tbuckley/cabot-search huggingface dataset:
Compliance and cancer chemotherapy
Authors: H. Smedley, D. Bratherton, K. Sikora
Journal: BMJ (1983)

between concentrations of serum folate and those of anticonvulsant, impairment of folate absorption by anticonvulsant is usually presumned to be the cause.The possibility that folate supplements might act to reduce plasma anticonvulsant levels by affecting their metabolism does not seem to have been considered.In Reynolds's study3 folate seemed to render the anticonvulsants less effective, though frequency of fits was not affected by folate supplements in the present work.Perhaps the problem might be clarified if free anticonvulsant levels were measured, as only these are relevant to anticonvulsant efficacy.Using ultrafiltration, we have found free levels to vary from 14% to 17% of the total during pregnancy for phenytoin and from 52% to 78% for phenobarbitone, in serial estimations on a single pregnant patient.Variation between patients in degree of binding, and consequently in free anticonvulsant levels, is wider.
Hypothalamopituitary Dysfunction Following Traumatic Brain Injury and Aneurysmal Subarachnoid Hemorrhage
Authors: Harald Jörn Schneider, Ilonka Kreitschmann-Andermahr, Ezio Ghigo, Günter Karl Stalla, Amar Agha
Journal: JAMA (2007)

Neuroendocrine dysfunction following traumatic brain injury and aneurysmal subarachnoid hemorrhage may occur with a much higher prevalence than previously suspected. This sequela is a potentially serious but treatable complication of brain injury.To review research on hypothalamopituitary dysfunction as an underdiagnosed consequence of traumatic brain injury and subarachnoid hemorrhage, the natural history of this complication, and the potential clinical and public health implications of posttraumatic hypopituitarism.The MEDLINE database was searched for articles published between 2000 and 2007 using any combination of the terms traumatic brain injury or subarachnoid hemorrhage with pituitary, hypopituitarism, growth hormone deficiency, hypogonadism, hypocortisolism, hypothyroidism, or diabetes insipidus. The reference lists of articles identified by this search strategy were also searched. All articles reporting original data on endocrine outcomes after traumatic brain injury or aneurysmal subarachnoid hemorrhage in peer-reviewed journals with regard to prevalence, pathogenesis, risk factors, outcomes, and clinical course were selected. We pooled data and calculated prevalence rates and 95% confidence intervals (CIs).We identified 19 studies including 1137 patients. The pooled prevalences of hypopituitarism in the chronic phase after traumatic brain injury and aneurysmal subarachnoid hemorrhage were 27.5% (95% confidence interval [CI], 22.8%-28.9%) and 47% (95% CI, 37.4%-56.8%), respectively. The pooled prevalence of hypopituitarism was greater in patients with severe compared with those with mild or moderate traumatic brain injury. Early neuroendocrine abnormalities were transient in some patients while, less commonly, hypopituitarism evolved over time in others. Patients with posttraumatic hypopituitarism showed an impaired quality of life and an adverse metabolic profile.Hypopituitarism is a common complication of both traumatic brain injury and aneurysmal subarachnoid hemorrhage and might contribute to morbidity and poor recovery after brain injury.
THE ASCH OPERATION FOR DEVIATIONS OF THE CARTILAGINOUS NASAL SEPTUM: WITH SOME CONDITIONS COMPLICATING ITS PERFORMANCE.
Authors: EMIL MAYER
Journal: JAMA (1903)

There are many varieties of deviation of the cartilaginous nasal septum. In some the occlusion is complete, in others partial, some are high up while others are close to the floor. In some there are adhesions resulting chiefly from previous attempts at their cure, principally caused by the use of escharotics, while in others the deviation of one side is associated with a dislocated columnar cartilage on the other, making it S-shaped; and finally diseased conditions may lurk behind the obstruction. The bony septum is likewise deviated at times. The record of a few of the complications of septal deviations is here presented. Case 1.— J. W., aged 17, was sent to the New York Eye and Ear Infirmary by one of our well-known laryngologists. His cartilaginous septum was deviated to the left. Occlusion was nearly complete, while on the right the columnar cartilage was dislocated, almost completely closing that
Long Isoforms of NRF1 Contribute to Arsenic-Induced Antioxidant Response in Human Keratinocytes
Authors: Rui Zhao, Yongyong Hou, Peng Xue, Courtney G. Woods, Jingqi Fu, Bo Feng, Dawei Guan, Guifan Sun, Jefferson Y. Chan, Michael P. Waalkes, Melvin E. Andersen, Jingbo Pi
Journal: Environmental Health Perspectives (2010)

BackgroundHuman exposure to inorganic arsenic (iAs), a potent oxidative stressor, causes various dermal disorders, including hyperkeratosis and skin cancer. Nuclear factor–erythroid 2–related factor 1 (NRF1, also called NFE2L1) plays a critical role in regulating the expression of many antioxidant response element (ARE)-dependent genes.ObjectivesWe investigated the role of NRF1 in arsenic-induced antioxidant response and cytotoxicity in human keratinocytes.ResultsIn cultured human keratinocyte HaCaT cells, inorganic arsenite (iAs3+) enhanced the protein accumulation of long isoforms (120–140 kDa) of NRF1 in a dose- and time-dependent fashion. These isoforms accumulated mainly in the nuclei of HaCaT cells. Selective deficiency of NRF1 by lentiviral short-hairpin RNAs in HaCaT cells [NRF1-knockdown (KD)] led to decreased expression of γ-glutamate cysteine ligase catalytic subunit (GCLC) and regulatory subunit (GCLM) and a reduced level of intracellular glutathione. In response to acute iAs3+ exposure, induction of some ARE-dependent genes, including NAD(P)H:quinone oxidoreductase 1 (NQO1), GCLC, and GCLM, was significantly attenuated in NRF1-KD cells. However, the iAs3-induced expression of heme oxygenase 1 (HMOX-1) was unaltered by silencing NRF1, suggesting that HMOX-1 is not regulated by NRF1. In addition, the lack of NRF1 in HaCaT cells did not disturb iAs3+-induced NRF2 accumulation but noticeably decreased Kelch-like ECH-associated protein 1 (KEAP1) levels under basal and iAs3+-exposed conditions, suggesting a potential interaction between NRF1 and KEAP1. Consistent with the critical role of NRF1 in the transcriptional regulation of some ARE-bearing genes, knockdown of NRF1 significantly increased iAs3+-induced cytotoxicity and apoptosis.ConclusionsHere, we demonstrate for the first time that long isoforms of NRF1 contribute to arsenic-induced antioxidant response in human keratinocytes and protect the cells from acute arsenic cytotoxicity.
Indomethacin-loaded polymeric nanocarriers based on amphiphilic polyphosphazenes with poly (N-isopropylacrylamide) and ethyl tryptophan as side groups: Preparation, in vitro and in vivo evaluation
Authors: Jian Xiang Zhang, Xiao Jing Li, Li Yan Qiu, Xiao Hui Li, Mei Qiu Yan, None Yi Jin, Kang Jie Zhu
Journal: Journal of Controlled Release (2006)
Intra-patient intra-tumoral immune heterogeneity is evident at progression on targeted therapy and immunotherapy for melanoma
Authors: Alexandre Reuben, Zachary A Cooper, Rodabe N Amaria, Marie A Forget, Cara Haymaker, Chantale Bernatchez, Pei-ling Chen, Michael T Tetzlaff, Lynda Chin, Karen C Dwyer, Jennifer A Wargo
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts There have been significant advances in the treatment of melanoma via the use of targeted therapy and immunotherapy, however a significant proportion of patients still progress on treatment. Intense research efforts are underway to better understand resistance, and multiple
Late CD8+ lymphocytic alveolitis after allogeneic bone marrow transplantation and chronic graft-versus-host disease.
Authors: V Leblond, H Zouabi, L Sutton, J M Guillon, C M Mayaud, T Similowski, C Beigelman, B Autran
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Late-onset interstitial pneumonitis following allogeneic bone marrow transplantation (BMT) is a rare condition usually caused by a variety of infective agents, although in some cases these are idiopathic. We investigated noninfectious late interstitial pneumonitis with lymphocytic alveolitis in seven allogeneic BMT recipients using bronchoalveolar lavage (BAL), lymphocyte phenotyping analysis, CT lung scans, and pulmonary function tests. The results were compared with those of a control group composed of similar patients with no pulmonary symptoms. Of 65 long-term survivors, seven were included in the study. All had chronic graft-versus-host disease (GVHD) and developed interstitial pneumonitis a median of 210 d (range 120 to 445 d) after BMT. BAL revealed lymphocytosis, with an overall expansion of CD8+ subsets (38 to 90%). Lymphocytic alveolitis was not observed in the control group. Pulmonary function tests revealed a restrictive syndrome, and biopsy samples obtained from 2 patients showed interstitial lymphoid infiltration with fibrosis of the alveolar walls. Of the 7 patients, six were cured by starting immunosuppressive drugs or increasing the dosage with a drastic improvement in respiratory symptoms within 1 mo. These findings suggest that CD8+ alveolitis may be observed in late interstitial pneumonitis in allogeneic BMT recipients and may be a pulmonary manifestation of chronic GVHD.
Comparison of Human Tissues and Mechanical Prostheses for Aortic Valve Replacement in Children
Authors: Flavian M. Lupinetti, Joanie Warner, Thomas K. Jones, S. Paul Herndon
Journal: Circulation (1997)

Background Aortic valve replacement in children is problematic because of complications of mechanical valves and uncertain outcomes associated with human valves. The results of pediatric aortic valve replacements over 5 years were reviewed. Methods and Results Mechanical valves were used exclusively during the first part of this series (n=26). Thereafter, 25 consecutive aortic valve replacements were performed with autografts (n=19) or allografts (n=6). Allografts were used for Marfan’s syndrome patients or those with unusable pulmonary valves. Among autograft/allograft recipients, 16 patients underwent 27 prior operations. In the mechanical group, 18 patients underwent 19 previous operations. Three patients in each group underwent a previous mechanical aortic valve replacement. Operative complications included two mild strokes and one pacemaker in the autograft/allograft group and three deaths and two pacemakers in the mechanical group. One autograft recipient required reoperation for pulmonary allograft stenosis. In the mechanical group, late complications included six cases of nonstructural degeneration and two cases of endocarditis, with three reoperations. Reoperation-free survival was 96% at 2 years in the autograft/allograft group and 80% at 2 years and 75% at 3 years in the mechanical group. Event-free survival was 96% at 2 years in the autograft/allograft group compared with 67% at 2 years and 49% at 3 years in the mechanical group ( P &lt;.05). Conclusions The frequency of reoperations for mechanical aortic valve replacement has been surprisingly high. Aortic valve replacement in children with only autografts or allografts achieves good early results.
Predictive value of cyclosporin A level for efficacy or renal dysfunction in psoriasis
Authors: G. FEUTREN, D. FRIEND, P. TIMONEN, A. BARNES, C. LABURTE
Journal: British Journal of Dermatology (1990)

Cyclosporin A (CyA) trough (pre-dose) levels were measured in whole blood with a radioimmunoassay (RIA) using specific monoclonal antibody in 193 patients receiving CyA for the treatment of psoriasis. These patients received either CyA 2.5 mg/kg/day (n = 134) or 5 mg/kg/day (n = 59). In addition, a subgroup of 94 patients also had CyA trough levels measured using a non-specific polyclonal RIA. Within each CyA dose group, no difference was detected between mean CyA trough levels in relation to success or failure nor to the presence or absence of renal dysfunction with the use of either the specific or non-specific RIA. Based on the experience in transplantation, CyA thresholds of 100 and 200 ng/ml (specific) were selected for the assessment of efficacy and renal dysfunction. The success rate was higher by 10-15% when the CyA level was above, rather than below, 100 ng/ml in both the CyA 2.5 mg and 5 mg/kg/day groups. A slightly increased incidence of renal dysfunction was only found in the 5 mg/kg/day group when the CyA level was above 200 ng/ml. Because of its low predictive value, measurement of the level of CyA was not particularly useful for monitoring patients with psoriasis treated with low-dose CyA.
Azole fungicides affect mammalian steroidogenesis by inhibiting sterol 14 alpha-demethylase and aromatase.
Authors: Jürg A Zarn, Beat J Brüschweiler, Josef R Schlatter
Journal: Environmental Health Perspectives (2002)

Azole compounds play a key role as antifungals in agriculture and in human mycoses and as non-steroidal antiestrogens in the treatment of estrogen-responsive breast tumors in postmenopausal women. This broad use of azoles is based on their inhibition of certain pathways of steroidogenesis by high-affinity binding to the enzymes sterol 14-alpha-demethylase and aromatase. Sterol 14-alpha-demethylase is crucial for the production of meiosis-activating sterols, which recently were shown to modulate germ cell development in both sexes of mammals. Aromatase is responsible for the physiologic balance of androgens and estrogens. At high doses, azole fungicides and other azole compounds affect reproductive organs, fertility, and development in several species. These effects may be explained by inhibition of sterol 14-alpha-demethylase and/or aromatase. In fact, several azole compounds were shown to inhibit these enzymes in vitro, and there is also strong evidence for inhibiting activity in vivo. Furthermore, the specificity of the enzyme inhibition of several of these compounds is poor, both with respect to fungal versus nonfungal sterol 14-alpha-demethylases and versus other P450 enzymes including aromatase. To our knowledge, this is the first review on sterol 14-alpha-demethylase and aromatase as common targets of azole compounds and the consequence for steroidogenesis. We conclude that many azole compounds developed as inhibitors of fungal sterol 14-alpha-demethylase are inhibitors also of mammalian sterol 14-alpha-demethylase and mammalian aromatase with unknown potencies. For human health risk assessment, data on comparative potencies of azole fungicides to fungal and human enzymes are needed.
Surgical Treatment in Patient with Non–Small-Cell Lung Cancer with Fissure Involvement: Anatomical versus Nonanatomical Resection
Authors: Giovanni Leuzzi, Alfredo Cesario, Stefano Cafarotti, Filippo Lococo, Valentina Dall’Armi, Pierluigi Novellis, Rosalia Romano, Alessandra Siciliani, Elisa Meacci, Pierluigi Granone, Stefano Margaritora
Journal: Journal of Thoracic Oncology (2013)
LOSS OF TEMPORAL LOCALIZATION AS A MANIFESTATION OF DISTURBED SELF-AWARENESS
Authors: Louis H. Cohen, Gregory N. Rochlin
Journal: American Journal of Psychiatry (1938)

A case is reported in which a patient presenting a history of some kind of "convulsive" disorder was found to have a loss of the ability to localize past events in time. This defect was studied intensively and has been explained as due to disturbed self-awareness. This explanation was supported by other evidence of disturbed self-awareness, namely, experiences indicative of disorganization of the body-self.
Role Conflicts and Their Ideological Resolution in Military Psychiatric Practice
Authors: ROY E. CLAUSEN, ARLENE K. DANIELS
Journal: American Journal of Psychiatry (1966)

The military psychiatrist may experience conflict between his role as psychiatrist and as military officer in several ways. The necessary change in emphasis from psychotherapy to consultation may run counter to his previous training and preference. Patients referred to him may suspect him as a "company" man, while line officers may regard him as patient-rather than service-oriented. The authors point out that a useful ideology for military psychiatry may be drawn out of various guidelines for conflict resolution pertaining to the entire Medical Corps, and they apply these to the specific conflicts likely to be encountered by the military psychiatrist.
Diversity and structure of human T cell receptor delta chain genes in peripheral blood gamma/delta-bearing T lymphocytes.
Authors: Y Takihara, J Reimann, E Michalopoulos, E Ciccone, L Moretta, T W Mak
Journal: The Journal of Experimental Medicine (1989)

We have investigated the diversity and repertoire of human TCR delta chain variable gene segments in the human peripheral blood CD4- CD8- (double-negative) population, using rearrangement and expression studies and sequence analyses. 20 TCR delta DNA clones were derived from the RNA of bulk-cultured double-negative T cells and their nucleotide sequences determined. These clones can be classified into six different V delta subfamilies. The distribution, however, was uneven in these cells, with 16 of 20 being derived from the V delta 1 (9) and V delta 2 (7) subfamilies. The remaining subfamilies, V delta 3, V delta 4, V delta 5, and V delta 6, were only represented by one clone each. The majority of these subfamilies seem to consist of a single member, in contrast with the closely linked V alpha subfamilies, which, in most cases, consist of multiple members. Our findings suggest that only a limited number of V delta genes are used in human peripheral blood double-negative T cells and that two major V delta subfamilies (V delta 1 and V delta 2) are used more frequently. Sequence comparison of our cDNA clones to V alpha clones indicates that there is no overlap in usage of V alpha and V delta gene segments, except for the V delta 4 (V alpha 6) subfamily. Comparison of the different V delta sequences suggests that the majority of the sequence diversity is concentrated in the junctions between V, D, and J segments and results from extensive N region diversity.
Changes in brain metabolism during hyperammonemia and acute liver failure: Results of a comparative1H-NMR spectroscopy and biochemical investigation
Authors: Diederik K. Bosman, Nicolaas E. P. Deutz, Albert A. De Graaf, Rene W. N. Vd Hulst, Hans M. H. Van Eijk, Wim M. M. J. Bovée, Martinus A. W. Maas, George G. A. Jörning, Robert A. F. M. Chamuleau
Journal: Hepatology (1990)

The effects of hyperammonemia on brain function have been studied in three different experimental models in the rat: acute liver ischemia, urease-treated animals and methionine sulfoximine-treated animals. To quantify the development of encephalopathy, clinical grading and electroencephalographic spectral analysis were used as indicators. In all three experimental models brain ammonia concentrations increased remarkably associated with comparable increases in severity of encephalopathy. Furthermore, in vivo 1H-nuclear magnetic resonance spectroscopy of a localized cerebral cortex region showed a decrease in glutamate concentration in each of the aforementioned experimental models. This decreased cerebral cortex glutamate concentration was confirmed by biochemical analysis of cerebral cortex tissue post mortem. Furthermore, an increase in cerebral cortex glutamine and lactate concentration was observed in urease-treated rats and acute liver ischemia rats. As expected, no increase in cerebral cortex glutamine was observed in methionine sulfoximine-treated rats. These data support the hypothesis that ammonia is of key importance in the pathogenesis of acute hepatic encephalopathy. Decreased availability of cerebral cortex glutamate for neurotransmission might be a contributing factor to the pathogenesis of hyperammonemic encephalopathy. A surprising new finding revealed by 1H-nuclear magnetic resonance spectroscopy was a decrease of cerebral cortex phosphocholine compounds in all three experimental models. The significance of this finding, however, remains speculative.
Cancer Among Nuclear Test Participants
Authors: Nathan Grossman
Journal: JAMA (1984)

<h3>To the Editor.—</h3> I find serious fault with the article on cancer among nuclear test participants by Caldwell et al in a recent issue of<i>JAMA</i>.<sup>1</sup>The authors claim to have found no statistically significant increase in the incidence of any cancer other than leukemia. However, the authors are unable to account for 145 members (4.5%) of the cohort under study. The fate of these members could markedly effect the outcome of the study. The authors state, "We have assumed that they were alive and free of cancer." Proper methodology can allow no such assumption. It is likely that a portion of these men could not be located because of death from cancer. Such a possibility might well have invalidated the authors' findings.
Treatment of Intracranial Aneurysms
Authors: Robert Karis
Journal: JAMA (1978)

<h3>To the Editor.—</h3> The 5% mortality for patients with intracranial aneurysms reported by Ballenger et al (237:1845, 1977) is a tribute to the care their patients receive. I would question, however, whether this low rate can be attributed to surgery. Ballenger et al state that of patients who have survived the first subarachnoid hemorrhage (SAH), "more than 40% will suffer a recurrence within the first eight weeks, and 60% of these second hemorrhages will prove to be fatal. The overwhelming majority of such instances will occur in the first two weeks after the initial hemorrhage. One day after the initial SAH, a conservatively treated patient in good condition has only a 50% chance of surviving one year. The chief advantage of intracranial surgery over alternative forms of treatment is that it offers the patient definitive protection from recurrent hemorrhage with its attendant mortality." Or does it? The average time to
Exercise as a tool for studying acute changes in airways resistance.
Authors: N M Connolly
Journal: Thorax (1970)

Exercise Tests in Assessing Children with Lung or Heart Disease S. GODFREY The commonest symptom of children with lung or heart disease is shortness of breath on exertion or inability to exercise.Conventional tests at rest never really evaluate this complaint.Almost all children of 5 and over can be persuaded to perform graded work on a cycle ergometer.Simply
Haemorrhoids and transient receptor potential vanilloid 1
Authors: F F di Mola, H Friess, J Koninger, F Selvaggi, I Esposito, M W Buchler, P di Sebastiano
Journal: Gut (2006)

Haemorrhoids are extremely common, and approximately 10 million people are affected by haemorrhoidal disease in the USA.1 Many causes have been proposed to explain the pathogenesis of symptomatic haemorrhoids. The pathophysiological theory, made popular by Thomson’s studies, in which the elastic support of the anal cushions is thought to be broken, is currently the best accepted.1

The function and control of anorectal arteriovenous anastomoses remain unclear as does the existence of individual susceptibility to haemorrhoidal disease, which is influenced by socioeconomic, cultural, and psychological factors.1 Previous studies have established that intake of hot pepper and alcohol abuse may influence disease progression and cause acute exacerbation of haemorrhoidal disease.2

We investigated haemorrhoidal disease and transient receptor potential vanilloid 1 (TPVR1), the receptor for capsaicin, the spicy component contained in plants of the genus Capsicum .3 TPVR1 is a non-selective cation channel that is expressed and stimulates primary sensory neurones. Noxious heat and capsaicin directly activate TPVR1. TPVR1 acts as an ion channel with increased permeability to Na+ and Ca2+ ions, which in turn causes neuronal depolarisation with sensation …