tbuckley/cabot-search huggingface dataset:
Pneumocystis carinii Pneumonia: A Comparison Between Patients with the Acquired Immunodeficiency Syndrome and Patients with Other Immunodeficiencies
Authors: JOSEPH A. KOVACS
Journal: Annals of Internal Medicine (1984)

Clinical features of 49 episodes of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome were compared with those of 39 episodes in patients with other immunosuppressive diseases. At presentation patients with the syndrome were found to have a longer median duration of symptoms (28 days versus 5 days, p = 0.0001), lower mean respiratory rate (23.4 versus 30, p = 0.005), and higher median room air arterial oxygen tension (69 mm Hg versus 52 mm Hg, p = 0.0002). The survival rate from 1979 to 1983 was similar for the two groups (57% and 50% respectively). Patients with the syndrome had a higher incidence of adverse reactions to trimethoprim-sulfamethoxazole (22 of 34 versus 2 of 17, p = 0.0007). Survivors with the syndrome at initial presentation had a significantly lower respiratory rate, and higher room air arterial oxygen tension, lymphocyte count, and serum albumin level compared to nonsurvivors. Pneumocystis carinii pneumonia presents as a more insidious disease process in patients with the syndrome, and drug therapy in these patients is complicated by frequent adverse reactions.
Causes of death in autosomal dominant polycystic kidney disease.
Authors: G M Fick, A M Johnson, W S Hammond, P A Gabow
Journal: Journal of the American Society of Nephrology (1995)

To determine the causes of death in autosomal dominant polycystic kidney disease (ADPKD) patients and to examine whether the extrarenal manifestations of ADPKD influence the causes of death, the medical records of 129 patients who died between 1956 and 1993 were reviewed; 58% of the 129 patients had an autopsy performed. Seventy-seven percent died after reaching ESRD. The mean age at death increased from 51 yr for those who died before 1975 to 59 yr for those who died after 1975, reflecting the introduction of renal replacement therapies. The most common cause of death before 1975 was infection (30%), followed by uremia (28%) and cardiac disease (21%); after 1975, these were cardiac disease (36%) and infection (24%). Infection was equally prevalent before and after 1975, presenting as sepsis in 94% and directly relating to ADPKD in 47% of these patients. Underlying factors for cardiac death were cardiac hypertrophy, seen in 89% of all autopsied patients, and coronary artery disease, seen in 81%. A neurologic event was the cause of death in 12% of patients; these were ruptured intracranial aneurysm in 6%, hypertensive intracranial hemorrhage in 5%, and ischemic stroke in 1%. The mean age of those who died of ruptured intracranial aneurysm was 37 yr. No patient died of renal cancer. Liver cysts were the most common extrarenal manifestation, seen in 70% of the autopsied cases; cysts in other organs were very rare. Colonic diverticula were found in 21%. Thus, the renal and extrarenal manifestations of ADPKD are important contributors to morbidity and mortality.
Authors' response to Hassan et al
Authors: A. Graser, F. T. Kolligs
Journal: Gut (2010)

et al (in the January issue of Gut), 1 we agree that not all patients in whom diminutive polyps are identified should be referred to colonoscopy for resection of these lesions.However, we noted in our trial 2 that high resolution CT colonography (CTC) allows for reliable identification of lesions that are <10 mm; even polyps that are <6 mm in size will be detected at a sensitivity of 72% if they are adenomas, and 59% if they are non-
Impact of Combined Deficiency of Hepatic Lipase and Endothelial Lipase on the Metabolism of Both High-Density Lipoproteins and Apolipoprotein B–Containing Lipoproteins
Authors: Robert J. Brown, William R. Lagor, Sandhya Sankaranaravanan, Tomoyuki Yasuda, Thomas Quertermous, George H. Rothblat, Daniel J. Rader
Journal: Circulation Research (2010)

Rationale : Hepatic lipase (HL) and endothelial lipase (EL) are extracellular lipases that both hydrolyze triglycerides and phospholipids and display potentially overlapping or complementary roles in lipoprotein metabolism. Objective : We sought to dissect the overlapping roles of HL and EL by generating mice deficient in both HL and EL (HL/EL-dko) for comparison with single HL-knockout (ko) and EL-ko mice, as well as wild-type mice. Methods and Results : Reproduction and viability of the HL/EL-dko mice were impaired compared with the single-knockout mice. The plasma levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, non–HDL cholesterol, and phospholipids in the HL/EL-dko mice were markedly higher than those in the single-knockout mice. Most notably, the HL/EL-dko mice exhibited an unexpected substantial increase in small low-density lipoproteins. Kinetic studies with [ 3 H]cholesteryl ether–labeled very-low-density lipoproteins demonstrated that the HL/EL-dko mice accumulated counts in the smallest low-density lipoprotein–sized fractions, as assessed by size exclusion chromatography, suggesting that it arises from lipolysis of very-low-density lipoproteins. HDL from all 3 lipase knockout models had an increased cholesterol efflux capacity but reduced clearance of HDL cholesteryl esters versus control mice. Despite their higher HDL cholesterol levels, neither HL-ko, EL-ko, nor HL/EL-dko mice demonstrated an increased rate of macrophage reverse cholesterol transport in vivo. Conclusions : These studies reveal an additive effect of HL and EL on HDL metabolism but not macrophage reverse cholesterol transport in mice and an unexpected redundant role of HL and EL in apolipoprotein B lipoprotein metabolism.
Are Social Psychiatry and Community Pshchiatry Subsepecialties of Psychiatry?
Authors: F. C. REDLICH, MAX PEPPER
Journal: American Journal of Psychiatry (1968)

Exploration of social systems and cultures and their impact on individuals is an interdisciplinary endeavor; psychiatry is only one of many disciplines that have made important contributions. Social scientists and dynamic psychiatrists can learn from each other as well as from the other people they relate to. To call the new applied science of groups and organizations "social psychiatry" or "community psychiatry" seems to the authors somewhat presumptuous. A bold interdisciplinary approach in training and research may be necessary to develop a needed new applied science.
Characterization of the Sodium/Hydrogen Exchanger NHA2
Authors: Daniel G. Fuster, Jianning Zhang, Mingjun Shi, I. Alexandru Bobulescu, Stefan Andersson, Orson W. Moe
Journal: Journal of the American Society of Nephrology (2008)

Cation/proton exchange has been recognized for decades in mammalian mitochondria, but the exchanger proteins have eluded identification. In this study, a cDNA from a human brain library, previously designated NHA2 in the genome, was cloned and characterized. The NHA2 transcript bears more similarity to prokaryotic than known eukaryotic sodium/proton exchangers, but it was found to be expressed in multiple mammalian organs and cultured cells. A mAb to NHA2 was generated and found to label an approximately 55-kD native protein in multiple tissues and cell lines. The specificity of this antibody was confirmed by demonstrating the loss of the native NHA2 band on immunoblots when cultured cells were treated with NHA2-specific small interfering RNA. Although NHA2 protein was detected in multiple organs, within each, its expression was restricted to specific cell types. In the kidney, co-localization with calbindin 28k and reverse transcription-PCR of microdissected tubules revealed that NHA2 is limited to the distal convoluted tubule. In cell lines, native NHA2 was localized both to the plasma membrane and to the intracellular compartment; immunogold electron microscopy of rat distal convoluted tubule demonstrated NHA2 predominantly but not exclusively on the inner mitochondrial membrane. Furthermore, co-sedimentation of NHA2 antigen and mitochondrial membranes was observed with differential centrifugation, and two mitochondrial markers co-localized with NHA2 in cultured cells. Regarding function, human NHA2 reversed the sodium/hydrogen exchanger-null phenotype when expressed in sodium/hydrogen exchanger-deficient yeast and restored the ability to defend high salinity in the presence of acidic extracellular pH. In summary, NHA2 is a ubiquitous mammalian sodium proton/exchanger that is restricted to the distal convoluted tubule in the kidney.
Costs of an Emergency Department—Based Accelerated Diagnostic Protocol vs Hospitalization in Patients With Chest Pain
Authors: Rebecca R. Roberts, Robert J. Zalenski, Edward K. Mensah, Robert J. Rydman, Ginevra Ciavarella, Leon Gussow, Krishna Das, Linda M. Kampe, Brian Dickover, Michael F. McDermott, Andrea Hart, Helen E. Straus, Daniel G. Murphy, Ravi Rao
Journal: JAMA (1997)

More than 3 million patients are hospitalized yearly in the United States for chest pain. The cost is over $3 billion just for those found to be free of acute disease. New rapid diagnostic tests for acute myocardial infarction (AMI) have resulted in the proliferation of accelerated diagnostic protocols (ADPs) and chest pain observation units.To determine whether use of an emergency department (ED)-based ADP can reduce hospital admission rate, total cost, and length of stay (LOS) for patients needing admission for evaluation of chest pain.Prospective randomized controlled trial comparing admission rate, total cost, and LOS for patients treated using ADP vs inpatient controls. Total costs were determined using empirically measured resource utilization and microcosting techniques.A large urban public teaching hospital serving a predominantly African American and Hispanic population.A sample of 165 patients was randomly selected from a larger consecutive sample of 429 patients with chest pain concurrently enrolled in an ADP diagnostic cohort trial. Eligible patients presented to the ED with clinical findings suggestive of AMI or acute cardiac ischemia (ACI) but at low risk using a validated predictive algorithm.Primary outcomes measured for each subject were LOS and total cost of treatment.The hospital admission rate for ADP vs control patients was 45.2% vs 100% (P<.001). The mean total cost per patient for ADP vs control patients was $1528 vs $2095 (P<.001). The mean LOS measured in hours for ADP vs control patients was 33.1 hours vs 44.8 hours (P<.01).In this trial, ADP saved $567 in total hospital costs per patient treated. Use of ED-based ADPs can reduce hospitalization rates, LOS, and total cost for low-risk patients with chest pain needing evaluation for possible AMI or ACI.
Scottish postoperative care is improving
Authors: B. Christie
Journal: BMJ (2003)

The number of cases in Scotland where poor care contributed to or caused the death of a surgical patient is continuing to fall, according to the latest report of the Scottish audit of surgical mortality.

Issues of concern that played a part in the patient's death were identified in 7.6% of the 4049 audited deaths in 2001, compared with 10.1% in 2000 and 9.9% in 1999. The most common problems were delays in operating, inadequate preoperative assessment, unsatisfactory medical management, and delays …
Rho-Kinase Inhibition Blunts Renal Vasoconstriction Induced by Distinct Signaling Pathways In Vivo
Authors: Alessandro Cavarape, Nicole Endlich, Roberta Assaloni, Ettore Bartoli, Michael Steinhausen, Niranjan Parekh, Karlhans Endlich
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. In addition to intracellular calcium, which activates myosin light chain (MLC) kinase, MLC phosphorylation and hence contraction is importantly regulated by MLC phosphatase (MLCP). Recent evidence suggests that distinct signaling cascades of vasoactive hormones interact with the Rho/Rho kinase (ROK) pathway, affecting the activity of MLCP. The present study measured the impact of ROK inhibition on vascular F-actin distribution and on vasoconstriction induced by activation/inhibition of distinct signaling pathways <i>in vivo</i> in the microcirculation of the split hydronephrotic rat kidney. Local application of the ROK inhibitors Y-27632 or HA-1077 induced marked dilation of pre- and postglomerular vessels. Activation of phospholipase C with the endothelin ET<sub>B</sub> agonist IRL 1620, inhibition of soluble guanylyl cyclase with 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), or inhibition of adenylyl cyclase with the adenosine A<sub>1</sub> agonist N<sup>6</sup>-cyclopentyladenosine (CPA) reduced glomerular blood flow (GBF) by about 50% through vasoconstriction at different vascular levels. ROK inhibition with Y-27632 or HA-1077, but not protein kinase C inhibition with Ro 31-8220, blunted ET<sub>B</sub>-induced vasoconstriction. Furthermore, the reduction of GBF and of vascular diameters in response to ODQ or CPA were abolished by pretreatment with Y-27632. ROK inhibitors prevented constriction of preglomerular vessels and of efferent arterioles with equal effectiveness. Confocal microscopy demonstrated that Y-27632 did not change F-actin content and distribution in renal vessels. The results suggest that ROK inhibition might be considered as a potent treatment of renal vasoconstriction, because it interferes with constriction induced by distinct signaling pathways in renal vessels without affecting F-actin structure. E-mail: alessandro.cavarape@dpmsc.uniud.it
Place of residence and distance to medical care influence the diagnosis of hepatitis C: A population-based study
Authors: Elisabeth Monnet, Estelle Collin-Naudet, Solange Bresson-Hadni, Anne Minello, Vincent Di Martino, Didier Carel, Valérie Jooste, Alice Gagnaire, Philippe Evrard, Bénédicte Obert-Clerc, Jean-Philippe Miguet, Patrick Hillon
Journal: Journal of Hepatology (2005)
Helicobacter pylori represses proton pump expression and inhibits acid secretion in human gastric mucosa
Authors: A. Saha, C. E. Hammond, C. Beeson, R. M. Peek, A. J. Smolka
Journal: Gut (2010)

Helicobacter pylori infection of gastric mucosa causes gastritis and transient hypochlorhydria, which may provoke emergence of a mucosal precancer phenotype; H pylori strains containing a cag pathogenicity island (PAI) augment cancer risk. Acid secretion is mediated by the catalytic alpha subunit of parietal cell H,K-ATPase (HKalpha). In AGS gastric epithelial cells, H pylori induces nuclear factor-kappaB (NF-kappaB) binding to and repression of transfected HKalpha promoter activity. This study sought to identify bacterial genes involved in HKalpha repression and to assess their impact on acid secretion.AGS cells transfected with an HKalpha promoter construct or human gastric body biopsies were infected with wild-type (wt) or isogenic mutant (IM) H pylori strains. AGS cell HKalpha promoter activity, and biopsy HKalpha mRNA, protein and H(+) secretory activity were measured by luminometry, reverse transcription-PCR, immunoblotting and extracellular acidification, respectively. Wt H pylori and DeltavacA, DeltaureA, Deltaslt and DeltaflaA IM strains repressed HKalpha promoter activity by approximately 50%, a DeltacagA IM strain repressed HKalpha by approximately 33%, and DeltacagE, DeltacagM and DeltacagL IM strains elicited no HKalpha repression. Wt H pylori-infected biopsies had markedly reduced HKalpha mRNA and protein compared with IM strain infections or mock-infected controls. Histamine-stimulated, SCH28080-sensitive biopsy acid secretion was significantly inhibited by wt but not by DeltacagL IM H pylori infection compared with vehicle-only controls.It is concluded that H pylori cag PAI gene products CagE, CagM, CagL and, possibly, CagA are mechanistically involved in repression of HKalpha transcription. Further, acute H pylori infection of human gastric mucosa downregulates parietal cell H,K-ATPase expression, significantly inhibiting acid secretion.
Cancer Incidence and Mortality After Treatment With Folic Acid and Vitamin B&lt;sub&gt;12&lt;/sub&gt;
Authors: Marta Ebbing
Journal: JAMA (2009)

Recently, concern has been raised about the safety of folic acid, particularly in relation to cancer risk.To evaluate effects of treatment with B vitamins on cancer outcomes and all-cause mortality in 2 randomized controlled trials.Combined analysis and extended follow-up of participants from 2 randomized, double-blind, placebo-controlled clinical trials (Norwegian Vitamin Trial and Western Norway B Vitamin Intervention Trial). A total of 6837 patients with ischemic heart disease were treated with B vitamins or placebo between 1998 and 2005, and were followed up through December 31, 2007.Oral treatment with folic acid (0.8 mg/d) plus vitamin B(12) (0.4 mg/d) and vitamin B(6) (40 mg/d) (n = 1708); folic acid (0.8 mg/d) plus vitamin B(12) (0.4 mg/d) (n = 1703); vitamin B(6) alone (40 mg/d) (n = 1705); or placebo (n = 1721).Cancer incidence, cancer mortality, and all-cause mortality.During study treatment, median serum folate concentration increased more than 6-fold among participants given folic acid. After a median 39 months of treatment and an additional 38 months of posttrial observational follow-up, 341 participants (10.0%) who received folic acid plus vitamin B(12) vs 288 participants (8.4%) who did not receive such treatment were diagnosed with cancer (hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.03-1.41; P = .02). A total of 136 (4.0%) who received folic acid plus vitamin B(12) vs 100 (2.9%) who did not receive such treatment died from cancer (HR, 1.38; 95% CI, 1.07-1.79; P = .01). A total of 548 patients (16.1%) who received folic acid plus vitamin B(12) vs 473 (13.8%) who did not receive such treatment died from any cause (HR, 1.18; 95% CI, 1.04-1.33; P = .01). Results were mainly driven by increased lung cancer incidence in participants who received folic acid plus vitamin B(12). Vitamin B(6) treatment was not associated with any significant effects.Treatment with folic acid plus vitamin B(12) was associated with increased cancer outcomes and all-cause mortality in patients with ischemic heart disease in Norway, where there is no folic acid fortification of foods.clinicaltrials.gov Identifier: NCT00671346.
Family Structure and Depressive Symptoms in Men Preceding and Following the Birth of a Child
Authors: Kirby Deater-Deckard, Kevin Pickering, Judith F. Dunn, Jean Golding, None The Avon Longitudinal Study of Pregnancy, Childhood Study Team
Journal: American Journal of Psychiatry (1998)

The prevalence and etiology of pre- and postpartum depressive symptoms in women in a variety of family forms have been well documented, but relatively little research has been conducted on the adjustment of their male partners. The authors' goals in this study were 1) to estimate rates of depression during the pregnancy and 8 weeks following the birth of a child in a large representative community sample of fathers in different family structures and 2) to explore the role of stressful life events, social and emotional support, the quality of the partner relationship, and socioeconomic circumstances.This study describes the relations of family setting and other correlates to men's depressive symptoms during the pregnancies (18 weeks gestation, on average) and 8 weeks after the births of children for 7,018 partners of female participants in the Avon Longitudinal Study of Pregnancy and Childhood.Men living in stepfamilies had-significantly higher levels of depressive symptoms before and after the birth than did men in more traditional families. The effect of stepfamily status on depression was mediated by education, life events, social support, social network, and level of aggression in the partnership.There are similarities in the patterns and correlates of depression after the birth of a child for men and women. These findings point to the importance of family and partnership ecology in the adjustment of men before and after the birth of a child.
The effect of adiposity measured by dual-energy X-ray absorptiometry on lung function
Authors: T. J. T. Sutherland, A. Goulding, A. M. Grant, J. O. Cowan, A. Williamson, S. M. Williams, M. A. Skinner, D. R. Taylor
Journal: European Respiratory Journal (2008)

Respiratory function is impaired in obesity but there are limitations with body mass index and skin-fold thickness in assessing this effect. The present authors hypothesised that the regional distribution of body fat and lean mass, as measured by dual-energy X-ray absorptiometry (DXA), might be more informative than conventional measurements of total body fat. In total, 107 subjects (55 female, 51.4%) aged 20-50 yrs with no respiratory disease were recruited. Respiratory function tests, anthropometric measurements and a DXA scan were performed. Partial correlation and linear regression analyses were used to explore the effect of adiposity and lean body mass on respiratory function. The majority of respiratory function parameters were significantly correlated with DXA and non-DXA measurements of body fat. Neither thoracic nor abdominal fat had a greater effect. There were some differences in the effect of adiposity between the sexes. Respiratory function was negatively associated with lean body mass in females but positively associated in males. This disappeared after adjustment in females but remained in males. The effects of thoracic and abdominal body fat on respiratory function are comparable but cannot be separated from one another.
Signaling in Malignant Astrocytomas: Role of Neural Stem Cells and Its Therapeutic Implications
Authors: Sheila R. Alcantara Llaguno, Jian Chen, Luis F. Parada
Journal: Clinical Cancer Research (2009)

Abstract Malignant astrocytomas are infiltrative and aggressive brain tumors. Conventional forms of therapy have not been effective in controlling this incurable disease. Recent advances in understanding the molecular biology of these tumors have revealed potential mechanisms by which astrocytoma cells undergo tumor initiation, progression, and maintenance, as well as possible avenues for targeted therapeutics. Studies on the role of neural stem cells as cells of origin and tumor-propagating cells have also greatly increased our understanding of the biology and clinical behavior of these tumors. An integrated view of the genetics, signal transduction, and cell biology of astrocytomas, as well as clinical data from patients, will provide a more useful approach in designing novel therapies for this devastating disease. (Clin Cancer Res 2009;15(23):7124–9)
If the treatment works, do we need to know why?: the promise of immunotherapy for experimental medicine
Authors: Michael R. Ehrenstein, Claudia Mauri
Journal: The Journal of Experimental Medicine (2007)

There has been much fanfare, and rightly so, heralding a revolution in the treatment of autoimmune disease using biologic agents—antibodies or other molecules that specifically target known mediators of disease. But not all patients respond to even the most successful biologic agent, which may provide clues about alternate disease mechanisms. Studies aimed at understanding the mechanism of action of biologic agents will yield significant benefits for experimental medicine.