tbuckley/cabot-search huggingface dataset:
Prevalence and Characteristics of a Family History of End-Stage Renal Disease among Adults in the United States Population
Authors: William McClellan, Rebecca Speckman, Leslie McClure, Virginia Howard, Ruth C. Campbell, Mary Cushman, Paul Audhya, George Howard, David G. Warnock
Journal: Journal of the American Society of Nephrology (2007)

This report describes the prevalence and characteristics of people with a family history of ESRD in a first-degree relative (FH-ESRD). This is a cross-sectional study of individuals in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, a population-based sample of US residents who are 45 yr and older. FH-ESRD was ascertained at baseline among 12,030 participants of the cohort, and multivariate logistic regression was used to identify characteristics that were independently associated with FH-ESRD. FH-ESRD was reported by 9.5% of participants. Individual characteristics that were independently associated with FH-ESRD included black race (odds ratio [OR] 2.14; 95% confidence interval [CI] 1.82 to 2.53); female gender (OR 1.28; 95% CI 1.08 to 1.51); a history of diabetes (OR 1.22; 95% CI 1.02 to 1.47); a 1-SD change in the log of the C-reactive protein level (OR 1.10; 95% CI 1.01 to 1.19); and World Health Organization body mass index weight categories normal (OR 2.11; 95% CI 0.66 to 6.79), overweight (OR 2.64; 95% CI 0.82 to 8.42), and obese (OR 3.48; 95% CI 1.09 to 11.1) compared with underweight. Black but not white individuals with FH-ESRD were more likely to have an estimated GFR <60 ml/min per 1.73 m(2). There is a high prevalence of FH-ESRD among US adults, and the prevalence of FH-ESRD was higher among lack individuals. Individuals with a positive family history were more likely to have diabetes and to be obese. If confirmed, then these findings suggest that individuals with FH-ESRD may benefit from interventions to improve the detection and treatment of chronic kidney disease risk factors such as diabetes and obesity.
Supramaximal cholecystokinin displaces Munc18c from the pancreatic acinar basal surface, redirecting apical exocytosis to the basal membrane
Authors: Herbert Y. Gaisano, Manfred P. Lutz, Juergen Leser, Laura Sheu, Grit Lynch, Lan Tang, Yoshikazu Tamori, William S. Trimble, Anne Marie F. Salapatek
Journal: Journal of Clinical Investigation (2001)

Exocytosis at the apical surface of pancreatic acinar cells occurs in the presence of physiological concentrations of cholecystokinin (CCK) but is inhibited at high concentrations. Here we show that Munc18c is localized predominantly to the basal membranes of acinar cells. Supramaximal but not submaximal CCK stimulation caused Munc18c to dissociate from the plasma membrane, and this displacement was blocked by protein kinase C (PKC) inhibitors. Conversely, whereas the CCK analog CCK-OPE alone failed to displace Munc18c from the membrane, this agent caused Munc18c displacement following minimal PKC activation. To determine the physiological significance of this displacement, we used the fluorescent dye FM1-43 to visualize individual exocytosis events in real-time from rat acinar cells in culture. We showed that supramaximal CCK inhibition of secretion resulted from impaired apical secretion and a redirection of exocytic events to restricted basal membrane sites. In contrast, CCK-OPE evoked apical exocytosis and could only induce basolateral exocytosis following activation of PKC. Infusion of supraphysiological concentrations of CCK in rats, a treatment that induced tissue changes reminiscent of mild acute pancreatitis, likewise resulted in rapid displacement of Munc18c from the basal membrane in vivo.
Autoimmune (idiopathic) thrombocytopenic purpura
Authors: Simon Karpatkin
Journal: The Lancet (1997)

Autoimmune thrombocytopenic purpura (ATP), also referred to as idiopathic thrombocytopenic purpura, is a common clinical disorder of immune regulation seen more often in females than males (3:1). Autoantibody (usually 7S IgG) is produced against platelets and, possibly, megakaryocytes, leading to the phagocytic destruction of these cells. The resultant thrombocytopenia induces purpura and haemorrhage if the platelet count reaches a critical level (usually <30000/μL). The disease is often complicated by the transfer of anti-platelet antibody across the placenta with resultant neonatal thrombocytopenia, purpura, and haemorrhage. Because of the immunological nature of the disorder, in which the host's immune system destroys the host's platelets (figure 1) I and others recommend that the term “idiopathic” be replaced by “autoimmune”. 1 Karpatkin S Autoimmune thrombocytopenic purpura. Semin Hematol. 1985; 22: 260-288 PubMed Google Scholar
Long-term Events in Adult Patients with Clinical Stage IA-IIA Nonbulky Hodgkin's Lymphoma Treated with Four Cycles of Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine and Adjuvant Radiotherapy: A Single-Institution 15-Year Follow-up
Authors: Ercole Brusamolino, Ambrogia Baio, Ester Orlandi, Luca Arcaini, Francesco Passamonti, Vassiliki Griva, William Casagrande, Cristiana Pascutto, Pietro Franchini, Mario Lazzarino
Journal: Clinical Cancer Research (2006)

Abstract Purpose: To report on long-term events after short doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy and adjuvant radiotherapy in favorable early-stage Hodgkin's lymphoma. Experimental Design: We monitored late events and causes of death over 15 years (median follow-up, 120 months) in 120 patients with nonbulky stage IA-IIA Hodgkin's lymphoma, treated with four cycles of ABVD and limited radiotherapy. Pulmonary and cardiac function tests were done throughout the follow-up. Outcome measures included cause-specific mortality, standardized mortality ratio, and standardized incidence ratio for secondary neoplasia. Results: Projected 15-year event-free and overall survival were 78% and 86%, and tumor mortality was 3%. Standardized mortality ratio was significantly higher than 1 for both males (2.8; P = 0.029) and females (9.4; P = 0.003). The risk of cardiovascular events at 5 and 12 years was 5.5% and 14%, with a median latent time of 67 months (range: 23-179 months) from the end of radiotherapy. Pulmonary toxicity developed in 8% of patients; all had received mediastinal irradiation and the median time from radiotherapy to pulmonary sequelae was 76 weeks (range: 50-123 weeks). The risk of secondary neoplasia at 5 and 12 years was 4% and 8%, respectively, with no cases of leukemia. Fertility was preserved. Conclusions: Long-term events were mostly related to radiotherapy; the role of short ABVD chemotherapy was very limited, as documented by fertility preservation and lack of secondary myelodysplasia/leukemia. A proportion of patients died from causes unrelated to disease progression and the excess mortality risk was mostly due to the occurrence of secondary neoplasms and cardiovascular diseases. A moderate dose reduction of radiotherapy from 40-44 Gy to 30-36 Gy did not decrease the risk of late complications; abolishing radiotherapy in nonbulky early-stage Hodgkin's lymphoma is being evaluated.
Pooled waiting lists
Authors: K. Jones
Journal: Journal of the Royal Society of Medicine (2003)

Mr Ramchandani and his colleagues report the attitudes of hospital consultants, general practitioners and patients to pooled waiting lists for cataract surgery (December 2002 JRSM1). I think that this strategy could improve efficiency in my own specialty, gynaecology.

In the UK patients are traditionally admitted to gynaecology units under a named consultant. In essence, this means that NHS consultants ‘work together in isolation’. By contrast, in Continental Europe referrals to gynaecology units tend to be ‘generic’. Patients are the responsibility of the whole department, headed by a chief of staff. They are looked after by teams with an appropriate special interest, and the most suitable surgeon is internally allocated to each patient. This achieves uniformity of practice and equality of patient care. The patient turn-over is quick and there are no waiting lists for investigations.

This arrangement has other benefits. It should reduce the disparities that arise when inexperienced specialist registrars enter the system. In the European units I have visited, groups of consultants work together in the operating theatre or the clinic. This provides clinicians with the opportunity to monitor each other's performance, update techniques, and expand repertoires and to reciprocate teaching opportunities. This arrangement also facilitates audit and learning, and enhances patient safety. It truly is lifelong learning.

One of the arguments against the European structure is that UK consultants would not want to sacrifice their clinical autonomy and work under a ‘chief of staff’. This argument is becoming less tenable. We are directly accountable to the clinical or medical director through appraisal and revalidation as part of our jobs plans. Besides, if our management is evidence based and ‘best practice’ it should be consistent with that of our colleagues. Therefore, I do not see loss of traditional autonomy as an important issue.
AN EXPERIMENTAL STUDY OF DIATHERMY
Authors: Ronald V. Christie
Journal: The Journal of Experimental Medicine (1928)

1. A method is described for measuring the relative impedance of living cells to diathermy currents. 2. The diathermy current penetrates the living cell, and heat production is intracellular as well as extracellular. 3. A small proportion of the impedance of living cells to the diathermy current seems not to lead to the production of heat. 4. Evidence is given that the addition of saponin produces an appreciable increase in the conductivity of an electrolyte. Its use is therefore contraindicated when electrical measurements are being made on biological material. 5. The currents used in diathermy behave as do high frequency currents of the pure sine wave form in respect to their passage through biological material.
Management of solitary pulmonary nodules: how do thoracic computed tomography and guided fine needle biopsy influence clinical decisions?
Authors: D R Baldwin
Journal: Thorax (2002)

<b>Background:</b> Computed tomography (CT) and fine needle guided biopsy (FNB) are often used in the assessment of patients with lung nodules. The influence of these techniques on clinical decision making has not been quantified, especially for small solitary pulmonary nodules (SPN) where the probability of malignancy is lower. A study was undertaken to determine the effect of CT and FNB derived information on clinical decision making in patients with a solitary pulmonary nodule &lt; 3 cm in diameter on initial chest radiography. <b>Methods:</b> Clinical, physiological, and outcome data on 114 patients with an SPN &lt; 3 cm who had subsequent thoracic CT and FNB were extracted from the records of a specialist cardiorespiratory hospital in Auckland, New Zealand. Chest radiographs and CT scans were reported according to specified criteria by a thoracic radiologist. Computer generated summary sheets were used to present cases to each of six clinicians. Each case was presented three times: (1) with clinical data and chest radiograph only; (2) with the addition of the CT report; and (3) with all data including the result of the FNB. Clinicians were asked to specify their management on each occasion and to estimate the probability of the lesion being malignant. Reproducibility was assessed by re-evaluating 24 cases 1 month later. <b>Results:</b> 33 (29%) nodules were benign, 35 (31%) nodules (malignant) were resected with negative node sampling, and 46 (40%) had a non-curative outcome (radiotherapy, incomplete resection, refused therapy). Intra-clinician decision making was consistent for all three levels of clinical data (median κ values 0.79–0.89). Agreement between clinicians on the need for surgery was lowest with chest radiography alone (κ=0.33), rose with CT information (κ=0.44), and increased further with the addition of the FNB data (κ=0.57). The proportion of successful decisions on surgical intervention (against the known outcome) increased with the addition of CT reports and further with FNB reports (p=0.006, Friedman9s test). The major benefit of the information added by CT and FNB reports was a reduction in unnecessary surgery, especially when the clinical perception of pre-test probability of malignancy was intermediate (31–70%). FNB data contributed most to the benefit (p&lt;0.001). The addition of CT and FNB was cost efficient and can be applied specifically to patients with a low or intermediate probability of malignancy. <b>Conclusion:</b> Both CT and FNB make cost effective contributions to the clinical management of SPN &lt; 3 cm in diameter by reducing unnecessary operations and increasing agreement between physicians on the need for surgery.
Too much fat for the gut's microbiota
Authors: Herbert Tilg, Julian R Marchesi
Journal: Gut (2012)

The gastrointestinal tract contains a diverse microbial community which is predominantly bacterial and which we refer to as the gut microbiota. For example, the human gut microbiota is assumed to consist of at least 1014 bacteria, composed of more than 1000 species with more than 150 species per individual. Apart from contributing substantial beneficial functions to the host (eg, digestion of indigestible plant polysaccharides and production of short chain fatty acids), the potential of the microbiota to interact with the host and modulate its physiology seems to be tremendous. In addition, many ‘environmental’ and not yet identified factors might be able to affect and modulate the gut's microbial composition and functions, with implications for the host.
What do chronic obstructive pulmonary disease patients die from? Amultiple cause coding analysis
Authors: A.L. Hansell, J.A. Walk, J.B. Soriano
Journal: European Respiratory Journal (2003)

Information on obstructive lung disease (OLD) deaths is generally derived from the underlying cause of death on the death certificate. This neglects information on other conditions mentioned and may underestimate the burden of disease. Descriptive analyses of all conditions mentioned on the death certificate for all decedents where OLD (chronic obstructive pulmonary disease or asthma) was mentioned as a contributing cause of death were conducted for England and Wales for 1993-1999. OLD was mentioned in 312,664 or 8.0% of all deaths. OLD comprised the underlying cause of death in 59.8% of deaths with any mention of OLD. Where OLD was not the underlying cause of death, the leading causes by the International Classification of Disease version 9 chapter were diseases of the circulatory system, neoplasms, and non-OLD diseases of the respiratory system. The top single causes were acute myocardial infarction, other ischaemic heart disease, and lung cancer. The current analysis confirms that using the underlying cause of death underestimates the contribution of obstructive lung disease to mortality in England and Wales, in contrast to myocardial infarction where underlying cause of death captures most (94%) mentions on the death certificate.
Image-Based Predictive Modeling of Heart Mechanics
Authors: V.Y. Wang, P.M.F. Nielsen, M.P. Nash
Journal: Annual Review of Biomedical Engineering (2015)

Personalized biophysical modeling of the heart is a useful approach for noninvasively analyzing and predicting in vivo cardiac mechanics. Three main developments support this style of analysis: state-of-the-art cardiac imaging technologies, modern computational infrastructure, and advanced mathematical modeling techniques. In vivo measurements of cardiac structure and function can be integrated using sophisticated computational methods to investigate mechanisms of myocardial function and dysfunction, and can aid in clinical diagnosis and developing personalized treatment. In this article, we review the state-of-the-art in cardiac imaging modalities, model-based interpretation of 3D images of cardiac structure and function, and recent advances in modeling that allow personalized predictions of heart mechanics. We discuss how using such image-based modeling frameworks can increase the understanding of the fundamental biophysics behind cardiac mechanics, and assist with diagnosis, surgical guidance, and treatment planning. Addressing the challenges in this field will require a coordinated effort from both the clinical-imaging and modeling communities. We also discuss future directions that can be taken to bridge the gap between basic science and clinical translation.
Serum pyridoxal in patients with rheumatoid arthritis.
Authors: C R Sanderson, R E Davis, C E Bayliss
Journal: Annals of the Rheumatic Diseases (1976)

Abnormalities of tryptophan metabolism have been reported in patients with rheumatoid arthritis (RA) and it has been suggested that these abnormalities are the result of disordered vitamin B6 metabolism. Fasting serum pyridoxal, assayed by an automated microbiological system, was found to be below normal in 35 out of 42 patients with RA while a similar abnormality was found in 8 out of 35 patients with osteoarthrosis (OA). Within the RA group the abnormality could not be related to the age, sex, or drug therapy of individuals but of the 8 patients with OA and a low serum pyridoxal, 7 were receiving indomethacin either alone or in conjunction with aspirin.
What the Industrial Revolution Did for Us: Modern Medicine
Authors: T. Jackson
Journal: BMJ (2003)

BBC 2, 28 October at 8 pm Rating:![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Presenter Dan Cruickshank has an infectious, donnish enthusiasm and joie de vivre that television producers obviously believe lends popular appeal to subjects that some viewers might otherwise consider dry as dust. In the latest episode of What the Industrial Revolution Did for Us , Cruickshank brought his straightforward storytelling and capacity for wonder to bear on the earliest controlled medical trials and the birth of modern medicine. Introducing us to the achievements and discoveries of the likes of vaccine pioneer Edward Jenner, James Lind, who discovered the cause of scurvy, and William Withering, who is credited with introducing digitalis to medical science, Cruickshank … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
SC68896, a Novel Small Molecule Proteasome Inhibitor, Exerts Antiglioma Activity <i>In vitro</i> and <i>In vivo</i>
Authors: Patrick Roth, Maria Kissel, Caroline Herrmann, Günter Eisele, Johann Leban, Michael Weller, Friederike Schmidt
Journal: Clinical Cancer Research (2009)

Glioblastomas are among the most lethal neoplasms, with a median survival of <1 year. Modulation of the proteasome function has emerged as a novel approach to cancer pharmacotherapy. Here, we characterized the antitumor properties of SC68896, a novel small molecule proteasome inhibitor.Different tumor cell lines were tested by crystal violet staining for sensitivity to SC68896, given alone or in combination with death ligands. The molecular mechanisms mediating SC68896-induced cell death and changes in cell cycle progression were assessed by immunoblot and flow cytometry. An orthotopic human glioma xenograft model in nude mice was used to examine the in vivo activity of SC68896.SC68896 inhibits the proliferation of cell lines of different types of cancer, including malignant glioma. Exposure of LNT-229 glioma cells to SC68896 results in a concentration- and time-dependent inhibition of the proteasome, with a consequent accumulation of p21 and p27 proteins, cell cycle arrest, caspase cleavage, and induction of apoptosis. Using RNA interference, we show that the effect of SC68896 on glioma cells is facilitated by wild-type p53. SC68896 sensitizes glioma cells to tumor necrosis factor-related apoptosis-inducing ligand and CD95 ligand and up-regulates the cell surface expression of the tumor necrosis factor-related apoptosis-inducing ligand receptor cell death receptors 4 and 5, which may contribute to this sensitization. Intracerebral glioma-bearing nude mice treated either i.p. or intratumorally with SC68896 experience prolonged survival.SC68896 is the first proteasome inhibitor that exerts antiglioma activity in vivo. It may represent a novel prototype agent for the treatment of malignant gliomas and warrants clinical evaluation.
Intra-specific heterogeneity of the rDNA internal transcribed spacer in the Simulium damnosum (Diptera: Simuliidae) complex
Authors: J. Tang, L. Toe, C. Back, T. R. Unnasch
Journal: Molecular Biology and Evolution (1996)

The internal transcribed spacer (ITS) of the rRNA gene cluster has been used as a model for the study of the action of concerted evolution and molecular drive on repeated sequence families. In contrast to this general finding, preliminary DNA sequence analysis of cloned representatives of the ITS from the West African black fly species complex Simulium damnosum s.1. demonstrated extensive intra-individual and intra-specific polymorphisms. Variability in the ITS was primarily confined to the ITS1 domain. The degree and type of intra-individual and intra-specific variability within the ITS was further characterized using gel electrophoresis, DNA hybridization, and heteroduplex analysis of the PCR products generated from the ITS1 domain. ITS1 copies from individual S. damnosum s.1. differed in length and sequence composition. These results, when taken together, demonstrate that a large degree of intra-individual and intra-specific heterogeneity exists in the ITS of S. damnosum s.1. The intra-individual heterogeneity was greater in the savanna-dwelling than forest-dwelling sibling species of S. damnosum s.1. This heterogeneity may be due in part to inter-breeding among sympatric sibling species, coupled with disturbance of S. damnosum s.1. populations resulting from intensive vector control efforts.
MITOCHONDRIAL ANTIBODIES IN PRIMARY BILIARY CIRRHOSIS
Authors: Peter A. Berg, Deborah Doniach, Ivan M. Roitt
Journal: The Journal of Experimental Medicine (1967)

The antigen reacting with complement-fixing antibodies in the sera of patients with primary biliary cirrhosis was localized predominantly in the mitochondrial fraction of tissue homogenates obtained by differential centrifugation. Purified mitochondrial preparations had a high content of the antigen whereas purified lysosomes failed to fix complement with PBC sera. Analysis of a number of fractionation experiments showed a high correlation between antigen content and the mitochondrial enzyme succinic dehydrogenase in all fractions. There was much poorer correlation with lysosomal and micrososomal enzyme markers. The patterns of staining obtained with a fluorescein conjugate of IgG from a PBC patient closely paralleled those obtained with a histochemical method for the demonstration of succinic dehydrogenase, further confirming the mitochondrial localization of the antigen. Staining was brightest in cells containing mitochondria with well-developed cristae. Studies on mitochondria fragmented by osmotic lysis, hexane, lysolecithin, and ultrasound suggest that the antigen is associated with the mitochondrial inner membranes.