tbuckley/cabot-search huggingface dataset:
NUTRITIONAL EDEMA IN THE DOG
Authors: A. A. Weech, E. Goettsch, E. B. Reeves
Journal: The Journal of Experimental Medicine (1935)

The manner in which edema develops in dogs maintained on a diet low in protein is described. Pre-edematous fullness of the tissues is observed for some weeks before palpable edema develops. The state of pre-edema does not merge gradually with that of true edema but rather the transition is relatively sudden. Among twenty dogs the time required for the production of edema varied from 35 to 100 days and averaged 61 days. With three animals in which the nitrogen metabolism was studied during the period before edema had developed, the observed loss of weight was consistently less than the theoretical loss of weight calculated from the negative nitrogen balance. Reasons are given for interpreting the discrepancy as evidence of increasing retention of fluid during the stage of pre-edema. In general the weight curve does not rise during the transition from pre-edema to edema. However, the weight does increase rapidly when fluid is accumulating in the peritoneal cavity. The level of serum albumin which is critical for the development of edema varied between 1.04 and 2.17 gm. per cent. The range is sufficiently wide to suggest the existence of other factors of importance in determining the exact time of appearance of edema. During the phase of recovery the level of albumin which is critical for the disappearance of edema may be appreciably higher than the level which was critical for the formation of edema. Among thirty samples of edema fluid the protein concentration was from 0.02 to 0.72 gm. per cent. The average protein level was 0.230 and the median level 0.165 gm. per cent. A positive correlation is not demonstrable between the duration of edema and the protein content of edema fluid. A difference in behavior toward fluid retention between subcutaneous tissue and peritoneal cavity is pointed out. Subcutaneous tissue is more resistant to acute stress and less resistant to prolonged or repeated stress than the peritoneal cavity. The rôle of tissue pressure in the etiology of edema is discussed. It is suggested that the critical level of protein in the serum is the concentration which permits the attainment in the tissue spaces of mechanical pressure great enough to break down the restraining action of the connective tissue boundaries of the spaces.
Major Histocompatibility Complex Class II Presentation of Cell-associated Antigen Is Mediated by CD8α+ Dendritic Cells In Vivo
Authors: Yanet Valdez, Weiling Mah, Monte M. Winslow, Lixin Xu, Peter Ling, Sarah E. Townsend
Journal: The Journal of Experimental Medicine (2002)

Antigen-specific B cells express major histocompatibility complex class II and can present antigen directly to T cells. Adoptive transfer experiments using transgenic B and T cells demonstrated that antigen-specific B cells can also efficiently transfer antigen to another cell for presentation to T cells in vivo. To identify the antigen-presenting cell that receives antigens from B cells, a strategy was developed to follow the traffic of B cell–derived proteins in vivo. B cells were labeled with the fluorescent dye CFSE and loaded with antigen, before adoptive transfer into recipient mice. Populations of splenocytes from the recipient mice were later assayed for the presence of fluorescent proteins and for the ability to activate T cells. A small number of CD8α+CD4−CD11blo dendritic cells (DCs) contain proteins transferred from B cells and these DCs effectively present antigens derived from the B cells to T cells. The results suggest that CD8α+ DCs sample the cells and membranes in their environment for presentation to T cells circulating through the T cell zone. This function of CD8α+ DCs may be relevant to the priming of an immune response or the induction of T cell tolerance.
SIMPLE PREDICTION OF LONG-TERM MORTALITY AMONG HYPERTENSIVE PATIENTS WITH CORONARY ARTERY DISEASE: NEW DATA FROM AN EXTENDED FOLLOW-UP OF THE INTERNATIONAL VERAPAMIL-SR/TRANDOLAPRIL STUDY (INVEST)
Authors: Anthony A. Bavry, Yan Gong, Dharam Kumbhani, Peter Kowey, Eranga Haththotuwa, Eileen Handberg
Journal: Journal of the American College of Cardiology (2012)
Hepatocellular carcinoma in Budd-Chiari syndrome: characteristics and risk factors
Authors: R Moucari, P-E Rautou, D Cazals-Hatem, A Geara, C Bureau, Y Consigny, C Francoz, M-H Denninger, V Vilgrain, J Belghiti, F Durand, D Valla, A Plessier
Journal: Gut (2008)

<h3>Background and aim:</h3> To analyse the characteristics of and the factors associated with the development of hepatocellular carcinoma (HCC) in patients with Budd–Chiari syndrome (BCS). <h3>Patients and methods:</h3> 97 consecutive patients with BCS and a follow-up ⩾1 year were evaluated retrospectively. Liver nodules were evaluated using serum α-fetoprotein (AFP) level and imaging features (CT/MRI). Biopsy of nodules was obtained when one of the following criteria was met: number ⩽3, diameter ⩾3 cm, heterogeneity, washout on portal venous phase, increase in size on surveillance, or increase in AFP level. <h3>Results:</h3> Patients were mainly Caucasian (69%) and female (66%). Mean age at the diagnosis of BCS was 35.8 (SE 1.2 years), and median follow-up 5 years (1–20 years). The inferior vena cava (IVC) was obstructed in 13 patients. Liver nodules were found in 43 patients, 11 of whom had HCC. Cumulative incidence of HCC during follow-up was 4%. Liver parenchyma adjacent to HCC showed cirrhosis in nine patients. HCC was associated with male sex (72.7% <i>v</i> 29.0%, p = 0.007); factor V Leiden (54.5% <i>v</i> 17.5%, p = 0.01); and IVC obstruction (81.8% <i>v</i> 4.6%, p&lt;0.001). Increased levels of serum AFP were highly accurate in distinguishing HCC from benign nodules: PPV = 100% and NPV = 91% for a cut-off level of 15 ng/ml. <h3>Conclusion:</h3> The incidence of HCC in this large cohort of BCS patients was similar to that reported for other chronic liver diseases. IVC obstruction was a major predictor for HCC development. Serum AFP appears to have a higher utility for HCC screening in patients with BCS than with other liver diseases.
Mismatch Repair Deficiency Does Not Mediate Clinical Resistance to Temozolomide in Malignant Glioma
Authors: Jill A. Maxwell, Stewart P. Johnson, Roger E. McLendon, David W. Lister, Krystle S. Horne, Ahmed Rasheed, Jennifer A. Quinn, Francis Ali-Osman, Allan H. Friedman, Paul L. Modrich, Darell D. Bigner, Henry S. Friedman
Journal: Clinical Cancer Research (2008)

A major mechanism of resistance to methylating agents, including temozolomide, is the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT). Preclinical data indicates that defective DNA mismatch repair (MMR) results in tolerance to temozolomide regardless of AGT activity. The purpose of this study was to determine the role of MMR deficiency in mediating resistance in samples from patients with both newly diagnosed malignant gliomas and those who have failed temozolomide therapy.The roles of AGT and MMR deficiency in mediating resistance in glioblastoma multiforme were assessed by immunohistochemistry and microsatellite instability (MSI), respectively. The mutation status of the MSH6 gene, a proposed correlate of temozolomide resistance, was determined by direct sequencing and compared with data from immunofluorescent detection of MSH6 protein and reverse transcription-PCR amplification of MSH6 RNA.Seventy percent of newly diagnosed and 78% of failed-therapy glioblastoma multiforme samples expressed nuclear AGT protein in > or = 20% of cells analyzed, suggesting alternate means of resistance in 20% to 30% of cases. Single loci MSI was observed in 3% of patient samples; no sample showed the presence of high MSI. MSI was not shown to correlate with MSH6 mutation or loss of MSH6 protein expression.Although high AGT levels may mediate resistance in a portion of these samples, MMR deficiency does not seem to be responsible for mediating temozolomide resistance in adult malignant glioma. Accordingly, the presence of a fraction of samples exhibiting both low AGT expression and MMR proficiency suggests that additional mechanisms of temozolomide resistance are operational in the clinic.
Mental Disorders and the Use of Alternative Medicine: Results From a National Survey
Authors: Jürgen Unützer, Ruth Klap, Roland Sturm, Alexander S. Young, Tonya Marmon, Jess Shatkin, Kenneth B. Wells
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The study examined the relationship between mental disorders and the use of complementary and alternative medicine. METHOD: Data from a national household telephone survey conducted in 1997–1998 (N=9,585) were used to examine the relationships between use of complementary and alternative medicine during the past 12 months and several demographic variables and indicators of mental disorders. Structured diagnostic screening interviews were used to establish diagnoses of probable mental disorders. RESULTS: Use of complementary and alternative medicine during the past 12 months was reported by 16.5% of the respondents. Of those respondents, 21.3% met diagnostic criteria for one or more mental disorders, compared to 12.8% of respondents who did not report use of alternative medicine. Individuals with panic disorder and major depression were significantly more likely to use alternative medicine than those without those disorders. Respondents with mental disorders who reported use of alternative medicine were as likely to use conventional mental health services as respondents with mental disorders who did not use alternative medicine. CONCLUSIONS: We found relatively high rates of use of complementary and alternative medicine among respondents who met criteria for common mental disorders. Practitioners of alternative medicine should look for these disorders in their patients, and conventional medical providers should ask their depressed and anxious patients about the use of alternative medicine. More research is needed to determine if individuals with mental disorders use alternative medicine because conventional medical care does not meet their health care needs.
Varied Effects of Atypical Neuroleptics on P50 Auditory Gating in Schizophrenia Patients
Authors: Lawrence E. Adler, Ann Olincy, Ellen M. Cawthra, Kara A. McRae, Josette G. Harris, Herbert T. Nagamoto, Merilyne C. Waldo, Mei-Hua Hall, Amanda Bowles, Laurie Woodward, Randal G. Ross, Robert Freedman
Journal: American Journal of Psychiatry (2004)

Sensory gating deficits found in schizophrenia can be assessed by using a paired auditory stimulus paradigm to measure auditory evoked response. The ratio of the P50 response amplitude of the second or test stimulus to that of the first or conditioning stimulus is expressed as a percentage. Normal subjects generally suppress the second response and typically have ratios of less than 40%. Subjects with schizophrenia and half their first-degree relatives have deficits in sensory gating, with P50 ratios that are generally greater than 50%. Treatment with typical neuroleptics does not reverse this deficit. However, previous studies have shown that treatment with clozapine, an atypical neuroleptic, ameliorates this deficit in clinically responsive patients. This study sought to determine whether other atypical neuroleptics improve P50 ratios.P50 evoked potential recordings were obtained from 132 patients with schizophrenia and 177 healthy comparison subjects. Eighty-eight patients were being treated with atypical neuroleptics (clozapine [N=26], olanzapine [N=31], risperidone [N=22], and quetiapine [N=9]). Thirty-four patients were taking typical neuroleptics, and 10 were unmedicated.Healthy subjects exhibited P50 suppression that was significantly better than the schizophrenia patients receiving typical neuroleptics (mean=19.8% [SD=21.0%] versus 110.1% [SD=87.9%]). Patients receiving atypical neuroleptics had a mean P50 ratio that fell between these two means (mean=70.4%, SD=53.7%). When patients treated with different atypical neuroleptics were compared, only the clozapine group had mean P50 ratios that were in the normal range. All other groups exhibited auditory P50 response inhibition that was significantly poorer than that of the healthy subjects.Improvement in P50 gating appears to be greatest in patients treated with clozapine.
Effect of hematin administration to patients with protoporphyria and liver disease
Authors: Joseph R. Bloomer, Claus A. Pierach
Journal: Hepatology (1982)

Hepatic damage in protoporphyria appears to be caused by a toxic effect of excess protoporphyrin. Therapy which reduces the formation of excess protoporphyrin may, therefore, be helpful. We examined the effects of hematin administered i.v. to two patients with protoporphyria and decompensated cirrhosis. Neither patient had side effects from the compound or manifested signs of toxicity. The vascular disappearance of hematin in one patient was similar to that in patients with porphyria who do not have structural liver disease. In both patients, biochemical changes occurred that were compatible with a reduced rate of protoporphyrin formation. Thus, hematin administration may be useful in treating patients with protoporphyria who develop liver disease.
The transcription factor JunD mediates transforming growth factor -induced fibroblast activation and fibrosis in systemic sclerosis
Authors: K. Palumbo, P. Zerr, M. Tomcik, S. Vollath, C. Dees, A. Akhmetshina, J. Avouac, M. Yaniv, O. Distler, G. Schett, J. H. W. Distler
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objectives</h3> Transforming growth factor β (TGFβ) has been identified as a key player in fibrotic diseases. However, the molecular mechanisms by which TGFβ activates fibroblasts are incompletely understood. Here, the role of JunD, a member of the activator protein 1 (AP-1) family of transcription factors, as a downstream mediator of TGFβ signalling in systemic sclerosis (SSc), was investigated. <h3>Methods</h3> The expression of JunD was analysed by real-time PCR, immunofluorescence, western blotting and immunohistochemistry. The canonical Smad pathway was specifically targeted by small interfering (si)RNA. The expression of extracellular matrix proteins in JunD deficient (JunD<sup>−/−</sup>) fibroblasts was analysed by real-time PCR and hydroxyproline assays. The mouse model of bleomycin-induced dermal fibrosis was used to assess the role of JunD in experimental fibrosis. <h3>Results</h3> JunD was overexpressed in SSc skin and in cultured fibroblasts in a TGFβ dependent manner. The expression of JunD colocalised with pSmad 3 in fibrotic skin and silencing of Smad 3 or Smad 4 by siRNA prevented the induction of JunD by TGFβ. JunD<sup>−/−</sup> fibroblasts were less responsive to TGFβ and released less collagen upon stimulation with TGFβ. Moreover, JunD<sup>−/−</sup> mice were protected from bleomycin-induced fibrosis with reduced dermal thickening, decreased myofibroblast counts and lower collagen content of lesional skin. <h3>Conclusions</h3> These data demonstrate that JunD is overexpressed in SSc and that JunD is a mediator of the profibrotic effects of TGFβ. Considering that inhibitors of AP-1 signalling have recently been developed and are available for clinical trials in SSc, these findings may have translational implications.
Soluble Tumor Necrosis Factor Receptor 2 Is Independently Associated With Brachial-Ankle Pulse-Wave Velocity in Nonobese Japanese Type 2 Diabetic Patients
Authors: Minako Ohgushi, Ataru Taniguchi, Mitsuo Fukushima, Yoshikatsu Nakai, Akira Kuroe, Michihiro Ohya, Yutaka Seino
Journal: Diabetes Care (2006)

Type 2 diabetes is associated with high mortality and morbidity due to atherosclerosis. Biermen (1) estimated that typical risk factors, including blood pressure, cholesterol, and smoking, can account for no more than 30% of excess cardiovascular risk factor in diabetic patients. Thus, other factors seem to play a role in the progression of atherosclerosis in diabetes.

Aortic stiffness measured by pulse- wave velocity (PWV) is shown to be highly predictive of cardiovascular mortality in type 2 diabetic patients (2). While age and blood pressure are shown …
AMNIOCENTESES AND THE ALPHA-FETOPROTEIN SCREENING PROGRAMME
Authors: M.A. Ferguson-Smith, A.A.M. Gibson, C.R. Whitfield, J.G. Ratcliffe, C.O. Carter, K.A. Evans, Nicholas Wald, Sheila Barker, Howard Cuckle, David Brock, Gordon Stirrat
Journal: The Lancet (1979)
Benzodiazepines in a Health-Catalog Product
Authors: Stuart C. Bogema
Journal: JAMA (1990)

<h3>To the Editor.—</h3> A manufacturing company in the Northwest administered a routine preemployment drug test to a 56-year-old engineer. Its results were reported to the medical review officer by the testing laboratory as "positive for benzodiazepines" with the finding of oxazepam, 310 ng/mL, and nordiazepam, 150 ng/mL, on gas chromatography—mass spectrometry confirmation. The prospective employee convincingly denied any use of a prescription medicine, including a benzodiazepine. A repeated test was requested on the retained positive urine sample. It too was reported positive for a benzodiazepine. The prospective employee reported that he had regularly used a nonprescription health product obtained by catalog from a California address. It was a dark-brown, round pill labeled "NAN-LIEN CHUIFONG TOUKUWAN" that had been recommended to him by a colleague at work to treat his chronic neck pains. A sample submitted to the laboratory was analyzed by fullscan gas chromatography-mass spectrometry (Hewlett-Packard 5970). It was
Occlusion of the Inferior Vena Cava
Authors: Leonard Berlin, Irving Waldman, John K. Fong
Journal: JAMA (1965)

Five cases of obstruction of the inferior vena cava were observed. This condition is most commonly caused by thrombophlebitis. It is usually associated with only mild symptoms and signs, since collateral circulation is abundant and competent. Occasionally, however, the obstruction may cause edema of the leg, varicosities, dilatation of the superficial abdominal veins, varicocele, and hemorrhoids, and may even be fatal when the occlusion extends proximal to the renal veins. A definite diagnosis of occlusion can be made only by inferior vena cavography.
Tumor-Infiltrating FOXP3<sup>+</sup> T Regulatory Cells Show Strong Prognostic Significance in Colorectal Cancer
Authors: Paul Salama, Michael Phillips, Fabienne Grieu, Melinda Morris, Nik Zeps, David Joseph, Cameron Platell, Barry Iacopetta
Journal: Journal of Clinical Oncology (2008)

To determine the prognostic significance of FOXP3(+) lymphocyte (Treg) density in colorectal cancer compared with conventional histopathologic features and with CD8(+) and CD45RO(+) lymphocyte densities.Tissue microarrays and immunohistochemistry were used to assess the densities of CD8(+), CD45RO(+), and FOXP3(+) lymphocytes in tumor tissue and normal colonic mucosa from 967 stage II and stage III colorectal cancers. These were evaluated for associations with histopathologic features and patient survival.FOXP3(+) Treg density was higher in tumor tissue compared with normal colonic mucosa, whereas CD8(+) and CD45RO(+) cell densities were lower. FOXP3(+) Tregs were not associated with any histopathologic features, with the exception of tumor stage. Multivariate analysis showed that stage, vascular invasion, and FOXP3(+) Treg density in normal and tumor tissue were independent prognostic indicators, but not CD8(+) and CD45RO(+). High FOXP3(+) Treg density in normal mucosa was associated with worse prognosis (hazard ratio [HR] = 1.51; 95% CI, 1.07 to 2.13; P = .019). In contrast, a high density of FOXP3(+) Tregs in tumor tissue was associated with improved survival (HR = 0.54; 95% CI, 0.38 to 0.77; P = .001).FOXP3(+) Treg density in normal and tumor tissue had stronger prognostic significance in colorectal cancer compared with CD8(+) and CD45RO(+) lymphocytes. The finding of improved survival associated with a high density of tumor-infiltrating FOXP3(+) Tregs in colorectal cancer contrasts with several other solid cancer types. The inclusion of FOXP3(+) Treg density may help to improve the prognostication of early-stage colorectal cancer.
Phase I and Pharmacologic Study of Oral ZD9331, A Novel Nonpolyglutamated Thymidylate Synthase Inhibitor, in Adult Patients With Solid Tumors
Authors: Maja J.A. de Jonge, Cornelis J.A. Punt, Alex Sparreboom, André S.T. Planting, M.E.W.J. Peters, Jacqueline van de Schraaf, Ann Jackman, Rob Smith, Pieter H.M. de Mulder, Jaap Verweij
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To assess the toxicity profile and dose-limiting toxicities (DLTs), to determine the maximum-tolerated dose, and to study the pharmacokinetics of ZD9331 when administered orally to patients with advanced solid tumors. PATIENTS AND METHODS: Patients were treated with oral ZD9331 given once daily (od) or twice daily (bid) for 5, 7, or 10 days; cycles were repeated every 21 days at doses ranging from 2.5 to 40 mg. For pharmacokinetic analysis, plasma sampling was performed during the first course and assayed using a validated liquid chromatographic–tandem mass spectrometry assay. Plasma levels of 2′-deoxyuridine were measured as a surrogate marker for TS inhibition. RESULTS: Forty-two patients received a total of 166 courses. The DLTs were myelosuppression and skin rash. Dose escalation of oral ZD9331 from 2.5 to 40 mg, as a single daily dose, resulted in a less than proportional increase in the plasma area under the concentration-time curve of ZD9331. The plasma drug exposure per cycle for the schedules 20 mg od for 5 days, 10 mg od for 10 days, and 10 mg bid for 5 days, all resulting in a total dose per cycle of 100 mg, were comparable. One partial response was noted in a patient with gastric cancer. CONCLUSION: DLTs in this phase I study of oral ZD9331 were myelosuppression and skin toxicity. The recommended dose for phase II studies of oral ZD9331 is 20 mg od for 5 consecutive days, every 3 weeks.
Screening Pelvic Examination in Adult Women: A Clinical Practice Guideline From the American College of Physicians
Authors: Amir Qaseem, Linda L. Humphrey, Russell Harris, Melissa Starkey, Thomas D. Denberg
Journal: Annals of Internal Medicine (2014)

Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the utility of screening pelvic examination for the detection of pathology in asymptomatic, nonpregnant, adult women. Methods: This guideline is based on a systematic review of the published literature in the English language from 1946 through January 2014 identified using MEDLINE and hand-searching. Evaluated outcomes include morbidity; mortality; and harms, including overdiagnosis, overtreatment, diagnostic procedure–related harms, fear, anxiety, embarrassment, pain, and discomfort. The target audience for this guideline includes all clinicians, and the target patient population includes asymptomatic, nonpregnant, adult women. This guideline grades the evidence and recommendations using the ACP's clinical practice guidelines grading system. Recommendation: ACP recommends against performing screening pelvic examination in asymptomatic, nonpregnant, adult women (strong recommendation, moderate-quality evidence).