tbuckley/cabot-search huggingface dataset:
Cognitive and Motor Outcomes of Cocaine-Exposed Infants
Authors: Lynn T. Singer, Robert Arendt, Sonia Minnes, Kathleen Farkas, Ann Salvator, H. Lester Kirchner, Robert Kliegman
Journal: JAMA (2002)

ContextMaternal use of cocaine during pregnancy remains a significant public health problem, particularly in urban areas of the United States and among women of low socioeconomic status. Few longitudinal studies have examined cocaine-exposed infants, however, and findings are contradictory because of methodologic limitations.ObjectiveTo assess the effects of prenatal cocaine exposure on child developmental outcomes.DesignLongitudinal, prospective, masked, comparison birth cohort study with recruitment in 1994-1996.SettingObstetric unit of a large US urban teaching hospital.ParticipantsFour hundred fifteen consecutively enrolled infants (218 cocaine-exposed and 197 unexposed) identified from a high-risk, low–socioeconomic status, primarily black (80%) population screened through clinical interview and urine and meconium samples for drug use. The retention rate was 94% at 2 years of age.Main Outcome MeasuresThe Bayley Mental and Motor Scales of Infant Development, assessed at 6.5, 12, and 24 months of corrected age.ResultsControlled for confounding variables, cocaine exposure had significant effects on cognitive development, accounting for a 6-point deficit in Bayley Mental and Motor Scales of Infant Development scores at 2 years, with cocaine-exposed children twice as likely to have significant delay (mental development index <80) (odds ratio, 1.98; 95% confidence interval, 1.21-3.24; P = .006). For motor outcomes, there were no significant cocaine effects.ConclusionsCocaine-exposed children had significant cognitive deficits and a doubling of the rate of developmental delay during the first 2 years of life. Because 2-year outcomes are predictive of later cognitive outcomes, it is possible that these children will continue to have learning difficulties at school age.
Synaptopodin regulates the actin-bundling activity of α-actinin in an isoform-specific manner
Authors: Katsuhiko Asanuma, Kwanghee Kim, Jun Oh, Laura Giardino, Sophie Chabanis, Christian Faul, Jochen Reiser, Peter Mundel
Journal: Journal of Clinical Investigation (2005)

Synaptopodin is the founding member of a novel class of proline-rich actin-associated proteins highly expressed in telencephalic dendrites and renal podocytes. Synaptopodin-deficient (synpo–/–) mice lack the dendritic spine apparatus and display impaired activity-dependent long-term synaptic plasticity. In contrast, the ultrastructure of podocytes in synpo–/– mice is normal. Here we show that synpo–/– mice display impaired recovery from protamine sulfate–induced podocyte foot process (FP) effacement and LPS-induced nephrotic syndrome. Similarly, synpo–/– podocytes show impaired actin filament reformation in vitro. We further demonstrate that synaptopodin exists in 3 isoforms, neuronal Synpo-short (685 AA), renal Synpo-long (903 AA), and Synpo-T (181 AA). The C terminus of Synpo-long is identical to that of Synpo-T. All 3 isoforms specifically interact with α-actinin and elongate α-actinin–induced actin filaments. synpo–/– mice lack Synpo-short and Synpo-long expression but show an upregulation of Synpo-T protein expression in podocytes, though not in the brain. Gene silencing of Synpo-T abrogates stress-fiber formation in synpo–/– podocytes, demonstrating that Synpo-T serves as a backup for Synpo-long in synpo–/– podocytes. In concert, synaptopodin regulates the actin-bundling activity of α-actinin in highly dynamic cell compartments, such as podocyte FPs and the dendritic spine apparatus.
Progress in Anaesthesia
Authors: W. W. Mushin
Journal: BMJ (1963)

Background/Aim: Pathological fractures are rare, suspicious and in some cases mentioned as the first sign of a malignant tumor. We present an uncommon case with a pathological fracture of the tibia diaphysis as the first sign of severe hyperparathyroidism. Case Report: We report the case of a female patient who was referred to the emergency department with a history of progressively worsening pain in the lower left leg and an inability to fully bear weight. No history of trauma or any other injury was reported. An x-ray revealed an extensive osteolytic lesion in the tibial shaft with cortical bone destruction. Conclusion: Our case, together with very few cases described in the current literature, emphasizes that in the presence of hypercalcemia and lytic lesions primary hyperparathyroidism should always be considered as a differential diagnosis. Lytic bone lesions can lead to pathological fractures and severe impairment of quality of life.
Evaluation and Validation of A Bee Venom Sting Challenge Performed by A MICRO-Syringe
Authors: Maurizio Giuseppe Severino, Gabriele Cortellini, Elisabetta Francescato, Stefano Turillazzi, Igino Spadolini, Anthi Rogkakou, Giovanni Passalacqua
Journal: Journal of Allergy and Clinical Immunology (2013)
Acland's Video Atlas of Human Anatomy
Authors: A. Hall
Journal: BMJ (2010)

<h3>ABSTRACT</h3> In plants, high complementarity between microRNAs (miRNAs) and their target genes is a prerequisite for a miRNA-target interaction (MTI). However, evidence suggests there are complexities beyond complementarity that impacts the strength of the MTI. To explore this, the bioinformatic pipeline TRUEE (Targets Ranked Using Experimental Evidence) was applied to strongly conserved miRNAs to identity their high evidence (HE) targets across species. For each miRNA family, HE targets predominantly consisted of homologues from one conserved target gene family (primary family). If an additional HE target family(s) was identified (secondary family), it was likely functionally related to the primary family. Many primary target families contained highly conserved nucleotide sequences flanking their miRNA binding-sites that were enriched in HE homologues across species, suggesting these sequences facilitate miRNA-mediated regulation. A subset of these flanking sequences are predicted to form conserved RNA secondary structures that preferentially base-pair with the miRNA binding-site, implying that these sites are highly structured. Functional testing of the conserved flanking sequences of the miR160 target, <i>AUXIN RESPONSE FACTOR 10</i> (<i>ARF10</i>), found that mutations within these flanking sequences resulted in attenuated <i>ARF10</i> silencing. Our findings support the notion that features beyond complementarity at highly conserved miRNA binding-sites underpin these ancient MTIs.
Abstract 313: ATDC drives bladder cancer formation by promoting methylation of the PTEN promoter and inhibition of p53 function.
Authors: Phillip Palmbos, Lidong Wang, Huibin Yang, Taylor Detzler, Gina Ney, Justin Hart, Stephanie Daignault-Newton, L. Priya Kunju, Chandan Kumar-Sinha, Monica Liebert, Mats Ljungman, Diane Simeone
Journal: Cancer Research (2013)

Abstract Bladder cancer is the 5th most common malignancy and a significant cause of morbidity and mortality, but the molecular events leading to its development are incompletely understood. We have identified an oncogene, Ataxia-Telangiectasia Group D Complementing (ATDC) gene, which drives formation and progression of pancreatic and bladder tumors. To better characterize the oncogenic function of ATDC, we generated transgenic (tg) mice which overexpress ATDC and the predominant phenotype of these mice was the development of non-invasive and muscle-invasive urothelial carcinomas. Tg bladder tumors were histologically identical to human tumors and displayed a similar gene expression signature to human invasive bladder tumors. ATDC expression was assessed in a tissue microarray and was highly up-regulated in 70% of human invasive bladder tumors (173/252). High expression of ATDC correlated with more advanced stage disease and worse survival after chemotherapy (p = 0.002). ATDC knockdown in human bladder cancer cell lines correlated with increased sensitivity to chemotherapy in vitro and decreased proliferation and invasion both in vitro and in vivo in a human bladder cancer xenograft model. To understand the mechanism of ATDC-mediated tumor formation, we modulated ATDC expression in normal and bladder cancer cells lines. ATDC overexpression down-regulated PTEN levels via DNA promoter methylation by DNMT3A in both tg mouse tumors and human cell lines. IHC analysis of ATDC, PTEN and DNMT3A expression in human bladder tumors specimens demonstrated similar findings. ATDC was also found to bind to p53 and inhibit p53 mediated functions. These findings establish ATDC as a novel determinant of bladder cancer initiation, progression and resistance to treatment which mediates tumorigenesis by down-regulation of PTEN expression and inhibition of p53. Citation Format: Phillip Palmbos, Lidong Wang, Huibin Yang, Taylor Detzler, Gina Ney, Justin Hart, Stephanie Daignault-Newton, L. Priya Kunju, Chandan Kumar-Sinha, Monica Liebert, Mats Ljungman, Diane Simeone. ATDC drives bladder cancer formation by promoting methylation of the PTEN promoter and inhibition of p53 function. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 313. doi:10.1158/1538-7445.AM2013-313
Role Perceptions in Freshman and Senior Medical Students
Authors: Maurice Korman
Journal: JAMA (1963)

IN THE LAST FEW DECADES, medicine has seen a proliferation of roles and continuing division of labor leading to ever increasing specialization. It has been suggested that the Industrial Revolution has reached medicine and that there will be a greater and greater partialization of the work of physicians and the related medical personnel in future years. The professional activities of the physician can be looked at from a number of different vantage points. He can devote his time to general practice or to a specialty; he may become a researcher, a public health physician, a hospital administrator, or a medical school teacher. He can also be identified by his concentration in one area of medicine, whether he practices it, teaches it, or experiments in it. In this context he is labeled in 1 of 18 categories, for example, as an anesthesiologist, an obstetrician, etc. In addition, there are other dimensions
The Role of the DNA Damage Checkpoint Pathway in Intraductal Papillary Mucinous Neoplasms of the Pancreas
Authors: Yoshihiro Miyasaka, Eishi Nagai, Hiroshi Yamaguchi, Kei Fujii, Takahiro Inoue, Kenoki Ohuchida, Tomomi Yamada, Kazuhiro Mizumoto, Masao Tanaka, Masazumi Tsuneyoshi
Journal: Clinical Cancer Research (2007)

Intraductal papillary mucinous neoplasms (IPMN) are known to show a transition from adenoma to carcinoma accompanied by several molecular abnormalities. ATM-Chk2-p53 DNA damage checkpoint activation, which is involved in prevention of the progression of several tumors, was analyzed to evaluate the role of the DNA damage checkpoint in the progression of IPMNs.One hundred and twenty-eight IPMNs were classified into four groups (intraductal papillary mucinous adenoma, borderline IPMN, noninvasive intraductal papillary mucinous carcinoma, and invasive intraductal papillary mucinous carcinoma) and stained immunohistochemically using antibody for Thr(68)-phosphorylated Chk2. Expression of ATM, Chk2, and p21(WAF1) and accumulation of p53 were also analyzed.Chk2 phosphorylation was shown in all adenomas and showed a significant decreasing trend with the progression of atypia (P < 0.0001 by the Cochran-Armitage test for trend). Expression of p21(WAF1) also exhibited a decreasing tendency (P < 0.0001), reflecting DNA damage checkpoint inactivation. p53 accumulation was mostly detected in malignant IPMNs. It was suggested that the DNA damage checkpoint provides a selective pressure for p53 mutation.Our findings indicate that DNA damage checkpoint activation occurs in the early stage of IPMNs and prevents their progression. It is suggested that disturbance of the DNA damage checkpoint pathway due to Chk2 inactivation or p53 mutation contributes to the carcinogenesis of IPMNs.
ACQUIRED NON-MALIGNANT STRICTURE OF THE RECTUM.—CAUSES, SYMPTOMS AND TREATMENT.
Authors: W. DUFF BULLARD
Journal: JAMA (1902)

The position here taken by the writer was assumed by him first in an article published in the<i>New York Medical Record.</i>On that occasion he expressed the opinion that the "great majority of observers had been led to consider syphilis the causative factor in the production of rectal stricture by the fact that this condition has most frequently been observed in syphilitic subjects." Since that time he has become more thoroughly convinced of the correctness of this view, and he still believes that it is much more rational to assume that syphilis is not immediately responsible for such lesions. The following reasons appear to him to justify the stand he has taken: Endarteritis is a well-recognized state in syphilis. This change in the vascular system, combined with the resultant low state of nutrition, renders the mucosa of the rectum less resistant to irritants and trauma. Under these circumstances small
Ablation reduced recurrent atrial tachyarrhythmia more than antiarrhythmic drugs in paroxysmal AF
Authors: Yee C. Lau, Gregory Y.H. Lip
Journal: Annals of Internal Medicine (2014)

Source Citation Morillo CA, Verma A, Connolly SJ, et al; RAAFT-2 Investigators. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation (RAAFT-2): a randomized trial. JAMA. 2014;311:692-700. 24549549
Temporal Specification and Bilaterality of Human Neocortical Topographic Gene Expression
Authors: Mihovil Pletikos, André M.M. Sousa, Goran Sedmak, Kyle A. Meyer, Ying Zhu, Feng Cheng, Mingfeng Li, Yuka Imamura Kawasawa, Nenad Šestan
Journal: Neuron (2014)
Spironolactone prophylaxis in mountain sickness.
Authors: G Turnbull
Journal: BMJ (1980)

malignant processes did develop, by contrast, in others of their patients, who had received irradiation alone or in combination with various other multiple-agent chemotherapy regimens, in conformity with data presented by several other investigators.1-3A possible explanation for these results lies in the observation reported by the Late Effects Study Group, which found that actinomycin D appeared to decrease the risk of radiationassociated second malignant neoplasms by a factor of 7.4 Adriamycin, one of the agents in ABVD, resembles actinomycin D in certain fundamental and clinical ways.Both are antibiotics that intercalate-in the DNA molecule and both are radiation enhancers and reactivators.5t; Thus it is possible that adriamycin is acting like actinomycin D in protecting against radiation-associated cancers.This possibility is given some credence in view of the fact that 2 60, of the patients reported by Mr Valagussa and his colleagues who received only irradiation developed second tumours within five years and 14 9o0 did so within 10 years.Of additional interest is the fact that second tumours were observed in irradiated patients given the five-drug regimen MABOP.The latter contains adriamycin, but also includes nitrogen mustard and procarbazine.The latter two alkylating agents have been widely held to be oncogenic in their own right.7 8 This suggests that adriamycin-if it does act like actinomycin D in protecting against second tumours following irradiation-is not efficient for this purpose when alkylating agents are concerned.It will be important to see whether the experience accumulated in other groups of irradiated patients who receive adriamycin with or without alkylating agents with high oncogenic potential duplicate the very in- terestinig and thought-provoking results reported by the Milan investigators.The implications regarding choice of treatment for patients requiring combined chemotherapy and radiation therapy are obvious.
MitoNEET-driven alterations in adipocyte mitochondrial activity reveal a crucial adaptive process that preserves insulin sensitivity in obesity
Authors: Christine M Kusminski, William L Holland, Kai Sun, Jiyoung Park, Stephen B Spurgin, Ying Lin, G Roger Askew, Judith A Simcox, Don A McClain, Cai Li, Philipp E Scherer
Journal: Nature Medicine (2012)
Effect of corticosteroids on sputum sol-phase protease inhibitors in chronic obstructive pulmonary disease.
Authors: J Wiggins, J A Elliott, R D Stevenson, R A Stockley
Journal: Thorax (1982)

Corticosteroids caused a reduction in the ratio of sol-phase sputum concentration to serum concentration of albumin in 12 patients with chronic obstructive bronchitis, suggesting a reduction in protein transudation. Alpha-1-antitrypsin values followed the same pattern as those of albumin in both the control and treatment periods, confirming the similar behaviour of the two proteins. The alpha 1-antichymotrypsin ratios were on average three times higher than those of albumin in the control period, confirming the presence of local mechanisms in the lung for preferentially concentrating this protein. The sputum-to-serum ratio of alpha 1-antichymotrypsin, however, rose during steroid treatment with the result that there was a selective increase in this protease inhibitor, which may be of potential benefit to such patients.
Pulsatile insulin release from pancreatic islets with nonoscillatory elevation of cytoplasmic Ca2+.
Authors: J Westerlund, E Gylfe, P Bergsten
Journal: Journal of Clinical Investigation (1997)

The relationship between insulin release and cytoplasmic Ca2+ concentration ([Ca2+]i) was studied in isolated pancreatic islets from ob/ob mice. Although [Ca2+]i was low and stable in the presence of 3 mM glucose, basal insulin release exhibited low amplitude pulsatility, with a frequency of 0.32 +/- 0.04 min-1. Depolarization by raising K+ from 5.9 to 30.9 mM or by the addition of 1 mM tolbutamide caused a pronounced initial insulin pulse followed by declining pulses, but there was no change in frequency. This decline in amplitude of the insulin pulses was prevented in similar experiments performed in the presence of 11 mM glucose. Corresponding measurements of [Ca2+]i in islets exposed to tolbutamide or the high K+ concentration revealed stable elevations without oscillations. Although the [Ca2+]i level is an important determinant for the rate of secretion, the results indicate that pulsatile insulin release does not always depend on [Ca2+]i oscillations. It is suggested that cyclic generation of ATP may fuel pulsatile release under conditions when [Ca2+]i remains stable.
Age and sex influences on fall characteristics.
Authors: T W O'Neill, J Varlow, A J Silman, J Reeve, D M Reid, C Todd, A D Woolf
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVE--To investigate age and sex influences on fall characteristics. METHODS--A total of 1243 subjects (517 males and 726 females) aged 50 years and over and drawn from population based sampling frames were invited to complete an interviewer administered questionnaire concerning descriptive characteristics of falls experienced in the previous four months. Information collected included details about the part of the body to strike the ground, direction of the fall, level of trauma and whether or not injury or fracture was sustained. RESULTS--One hundred and seventy two subjects reported a fall in the previous four months. Restricting analysis to the 142 subjects who fell from a standing height or less, females aged 50-64 years were more than twice as likely to fall onto their hand compared with older females (odds ratio (OR) = 2.2; 95% confidence interval (CI) 0.8 to 6.2) and at all ages (50+) were more than three times as likely to fall on their hip compared with males (OR = 3.4; 95% CI 1.0 to 11.5). Compared with older males, males aged 50-64 were more likely to fall sideways (OR = 5.1; 95% CI 1.5 to 17.4) and less likely to fall forwards (OR = 0.4; 95% CI 0.1 to 1.1). CONCLUSION--There is a potentially clinically important variation in fall type by age and sex. In particular, this variation might explain patterns of occurrence of hip and Colles9 fracture.
Vaginal Melanoma Mimicking Bladder FDG Activity in a Patient With Chronic Renal Failure
Authors: Guyan M. Thambugala, Michael J. Fulham, Armin Mohamed
Journal: Clinical Nuclear Medicine (2005)

A 44-year-old woman with chronic renal failure presented with persistent vaginal bleeding. On examination, there was a 4-cm tumor in the vagina and a biopsy showed melanoma. There was no history of melanoma. Computed tomography of the chest, abdomen, and pelvis demonstrated a vaginal tumor with no evidence of metastatic disease. Fluorodeoxyglucose positron emission tomography was performed for preoperative evaluation and exclusion of metastatic disease, and these images are presented.
Quinidine-Digoxin Interaction
Authors: Wittich Doering
Journal: New England Journal of Medicine (1979)

Administration of quinidine with digoxin increased serum digoxin concentrations in 79 patients and five volunteers. In 38 patients on a constant glycoside maintenance dose, the addition of quinidine to digoxin therapy resulted in a mean 2.5-fold increase (from 0.98 +/- 0.37 to 2.47 +/- 0.71 ng per milliliter, mean +/- 1 S.D.) (P less than 0.001). The addition of quinidine decreased renal glycoside clearance (from 91.6 +/- 27.8 to 40.6 +/- 15.8 ml per minute) (P less than 0.001). Unlike other investigations, our studies provided no evidence that quinidine displaced digoxin at specific cardiac binding sites. The elevated digoxin levels found during quinidine administration suggest a 30 to 50 per cent reduction of the digoxin dose. Adverse reactions to combined quinidine-digoxin therapy may be partly due to digitalis intoxication.
THE USE OF A MODIFIED DRINKER RESPIRATOR IN TREATMENT OF ASPHYXIA NEONATORUM
Authors: DOUGLAS P. MURPHY
Journal: JAMA (1930)

The treatment of asphyxia has a twofold object: it should initiate respiration, but it should also satisfy respiratory needs until normal breathing is established. The usual methods of treating asphyxia neonatorum are inefficient in the latter respect. Mildly asphyxiated infants respond fairly promptly to the customary means of initiating respiration, whereas more severely asphyxiated infants may make no attempt to breathe although the heart is beating vigorously. In the treatment of the latter group, the problem is one of effecting a respiratory interchange sufficient to meet the needs of the infant during that critical period; for it is quite likely that certain of these deeply asphyxiated infants will finally develop a normal respiratory activity, if life can be maintained long enough. A machine has recently been developed by Philip Drinker<sup>1</sup>by means of which prolonged artificial respiration has been successfully administered to adults and children suffering from acute respiratory