tbuckley/cabot-search huggingface dataset:
Mechanisms of filtration failure during postischemic injury of the human kidney. A study of the reperfused renal allograft.
Authors: V Alejandro, J D Scandling, R K Sibley, D Dafoe, E Alfrey, W Deen, B D Myers
Journal: Journal of Clinical Investigation (1995)

Postischemic filtration failure in experimental animals results primarily from depression of the transcapillary hydraulic pressure difference (delta P), a quantity that cannot be determined in humans. To circumvent this limitation we determined the GFR and each of its remaining determinants in transplanted kidneys. Findings in 12 allografts that exhibited subsequent normofiltration (group 1) were compared with those in 11 allografts that exhibited persistent hypofiltration (group 2). Determinations were made intraoperatively in the exposed graft after 1-3 h of reperfusion. GFR (6 +/- 2 vs 29 +/- 5 ml/min) and renal plasma flow by Doppler flow meter (140 +/- 30 vs 315 +/- 49 ml/min) were significantly lower in group 2 than group 1. Morphometric analysis of glomeruli obtained by biopsy and a structural hydrodynamic model of viscous flow revealed the glomerular ultrafiltration coefficient to be similar, averaging 3.5 +/- 0.6 and 3.1 +/- 0.2 ml/(min.mmHg) in group 2 vs 1, respectively. Corresponding values for plasma oncotic pressure were also similar, averaging 19 +/- 1 vs 21 +/- 1 mmHg. We next used a mathematical model of glomerular ultrafiltration and a sensitivity analysis to calculate the prevailing range for delta P from the foregoing measured quantities. This revealed delta P to vary from only 20-21 mmHg in group 2 vs 34-45 mmHg in group 1 (P < 0.001). Further morphometric analysis revealed the diameters of Bowman's space and tubular lumens, as well as the percentage of tubular cells that were necrotic or devoid of brush border, to be similar in the two groups. We thus conclude (a) that delta P depression is the predominant cause of hypofiltration in this form of postischemic injury; and (b) that afferent vasoconstriction rather than tubular obstruction is the proximate cause of the delta P depression.
Markedly Diminished Epidermal Keratinocyte Expression of Intercellular Adhesion Molecule-1 (ICAM-1) in Sézary Syndrome
Authors: Brian J. Nickoloff
Journal: JAMA (1989)

In mycosis fungoides the malignant T cells express lymphocyte function-associated antigen-1, which allows them to bind to epidermal keratinocytes expressing the gamma interferon-inducible intercellular adhesion molecule-1. In this report, a patient with leukemic-stage mycosis fungoides (Sézary syndrome) had widespread erythematous dermal infiltrates containing malignant T cells, but without any epidermotropism. We discovered that the T cells expressed normal amounts of functional lymphocyte function-associated antigen-1, but the keratinocytes did not express significant levels of intercellular adhesion molecule-1, which was probably due to the inability of the malignant T cells to produce gamma interferon. These results support the concept that the inability of malignant T cells to enter the epidermis may contribute to emergence of more clinically aggressive T- cell clones that are no longer confined to the skin, but infiltrate the blood, lymph nodes, and viscera, as is seen in Sézary syndrome. (<i>JAMA</i>. 1989;261:2217-2221)
Therapy for β-Thalassemia -- A Paradigm for the Treatment of Genetic Disorders
Authors: George J. Dover, David Valle
Journal: New England Journal of Medicine (1994)

β-Thalassemia is one of the most common single-gene disorders. More than 100 mutations in or around the β-globin gene are known to cause decreased production of β-globin, which in turn leads to the excess accumulation of unstable α-globin chains, ineffective erythropoiesis, and shortened red-cell survival. Although the clinical severity of β-thalassemia varies considerably, most patients who are homozygous for β-thalassemia become dependent on transfusions and thus have the transfusion-related complications of iron overload, alloimmunization, and viral infection. Recent advances in basic and clinical research offer the clinician not only new approaches to the treatment of these patients but also the . . .
Intragenomic repair heterogeneity of DNA damage.
Authors: D A Scicchitano, P C Hanawalt
Journal: Environmental Health Perspectives (1992)

The mutagenic and carcinogenic consequences of unrepaired DNA damage depend upon its precise location with respect to the relevant genomic sites. Therefore, it is important to learn the fine structure of DNA damage, in particular, proto-oncogenes, tumor-suppressor genes, and other DNA sequences implicated in tumorigenesis. Both the introduction and the repair of many types of DNA lesions are heterogeneous with respect to chromatin structure and/or gene activity. For example, cyclobutane pyrimidine dimers are removed more efficiently from the transcribed than the nontranscribed strand of the dhfr gene in Chinese hamster ovary cells. In contrast, preferential strand repair of alkali-labile sites is not found at this locus. In mouse 3T3 cells, dimers are more efficiently removed from an expressed proto-oncogene than from a silent one. Persistent damage in nontranscribed domains may account for genomic instability in those regions, particularly during cell proliferation as lesions are encountered by replication forks. The preferential repair of certain lesions in the transcribed strands of active genes results in a bias toward mutagenesis owing to persistent lesions in the nontranscribed strands. Risk assessment in environmental genetic toxicology requires assays that determine effective levels of DNA damage of producing malignancy. The existence of nonrandom repair in the mammalian genome casts doubt on the reliability of overall indicators of carcinogen-DNA binding and lesion repair for such determinations. Tissue-specific and cell-specific differences in the coordinate regulation of gene expression and DNA repair may account for corresponding differences in the carcinogenic response to particular environmental agents.
Matrix Metalloproteinase Inhibition Attenuates Left Ventricular Remodeling and Dysfunction in a Rat Model of Progressive Heart Failure
Authors: J. Thomas Peterson, Hussein Hallak, Linda Johnson, Hua Li, Patrick M. O’Brien, Drago R. Sliskovic, Thomas M. A. Bocan, Mytsi L. Coker, Takuma Etoh, Francis G. Spinale
Journal: Circulation (2001)

Matrix metalloproteinase (MMP) activation contributes to tissue remodeling in several disease states, and increased MMP activity has been observed in left ventricular (LV) failure. The present study tested the hypothesis that MMP inhibition would influence LV remodeling and function in developing LV failure.LV size and function were measured in 5 groups of rats: (1) obese male spontaneously hypertensive heart failure rats (SHHF) at 9 months (n=10), (2) SHHF at 13 months (n=12), (3) SHHF rats treated with an MMP inhibitor during months 9 to 13 (PD166793 5 mg. kg(-1). d(-1) PO; n=14), (4) normotensive Wistar-Furth rats (WF) at 9 months (n=12), and (5) WF at 13 months (n=12). Plasma concentrations of the MMP inhibitor (116+/-11 micromol/L) reduced in vitro LV myocardial MMP-2 activity by approximately 100%. LV function and geometry were similar in WF rats at 9 and 13 months. LV peak +dP/dt was unchanged at 9 months in SHHF but by 13 months was reduced in the SHHF group compared with WF (3578+/-477 versus 5983+/-109 mm Hg/s, P</=0.05). LV volume measured at an equivalent ex vivo pressure (10 mm Hg) was increased in SHHF at 9 months compared with WF (443+/-12 versus 563+/-33 mL, P</=0.05) and increased further by 13 months (899+/-64 mL, P</=0.05). LV myocardial MMP-2 activity was increased by approximately 2-fold in SHHF at 9 and 13 months. With MMP inhibition, LV peak +dP/dt was similar to WF values and LV volume was reduced compared with untreated SHHF values (678+/-28 mL, P</=0.05).MMP activity contributes to LV dilation and progression to LV dysfunction in a rodent HF model, and direct MMP inhibition can attenuate this process.
"SOCIALIZED MEDICINE" AND "SOCIAL MEDICINE"
Authors: E. M. Bluestone
Journal: JAMA (1952)

To the Editor:—  Social medicine, which is the finest flower of modern medical practice, has been tarred of late with the brush of socialized medicine in a confusion of semantic errors, and much harm will be done if we do not lift this term out of the controversial atmosphere in which it now appears. The two should not be used indiscriminately and interchangeably. As matters now stand, some who are trying to save and perpetuate the term social medicine consider these terms antithetical, while others consider them synonymous. They are sometimes made to stand in relation to each other like the mountain of Ebal and the mountain of Gerizim. As a matter of fact, they stand for two different concepts, the one referring to its identity with government and the other indicating a wholesome and productive partnership between the two converging disciplines of sociology and medical practice. The two look
Hormone Replacement Therapy and Longitudinal Changes in Blood Pressure in Postmenopausal Women
Authors: Angelo Scuteri, Angelo J.G. Bos, Larry J. Brant, Laura Talbot, Edward G. Lakatta, Jerome L. Fleg
Journal: Annals of Internal Medicine (2001)

The incidence of hypertension in postmenopausal women exceeds that in age-matched men. Longitudinal studies relating hormone replacement therapy (HRT) to blood pressure changes are sparse.To investigate the association between HRT and longitudinal changes in blood pressure in postmenopausal women.Longitudinal observational study.Community-dwelling volunteers.226 healthy, normotensive postmenopausal women from the Baltimore Longitudinal Study of Aging with a mean (+/-SD) age of 64 +/- 10 years were followed for 5.7 +/- 5.3 years. Seventy-seven women used both estrogen and progestin, and 149 used neither.Lifestyle variables, blood pressure, and traditional cardiovascular risk factors were measured at baseline and approximately every 2 years thereafter.Systolic blood pressure at baseline was similar in HRT users and nonusers (133.9 +/- 16.0 mm Hg vs. 132.4 +/- 14.8 mm Hg). Over time, average systolic blood pressure increased less in HRT users than nonusers, independent of other cardiovascular risk factors, physical activity, and alcohol use. For example, HRT users who were 55 years of age at their first Baltimore Longitudinal Study of Aging visit experienced a 7.6-mm Hg average increase in systolic blood pressure over 10 years; in contrast, the average increase in nonusers was 18.7 mm Hg. The lesser increase in systolic blood pressure in HRT users was more evident at older age. Diastolic blood pressure, which did not change statistically over time in either group, was not associated with HRT.Postmenopausal women taking HRT have a smaller increase in systolic blood pressure over time than those not taking HRT. This difference is intensified at older ages.
EXPERIENCE WITH PHOTIC STIMULATION IN PSYCHIATRIC RESEARCH
Authors: GEORGE A. ULETT
Journal: American Journal of Psychiatry (1957)

Intermittent photic stimulation has been of value in psychiatric research in a number of areas which include: (1) the development of screening techniques based upon the EEG driving response and subjective responses to photic stimulation; (2) correlated studies of photic stimulation with psychological tests; (3) studies relating driving response to clinical symptomatology; (4) use in provoking paroxysmal or psychiatric symptoms; (5) use of photic stimulation, together with a convulsant drug to study differences in convulsive thresholds among patients of various diagnostic groups; (6) as a treatment method in photo-shock, and (7) for studies of the neurophysiology of learning.
Laser management of diabetic retinopathy
Authors: J. G F Dowler
Journal: Journal of the Royal Society of Medicine (2003)

The UK National Service Framework for Diabetes recommends nationwide screening of people with diabetes for development of sight-threatening retinopathy.1 All health workers who provide diabetes care require an understanding of the common ophthalmic treatments that can be offered for such disease. The principal conditions to consider are diabetic maculopathy and proliferative retinopathy.

In diabetic maculopathy, central vision may be compromised by macular (central retinal) oedema with varying degrees of ischaemia. The oedema may respond to laser therapy, ischaemia does not. Therapy takes the form of ‘focal’ (Figure 1) or ‘grid’ (Figure 2) macular laser, consisting of up to 200 small (e.g. 100 μm) gently applied burns to areas of central retinal thickening. This tends to encourage resolution of thickening.



Figure 1

Focal macular laser therapy for focal macular oedema. Fluorescein angiography reveals focal leakage from diabetic microvascular abnormalities (white arrow). Laser burns (white spots) are placed on the area of thickened retina. Colour version available ...





Figure 2

Grid macular laser therapy for diffuse macular oedema. Fluorescein angiography reveals diffuse leakage from diabetic microvascular abnormalities (white arrows). Laser burns (spots) are placed on the area of thickened retina. Colour version available ...



In proliferative retinopathy, central and peripheral vision may be compromised by bleeding from new vessels arising on the optic disc (NVD) or elsewhere in the retina (NVE). These vessels typically bleed because of the tendency of the overlying vitreous gel, to which the new vessels are attached, to retract, stretching vessels between vitreous and retina. Therapy takes the form of panretinal photocoagulation, in which perhaps 2000 large (e.g. 500 μm) burns, of greater intensity than employed in macular laser, are applied to retina outside the central thirty-degree zones (Figure ​(Figure3a3a​3a3b). 3b). This tends to encourage a reduction in the calibre of new vessels.



Figure 3a

Panretinal photocoagulation for proliferative retinopathy. Laser burns (spots) are placed outside central retina (a) as can be seen in the fluorescein angiogram





Figure 3b

Panretinal photocoagulation for proliferative retinopathy. Laser burns (spots) are placed outside central retina (b). Colour version available on [www.jrsm.org]
Use of an elemental diet (Vivonex) in the management of bile acid-induced diarrhoea.
Authors: L M Nelson, H A Carmichael, R I Russell, S T Atherton
Journal: Gut (1977)

The effect of a low fat containing elemental diet (Vivonex) on faecal bile acid excretion was studied in six patients with cholerheic diarrhoea, two normal controls, and four patients with non-cholerheic diarrhoea. The total faecal bile acid excretion for the patients with bile acid-induced diarrhoea was significantly reduced fron 6-37+/- 1-64 mmol/24 h (mean +/- SEM) to 2-70 +/- 1-12 mmol/24 h during Vivonex treatment (p less than 0-05). A marked improvement in the diarrhoea of these patients occurred; the number of stools per day decreased and there was less urgency associated with the diarrhoea. No significant reduction in faecal bile acid excretion was observed for the control and non-cholerheic diarrhoea groups. An elemental diet of this type may be of value in the management of patients with bile acid-induced diarrhoea unresponsive to other forms of therapy, and may be of particular value in patients with Crohn9s disease.
Thrombocytopenic Purpura Associated with Tuberculous Splenomegaly and Tuberculosis of the Bone Marrow
Authors: Benjamin A. Gouley, Nathan Blumberg, Reginald J. Grayson
Journal: New England Journal of Medicine (1949)

WHEN splenectomy in thrombocytopenic patients has on occasion revealed the tuberculous origin of a splenic enlargement, the post-operative results have been dramatic. Surgical intervention has removed both a fatal tuberculoma and a serious blood dyscrasia.1 , 2 Further knowledge of this apparently rare combination will probably show that such a surgical "cure" is not to be anticipated in every case because of developments such as those reported below — namely, the association of "primary" tuberculosis of the spleen, thrombocytopenic purpura and a widespread tuberculosis of the bone marrow. We are unable to find a similar grouping of such lesions, which almost certainly . . .
Headache: Diagnosis and Treatment
Authors: Dhirendra S. Bana
Journal: JAMA (1994)

Headache management is often as much an art as a science. Although genetic testing may soon provide a powerful tool, physicians as yet lack tests for headache diagnosis and must rely almost entirely on the subjective information obtained from the patient history and their own personal observations made by examination during the course of the headache. The disabling and chronic pain of those afflicted with severe headache is often coupled with the emotional responses of overreaction, depression, and withdrawal, with dev
Acute Regulation of Epithelial Sodium Channel by Anionic Phospholipids
Authors: He-Ping Ma, Douglas C. Eaton
Journal: Journal of the American Society of Nephrology (2005)

Anionic phospholipids such as phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3) are normally located in the inner leaflet of the plasma membrane, where these anionic phospholipids can regulate transmembrane proteins, including ion channels and transporters. Recent work has demonstrated that (1) ATP inhibits the renal epithelial sodium channel (ENaC) via a phospholipase C–dependent pathway that reduces PIP2, (2) aldosterone stimulates ENaC via phosphoinositide 3-kinase, and (3) PIP2 and PIP3 regulate ENaC. Several lines of evidence show that ATP stimulation of purinergic P2Y receptors hydrolyzes PIP2 and that aldosterone stimulation of steroid receptors induces PIP3 formation. These studies together suggest that one primary mechanism for regulating ENaC is by alteration of anionic phospholipids and that the receptor-mediated and hormonal regulation of ENaC works through a variety of signaling pathways, but many of these pathways finally alter ENaC activity by regulating the formation or degradation of anionic phospholipids. Therefore, changes in the concentration of PIP2 and PIP3 are hypothesized to participate in the regulation of ENaC by purinergic and corticoid receptors. The underlying mechanism may be associated with a physical interaction of the positively charged cytoplasmic domains of the β- and γ-ENaC with the negatively charged membrane phospholipids. The exact nature of this interaction will require further investigation.
Should Physicians Prescribe Prayer for Health? Spiritual Aspects of Well-being Considered
Authors: Charles Marwick
Journal: JAMA (1995)

SHOULD PHYSICIANS write "prayer" or "more frequent participation in religious observances" when prescribing for their patients? Some physicians, chaplains, pastoral workers, and sociologists would answer affirmatively. "There is at work an integration of medicine with religion, of spirituality with medical practice, the twin guardians of healing through the ages," said Dale Matthews, MD, associate professor of medicine, Georgetown University School of Medicine, Washington, DC, at a meeting presented as "the first conference on Spiritual Dimensions in Clinical Research." The meeting, meant to "explore the current body of knowledge and emerging trends in the area of spirituality and health," was held in Leesburg, Va, by the National Institute for Healthcare Research, a private organization devoted to examining the role of religious commitment in improving patient care and well-being. The agenda concentrated on three general areas: alcohol and other drug abuse, mental health, and physical health. Conferees reviewed the current status of
A monoclonal antibody raised by immunising mice with group A streptococci binds to agalactosyl IgG from rheumatoid arthritis.
Authors: G A Rook, J Steele, T Rademacher
Journal: Annals of the Rheumatic Diseases (1988)

It was shown recently that the IgG of patients with rheumatoid arthritis tends to lack the terminal galactose normally present on the conserved N-linked oligosaccharide situated on the CH2 domain. This results in the exposure of a terminal N-acetylglucosamine linked beta 1-2 to mannose. It is reported here that mice immunised with the peptidoglycan/polysaccharide complex of group A streptococci can be used as a source of monoclonal antibodies binding to this epitope. It may be significant that the organism responsible for rheumatic fever evokes antibodies binding to an abnormality of IgG found in rheumatoid arthritis.
Emergency naloxone for heroin overdose: Over the counter availability needs careful consideration
Authors: Andrew Byrne
Journal: BMJ (2006)

EDITOR—In their support for making naloxone freely available, Strang et al state that naloxone saves lives,1 yet it can also be dangerous, even lethal.2 Many other reports of adverse reactions are from use in health care, so more harm is likely in the hands of untrained people, especially as some may be intoxicated themselves when the drug is used. This needs to be carefully balanced …
Withdrawal from long-term benzodiazepine treatment.
Authors: H Petursson, M H Lader
Journal: BMJ (1981)

Long-term, normal-dose benzodiazepine treatment was discontinued in 16 patients who were suspected of being dependent on their medication. The withdrawal was gradual, placebo-controlled, and double-blind. All the patients experienced some form of withdrawal reaction, which ranged from anxiety and dysphoria to moderate affective and perceptual changes. Symptom ratings rose as the drugs were discontinued, but usually subsided to prewithdrawal levels over the next two to four weeks. Other features of the withdrawal included disturbance of sleep and appetite and noticeable weight loss. Electroencephalography showed appreciable reduction in fast-wave activity as the drugs were withdrawn, and an improvement in psychological performance was recorded by the Digit Symbol Substitution Test. Because of the risk of dependence on benzodiazepines these agents should probably not be given as regular daily treatment for chronic anxiety.
Consistency of SINE Insertion Topology and Flanking Sequence Tree: Quantifying Relationships Among Cetartiodactyls
Authors: J. Koji Lum, Masato Nikaido, Mitsuru Shimamura, Hidetoshi Shimodaira, Andrew M. Shedlock, Norihiro Okada, Masami Hasegawa
Journal: Molecular Biology and Evolution (2000)

Short interspersed nuclear elements (SINEs) have been used to generate unambiguous phylogenetic topologies relating eukaryotic taxa. The irreversible nature of SINE retroposition is supported by a large body of comparative genome data and is a fundamental assumption inherent in the value of this qualitative method of inference. Here, we assess the key assumption of unidirectional SINE insertion by comparing the SINE insertion–derived topology and the phylogenetic tree based on seven independent loci of five taxa in the order Cetartiodactyla (Cetacea + Artiodactyla). The data sets and analyses were largely independent, but the loci were, by definition, linked, and thus their consistency supported an irreversible pattern of SINE retroposition. Moreover, our analyses of the flanking sequences provided estimates of divergence times among cetartiodactyl lineages unavailable from SINE insertion analysis alone. Unexpected rate heterogeneity among sites of SINE-flanking sequences and other noncoding DNA sequences were observed. Sequence simulations suggest that this rate heterogeneity may be an artifact resulting from the inaccuracies of the substitution model used.
Splenic stroma drives mature dendritic cells to differentiate into regulatory dendritic cells
Authors: Minghui Zhang, Hua Tang, Zhenhong Guo, Huazhang An, Xuejun Zhu, Wengang Song, Jun Guo, Xin Huang, Taoyong Chen, Jianli Wang, Xuetao Cao
Journal: Nature Immunology (2004)