based on fasting glucose and American Diabetes Association criteria. RESULTS—Fasting insulin was 19.7 pmol/l higher among nonobese (BMI &amp;lt;30 kg/m2) black women compared with white women (race and obesity interaction term, P &amp;lt; 0.01). There were no differences among men. Among nonobese women, the relative risk for developing diabetes was similar between racial groups: 1.4 (95% CI 1.2–1.5) and 1.3 (1.2–1.4) per 60 pmol/l increase in insulin (P &amp;lt; 0.01) for black and white women, respectively (interaction term, P = 0.6). Findings were similar among men. Adjusting for established risk factors did not attenuate this association. CONCLUSIONS—Nonobese black women have higher fasting insulin levels than nonobese white women, and fasting insulin is an equally strong predictor of diabetes in both groups. These results suggest one mechanism to explain the excess incidence of diabetes in nonobese black women but do not explain the excess among black men. Future research should evaluate additional factors: genetic, environmental, or the combination of both, which might explain higher fasting insulin among black women when compared with white women.