tbuckley/cabot-search huggingface dataset:
Nitric oxide regulates basal systemic and pulmonary vascular resistance in healthy humans.
Authors: J S Stamler, E Loh, M A Roddy, K E Currie, M A Creager
Journal: Circulation (1994)

BACKGROUND The endothelium synthesizes and releases a relaxing factor with the physiochemical properties of nitric oxide (NO). However, the role of endothelium-derived NO in the basal regulation of systemic and pulmonary vascular resistance in humans is not known. Our primary objectives were to determine the effects of inhibiting NO synthesis on blood pressure and systemic vascular resistance and to establish the role of endothelium-derived NO in the regulation of normoxic pulmonary vascular tone. METHODS AND RESULTS We studied the systemic and pulmonary hemodynamic effects of NG-monomethyl-L-arginine (L-NMMA, 0.03 to 1.0 mg.kg-1.min-1 IV), an NO synthase inhibitor, in 11 healthy volunteers, aged 33 +/- 2 years. An arterial cannula and a pulmonary artery catheter were placed in each subject to measure blood pressure, pulmonary artery pressure, and pulmonary capillary wedge pressure. Cardiac output was determined by the Fick technique, and systemic and pulmonary vascular resistances were calculated. Serum NO levels (free and protein bound) were measured by chemiluminescence in 5 subjects. Six of the subjects also received phenylephrine (25 to 100 micrograms/min IV) to compare the cardiac hemodynamic effects of L-NMMA with those of a direct-acting vasoconstrictor. L-NMMA caused dose-dependent increases in both blood pressure and systemic vascular resistance. At the highest dose of L-NMMA, there was a 15.5 +/- 1.3% increase in mean blood pressure and a 63.4 +/- 8.2% increase in systemic vascular resistance (each P &lt; .01). Pulmonary vascular resistance increased 39.8 +/- 9.4% (P &lt; .01), whereas mean pulmonary artery pressure did not change. Administration of L-NMMA also reduced cardiac output by 27.8 +/- 2.9% and stroke volume by 15.4 +/- 3.5% (each P &lt; .01). Serum NO levels decreased 65 +/- 10% from basal values (P &lt; .05), confirming inhibition of endogenous NO production. Phenylephrine increased blood pressure to a level comparable to that observed with L-NMMA. The decline in stroke volume was greater with L-NMMA than with phenylephrine (P &lt; .01). CONCLUSIONS This study demonstrates that basal release of endothelium-derived NO is directly involved in the determination of systemic vascular resistance and, therefore, blood pressure in healthy humans. In addition, NO regulates basal normoxic pulmonary vascular tone. The complex hemodynamic effects of NO are composite properties of its actions on systemic and pulmonary vascular resistance and cardiac function.
DEXAMETHASONE-RESPONSIVE HYPERTENSION IN YOUNG WOMEN WITH SUPPRESSED RENIN AND ALDOSTERONE
Authors: W.H.L. Hoefnagels, J.A. Hofman, A.G.H. Smals, J.I.M. Drayer, P.W.C. Kloppenborg, ThJ. Benraad
Journal: The Lancet (1978)
Anisotropic Reentry in a Perfused 2-Dimensional Layer of Rabbit Ventricular Myocardium
Authors: Martin J. Schalij, Lucas Boersma, Maya Huijberts, Maurits A. Allessie
Journal: Circulation (2000)

Anisotropy creates nonuniformity in electrical propagation and may contribute to the occurrence of unidirectional conduction block and reentry. We describe the characteristics of reentrant tachycardia in a 2D layer of anisotropic ventricular myocardium.A Langendorff-perfused epicardial sheet (1.0+/-0.4 mm, n=35) was created by freezing the intramural layers of the rabbit left ventricle. Epicardial activation maps were constructed by use of different high-resolution mapping arrays connected to a mapping system. In 5 experiments, monophasic action potentials were recorded. In the intact left ventricle, no arrhythmias except VF could be induced. After freezing, programmed electrical stimulation or rapid pacing led to the induction of sustained VT (cycle length 130+/-11 ms). VT was caused by reentry around a functional line of block oriented parallel to the epicardial fiber direction. Action potential recordings demonstrated that the central line of block was kept refractory by electrotonic currents generated by the depolarization waves propagating at either side of the line of block. At the pivot points of the line of block, the pronounced curvature of the turning wave and abrupt loading changes created an excitable gap of 30 ms in the reentrant pathway.In uniform anisotropic myocardium, reentry around a functional Z-shaped line of block may occur. The core of the circuit is kept refractory by electrotonic currents. The pronounced wave-front curvature and abrupt loading changes at the pivot points cause local conduction delay and create a small excitable gap.
EFFECTS OF DIET ON THE DEVELOPMENT AND STRUCTURE OF THE UTERUS
Authors: M. Campbell
Journal: BMJ (1907)

J 1229 thought further that the strain of another four,months of pregnancy, increasing, as inevita-bly it must, during the latter part of the term, would be too much for the weakened heart, and that, therefore, it was justifiable to terminate the pregnancy.If you decide to induce abortion in one of these cases, then the best method is to give an anaesthetic, to dilate the cervix, and to empty the uterus at one sitting.The class of case, then, in which abortion thould be induced, is that in which ordinary medicinal treatment has produced no or only very little improvement in the general symptoms, and in which no further improvement in the cardiac condition is likely, so that it is essential that the strain of a long pregnancy should be avoided if possible.The following case is an illustration of the class in which premature labour may be induced.
The Diabetic Pancreas
Authors: David L. Horwitz
Journal: JAMA (1986)

The pace of diabetes research has shown tremendous acceleration. In the past decade, we have seen the classification of diabetes into types I and II, along with more specific definition of a number of minor types of diabetes. Methodology for studying the immunology and cell biology of diabetes has improved tremendously, leading to an increased understanding of the pathogenesis and, to some extent, the etiology of both types of diabetes. Therefore, a new edition of<i>The Diabetic Pancreas</i>, first published in 1977, is particularly welcome. The primary strength of this book is in its description of the morphology of the endocrine pancreas. In one volume can be found comprehensive descriptions of normal islet cell histology and ultrastructure, islets in both types of diabetes, and islets in a number of other conditions related to diabetes, such as infants of diabetic mothers, hemochromatosis, and viral diabetes. Comprehensive descriptions of comparative islet morphology
Surgeons at the Bailey: English Forensic Medicine to 1878
Authors: W. F. Bynum
Journal: JAMA (1986)

The Guildhall Library in London contains a magnificent collection of books and manuscripts pertaining to all aspects of English and especially London history. For the past three decades or so, there have been few more faithful users of the library's holdings than Dr Forbes, long-time professor of anatomy and now a senior research scholar in the history of medicine at Yale. A steady stream of books and articles has established him as one of the chief chroniclers of health and disease and life and death in the English capital from early modern times until the 19th century. His work has been characterized by the patient exploitation of the raw material of social, demographic, and medical history: parish records of births, marriages, and deaths; reports of coroners' inquests; and the accounts of trials, especially those contained in the<i>Old Bailey Sessions Papers</i>, a vast series of printed transcripts, dating from 1684,
Long-Term Outcome of Patients with Relapsed and Refractory Germ Cell Tumors Treated with High-Dose Chemotherapy and Autologous Bone Marrow Rescue
Authors: E. Randolph Broun, Craig R. Nichols, Patricia Kneebone, Stephen D. Williams, Patrick J. Loehrer, Lawrence H. Einhorn, Guido J. K. Tricot
Journal: Annals of Internal Medicine (1992)

Objective: To review the long-term outcome of patients with recurrent and refractory germ cell tumors treated with high-dose chemotherapy and autologous bone marrow rescue. Design: Cohort study. Setting: A university hospital. Patients: Forty consecutive patients with recurrent or refractory germ cell tumors treated at Indiana University between September 1986 and June 1989. Interventions: Patients were treated with high-dose carboplatin (900 to 2000 mg/m2 body surface area) and etoposide (1200 mg/m2). Three patients also received ifosfamide (10g/m2). All patients had autologous bone marrow rescue. Of the 40 study patients, 26 received two full courses of therapy. Measurements: Patient charts were reviewed to determine the rate and duration of complete and partial remission and the number of long-term, disease-free survivors. The influence of cisplatin-refractory disease and the site of the primary tumor on the incidence of remission and survival were also investigated. Results: Of the 40 study patients, 26 (65%) responded to treatment; 12 (30%) achieved a complete response, and 14 (35%) achieved a partial response. Of the 12 complete responders, 5 relapsed, and 1 died of treatment-related acute leukemia 27.5 months after treatment without evidence of germ cell cancer. Six (15%) of the original 40 patients, of whom 3 were refractory to cisplatin, remained in complete remission after at least 24 months of follow-up. Eight of 40 patients had primary mediastinal germ cell tumors with no complete remissions and a median survival of 2 months (range, 0.5 to 9.0 months). Conclusions: Treatment with high-dose carboplatin and etoposide in conjunction with autologous bone marrow rescue in patients with relapsed or refractory germ cell tumors is a potentially curative therapeutic option, even for heavily pretreated or cisplatinrefractory patients. Some degree of disease resistance to cisplatin can be overcome with dose escalation of platinum compounds. Patients with multiple recurrences of relapsed or refractory primary mediastinal germ cell tumors were not helped by this approach.
Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with downregulation of inflammatory cytokines and differential upregulation of transforming growth factor beta, interleukin 4, and prostaglandin E expression in the brain.
Authors: S J Khoury, W W Hancock, H L Weiner
Journal: The Journal of Experimental Medicine (1992)

Experimental autoimmune encephalomyelitis (EAE) in the Lewis rat is a self-limited inflammatory process localized to the central nervous system that is induced by the injection of myelin basic protein (MBP) in adjuvant. Oral administration of MBP suppresses EAE, and this suppression is mediated by CD8+ T cells that adoptively transfer protection and suppress both in vitro and in vivo by the release of transforming growth factor (TGF) beta after antigen-specific triggering. Furthermore, oral tolerance to MBP is enhanced by the concomitant oral administration of lipopolysaccharide (LPS). The present study was undertaken to determine whether the disease course in EAE and its suppression by oral tolerization to MBP is associated with distinct patterns of cytokine expression in the target organ. Detailed immunohistology of the brain was performed at the peak of clinical disease (day 14 after immunization) and after recovery (day 18) in control (ovalbumin [OVA]-fed), MBP-fed, and MBP plus LPS-fed animals. Brains from OVA-fed animals at the peak of disease showed perivascular infiltration with activated mononuclear cells which secreted the inflammatory cytokines interleukins (IL) 1, 2, 6, 8, TNF-alpha, and interferon gamma. The inhibitory cytokines TGF-beta and IL-4, and prostaglandin E2 (PGE2) were absent. In MBP orally tolerized animals there was a marked reduction of the perivascular infiltrate and downregulation of all inflammatory cytokines. In addition, there was upregulation of the inhibitory cytokine TGF-beta. In MBP plus LPS orally tolerized animals, in addition to upregulation of TGF-beta and reduction of inflammatory cytokines, there was enhanced expression of IL-4 and PGE2, presumably secondary to activation of an additional population of immunoregulatory cells. In OVA-fed animals that had recovered (day 18), staining for inflammatory cytokines diminished, and there was the appearance of TGF-beta and IL-4. These results suggest that suppression of EAE, either induced by oral tolerization or that which occurs during natural recovery is related to the secretion of inhibitory cytokines or factors that actively suppress the inflammatory process in the target organ.
288. Bi-Modality Induction of TNFα: Neoadjuvant Chemoradiotherapy and TNFerade™ in Patients with Locally Advanced, Resectable Esophageal Carcinoma
Authors: Neil Senzer, Kenneth Chang, Stephen Swisher, Tony Reid, Ann Mauer, Amitabh Chak, Harlan Pinto, John Nemunaitis
Journal: Molecular Therapy (2006)

TNFα has potent anti-tumor activity the mechanisms of which include anti-vascular hemorrhagic necrosis, tumor cytotoxicity (e.g., ceramide and unfolded protein response), and immunologic mediation. The side effects of systemic TNFα (MTD 14,800 pg/ ml) limit clinical use to tightly controlled local/regional perfusion. TNFerade is a second-generation (E1-, partial E3-, and E4-deleted) adenovector carrying the transgene encoding for TNFα under the control of the radio-, chemo-inducible Egr-1 promoter designed to optimize spatial and temporal gene expression following radiation and chemotherapy. This was a phase I dose escalation study in patients with resectable, locally advanced esophageal carcinoma of neoadjuvant cisplatin (75 mg/m2, days 1 and 29), continuous infusion 5-fluorouracil (1000 mg/m2/day for 96 hours, starting days 1 and 29), radiation therapy (45 Gy/25 fractions/2.0 Gy fx) and weekly intratumoral TNFerade via endoscopic injection at 4×108, 4×109, 4×1010 and 4×1011 pu. 24 patients were entered. The MTD was not reached. There was one death due to pulmonary embolism (PE) and 3 PE in the 4×1011 cohort; a 16.7% incidence during active therapy. Pathologic complete response was documented in 36% of patients and nodal downstaging to pN0 in 56%. At a follow-up range of 16.3–33.9 months, the overall survival is 83% at 18 months and 73% at 24 months. These data will be updated and contextualized.
Psychosocial predisposing factors for infantile colic.
Authors: P Rautava, H Helenius, L Lehtonen
Journal: BMJ (1993)

OBJECTIVE--To study associations between characteristics of families during the first pregnancy and after childbirth and the development of infantile colic. DESIGN--Randomised, stratified cluster sampling. Follow up from the first visit to a maternity health care clinic during pregnancy to three months after birth with confidential semistructured questionnaires. SETTING--Maternity health care clinics in primary health care centres in Finland. SUBJECTS--1443 nulliparous women and 1407 partners. Altogether 1333 women and 1279 men returned the questionnaires. When the infants were 3 months old 1208 women and 1115 men returned questionnaires. MAIN OUTCOME MEASURES--Marital relationship; personal and social behaviour of parents during the pregnancy and their coping with the pregnancy; mothers9 physical health and events, symptoms, and experiences in relation to pregnancy; self confidence and experiences of mothers and fathers in relation to childbirth; and parents9 sociodemographic and educational variables. Measure of colic when the infant was 3 months old. RESULTS--Experience of stress and physical symptoms during the pregnancy, dissatisfaction with the sexual relationship, and negative experiences during childbirth were associated with the development of colic in the baby. None of the sociodemographic factors was associated with colic. CONCLUSIONS--Early preventive health work during pregnancy should attempt to improve parents9 tolerance of symptoms of stress and ability to cope and increase their confidence in parenting abilities.
137 KINETICS OF TRANSFORMING GROWTH FACTOR-β1 AND ENDOTHELIN-1 MRNA EXPRESSION IN HUMAN LIVER-DERIVED CELLS EXPOSED TO CYCLOSPORINE OR SIROLIMUS
Authors: G. Occhino, E. Boccato, R. Minisini, P. Toniutto, C. Fabris, M. Pirisi
Journal: Journal of Hepatology (2010)
Effects of partial hepatectomy on hepatic insulinlike growth factor binding protein-1 expression
Authors: Aziz Ghahary, Gerald Y. Minuk, Jiangming Luo, Tony Gauthier, Liam J. Murphy
Journal: Hepatology (1992)

Insulinlike growth factor binding proteins modulate the action of the insulinlike growth factors in various bioassays and may regulate the bioavailability of the insulinlike growth factors in vivo. Because the insulinlike growth factors may influence hepatic regeneration, we have examined the effect of partial hepatectomy on serum insulinlike growth factor binding proteins and on the abundance of insulinlike growth factor binding protein-1 messenger RNA in the liver. All rats were fasted before and after partial hepatectomy or sham operation to avoid the confounding effects of difference in food intake. Using a conventional protocol, 70% of the liver was removed, and groups of four or five rats were killed at different intervals after partial hepatectomy. Sham-operated rats served as controls. Pooled sera from each group of rats were analyzed by ligand blotting with 125I-insulinlike growth factor-I. Liver RNA from individual rats was analyzed by slot-blot and Northern-blot hybridization. A small decrease in the 39- to 42-kD insulinlike growth factor binding protein was apparent in sera from both the sham-operated and partial hepatectomized rats. In contrast, a dramatic increase (fivefold) in the 29-kD serum insulinlike growth factor binding protein (insulinlike growth factor binding protein-1) was apparent only in the partial hepatectomized rats. Hepatic insulinlike growth factor binding protein-1 messenger RNA abundance was significantly increased (1.99 +/- 0.18-fold; p less than 0.05) at 1 hr, reached a peak of 2.32 +/- 0.22-fold (p less than 0.01) at 3 hr after partial hepatectomy and returned to basal levels over the subsequent 6 to 12 hr.(ABSTRACT TRUNCATED AT 250 WORDS)
Acute heart failure due to autoimmune myocarditis under pembrolizumab treatment for metastatic melanoma
Authors: Heinz Läubli, Cathrin Balmelli, Matthias Bossard, Otmar Pfister, Kathrin Glatz, Alfred Zippelius
Journal: Journal for ImmunoTherapy of Cancer (2015)

Antibodies that stimulate the immune system by targeting inhibitory T cell receptors were successfully introduced into oncological practice and are capable to overcome tumor-induced immune evasion. In particular, targeting of the inhibitory receptors CTLA-4 and PD-1 or its ligand PD-L1 have been shown to be beneficial for patients with melanoma, renal cell cancer, non-small cell lung cancer and a growing list of other cancers with impressive response rates. Here, we report a severe, potentially life-threatening side effect of anti-PD-1 immunotherapy with pembrolizumab, which has not been previously described in the literature. A 73-year-old woman with metastatic uveal melanoma treated with pembrolizumab in third line developed severe heart failure due to pembrolizumab-mediated autoimmune myocarditis. Echocardiographic studies revealed a severely impaired left ventricular function with dyssynchrony. All tests for cardiotropic viruses were negative and histological analysis of a myocardial biopsy showed lymphocytic infiltration with a predominance of CD8 positive cells and a reduction of FOXP3 positive regulatory T cells. After initiation of corticosteroids and guideline-conform heart failure therapy, the symptoms rapidly improved and the left ventricular function recovered. While autoimmune myocarditis is a documented side effect of other checkpoint inhibitors, as for example ipilimumab and in one case with anti-PD-L1 antibody, it is not described for anti-PD-1-antibodies like pembrolizumab or nivolumab. As the FDA recently approved both pembrolizumab and nivolumab for melanoma progressing after anti-CTLA-4 treatment with ipilimumab, more patients will soon receive anti-PD-1 therapy. Thus, it is important to be aware of such rare, but severe immune-related adverse events.
EVALUATION OF A SIMPLE SURGICAL TREATMENT OF AXILLARY HYPERHIDROSIS
Authors: J. A. GILLIESPIE, S. P. KANE
Journal: British Journal of Dermatology (1970)

SUMMARY.– The effectiveness of the removal of an ellipse of central axillary skin in treating axillary hyperhidrosis has been assessed. In suitable subjects this simple operation would appear to be well worthwhile.
Inmunohistochemical Profile of Solid Cell Nest of Thyroid Gland
Authors: María José Ríos Moreno, Hugo Galera-Ruiz, Manuel De Miguel, María Inés Carmona López, Matilde Illanes, Hugo Galera-Davidson
Journal: Endocrine Pathology (2011)

It is widely held that solid cell nests (SCN) of the thyroid are ultimobranchial body remnants. SCNs are composed of main cells and C cells. It has been suggested that main cells might be pluripotent cells contributing to the histogenesis of C cells and follicular cells, as well as to the formation of certain thyroid tumors. The present study sought to analyze the immunohistochemical profile of SCN and to investigate the potential stem cell role of SCN main cells. Tissue sections from ten cases of nodular hyperplasia (non-tumor goiter) with SCNs were retrieved from the files of the Hospital Infanta Luisa (Seville, Spain). Parathormone (PTH), calcitonin (CT), thyroglobulin (TG), thyroid transcription factor (TTF-1), galectin 3 (GAL3), cytokeratin 19 (CK 19), p63, bcl-2, OCT4, and SALL4 expression were evaluated by immunohistochemistry. Patient clinical data were collected, and tissue sections were stained with hematoxylin-eosin for histological examination. Most cells stained negative for PTH, CT, TG, and TTF-1. Some cells staining positive for TTF-1 and CT required discussion. However, bcl-2, p63, GAL3, and CK 19 protein expression was detected in main cells. OCT4 protein expression was detected in only two cases, and SALL4 expression in none. Positive staining for bcl-2 and p63, and negative staining for PTH, CT, and TG in SCN main cells are both consistent with the widely accepted minimalist definition of stem cells, thus supporting the hypothesis that they may play a stem cell role in the thyroid gland, although further research will be required into stem cell markers. Furthermore, p63 and GAL-3 staining provides a much more sensitive means of detecting SCNs than staining for carcinoembryonic antigen, calcitonin, or other markers; this may help to distinguish SCNs from their mimics.
Screening for Inherited Diseases
Authors: Charles A. Janeway
Journal: New England Journal of Medicine (1971)

The article on "Galactosemia Screening of Newborns in Massachusetts" in this issue of the Journal not only adds to our knowledge of a rare disease but highlights many of the difficulties of large-scale screening of population groups for inherited diseases. During the two periods covered by this survey, samples were tested from a total of 374,341 newborns, and only two infants with galactosemia were discovered, both of whom died of Escherichia coli during the neonatal period. Galactosemia clearly is a very rare inborn error of metabolism, unlike phenylketonuria (PKU), which has an incidence of approximately one in every 10,000 babies. . . .