tbuckley/cabot-search huggingface dataset:
Nondissociating cationic immune complexes can deposit in glomerular basement membrane.
Authors: T Caulin-Glaser, G R Gallo, M E Lamm
Journal: The Journal of Experimental Medicine (1983)

The mechanisms by which immune complexes deposit in the glomerular basement membrane have been the subject of much debate, with the relative importance of direct deposition of circulating immune complexes (IC) vs. formation of IC in situ from the binding of circulating antibody to structural or exogenous planted antigen being at issue. In order to determine whether intact IC can deposit as such, covalently linked IC were prepared by a two-step reaction involving the bifunctional reagent toluene-2,4-diisocyanate (TDI), the antigen bovine gamma globulin (BGG), and rabbit anti-BGG antibody. Antigen and antibody were covalently cross-linked, with little self-linkage of antigen or antibody, and IC were purified by gel filtration. The net charge of the complexes was varied by chemical means, either before or after IC formation. When cationic IC were injected intravenously into mice, there was codeposition of antigen and antibody diffusely in the glomerular basement membrane (GBM), and deposits were observed ultrastructurally in the laminae rarae, interna and externa, and the lamina densa. Thus, under conditions of restricted appropriate charge, intact IC can cross the glomerular basement membrane and deposit in subepithelial sites without being excluded by size alone.
Critical Role for Tumor Necrosis Factor–related Apoptosis-inducing Ligand in Immune Surveillance Against Tumor Development
Authors: Kazuyoshi Takeda, Mark J. Smyth, Erika Cretney, Yoshihiro Hayakawa, Nobuhiko Kayagaki, Hideo Yagita, Ko Okumura
Journal: The Journal of Experimental Medicine (2002)

Natural killer (NK) cells and interferon (IFN)-gamma have been implicated in immune surveillance against tumor development. Here we show that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plays a critical role in the NK cell-mediated and IFN-gamma-dependent tumor surveillance. Administration of neutralizing monoclonal antibody against TRAIL promoted tumor development in mice subcutaneously inoculated with a chemical carcinogen methylcholanthrene (MCA). This protective effect of TRAIL was at least partly mediated by NK cells and totally dependent on IFN-gamma. In the absence of TRAIL, NK cells, or IFN-gamma, TRAIL-sensitive sarcomas preferentially emerged in MCA-inoculated mice. Moreover, development of spontaneous tumors in p53(+/-) mice was also promoted by neutralization of TRAIL. These results indicated a substantial role of TRAIL as an effector molecule that eliminates developing tumors.
INSULIN COMA IN DECLINE
Authors: HAROLD BOURNE
Journal: American Journal of Psychiatry (1958)

Recent trends in the psychiatric literature reveal that disillusion with the insulin coma treatment of schizophrenia has steadily spread in the past 4 years. Since the method has no rationale, and since even its empirical basis now cannot withstand critical inspection, it is of interest to know why it gained almost unanimous acceptance. Probably three circumstances are at the bottom of it. The first is that a movement for the reform of mental hospitals and for their conversion from inactively custodial asylums to therapeutic centres, was bound to grow in the last 20 years. The second is that such a movement would inevitably have promoted treatment methods that involved optimistic and individual attention to psychotic persons. The third is that in the early 'thirties when all this began, schizophrenics were considered inherently inaccessible to psychotherapy, since Freud adumbrated that they were incapable of forming a transference relationship. It can safely be said, now that this fallacy has been exploded in the last decade, that were insulin coma a new treatment invented in 1958, it would have no hope of catching on in the way it did. It succeeded because it provided a personal approach to the schizophrenic, suitably disguised as a physical treatment so as to slip past the prejudices of the age. The work of Whitehorn and Betz (24) underlines this point most lucidly. Comparing two groups of psychiatrists, the one psychotherapeutically effective with schizophrenics, and the other ineffective, they found that only the results of the latter were enhanced by insulin coma therapy. In short, insulin coma treatment may come to be remembered as the first application of psychological healing for schizophrenics in the mass, and its achievement as an inadvertent one—the supply to persons hitherto considered impervious to it, of daily, devoted, personal care. In 1958, there are more rational ways of doing this, but apart from its irrationality, the insulin treatment exposes both patient and psychiatrist to a number of hazards which are no longer justified. It has a mortality which is not negligible; it is extravagant in the scarcest of mental hospital commodities, namely medical and nursing time; and worst of all, it effectively screens doctor and patient from other approaches to the problems of schizophrenia. The psychiatrist in training probably suffers most damage. Juniors are often posted to the insulin unit so that, at its foundations, their knowledge of schizophrenia requires no preoccupation with its subtle psychology and no experience of psychotherapy. Even the proper use of ECT is impeded because it is learnt as a casual procedure, administered sporadically and without system, as an adjuvant to the insulin ritual. One consequence of this is that the phenomena of convulsion dependence(8) are obscured and their correct management subverted. No doubt, the insulin treatment will be slower to depart than it was to be accepted. The "it-can't-do-any-harm-to-try" argument is not only destitute, it is false and dangerous for both patient and psychiatrist.
Natural History and Possible Reactivation of Human Papillomavirus in Human Immunodeficiency Virus–Positive Women
Authors: Howard D. Strickler, Robert D. Burk, Melissa Fazzari, Kathryn Anastos, Howard Minkoff, L. Stewart Massad, Charles Hall, Melanie Bacon, Alexandra M. Levine, D. Heather Watts, Michael J. Silverberg, Xiaonan Xue, Nicolas F. Schlecht, Sandra Melnick, Joel M. Palefsky
Journal: JNCI Journal of the National Cancer Institute (2005)

Little is known in human immunodeficiency virus (HIV)-positive women about how the combination of plasma HIV RNA level and CD4+ T-cell count is associated with the natural history of human papillomavirus (HPV) infection or about HPV reactivation--whether it occurs and with what frequency in HIV-positive women.HIV-positive (n = 1848) and -negative (n = 514) women were assessed at semiannual visits (total person-years = 5661) for cervicovaginal HPV with polymerase chain reaction assays and for squamous intraepithelial lesions (SILs) by Pap smear. We studied the prevalent detection of HPV and SILs with generalized estimating equations and the incident detection and persistence of HPV and SILs with multivariable Cox models. All statistical tests were two-sided.We observed a strong interaction between the associations of CD4+ and plasma HIV RNA strata with both prevalent (P(interaction) = .002) and incident (P(interaction) = .001) detection of HPV. Indeed, the hazard ratio for incident HPV detection peaked between 4.0 and 5.0, with either a CD4+ count of less than 200 cells per mm3 or an HIV RNA level of more than 100,000 copies per mL. Although incident HPV detection in all women was associated with the number of recent sex partners (P(trend)<.001), 22% of sexually inactive HIV-positive women with a CD4+ count of less than 200 cells/mm3 also had at least one incidentally detected HPV type. The association between CD4+/HIV RNA strata and HPV persistence was statistically significantly smaller (P<.001) than for incident HPV detection. SIL prevalence, incident detection, and persistence had similar associations with CD4+/HIV RNA strata as HPV (above).In HIV-positive women, plasma HIV RNA level and CD4+ count in combination appear to have a strong and statistically interactive association with incident detection of HPV, some of which may reflect HPV reactivation (e.g., in sexually inactive women). The more moderate association between HIV coinfection and HPV persistence could partly explain why cervical cancer rates have not reached more epidemic proportions in HIV-positive women.
Something better for the weekend?
Authors: Peter M.A. Calverley
Journal: European Respiratory Journal (2014)

“…and He rested on the seventh day from all His work, which He had made” 

Genesis 2:2 (King James’ Bible)

The idea of pausing for a day from the normal tasks of life has a long history, possibly began in Babylon where the 28th day of each lunar month was a rest day. Subsequently, this was taken up by the Abrahamic religions, Judaism, Christianity and Islam, which have done much to shape the pattern of the week for billions of people globally. Even Buddhists believe that every seventh or eighth day should be a day of rest, with only the Hindu’s not specifying a specific rest day. For centuries, the need to celebrate the Sabbath determined the ebb and flow of life but in the late 19th century, with growing industrialisation in Western Europe and North America, it became possible to take more time away from work. This led to the rise of organised sports on Saturday afternoons in non-Jewish communities and the idea of the weekend, when people who were no longer engaged in “productive” work had time to meet together and pursue other interests.

Of course, these social trends did not affect everyone. For instance, there is no evidence that illnesses are any less serious when they present at the weekend and for those patients who required hospital treatment, care givers were still needed. …
Implications of linking pharmacy and laboratory data to assess diabetes care.
Authors: R M Cohen
Journal: Diabetes Care (2000)

In principle, it should be simple to link patients’ laboratory studies with changes in their medications in order to assess the clinical decisions underlying their care. As individual care providers with an individual patient’s chart, we do it all the time. But evaluation of variations in care across patients, across providers, and across health care systems, while desirable, is presently a Herculean task. Such is the task that Wetzler and Snyder set for themselves in a study reported in this issue of Diabetes Care (1), in which they sought to determine whether providers met the American Diabetes Association’s practice guideline to initiate treatment when the HbA 1c concentration was found to be � 8%. They have made a good first step and, in the process, have highlighted some of the challenges that must be overcome to apply this strategy more broadly. The physicians participating in the
Water-holding by dietary fibre in vitro and its relationship to faecal output in man
Authors: A. M. Stephen, J. H. Cummings
Journal: Gut (1979)

The <i>in vitro</i> water-holding properties of 17 dietary fibre preparations, mainly food materials, bulk laxatives, and gel-forming polysaccharides, have been measured. Water uptake was measured by a centrifugation technique and also by a new method using sacs of dialysis tubing containing the material, immersed in simulated gut contents. The centrifugation technique could not be applied to gel-forming polysaccharides but the methods gave broadly similar results for other materials (<i>r</i>=0·85). The gel-forming polysaccharides in general held more water than the food fibres. Studies of matched pairs of materials which differed only slightly in chemical composition suggested that the presence of charged groups on the molecule encouraged water uptake. In the food materials water uptake was related to uronic acid content (<i>r</i>=0·87). Materials ground to a smaller particle size increase their water holding but this effect was small (+28%). The hypothesis that dietary fibre increases faecal bulk by virtue of its ability to hold water was tested by comparing the <i>in vitro</i> water-holding capacity of eight of the fibres with the changes they had produced when fed to human volunteers under controlled conditions. Of these materials pectin had the greatest water-holding capacity (56·2 g water/g material) but produced the smallest change in faecal weight (19%), while bran had the lowest water-holding (4·2 g/g) and the largest faecal weight changes (117%). Overall an inverse relationship (<i>r</i>=0·88) between water-holding and faecal bulking was found, suggesting that dietary fibre does not exert its effect on faecal weight simply by retaining water in the gut.
Hemodynamic Studies in Patients with Borderline Blood Pressure Elevation
Authors: STEVO JULIUS, JAMES CONWAY
Journal: Circulation (1968)

Ninety-four patients with occasionally elevated (borderline) blood pressure, 61 patients with asymptomatic established hypertension, and 63 normal subjects have been studied at rest and during a progressive exercise test on a cycle ergometer. Subjects with borderline blood pressure had increased cardiac output in the resting recumbent position, but this was not maintained in the sitting position or during exercise. In the resting recumbent position there was overlap in the total peripheral resistance of normal subjects and patients with borderline blood pressure, but when analyzed in relation to the cardiac output, the total peripheral resistance of patients with borderline blood pressure was significantly elevated. In the sitting position the peripheral resistance of the patients with borderline blood pressure was elevated and remained elevated during light exercise, but fell into the normal range at higher loads. In this respect patients with borderline blood pressure differed from hypertensive patients who maintain a higher peripheral resistance than the normal subjects do at all levels of exercise. In conclusion, patients with occasional elevation of blood pressure have an abnormal peripheral resistance in relation to cardiac output both at rest and at low levels of exercise. This observation may indicate a prehypertensive state.
Randomized Controlled Trial of a Prompt List to Help Advanced Cancer Patients and Their Caregivers to Ask Questions About Prognosis and End-of-Life Care
Authors: Josephine M. Clayton, Phyllis N. Butow, Martin H.N. Tattersall, Rhonda J. Devine, Judy M. Simpson, Ghauri Aggarwal, Katherine J. Clark, David C. Currow, Louise M. Elliott, Judith Lacey, Philip G. Lee, Michael A. Noel
Journal: Journal of Clinical Oncology (2007)

Purpose To determine whether provision of a question prompt list (QPL) influences advanced cancer patients’/caregivers’ questions and discussion of topics relevant to end-of-life care during consultations with a palliative care (PC) physician. Patients and Methods This randomized controlled trial included patients randomly assigned to standard consultation or provision of QPL before consultation, with endorsement of the QPL by the physician during the consultation. Consecutive eligible patients with advanced cancer referred to 15 PC physicians from nine Australian PC services were invited to participate. Consultations were audiotaped, transcribed, and analyzed by blinded coders; patients completed questionnaires before, within 24 hours, and 3 weeks after the consultation. Results A total of 174 patients participated (92 QPL, 82 control). Compared with controls, QPL patients and caregivers asked twice as many questions (for patients, ratio, 2.3; 95% CI, 1.7 to 3.2; P &lt; .0001), and patients discussed 23% more issues covered by the QPL (95% CI, 11% to 37%; P &lt; .0001). QPL patients asked more prognostic questions (ratio, 2.3; 95% CI, 1.3 to 4.0; P = .004) and discussed more prognostic (ratio, 1.43; 95% CI, 1.1 to 1.8, P = .003) and end-of-life issues (30% v 10%; P = .001). Fewer QPL patients had unmet information needs about the future (χ 2 1 = 4.14; P = .04), which was the area of greatest unmet information need. QPL consultations (average, 38 minutes) were longer (P = .002) than controls (average, 31 minutes). No differences between groups were observed in anxiety or patient/physician satisfaction. Conclusion Providing a QPL and physician endorsement of its use assists terminally ill cancer patients and their caregivers to ask questions and promotes discussion about prognosis and end-of-life issues, without creating patient anxiety or impairing satisfaction.
Late-breaking abstract: Pneumonia hospitalizations and long-term exposure to air pollution: A cohort study
Authors: Kristina Ranc, Per B. Brockoff, Reimer W. Thomsen, Ole Raaschou Nielsen, Matthias Ketzel, Steen S. Jensen, Anne Tjønneland, Kim Overvad, Zorana Jovanovic Andersen
Journal: European Respiratory Journal (2011)

Background:  Long-term exposure to air pollution has been associated with cardiovascular and chronic lung disease, but limited evidence exist on the risk for pneumonia.   Aim:  To investigate the effect of long-term exposure to traffic-related air pollution (up to 38 years) in Copenhagen and Aarhus on hospital admissions for pneumonia.   Methods:  We followed 57053 participants of Danish Cancer, Diet, and Health cohort, aged 50-65 years at baseline (1993-1997) in Danish hospital discharge register for first hospital admissions for pneumonia between baseline and 2010. The annual nitrogen dioxide (NO 2 ) levels were estimated at residential address since 1971 as a proxy of exposure to traffic-related air pollution. We modelled the association between mean NO 2  levels and hospitalizations for pneumonia using Cox regression.   Results:  During 12.7 years9 mean follow-up, 3024 (5.7%) out of 53239 eligible people were admitted to hospital for pneumonia. Mean NO 2  levels were significantly positively associated with risk for first pneumonia hospitalization in the full cohort (hazard ratio and 95% confidence interval per double mean exposure: 1.25; 1.13-1.35); with similar effect for first-ever pneumonia admission in 46462 people without earlier hospitalizations for pneumonia or co-morbid conditions defined by Charlson (1.23; 1.11-1.37), and in 6292 people with history of co-morbid conditions (1.22; 1.02-1.46), wheras enahnced association was observed in 485 people with a history of pneumonia hospitalizations (1.45; 0.85-2.47).   Conclusions:  Living in areas with high traffic-related air pollution increases the risk of hospitalization for pneumonia.
Characteristics of Hydrogen Ion Transport in Urinary Bladder of Water Turtle*
Authors: Philip R. Steinmetz
Journal: Journal of Clinical Investigation (1967)

The mechanism of acidification by the urinary bladder of the water turtle was studied in an in vitro system which permitted control and measurement of electrical and concentration driving forces. The rate of hydrogen ion secretion was measured by means of a pH stat technique in the absence of exogenous carbon dioxide and bicarbonate. Transport of hydrogen ion into the solution bathing the mucosal surface of the bladder was associated with the appearance of alkali in the serosal compartment. The mean rate of hydrogen ion secretion in the absence of electrical and concentration gradients across the bladder was 0.96 mumole/hr. The secretion rate was only slightly greater in the presence of the spontaneous potential difference. The maximal hydrogen ion gradient that could be generated by the bladder was 3.33 pH units in the presence of the spontaneous voltage and 3.02 pH units in the short-circuited state. Hydrogen ion secretion was markedly reduced by acetazolamide and anaerobiosis, which indicated that under our experimental conditions acidification depended on the production and enzymatic hydration of metabolic carbon dioxide. On the basis of the stoichiometry of the pH changes across the membrane under different conditions, it is suggested that the active transport mechanism for hydrogen ion is located near the mucosal surface of the epithelial cell and that the alkali generated in back of the pump moves passively into the serosal fluid along an electrochemical gradient.
Pancreatic response to secretion+CCK-PZ in European and North African adults and children.
Authors: G Palasciano, J F Saunieres, R Laugier, H Sarles
Journal: Gut (1979)

Pancreatic response to intravenous secretin GIH (1CU/kg) +CCK-PZ (3CHRU/kg) was investigated in European and North African normal subjects. The pancreatic responses were compared in two groups of 38 normal male adults and in two groups of nine normal nurslings (less than 1 year). Body weight and age were similar in the two adult groups and in the two nursling groups. The peaks of volume, electrolytes, and enzymes were determined in samples of duodenal aspirate after hormonal stimulation. In adult subjects the flow rate and electrolytes were not statistically different in the two groups, while enzyme outputs were lower in the North African group -73% for lipase (P less than 0.001), -54% for phospholipase (P less than 0.01), and -35% for chymotrypsin (P less than 0.05). On the other hand, in both groups of nursling subjects all parameters of pancreatic secretion were identical. The difference in the pattern of the pancreatic response to exogenous hormonal stimulation observed between the two groups of adult subjects could be related to genetic or acquired differences. The second hypothesis is, however, the most probable because the pancreatic secretion was similar in both groups of nursling subjects.
Effects of Continuous Aortic Flow Augmentation in Patients With Exacerbation of Heart Failure Inadequately Responsive to Medical Therapy
Authors: Barry Greenberg, Barbara Czerska, Reynolds M. Delgado, Robert Bourge, Michael R. Zile, Marc Silver, Marc Klapholz, Ernest Haeusslein, Mandeep R. Mehra, Paul Mather, William T. Abraham, James D. Neaton, B. Scott Brown, Irene C. Parker, Marvin A. Konstam
Journal: Circulation (2008)

Prior investigations suggest that superimposing continuous flow on aortic flow (continuous aortic flow augmentation) produces vasodilation, cardiac unloading, and improved cardiac performance.We compared percutaneous continuous aortic flow augmentation (flow <or=1.5 L/min for up to 96 hours) plus medical therapy versus medical therapy alone by randomizing 168 patients (device, n=109; control, n=59) hospitalized with heart failure, reduced left ventricular ejection fraction and cardiac index, elevated pulmonary capillary wedge pressure, and renal impairment or substantial diuretic requirement despite intravenous inotropes/vasodilators. The primary composite efficacy end point included pulmonary capillary wedge pressure (72 to 96 hours) and days alive out of hospital off mechanical support over 35 days. The population's illness severity posed unique challenges. Enrollment ended early because of an inability to demonstrate significant benefit on the primary composite end point (device, 17.4%; control, 13.6%; P=0.45) in the face of excess device group bleeding. Pulmonary capillary wedge pressure decreased from 28.8+/-6.3 mm Hg (mean+/-SD) to 24.9+/-7.2 mm Hg (average, 72 to 96 hours) and 28.9+/-7.1 to 26.5+/-6.2 mm Hg in the device and control groups, respectively (between-group P=0.074). Cardiac index progressively increased in the device (2.05+/-0.53 to 2.44+/-0.52 L min(-1) m(-2)) but not the control (between-group P<0.0001) group. Thirty-five-day Kansas City Cardiomyopathy Questionnaire Overall Summary scores increased by 38.4+/-22.7 and 31.2+/-26.0 points in the device and control groups (between-group P=0.10). Through 65 days, device-to-control hazard ratios were as follows: all-cause mortality, 1.05 (95% confidence interval, 0.60 to 1.82); death or heart failure hospitalization, 0.87 (95% confidence interval, 0.57 to 1.33); and heart failure hospitalization, 0.66 (95% confidence interval, 0.38 to 1.13). Major bleeds occurred in 16.5% in the device (7.3% treatment related) and 5.1% in the control (P=0.05) group.Continuous aortic flow augmentation improved cardiac performance, improving cardiac index and pulmonary capillary wedge pressure, but statistical significance for the primary efficacy end point was not attained. Hemodynamic and clinical observations provide direction toward additional studies to further investigate the clinical effects of this treatment.