tbuckley/cabot-search huggingface dataset:
Biological Rhythms, Mood Disorders, Light Therapy, and the Pineal Gland
Authors: James W. Jefferson
Journal: JAMA (1991)

The "seat of the soul," the "penis cerebri," the "sphincter that regulates the flow of thought"—terms such as these reflect historical speculations with regard to the role of the pineal gland. Given that one of its major functions is the synthesis and secretion of melatonin, a hormone that is intimately linked to light and darkness, the "third eye" is a more appropriate epithet. The title,<i>Biological Rhythms, Mood Disorders, Light Therapy, and the Pineal Gland</i>, suggests that the editors have undertaken quite a challenge, especially when their intended audience is "psychiatric clinicians, adult, child, and adolescent psychiatric residents, medical students, and other health professionals." Within the book is a little food for each of these groups, but not enough substance to guarantee survival. The author of the first chapter sets the tone for difficulties that a reader will confront by stating, "There is as much variability and confusion of interpretation
Familial risk of oral clefts by morphological type and severity: population based cohort study of first degree relatives
Authors: Åse Sivertsen, Allen J Wilcox, Rolv Skjærven, Hallvard Andreas Vindenes, Frank Åbyholm, Emily Harville, Rolv Terje Lie
Journal: BMJ (2008)

<b>Objective</b> To estimate the relative risk of recurrence of oral cleft in first degree relatives in relation to cleft morphology. <b>Design</b> Population based cohort study. <b>Setting</b> Data from the medical birth registry of Norway linked with clinical data on virtually all cleft patients treated in Norway over a 35 year period. <b>Participants</b> 2.1 million children born in Norway between 1967 and 2001, 4138 of whom were treated for an oral cleft. <b>Main outcome measure</b> Relative risk of recurrence of isolated clefts from parent to child and between full siblings, for anatomic subgroups of clefts. <b>Results</b> Among first degree relatives, the relative risk of recurrence of cleft was 32 (95% confidence interval 24.6 to 40.3) for any cleft lip and 56 (37.2 to 84.8) for cleft palate only (P difference=0.02). The risk of clefts among children of affected mothers and affected fathers was similar. Risks of recurrence were also similar for parent-offspring and sibling-sibling pairs. The “crossover” risk between any cleft lip and cleft palate only was 3.0 (1.3 to 6.7). The severity of the primary case was unrelated to the risk of recurrence. <b>Conclusions</b> The stronger family recurrence of cleft palate only suggests a larger genetic component for cleft palate only than for any cleft lip. The weaker risk of crossover between the two types of cleft indicates relatively distinct causes. The similarity of mother-offspring, father-offspring, and sibling-sibling risks is consistent with genetic risk that works chiefly through fetal genes. Anatomical severity does not affect the recurrence risk in first degree relatives, which argues against a multifactorial threshold model of causation.
Noncoding microRNAs: small RNAs play a big role in regulation of ADME?
Authors: Ai-Ming Yu, Yu-Zhuo Pan
Journal: Acta Pharmaceutica Sinica B (2012)

There are considerable interindividual variations in drug absorption, distribution, metabolism and excretion (ADME) in humans, which may lead to undesired drug effects in pharmacotherapy. Some of the mechanistic causes are known, e.g., genetic polymorphism, inhibition and induction of ADME enzymes and transporters, while others such as posttranscriptional regulation of ADME genes are under active study. MicroRNAs (miRNAs) are a large group of small, noncoding RNAs that control posttranscriptional expression of target genes. More than 1000 miRNAs have been identified in the human genome, which may regulate thousands of protein-coding genes. Some miRNAs directly or indirectly control the expression of xenobiotic-metabolizing cytochrome P450 enzymes, ATP-binding cassette or solute carrier transporters and/or nuclear receptors. Consequently, intervention of miRNA epigenetic signaling may alter ADME gene expression, change the capacity of drug metabolism and transport, and influence the sensitivity of cells to xenobiotics. In addition, the expression of some ADME regulatory miRNAs is significantly changed in cells following the exposure to a given drug, and the consequent changes in ADME gene expression might result in distinct ADME properties and drug response. In this review, we summarized recent findings on the role of noncoding miRNAs in epigenetic regulation of ADME genes and discussed the potential impact on pharmacokinetics and pharmacodynamics.
Radiosurgery for brain tumours
Authors: J. S Loeffler, C. Lindquist
Journal: BMJ (1999)

EDITOR—Brada and Cruickshank express their concerns about the lack of evidence based research in the field of radiosurgery.1 We agree that radiosurgery replaced neurosurgical resection or fractionated radiotherapy in the treatment of certain intracranial lesions before randomised controlled trials were performed.2–5 However, the original and continual biological basis for radiosurgery remains strong. …
Genes and Schizophrenia
Authors: Tracy Hampton
Journal: JAMA (2008)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Responsiveness to bradykinin in veins of hypercholesterolemic humans.
Authors: G V Bedarida, E Bushell, W E Haefeli, T F Blaschke, B B Hoffman
Journal: Circulation (1993)

Hypercholesterolemia impairs endothelium-dependent dilation in arteries. We tested the hypothesis that hypercholesterolemia impairs endothelium-dependent vasodilation by an interaction between elevated plasma lipoproteins and a presumably normal endothelium using human veins in vivo; veins do not generally develop atherosclerosis and are appropriate for testing functional alterations.Full dose-response curves were constructed in 13 hypercholesterolemic and 12 normocholesterolemic subjects by infusing bradykinin (0.25 to 508 ng/min) into hand veins preconstricted with the alpha-adrenergic agonist phenylephrine. The maximal relaxation induced by bradykinin was 80 +/- 38% in the controls and 103 +/- 40% in subjects with hypercholesterolemia (P = .08). Responsiveness to bradykinin was also determined after infusion of indomethacin (5.4 micrograms/min), a cyclooxygenase inhibitor, to block the contribution of prostaglandins; maximal responsiveness was greater in hypercholesterolemic subjects (112 +/- 41%) than in controls (81 +/- 31%) (P = .03). Hypercholesterolemic subjects were more sensitive to bradykinin, with an ED50 of 4.2 ng/min versus 10.9 ng/min in controls (P = .05); a similarly increased sensitivity was found in the presence of indomethacin. The response to a maximally effective dose of nitroglycerin was greater in hypercholesterolemic subjects (142 +/- 31%) versus 106 +/- 28% in controls (P = .007). In five hypercholesterolemic subjects, treated with lovastatin to normalize serum cholesterol concentrations, maximal responsiveness to bradykinin decreased from 103 +/- 52% to 80 +/- 28%.These results demonstrate that hypercholesterolemia in humans does not impair endothelium-derived relaxing factor-mediated venodilation.
Biological Research in the Evolution of Cancer Surgery: A Personal Perspective
Authors: Bernard Fisher
Journal: Cancer Research (2008)

Abstract During the 19th, and for most of the 20th century, malignant tumors were removed by mutilating radical anatomic dissection. Advances such as anesthesia, asepsis, and blood transfusion made possible increasingly more radical operations. There was no scientific rationale for the operations being performed. Surgery in the 20th century was dominated by the principles of William S. Halsted, who contended that the bloodstream was of little significance as a route of tumor cell dissemination; a tumor was autonomous of its host; and cancer was a local-regional disease that spread in an orderly fashion based on mechanical considerations. Halsted believed that both the extent and nuances of an operation influenced patient outcome and that inadequate surgical skill was responsible for the failure to cure. A new surgical era arose in 1957, when cancer surgery began to be influenced by laboratory and clinical research, with results contrary to Halstedian principles. A new hypothesis resulted in a scientific basis for cancer surgery. Clinical trials supported the thesis that operable cancer is a systemic disease and that variations in local-regional therapy are unlikely to substantially affect survival. Complex host-tumor relationships were shown to affect every aspect of cancer and, contrary to Halsted's thesis, the bloodstream is of considerable importance in tumor dissemination. Clinical trials also have shown that less radical surgery is justified. Studies have shown that improved survival can be achieved with systemic therapy after surgery. Such therapy can reduce both the incidence of distant disease and the tumor recurrence at the tumor site after minimal surgery. The use of systemic therapy in patients who have no identifiable metastatic disease is a drastic departure from previous strategies. New technological innovations resulting from engineering research have improved the quality of life of patients by eliminating the need for some surgical procedures. Because cancer is apt to be a systemic disease, however, clinical trials are necessary to determine the effect of these modalities on patient outcome. Although technological developments will continue to play a role in cancer therapy, research in molecular biology and genetics will dictate the future status of cancer treatment and, ultimately, the future of surgery. [Cancer Res 2008;68(24):10007–20]
S56 Does time since arrival affect site of TB disease in UK migrants?
Authors: SK Tamne, M Lalor, L Thomas, I Abubakar, I Abubakar, D Zenner
Journal: Thorax (2013)

<h3>Background</h3> In contrast to global tuberculosis (TB) epidemiology, the UK and many low incidence countries have a high proportion of cases with extra-pulmonary tuberculosis (ETB). Almost 70% of reported cases in the UK are non-UK born, and many of these develop TB within the first five years after entry to the UK. The aim of the study was to analyse whether time since entry to the UK was associated with site of disease among migrants. <h3>Methods</h3> All TB cases (n = 95,427) reported to national enhanced TB surveillance system in the UK from 2000–2011 were included. In univariable analysis we explored associations between site of disease and place of birth, ethnic group, gender, age and previous TB diagnosis, using proportions and unadjusted odds ratios. Logistic regression was used to assess the association between site of disease and time since entry to the UK, adjusted for significant confounders. <h3>Results</h3> A total of 86,754 cases had complete information for site of disease and place of birth. Of these, 46,284 (53%) cases had ETB increasing from 47% in 2000 to 58% in 2011. ETB was more common amongst the non-UK born (61%) compared with UK-born TB cases (36%). Cases who entered the UK more than one year ago were almost 3 times more likely to have ETB compared to UK born cases after adjusting for sex, age, ethnicity and previous TB diagnosis (aOR 2.98, 95% CI 2.89–3.07). Females (OR 1.22 95% CI 1.18–1.26), adults aged 30–60 years and individuals of black African/Indian subcontinent ethnicities were significantly more likely to have ETB. <h3>Conclusions</h3> ETB was associated with being non-UK born, having entered the UK more than a year before diagnosis, female gender, age 30–60 years, and ethnic group. Conveying our findings to healthcare workers in the UK may improve awareness of ETB in specific populations, which could help lead to earlier diagnosis.
Human drug discrimination and multiple chemical sensitivity: caffeine exposure as an experimental model.
Authors: T Eissenberg, R R Griffiths
Journal: Environmental Health Perspectives (1997)

Multiple chemical sensitivity is a controversial diagnosis. Rigorous, controlled, laboratory-based research can reduce this controversy and lead to potential clinical confirmatory tests. The literature on human caffeine discrimination provides a rigorous methodology that can address reports that patients who suffer multiple chemical sensitivity (MCS) are sensitive to usually well-tolerated chemical doses; the studies require patients to discriminate caffeine from placebo under double-blind conditions. Several issues relevant to the conduct of caffeine discrimination studies using MCS patients as subjects are addressed; these issues include study design, determination of safe and tolerable training doses, and discrimination training. Such research will benefit patients and clinicians dealing with a diagnosis of MCS.
Abstract LB-344: Senescence-related genes signature in high grade gliomas
Authors: Domenico Coppola, Lodovico Balducci, Dung-Tsa Chen, Steven Brem, Kathy Egan, William Dalton, Timothy Yeatman
Journal: Cancer Research (2010)

Abstract Background: The prognosis of high grade gliomas (HGG) worsens with the age of the patients. We hypothesized that overexpression of senescence-related genes indicates a poorer prognosis. Materials and Methods: Frozen tumor samples from 60 patients of different ages (32 to 88 years) with the histologic diagnosis of HGG were macrodissected and arrayed on a custom version of the Affymetrix HG-U133 + GeneChip. There were 29 events (deaths) with a median survival time of 20 months. A set of 14 known senescence-associated genes (SAGs) including CCL2, CCL7, CDKN1A, COPG, CSF2RB, CXCL1, ICAM1, IGFBP3, IL6, IL8, SAA4, TNFRSF11B, TNFSF11 and TP53 were the focus of the study (Campisi J. et al. PLoS Biology, 2008). An overall senescence score was generated using principal component analysis to reflect the combined effect of the senescence-associated gene signature. Pearson correlation and Cox proportional hazards regression were used to examine the association of each SAG and the senescence score with age at onset and overall patient survival. False discovery rate was used to adjust for multiple comparisons. Results: We found an age-related gradient in the senescence score representation of the combined SAGs (r = 0.40; p=0.0014). Ten SAGs were significantly correlated with age (false discovery rate at 5%): IGFBP3 (r=0.44), ICAM1 (r=0.40), IL6 (r=0.38), CDKN1A (r=0.35), TNFSF11 (r=0.34), TP53 (r=0.34), CXCL1 (r=0.31), CCL7 (r=0.30), COPG (r=0.29), and CSF2RB (r=0.29). The SAG signature was also correlated with poor prognosis (p=0.0098; median survival: 13 and 28 months, respectively, for high versus low senescence score). Two SAGs were significantly associated with patient survival: IL6 (14 versus 38 months) and COPG (13 versus 38 months). Conclusion: We report for the first time an SAG signature in HGG associated with age at onset and patient outcome. This signature composed of genes involved in cell cycle regulation, apoptosis, cell proliferation, and angiogenesis may define a more aggressive subtype of high-grade glioma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-344.
Gender differences in cardiac development: are hormones at the heart of the matter?
Authors: T Pham
Journal: Cardiovascular Research (2003)

See article by Valverde et al. [10] (pgaes 625–631) in this issue. 

Male/female differences in cardiac electrophysiology have long been noted, but only in recent years has there been an increased awareness and appreciation of the influence of a patient's sex on presentation of various cardiac arrhythmias [1]. One of the most dramatic and important differences between men and women regarding sex and arrhythmia is the greater risk in women of torsades de pointes induced by drugs that prolong repolarization [2]. Additionally, female gender is an independent risk factor for syncope and sudden death in the congenital long QT syndrome [3]. Although the molecular mechanisms for these sex-related differences are largely unknown, fundamental differences in the electrophysiology of the male and female hearts are postulated to be responsible. Women have faster resting heart rates and longer rate-corrected QTc intervals than men [4]. However, young boys and girls have similar heart rates and QT intervals [5,6]. From puberty through adult years, the duration of the QTc in men abbreviates and then gradually increases until the age of 50 when QTc approaches that of women [5]. These gender- and age-dependent changes in ventricular repolarization are also present in congenital LTQS patients [7,8]. Further, there is an age-dependent distribution of initial arrhythmic events [9]. The probability of a first ventricular tachyarrhythmia is higher in boys than … 

* Tel.: +1-305-243-5922; fax: +1-305-243-4555. tpham{at}med.miami.edu
Problems of the NHS reforms
Authors: C. R Paton
Journal: BMJ (1992)

uses current investment to defray dividends owing to past investors, which can possibly work only in an expanding economy (and is a questionable business practice).This is now being questioned.The famous buck referred to by Heginbotham stopped with Harry Truman, not some anonymous purchaser health authority.Truman did not avoid uncomfortable decisions, even in 1948 when he fought for his political life.It is in this spirit of personal integrity and accountability that the experimental Oregon scheme should be viewed.
Common or distinct deficits for auditory and visual hallucinations?
Authors: Johanna C. Badcock, Murray T. Maybery
Journal: Behavioral and Brain Sciences (2005)

The dual-deficit model of visual hallucinations (Collerton et al. target article) is compared with the dual-deficit model of auditory hallucinations (Waters et al., in press). Differences in cognitive mechanisms described may be superficial. Similarities between these models may provide the basis for a general model of complex hallucinations extended across disorders and modalities, involving shared (overlapping) cognitive processes.
Effects of the angiotensin-converting enzyme inhibitor perindopril on endothelial injury and hemostasis in rabbit endotoxic shock
Authors: Eric Wiel, Qian Pu, J�r�me Leclerc, Delphine Corseaux, R�gis Bordet, Niels Lund, Brigitte Jude, Beno�t Vallet
Journal: Intensive Care Medicine (2004)
Deceiving ourselves about self-deception
Authors: Stevan Harnad
Journal: Behavioral and Brain Sciences (2011)

Abstract Were we just the Darwinian adaptive survival/reproduction machines von Hippel &amp; Trivers invoke to explain us, the self-deception problem would not only be simpler, but also nonexistent. Why would unconscious robots bother to misinform themselves so as to misinform others more effectively? But as we are indeed conscious rather than unconscious robots, the problem is explaining the causal role of consciousness itself, not just its supererogatory tendency to misinform itself so as to misinform (or perform) better.
Resolution of lichen aureus in a 10-year-old child after topical pimecrolimus
Authors: M. Bohm, G. Bonsmann, T.A. Luger
Journal: British Journal of Dermatology (2004)

Sir, Lichen aureus (LA) is a rare and highly chronic skin disease which belongs to the group of pigmented purpuric dermatoses. There is no established therapy for LA. We report a patient with LA treated with topical pimecrolimus. A 10‐year‐old healthy boy presented to our department in January 2003 with an asymptomatic eruption on the left side of his upper chest. The lesions had started in September 2002 above the left clavicle and had been spreading since then. Antecedent trauma to the affected site was denied. Previous treatments consisted of emollients and low‐potency topical corticosteroids for 3 weeks. During the preceding 3 weeks topical corticosteroids had been discontinued. The lesions consisted of closely aggregated, orange‐brown lichenoid papules and erythematous and purpuric patches. They were located above and below the left clavicle, with one band spreading laterally and caudally into the axillary fold (Fig. 1a). The distribution of the lesions was asymmetrical and segmental, corresponding mainly to the second thoracic dermatome. Routine laboratory analysis including total leucocyte count, erythrocyte and platelet counts, liver and kidney function tests were unremarkable. Skin biopsy from the left side of the chest revealed a heavy band‐like infiltrate located in the upper dermis. The infiltrate consisted of lymphocytes and occasional macrophages with extravasation of red blood cells and haemosiderin deposits around the vessels. The mid‐dermis displayed a discrete perivascular lymphocytic infiltrate. Epidermal changes included focal parakeratosis and slight acanthosis. After written consent, topical treatment with 1% pimecrolimus cream (Elidel™) twice daily was started. Significant improvement was noticed already after 3 weeks. After 10 weeks, clearing of the lesions had been observed by the patient and his parents. Topical pimecrolimus was stopped. Review after a further 3 weeks showed that the lesions had undergone resolution with some residual brownish patches (Fig. 1b). No relapse occurred until October 2003, when a few new discrete purpuric spots were again noticed on the left clavicle. Pimecrolimus cream was reapplied twice daily. The lesions disappeared within 2 weeks and no relapse has occurred since then. Treatment with topical pimecrolimus was tolerated well. There were no side‐effects.
Exclusive Breastfeeding for 4 Months Protects Low Income Children from the Development of Atopic Dermatitis Until 1 Year of Age
Authors: R LEITE, A LEITE, I COSTA, D TALAMONTE, R DOSSANTOS, M DEMORAES, J DACOSTA, L DEOLIVEIRA, P REIS, N NERY
Journal: Journal of Allergy and Clinical Immunology (2008)