tbuckley/cabot-search huggingface dataset:
A Population-Based Study of Dementia in 85-Year-Olds
Authors: Ingmar Skoog, Lars Nilsson, Bo Palmertz, Lars-Arne Andreasson, Alvar Svanborg
Journal: New England Journal of Medicine (1993)

The aim of this study was to investigate the causes, severity, and prevalence of dementia in a representative sample of 494 85-year-olds living in Gothenburg, Sweden.The study included a psychiatric interview, neuropsychological and physical examinations, comprehensive laboratory tests, electrocardiography, chest radiography, computed tomography (CT) of the head, and analysis of cerebrospinal fluid. A person close to each subject was also interviewed. Dementia was defined according to the criteria proposed in the Diagnostic and Statistical Manual of Mental Disorders (third edition, revised), Alzheimer's disease according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association, and vascular dementia according to recently proposed criteria that incorporate information from CT scanning and the patient's neurologic history.The prevalence of dementia was 29.8 percent (147 subjects). The condition was mild in 8.3 percent, moderate in 10.3 percent, and severe in 11.1 percent. There were no significant sex-related differences in prevalence or severity. Of the subjects with dementia, 43.5 percent had Alzheimer's disease, 46.9 percent had vascular dementia (multi-infarct dementia in 34.6 percent, dementia related to cerebral hypoperfusion in 4.1 percent, and mixed dementia in 8.2 percent), and 9.5 percent had dementia due to other causes. The three-year mortality rate was 23.1 percent in the subjects without dementia, 42.2 percent in the patients with Alzheimer's disease, and 66.7 percent in the patients with vascular dementia. Infarcts detected by CT scanning were significantly more common in the subjects with dementia than in those without it (27.9 percent vs. 12.6 percent).Dementia was present in nearly a third of unselected 85-year-olds in Sweden. Almost half these subjects appeared to have vascular dementia, which may currently be more amenable to prevention or treatment than Alzheimer's disease.
Studies on an Intermittent Corticosteroid Dosage Regimen
Authors: John G. Harter, William J. Reddy, George W. Thorn
Journal: New England Journal of Medicine (1963)

CORTISOL and its derivatives are effective and necessary in the management of some patients with certain diseases, but their prolonged use may be associated with undesirable side effects ranging from minor and annoying ones to life-threatening reactions. The incidence of undesirable side effects varies from series to series, but the general consensus is that these effects are related to dosage and duration of therapy. Livingstone and Davies1 have reviewed their experience with steroids in asthma, which parallels in general our own previous experience.Since the therapeutic effects of steroids appeared to us to persist longer than their metabolic effects, it . . .
Medicine and books: Specialist Outreach Clinics in General Practice
Authors: Roland Petchey
Journal: BMJ (1998)

Ed Martin Roland, Jonathan Shapiro 

Radcliffe Medical Press, £15, pp 120 

ISBN 1 85775 218 X 

Specialist outreach clinics in general practice are not new, but their numbers have increased substantially since the introduction of general practitioner fundholding. Their character has probably altered also. Earlier schemes largely followed the “liaison-attachment” model, aimed at improving patient care through collaboration between general practitioners and specialists. 

Recent schemes mostly follow the “shifted outpatient” model: the location of care moves from hospital to the general practice surgery, but otherwise it remains unchanged. Most have been motivated by fundholders’ desire to improve access to outpatient services and to reduce the time and costs of waiting and travelling for their patients. The scope for this is considerable. Cumulatively, the 200 000 outpatients who annually attend a typical district general hospital spend an estimated lifetime (just over 67 years) travelling and waiting to be seen. 

The five case studies of outreach clinics described in this book substantially increase our understanding of their operation, but the evidence remains fragmentary and often contradictory. Their results are broadly consistent: outreach clinics are associated with increased satisfaction among patients (who value the convenience and familiarity of the setting and the continuity and seniority of care) and reduced time and costs of travel for patients. However, they probably increase NHS costs overall, because of staffing of outreach clinics by consultants only and the time and costs of travel that they incur for the consultants. There were also less quantifiable “system” costs (such as the impact on supervision and training of junior hospital staff). Whether these additional costs were offset by gains in effectiveness and quality of care remains unknown because comparisons of clinical outcomes (discharges, admissions, investigations) with outpatient clinics are confounded by differences in case mix and levels of staffing between the two settings. As presently constituted, they would probably not be cost effective on a large scale. 

Although fundholding is passing, key issues raised by outreach clinics remain. When reconfiguring services, how do we balance responsiveness to local needs against the drive to increase the cost effectiveness of the system overall? In the new NHS, how (and how far) do we take patient preferences into account or incorporate their costs into economic appraisals of services? The internal market contained few mechanisms for reconciling local benefits and system costs and no incentive for anyone to try. Joint commissioning and funding could do, but they do not guarantee a solution. Anyone looking for clear and level headed guidance on outreach clinics or struggling to develop services across traditional sector boundaries will find help here.
Use of an Internet-based protocol to collect clinical information and blood from patients with lung cancer who never smoked cigarettes
Authors: N. Girard, R. Klein, G. J. Riely, R. Reddy, M. G. Kris, W. Pao
Journal: Journal of Clinical Oncology (2009)

e19064 Background: At least 10% of patients develop lung cancer despite smoking &lt;100 cigarettes in a lifetime. These “never smokers” with lung cancer have a unique clinical course and likely represent a subgroup genetically distinct from lung cancer patients with a history of cigarette smoking. Few genes associated with the development of lung cancer in this population have been found. To identify genetic risk factors, we plan to perform genome-wide association studies (GWAS) but need to study a large group of cases - more than that seen at a single institution in a reasonable timeframe. To speed accrual, we hypothesized that we could use the internet to collect clinical information and blood from never smokers with lung cancer. Methods: We established an IRB- approved protocol to collect prospectively clinical information and blood samples from patients recruited via the internet. Interested patients enroll via the website ( www.mskcc.org/neversmokerswithlungcancer ), or by email ( neversmokerswithlungcancer@mskcc.org ). Eligibility criteria: age ≥18 yo, pathologic diagnosis of lung cancer, smoking history &lt;100 cigarettes in a lifetime, resident of the U.S. Study materials (information packet, screening questionnaire, consent form, and tissue sample collection kit) are directly sent to patients. Bloods are drawn at routine local doctor visits and returned to study investigators by free overnight shipping. All data are kept confidential. Results: The website went online on 14 Sept 2008. As of 5 Jan 2009, 70 patients from 25 states contacted us via the internet. 33 patients signed the consent form, 27 were eligible, and 19 sent blood samples. For those who sent blood, the median time between first email contact and receipt of blood was 29 days. Conclusions: Collection of clinical information and blood samples from cancer patients is feasible over the internet. We are expanding efforts to connect with individuals appropriate to this study, with a target of 2000 patients. The identification of risk variants associated with lung cancer through GWAS can facilitate the development of new strategies for prevention, diagnosis, and treatment. No significant financial relationships to disclose.
NIMG-37IMAGING CEREBRAL TRYPTOPHAN METABOLISM IN BRAIN TUMOR-ASSOCIATED DEPRESSION
Authors: Csaba Juhasz, Edit Bosnyak, David Kamson, Geoffrey Barger, Michael Behen, Sandeep Mittal
Journal: Neuro-Oncology (2015)

Background: Depression in patients with brain tumors is associated with impaired quality of life and shorter survival. Altered metabolism of tryptophan to serotonin and kynurenine metabolites may play a role in tumorassociated depression. Our recent studies with alpha[ 11 C]methyl-L-tryptophan (AMT)-PET in brain tumor patients indicated abnormal tryptophan metabolism not only in the tumor mass but also in normal-appearing contralateral brain. In the present study, we explored if tryptophan metabolism in such brain regions is associated with depression. Methods: Twenty-one patients (mean age: 57 years) with a brain tumor (10 meningiomas, 8 gliomas, and 3 brain metastases) underwent AMT-PET scanning. MRI and AMT-PET images were co-registered, and AMT kinetic parameters, including volume of distribution (VD’, an estimate of net tryptophan transport) and K (unidirectional uptake, related to tryptophan metabolism), were measured in the tumor mass and in unaffected cortical and subcortical regions contralateral to the tumor. Depression scores (based on the Beck Depression Inventory-II [BDI-II]) were correlated with tumor size, grade, type, and AMT-PET variables. Results: The mean BDI-II score was 12 ± 10 (range: 2–33); clinical levels of depression were identified in seven patients (33 %). High BDI-II scores were most strongly associated with high thalamic AMT K values both in the whole group (Spearman’s rho = 0.63, p= 0.004) and in the subgroup of 18 primary brain tumors (r= 0.68, p = 0.004). Frontal and striatal VD’ values were higher in the depressed subgroup than in non-depressed patients (p< 0.05); the group difference was even more robust when moderately/severely depressed patients were compared to patients with no/mild depression (frontal: p= 0.005; striatal: p< 0.001). Tumor size, grade, and tumor type were not related to depression scores. Conclusions: Abnormalities of tryptophan transport and metabolism in the thalamus, striatum, and frontal cortex, measured by PET, are associated with depression in patients with brain tumor. These changes may indicate an imbalance between the serotonin and kynurenine pathways and serve as a molecular imaging marker of brain tumor-associated depression. Trial registration: ClinicalTrials.gov NCT02367469
S127 Gene therapy for alpha-1-antitrypsin deficiency using a pseudotyped lentivirus vector
Authors: MC Paul-Smith, JF Gelinas, K Pytel, M Chan, C Meng, L Cammack, L Cameron, C Moran, I Pringle, L Davies, M Inoue, M Hasegawa, SC Hyde, DR Gill, EWFW Alton, U Griesenbach
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> A protease/anti-protease imbalance is a characteristic feature of inflammatory lung diseases such as cystic fibrosis (CF) and alpha-1-antitrypsin deficiency related emphysema. A recent trial of alpha-1-antitrypsin (hAAT) enzyme replacement therapy (ERT) suggested that hAAT can slow the progression of lung density loss in alpha-1-antitrypsin deficiency (Chapman <i>et al</i>, Lancet 2015). However, the results are modest and ERT is expensive, so gene therapy may be a more appropriate treatment strategy. The UK Cystic Fibrosis Gene Therapy Consortium has pseudotyped a simian immunodeficiency viral vector with the Sendai virus F and HN proteins (rSIV. F/HN) for efficient transduction of airway epithelial cells. <h3>Results</h3> Mice were transduced with rSIV. F/HN-hAAT (1.4e8 TU/mouse) by nasal instillation and culled 10 days post-transduction. hAAT levels in lung tissue homogenate and epithelial lining fluid (ELF) were 3 logs above controls (p &lt; 0.05), and hAAT concentration in ELF was 92 ± 28 μg/ml, similar to the therapeutic hAAT level in ELF of 70 μg/ml (Figure 1). For comparison, transfection of mouse lung with cationic lipid GL67A, used in the recent Phase IIb trial of non-viral gene therapy for cystic fibrosis, complexed to plasmids carrying hAAT only led to 0.4 ± 0.1 μg/ml in ELF. A neutrophil elastase (NE) activity assay showed that the recombinant hAAT successfully neutralised NE activity (p &lt; 0.05). In a separate experiment, mice were treated with a single dose of rSIV. F/HN-hAAT (4e7 TU/mouse) and quantification of hAAT one year post-transduction showed that expression was stable over this period. Here, we also demonstrate for the first time that rSIV. F/HN transduction of lung generates significant (p &lt; 0.05) levels of recombinant hAAT protein in serum. <h3>Conclusion</h3> In conclusion, rSIV. F/HN produces therapeutically relevant and long-lasting levels of hAAT in murine lung and may offer advantages over enzyme replacement therapy. In addition, we showed that hAAT escapes from the lung into the circulation which may be relevant for a range of diseases including diabetes and graft vs. host disease. <h3>Reference</h3> 1 Chapman KR, Burdon JG, Piitulainen E <i>et al.</i> Intravenous augmentation treatment and lung density in severe α1 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial.<i> Lancet</i>. 2015;<b>386</b>:360–8
B-cell non-Hodgkin lymphoma linked to Coxiella burnetii
Authors: Cléa Melenotte, Matthieu Million, Gilles Audoly, Audrey Gorse, Hervé Dutronc, Gauthier Roland, Michal Dekel, Asuncion Moreno, Serge Cammilleri, Maria Patrizia Carrieri, Camelia Protopopescu, Philippe Ruminy, Hubert Lepidi, Bertrand Nadel, Jean-Louis Mege, Luc Xerri, Didier Raoult
Journal: Blood (2015)
Diaper Diagnosis of Porphyria
Authors: S S Pollack, M S Rosenthal
Journal: New England Journal of Medicine (1994)

Figure 1. Diaper Diagnosis of Porphyria. A blood- and urine-soaked diaper from a neonate with organomegaly, hemolytic anemia, thrombocytopenia, and cutaneous blisters was photographed under ambient light with a flash apparatus (Panel A) and under Wood's light (320 to 420 nm) (Panel B). The child's parents were first cousins, but the family history was otherwise negative for porphyria. Subsequent investigation showed very high levels of porphyrins in urine, serum, red cells, and stool. Fluorescence of a diaper under Wood's light is an indication that further studies of porphyrin metabolism should be done.
Letter by Tsuda Regarding Article, “Association Between Visceral and Subcutaneous Adipose Depots and Incident Cardiovascular Disease Risk Factors”
Authors: Kazushi Tsuda
Journal: Circulation (2016)

I read with great interest the article by Abraham and colleagues dealing with the relationship between adipose depots and cardiovascular disease risk in men and women.The results of their study demonstrated that visceral adipose tissue volume was associated with the development of cardiovascular risk factors.In women, per 500-cm 3 increment in baseline visceral adipose tissue, glucose was 2.34 mg/dL higher and high-density lipoprotein cholesterol was 1.62 mg/dL lower.Higher subcutaneous adipose tissue volume was also associated with incident risk factors, particularly among women.In addition, the authors showed that lower visceral adipose tissue and subcutaneous adipose tissue attenuation were associated with the development of an adverse risk profile.These findings remained significant after adjustment for baseline fat volume among women.The authors proposed that there might be important differences between men and women in how adipose depots contribute to metabolic risk, and further suggested that both volume and quality of distinct adipose depots might contribute to metabolic risk for cardiovascular diseases.Evidence indicates that estrogen may have a close correlation with adipose depots.It has been proposed that estrogen deficiency may affect cardiovascular disease risk by mediating changes in body fat distribution. 2In addition, it was shown that hormone replacement therapy might prevent the increase in centrally distributed adiposity that was noted in postmenopausal women. 2 Recent studies have also demonstrated that estrogen deficiency might accelerate nonalcoholic steatohepatitis in ovariectomized mice fed a high-fat and high-cholesterol diet. 3n the other hand, one of the mechanisms underlying the protective effect of estrogen against cardiovascular diseases may be the enhancement of nitric oxide production.It has been demonstrated that vascular endothelial function might be markedly influenced by estrogen, and be improved by hormone replacement therapy in postmenopausal women. 4We have also shown that hormone replacement therapy significantly increases plasma nitric oxide metabolite levels in postmenopausal women. 5In this context, it is strongly suggested that changes in nitric oxide production by estrogen might modify the effects of adipose depots on cardiovascular diseases.Therefore, we would like to know whether the endogenous estrogen status might be related to the magnitudes of the effects of visceral adipose tissue and subcutaneous adipose tissue on cardiovascular risk factors, particularly among women.Further studies should be required to assess more precisely the relationships between adipose depots and sex hormones and their contribution to the metabolic risk and the progression of cardiovascular diseases.
Long-Term Outcomes of Myeloid Growth Factor Treatment
Authors: Gary H. Lyman, David C. Dale
Journal: Journal of the National Comprehensive Cancer Network (2011)

Myeloid growth factors are used to reduce myelotoxicity and the risk of infection after cancer chemotherapy and in patients with chronic neutropenia. This article addresses the long-term benefits and risks associated with granulocyte colony-stimulating factor (G-CSF) therapy in both settings. A systematic review of randomized controlled trials recently reported long-term outcomes regarding the risk of second malignancies and overall survival. Based on these studies, the risk for acute myeloid leukemia (AML) associated with known carcinogenic agents, such as chemotherapy, could not be distinguished from any risk associated with growth factor support. However, the enhanced delivery of chemotherapy dose intensity enabled by the use of G-CSF in these studies was associated with a significant reduction in all-cause mortality. Although some reduction in treatment-related mortality with G-CSF support may occur, the observed improvement in long-term survival likely relates to better disease control with more-intense G-CSF–supported chemotherapy. Myeloid growth factors have also been shown to benefit patients with severe chronic neutropenia. Almost all patients with cyclic, congenital, or idiopathic neutropenia experience response to G-CSFs. Treatment is titrated to determine a dose that provides a safe elevation in neutrophil counts. Reports have shown that patients can be maintained for years at the same dose after adjusting for growth and development. In congenital neutropenia, the inherent risk of developing myelodysplastic syndromes or AML requires careful monitoring, including routine blood counts and annual bone marrow examinations.
Patient and family perceptions of recruitment to cancer clinical trials (CCTs)
Authors: S. R. Enders, N. M. Horan, P. N. Lara, D. A. Paterniti
Journal: Journal of Clinical Oncology (2005)

6115 Background: Low accrual rates have created a need to investigate potential barriers and factors important to patient and family member decision-making about CCTs. Methods: To better understand how patients and family members make decisions regarding clinical trials, we conducted 42 semi-structured interviews with patients who were eligible for a CCT and their family members. We audio-taped and transcribed all interviews. All transcripts underwent iterative review by a multidisciplinary team who read the transcripts for predominant themes including factors that figured prominent in decision-making. Results: 52% (n=22) of interviewees were patients; 90% of interviewees were White. Patient age ranged from 34–84 years, with a mean of 60.5 years; family members from 32–86 years with a mean of 58 years. 41% (n=9) of patients were female; 80% (n=16) of family members were female. Patients presented with 8 different cancer diagnoses, including mesothelioma, breast, liver and kidney, with prostate and lung cancers most prevalent (n=12, 55%). 45% (n=10) of the patients had participated in more than one CCT. 16% (n=7) reported high school diploma or less education. Despite their enthusiasm and willingness to participate in CCTs, patients and family members reported the following reservations: having too many physicians in the process, getting too much information, not knowing the physician who was in charge of the study, no clear understanding of potential benefits, perceived lack of options, feeling that “the system” will benefit from their participation, and feeling there was not enough information about their disease or the trial to make a decision. Conclusions: Barriers reported by patients and family involved in clinical trials are likely to be enhanced in populations where lack of awareness, resources, or trust are prevalent. Attention to enhancing awareness about CCTs and available resources is necessary. No significant financial relationships to disclose.
Clinical Implications of the p53 Tumor-Suppressor Gene
Authors: Curtis C. Harris, Monica Hollstein
Journal: New England Journal of Medicine (1993)

The crucial differences between normal cells and cancer cells stem from discrete changes in specific genes controlling proliferation and tissue homeostasis. Over 100 such cancer-related genes have been discovered, several of which are implicated in the natural history of human cancer because they are consistently found to be mutated in tumors. The p53 tumor-suppressor gene is the most striking example because it is mutated in about half of almost all types of cancer arising from a wide spectrum of tissues. Other tumor-suppressor genes important in human cancers, such as adenomatous polyposis coli, Wilms' tumor type 1, and neurofibromatosis type 1, . . .