tbuckley/cabot-search huggingface dataset:
Recruitment of Myeloid but not Endothelial Precursor Cells Facilitates Tumor Regrowth after Local Irradiation
Authors: Sergey V. Kozin, Walid S. Kamoun, Yuhui Huang, Michelle R. Dawson, Rakesh K. Jain, Dan G. Duda
Journal: Cancer Research (2010)

Abstract Tumor neovascularization and growth might be promoted by the recruitment of bone marrow–derived cells (BMDC), which include endothelial precursor cells and “vascular modulatory” myelomonocytic (CD11b+) cells. BMDCs may also drive tumor regrowth after certain chemotherapeutic and vascular disruption treatments. In this study, we evaluated the role of BMDC recruitment in breast and lung carcinoma xenograft models after local irradiation (LI). We depleted the bone marrow by including whole-body irradiation (WBI) of 6 Gy as part of a total tumor dose of 21 Gy, and compared the growth delay with the one achieved after LI of 21 Gy. In both models, the inclusion of WBI induced longer tumor growth delays. Moreover, WBI increased lung tumor control probability by LI. Exogenous delivery of BMDCs from radiation-naïve donors partially abrogated the WBI effect. Myeloid BMDCs, primarily macrophages, rapidly accumulated in tumors after LI. Intratumoral expression of stromal-derived factor 1α (SDF-1α), a chemokine that promotes tissue retention of BMDCs, was noted 2 days after LI. Conversely, treatment with an inhibitor of SDF-1α receptor CXCR4 (AMD3100) with LI significantly delayed tumor regrowth. However, when administered starting from 5 days post-LI, AMD3100 treatment was ineffective. Lastly, with restorative bone marrow transplantation of Tie2-GFP–labeled BMDC population, we observed an increased number of monocytes but not endothelial precursor cells in tumors that recurred following LI. Our results suggest that an increase in intratumoral SDF-1α triggered by LI recruits myelomonocytes/macrophages which promotes tumor regrowth. Cancer Res; 70(14); 5679–85. ©2010 AACR.
Avoiding the pitfalls of sponsored multicentre research in general practice.
Authors: H A Waldron, R F Cookson
Journal: BMJ (1993)

Research in general practice is becoming increasingly popular, and most general practitioners will sooner or later have to decide whether to become involved with clinical trials sponsored by drug companies. This paper outlines the advantages and disadvantages of multicentre research--based on experience of running a research group since the early 1980s--to enable doctors to reach the appropriate decision and to avoid involvement in trials which are either unethical or ineffective.
Clinical, Colonoscopic, and Histological Profile of Colonic Tuberculosis in a Tertiary Hospital
Authors: J. F. Alvares, H. Devarbhavi, P. Makhija, S. Rao, R. Kottoor
Journal: Endoscopy (2005)

Background and Study Aims: Colonic tuberculosis is not uncommon in developing countries. As emigration to the West increases, it is worthwhile to recall the clinical, colonoscopic, and histopathological features of this condition. Patients and Methods: The clinical, colonoscopic and histopathological findings were evaluated in 43 patients with colonic tuberculosis. Results: Abdominal pain, weight loss, diarrhea, fever, and a lump in the abdomen were the commonest symptoms. Extraintestinal tuberculosis was present in 11 patients (26 %). Colonoscopy revealed ulcers in 30 patients (70 %), nodules in 24 (56 %), a deformed cecum and ileocecal valve in 17 (40 %), strictures in 10 (23 %), polypoid lesions in six (14 %), and fibrous bands forming mucosal bridges in three (7 %). The cecum and ascending colon were the commonest sites involved. Segmental tuberculosis was seen in six of the 32 patients (19 %) in whom full-length colonoscopy could be performed. Two or more sites were involved in 19 patients (44 %). Histopathology revealed well-formed granulomas in 23 patients (54 %). Fourteen of the above patients (61 %) had caseation and 11 (48 %) had confluence of the granulomas. Acid-fast bacilli were present in the biopsies from two patients (5 %). Ill-formed granulomas were seen in seven patients (16 %) and chronic inflammatory changes in 13 (30 %). Despite the various histopathological findings, all of the patients responded to antitubercular treatment and continued to remain asymptomatic during the follow-up period. Conclusions: Colonoscopy with biopsy is a useful method for diagnosing colonic tuberculosis. Even in the absence of the classic histopathological features, a therapeutic trial may be indicated in a given clinical and colonoscopic setting. Follow-up is essential.
Effects of endothelin receptor antagonist on cyclosporine-induced vasoconstriction in isolated rat renal arterioles.
Authors: D M Lanese, J D Conger
Journal: Journal of Clinical Investigation (1993)

Recent evidence suggests that the potent constrictor peptide, endothelin (ET) has a mediating role in cyclosporine A (CsA)-related renal vasoconstriction. However, the nature of the CsA-ET interaction and effect on the renal vasculature is uncertain. The purpose of the present study was twofold: (a) to determine if CsA exposure caused direct local release of ET from the endothelium of the renal microvasculature and (b) to determine if locally generated ET has paracrine effects on the underlying vascular smooth muscle to induce vasoconstriction. Experiments were performed in isolated rat renal arterioles. First it was determined that both afferent arteriole (AA) and efferent arteriole (EA) exhibited concentration-dependent decreases in lumen diameter to increasing molar concentrations of CsA. The AA was more sensitive to the vasoconstrictive effects of CsA than the EA. Next, the blocking effect of a recently synthesized putative ETA receptor antagonist was verified in both the AA and EA, where it was found that the cyclic peptide cyclo D-Asp-L-Pro-D-Val-L-Leu-D-Trp totally inhibited the vasoconstriction observed with ET addition. Finally, the role of locally stimulated ET in CsA-induced vasoconstriction was tested by determining the effect of the ETA receptor antagonist on CsA-induced AA and EA constriction. In the AA the vasoconstrictor effect of 10(-11) M CsA was completely blocked by the ETA receptor antagonist. However, in contrast to AA, 10(-11) M CsA in EA in the presence of the ETA receptor antagonist decreased EA lumen diameter by a mean of 41% from baseline (4.80 +/- 0.75 microns vs 7.80 +/- 0.84 microns, P < 0.05). This change in lumen diameter was similar to that induced by CsA alone. These data suggest that CsA directly constricts renal microvessels. This effect is mediated by ET in the AA but not the EA.
Changes in Risk Variables of Metabolic Syndrome Since Childhood in Pre-Diabetic and Type 2 Diabetic Subjects
Authors: Quoc Manh Nguyen, Sathanur R. Srinivasan, Ji-Hua Xu, Wei Chen, Gerald S. Berenson
Journal: Diabetes Care (2008)

That type 2 diabetes is associated with the metabolic syndrome is known. However, information is lacking regarding the long-term and adverse changes of metabolic syndrome variables in the development of type 2 diabetes from childhood to adulthood.Observations were examined, retrospectively, in a community-based cohort of normoglycemic (n = 1,838), pre-diabetic (n = 90), and type 2 diabetic (n = 60) subjects followed serially for cardiovascular risk factors during childhood (4-11 years), adolescence (12-18 years), and adulthood (19-44 years).Diabetic subjects versus normoglycemic subjects had significantly higher levels of subscapular skinfold, BMI, triglycerides, glucose, insulin, and homeostasis model assessment of insulin resistance and lower levels of HDL cholesterol beginning in childhood and higher levels of mean arterial pressure (MAP) in adolescence and adulthood. In a multivariate model including BMI, MAP, HDL cholesterol, LDL cholesterol, triglycerides, glucose, and insulin, adjusted for age, age(2), race, sex, and race x sex interaction, adverse changes in glucose and LDL cholesterol were independently associated with pre-diabetic subjects, whereas adverse changes in BMI, glucose, and HDL cholesterol were associated with diabetic subjects. As young adults, pre-diabetic and diabetic groups displayed a significantly higher prevalence of obesity, hypertension, dyslipidemia, hyperinsulinemia, and metabolic syndrome.These findings indicate that adverse levels of risk variables of metabolic syndrome, adiposity, and measures of glucose homeostasis accelerating since childhood characterize the early natural history of type 2 diabetes and underscore the importance of early prevention and intervention on risk factors beginning in childhood.
Severe allergic reaction to chlormethiazole.
Authors: A A Khan
Journal: BMJ (1976)

Severe allergic reaction to chlormethiazole Allergic reactions are not a recognised side effect of treatment with chlormethiazole.This paper describes a patient who suffered such a reaction after being treated for acute alcoholic withdrawal symptoms with chlormethiazole. Case reportThe patient was a married woman aged 48 years, Scottish by birth and unemployed.She was of medium build and weighed 57 kg.She was admitted to Hill Hospital, Hartwood, for treatment of chronic alcoholism.On admission she smelt of alcohol and was visually hallucinated with delirium tremens.On physical examination she was healthy, and all systems were normal.Treatment-She was started on oral chlormethiazole (Heminevrin), 2 capsules three times a day.No other drugs were prescribed.Adverse effect-Twelve hours later the patient developed a severe allergic reaction with profuse rash on her face, neck, and arms.The rash was blotchy in distribution with severe itching.Her face was swollen and she was in pain.The drug was withdrawn and she was started on the antihistamine chlorpheniramine maleate, one tablet three times a day, and given an antihistamine cream for local application.The rash and swelling disappeared after 24 hours, leaving behind some chaffing of the skin.
Rituximab therapy for chronic lymphocytic leukemia-associated autoimmune hemolytic anemia
Authors: Giovanni D'Arena, Luca Laurenti, Silvana Capalbo, Alfonso Maria D'Arco, Rosaria De Filippi, Gianpaolo Marcacci, Nicola Di Renzo, Sergio Storti, Catello Califano, Maria Luigia Vigliotti, Michela Tarnani, Felicetto Ferrara, Antonio Pinto
Journal: American Journal of Hematology (2006)

Autoimmune hemolytic anemia (AIHA) is a well-known complication of chronic lymphocytic leukemia (CLL). In recent years the anti-CD20 monoclonal antibody rituximab has been used for the therapy of steroid-refractory AIHA and autoimmune thrombocytopenia, either idiopathic or in association with CLL. We report the results of rituximab treatment for 14 patients suffering from CLL-associated AIHA. They developed a direct antiglobulin test positive AIHA at a mean time of 47 months (range 0–135 months) from the diagnosis of CLL. In 3 cases AIHA was diagnosed at the same time as CLL. Only 1 patient had fludarabine-related AIHA. All patients received steroids as first-line treatment. At a mean time of 46 days (range 1–210 days) from the diagnosis of AIHA all patients received rituximab at a dosage of 375 mg/m2/weekly for 4 weeks. All patients except 3 (2 died of cardiac failure or sepsis soon after the third cycle and 1 HCV-positive patient experienced a rise in serum amino transferases) completed the scheduled four programmed cycles. First injection side effects of rituximab were minimal. All but 2 patients showed an increase in hemoglobin levels in response to rituximab (mean value 3.6 g/dl; range 0.7–10 g/dl) and a reduction in the absolute lymphocyte count and lymph nodes and spleen volume. Nine patients required packed red cell transfusions before starting rituximab; 5 no longer needed transfusions just after the second cycle and another patient after the fourth cycle. Three patients (22%) were considered to fully respond and 7 (50%) only responded partially. At a mean follow-up of 17 months, 8 patients were still alive, 6 of them transfusion-free. Our results prove that the anti-CD20 monoclonal antibody is an effective and well-tolerated alternative treatment for CLL-associated AIHA. Am. J. Hematol. 81:598–602, 2006. © 2006 Wiley-Liss, Inc.
Declining Clinical Tradition
Authors: Jurgen Ruesch
Journal: JAMA (1962)

The 20-fold increase in funds for medical research over the short span of 15 years has seriously disrupted the operations of medical schools, training centers, and hospitals. A number of factors here discussed have combined to make the clinical disciplines less attractive to physicians. This trend is reflected in the declining number of applicants to medical schools and in the decline of their scholastic standing. The population needs competent clinicians, well-functioning health services, and hospitals. The medical sciences will have to be separated from clinical medicine. Although the 2 fields are complementary to each other, they attract different kinds of people, require different kinds of organization, and are based on different philosophies. The disorganizing effect of increasing support for medical science can be mitigated by increasing support for clinical medicine and the education of physicians.
Fetoscopic Direct Fetal Cardiac Access in Sheep
Authors: Thomas Kohl, Danja Strümper, Ralf Witteler, Gregor Merschhoff, Rasa Alexiene, Claudia Callenbeck, Boulos Asfour, Julia Reckers, Sebastian Aryee, Christian Vahlhaus, Johannes Vogt, Hugo Van Aken, Hans H. Scheld
Journal: Circulation (2000)

Background —Fetal cardiac interventions by direct ultrasound-guided approaches or open fetal cardiac surgery have been fraught with technical difficulties, as well as with significant maternal and fetal morbidity in humans. Therefore, the purpose of our study in sheep was to assess the feasibility and potential of fetoscopic direct fetal cardiac access. Methods and Results —In 15 anesthetized pregnant ewes (88 to 109 days of gestation; term, 145 days), 3 to 4 trocars were percutaneously placed in the uterus. Using videofetoscopic equipment, we assessed the feasibility of achieving direct fetal cardiac access. Minimally invasive direct fetal cardiac access by operative fetoscopy was achieved in 10 of the 15 fetal sheep. In 7 fetuses, the approach was successfully tested for fetal cardiac pacing (n=5) or antegrade fetal cardiac catheterization (n=2). Access was not achieved in 5 fetuses because of bleeding complications (n=2) or because the fetoscopic setup could not be established (n=3). All but 2 fetal sheep were alive at the end of the procedure. Acute fetal demise resulted from maternal hypotension or kinking of the fetal inferior caval vein by sternal suspension. Six ewes continued gestation; 3 of these went to term, with a normal fetal outcome. Two ewes died from septicemia 3 and 7 days after the procedure, and 1 ewe aborted 1 month after the procedure. Conclusions —Minimally invasive direct fetal cardiac access by operative fetoscopy is feasible in fetal sheep. The fetoscopic approach carries important potential for fetal cardiac pacing, antegrade fetal valvuloplasties, and resection of fetal intrapericardial teratomas in human fetuses.
Gastropathy and Ketoconazole Malabsorption in the Acquired Immunodeficiency Syndrome (AIDS)
Authors: Gerond Lake-Bakaar
Journal: Annals of Internal Medicine (1988)

Study Objective: To correlate oral ketoconazole absorption with gastric acid secretion in patients with the acquired immunodeficiency syndrome (AIDS). Design: Prospective measurement of maximal acid output and oral ketoconazole absorption with and without 0. 1 -N hydrochloric acid. Setting: Hospital in-patients in university medical center. Patients: Ten consecutive male patients with AIDS. Intervention: Maximal acid output was determined after pentagastrin stimulation in all patients. Serum ketoconazole levels were measured the day after ingestion of a 200-mg ketoconazole tablet in the fasted state. On the final day, ketoconazole was ingested with 200 mL of 0.1 -N hydrochloric acid. Measurements and Main Results: Maximal acid output was below 15 mEq/h in 7 of 10 patients. In all 7, the area under the serum ketoconazole concentration —time curve was below normal (1.4 ± 0.9 mg/h • L; mean ± SE), and absorption was normalized by hydrochloric acid (9.9 ± mg/h • L). Two of three patients with maximal acid outputs above 15 mEq/h had normal ketoconazole absorption (15.1 ± 6.7 mg/h • L). Conclusions: The bioavailability of oral ketoconazole is reduced in patients with AIDS, largely as a result of gastric hypochlorhydria. Ketoconazole tablets should therefore be given with acid in these patients.
Arrector pili muscles surround human facial vellus hair follicles
Authors: Y. NARISAWA, H. KOHDA
Journal: British Journal of Dermatology (1993)

Arrector pili muscles have been assumed to attach to one side of the hair follicle, specifically the posterior wall of the bulge area. In this study, we demonstrated immunohistochemically that desminreactive arrector pili muscle, admixed with the connective tissue sheath, is present around the entire circumference of the vellus hair follicle.
Erythropoietic Response and Outcomes in Kidney Disease and Type 2 Diabetes
Authors: Scott D. Solomon, Hajime Uno, Eldrin F. Lewis, Kai-Uwe Eckardt, Julie Lin, Emmanuel A. Burdmann, Dick de Zeeuw, Peter Ivanovich, Andrew S. Levey, Patrick Parfrey, Giuseppe Remuzzi, Ajay K. Singh, Robert Toto, Fannie Huang, Jerome Rossert, John J.V. McMurray, Marc A. Pfeffer
Journal: New England Journal of Medicine (2010)

Non–placebo-controlled trials of erythropoiesis-stimulating agents (ESAs) comparing lower and higher hemoglobin targets in patients with chronic kidney disease indicate that targeting of a lower hemoglobin range may avoid ESA-associated risks. However, target-based strategies are confounded by each patient's individual hematopoietic response.We assessed the relationship among the initial hemoglobin response to darbepoetin alfa after two weight-based doses, the hemoglobin level achieved after 4 weeks, the subsequent darbepoetin alfa dose, and outcomes in 1872 patients with chronic kidney disease and type 2 diabetes mellitus who were not receiving dialysis. We defined a poor initial response to darbepoetin alfa (which occurred in 471 patients) as the lowest quartile of percent change in hemoglobin level (<2%) after the first two standardized doses of the drug.Patients who had a poor initial response to darbepoetin alfa had a lower average hemoglobin level at 12 weeks and during follow-up than did patients with a better hemoglobin response (a change in hemoglobin level ranging from 2 to 15% or more) (P<0.001 for both comparisons), despite receiving higher doses of darbepoetin alfa (median dose, 232 μg vs. 167 μg; P<0.001). Patients with a poor response, as compared with those with a better response, had higher rates of the composite cardiovascular end point (adjusted hazard ratio, 1.31; 95% confidence interval [CI], 1.09 to 1.59) or death (adjusted hazard ratio, 1.41; 95% CI, 1.12 to 1.78).A poor initial hematopoietic response to darbepoetin alfa was associated with an increased subsequent risk of death or cardiovascular events as doses were escalated to meet target hemoglobin levels. Although the mechanism of this differential effect is not known, these findings raise concern about current target-based strategies for treating anemia in patients with chronic kidney disease. (Funded by Amgen; ClinicalTrials.gov number, NCT00093015.)
(33) Recurrent self-limiting cutaneous reticulosis
Authors: S.A. Khan
Journal: British Journal of Dermatology (1987)

Journal Article (33) Recurrent self‐limiting cutaneous reticulosis Get access S.A. Khan S.A. Khan Pontefract General Hospital Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 117, Issue s32, 1 June 1987, Pages 82–84, https://doi.org/10.1111/j.1365-2133.1987.tb12073.x Published: 01 June 1987
Immunoreactive corticotropin-releasing hormone and its binding sites in the rat ovary.
Authors: G Mastorakos, E L Webster, T C Friedman, G P Chrousos
Journal: Journal of Clinical Investigation (1993)

Corticotropin-releasing hormone (CRH), the principal neuropeptide regulator of pituitary ACTH secretion, is also produced at peripheral inflammatory sites, where it acts as a proinflammatory cytokine, and by the Leydig cell of the testis, where it exerts autocrine inhibition of testosterone biosynthesis. Because key ovarian functions, such as ovulation and luteolysis, represent aseptic inflammatory responses, and because the theca cell is the functional equivalent of the Leydig cell, we explored the CRH presence in the ovary, first, by specific CRH immunohistochemistry of adult cycling female Sprague-Dawley rat ovaries. We detected cytoplasmic immunoreactive CRH (IrCRH) in theca and stromal cells and in cells within the corpora lutea, at all phases of the estrous cycle. Using a specific radioimmunoassay, we measured IrCRH in extracts of rat ovaries (0.042-0.126 pmol/g wet tissue). The mobility of the ovarian IrCRH molecule was similar to that of rat/human CRH by reverse phase HPLC. To investigate the CRH action in the ovary, we identified, characterized, and localized CRH receptors in the rat ovary. Binding was linear with increasing tissue concentration, saturable, and of high affinity. Scatchard analysis of 125I-Tyr-ovine CRH competitive displacement curves indicated a high affinity binding site with a Kd of approximately 6 nM and a Bmax value of approximately 61 fM/mg protein. Autoradiographic studies revealed CRH receptors primarily in ovarian theca and stroma. We conclude that IrCRH and CRH receptors are present in rat ovaries, suggesting that this neuropeptide may play a regulatory role in this gonad, perhaps through its proinflammatory properties and/or by participating in the auto/paracrine regulation of steroid biosynthesis. Functional studies are necessary to define the role(s) of CRH in the ovary.
Renal Vein Valve
Authors: Paul T. McDonald
Journal: JAMA (1977)

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