Science.gov

Sample records for cyclophosphamide induced-chagas dilated

  1. Cyclophosphamide in dermatology.

    PubMed

    Kim, Janet; Chan, Jonathan J

    2017-02-01

    Cyclophosphamide is a chemotherapeutic agent which was first discovered in experimental tumours in rats, and it has since been widely used to treat malignancies and severe manifestations of various auto-immune diseases. High-dose chemotherapy and continuous daily oral regimens are associated with significant toxicity profiles, but i.v. pulsed regimens have lowered the rates of adverse effects in rheumatological studies. Cyclophosphamide has been shown to be useful in the treatment of severe autoimmune conditions due to its powerful immunosuppressive ability; however, it remains a relatively underused modality in dermatology. This article reviews the current literature on cyclophosphamide and its clinical applications in dermatology. © 2016 The Australasian College of Dermatologists.

  2. Dilated cardiomyopathy.

    PubMed

    Weintraub, Robert G; Semsarian, Christopher; Macdonald, Peter

    2017-02-09

    Dilated cardiomyopathy is defined by the presence of left ventricular dilatation and contractile dysfunction. Genetic mutations involving genes that encode cytoskeletal, sarcomere, and nuclear envelope proteins, among others, account for up to 35% of cases. Acquired causes include myocarditis and exposure to alcohol, drugs and toxins, and metabolic and endocrine disturbances. The most common presenting symptoms relate to congestive heart failure, but can also include circulatory collapse, arrhythmias, and thromboembolic events. Secondary neurohormonal changes contribute to reverse remodelling and ongoing myocyte damage. The prognosis is worst for individuals with the lowest ejection fractions or severe diastolic dysfunction. Treatment of chronic heart failure comprises medications that improve survival and reduce hospital admission-namely, angiotensin converting enzyme inhibitors and β blockers. Other interventions include enrolment in a multidisciplinary heart failure service, and device therapy for arrhythmia management and sudden death prevention. Patients who are refractory to medical therapy might benefit from mechanical circulatory support and heart transplantation. Treatment of preclinical disease and the potential role of stem-cell therapy are being investigated.

  3. Cyclophosphamide in diffuse lung damage.

    PubMed

    Musiatowicz, B; Sulkowska, M; Sulik, M; Famulski, W; Dziecioł, J; Sobaniec-Lotowska, M; Baltaziak, M; Arciuch, L; Rółkowski, R; Jabłońska, E

    1997-01-01

    Some cyclophosphamide toxic effects on lung tissue are presented. Cyclophosphamide metabolism, pathogenesis of lung damage and morphological lung tissue changes caused by that agent were characterized. Attention was focused on BAL evaluation as a useful method in the monitoring of lung tissue damage degree.

  4. Dilating Eye Drops

    MedlinePlus

    ... sometimes used to treat eye diseases, such as amblyopia and inflammation. How long do dilating drops last? ... used to treat certain eye diseases, such as amblyopia and inflammation in the eye. These therapeutic dilating ...

  5. Neonatal dilated cardiomyopathy.

    PubMed

    Soares, Paulo; Rocha, Gustavo; Pissarra, Susana; Soares, Henrique; Flôr-de-Lima, Filipa; Costa, Sandra; Moura, Cláudia; Dória, Sofia; Guimarães, Hercília

    2017-03-01

    Cardiomyopathies are rare diseases of the heart muscle, of multiple causes, that manifest with various structural and functional phenotypes but are invariably associated with cardiac dysfunction. Dilated cardiomyopathy is the commonest cardiomyopathy in children, and the majority present before one year of age. Its etiology may be acquired or genetic. Myocarditis is an important cause and is responsible for the majority of acquired cases. Inherited (familial) forms of dilated cardiomyopathy may occur in 25-50% of patients. Echocardiographic and tissue Doppler studies are the basis for diagnosis of dilated cardiomyopathy in most patients. Marked dilatation of the left ventricle with global hypokinesis is the hallmark of the disease. This review will cover the classification, epidemiology and management of newborns with dilated cardiomyopathy. In particular, a comprehensive and up-to-date review of the genetic study of dilated cardiomyopathy and of detailed echocardiographic assessment of these patients will be presented.

  6. Green tea extract increases cyclophosphamide-induced teratogenesis by modulating the expression of cytochrome P-450 mRNA.

    PubMed

    Park, Dongsun; Jeon, Jeong Hee; Shin, Sunhee; Joo, Seong Soo; Kang, Dae-Hyuck; Moon, Seol-Hee; Jang, Min-Jung; Cho, Yeoung Mi; Kim, Jae Wook; Ji, Hyeong-Jin; Ahn, Byeongwoo; Oh, Ki-Wan; Kim, Yun-Bae

    2009-01-01

    The effects of green tea extract (GTE) on the fetal development and external, visceral and skeletal abnormalities induced by cyclophosphamide were investigated in rats. Pregnant rats were daily administered GTE (100mg/kg) by gavage for 7 d, from the 6th to 12th day of gestation, and intraperitoneally administered with cyclophosphamide (11mg/kg) 1h after the final treatment. On the 20th day of gestation, maternal and fetal abnormalities were determined by Cesarian section. Cyclophosphamide was found to reduce fetal and placental weights without increasing resorption or death. In addition, it induced malformations in live fetuses; 94.6%, 41.5% and 100% of the external (skull and limb defects), visceral (cleft palate and ureteric dilatation) and skeletal (acrania, vertebral/costal malformations and delayed ossification) abnormalities. When pre-treated with GTE, cyclophosphamide-induced body weight loss and abnormalities of fetuses were remarkably aggravated. Moreover, repeated treatment with GTE greatly increased mRNA expression and activity of hepatic cytochrome P-450 (CYP) 2B, which metabolizes cyclophosphamide into teratogenic acrolein and cytotoxic phosphoramide mustard, while reducing CYP3A expression (a detoxifying enzyme). The results suggest that repeated intake of GTE may aggravate cyclophosphamide-induced body weight loss and malformations of fetuses by modulating CYP2B and CYP3A.

  7. Cyclophosphamide treatment in polyarteritis nodosa.

    PubMed

    Oriente, P; Riccio, A; Farinaro, C; Farinaro, E; Scarpa, R; Vignone, L; Pucino, A

    1986-06-01

    Five male patients with polyarteritis nodosa were treated with cyclophosphamide as follows: 3 mg/Kg/die i.v. up to maximum of 3 g.; subsequently, 200 mg/die per os for two weeks, then 100 mg per os every other day for three months; finally, 100 mg every fourth day until the 18th month. One patient, who also had fever, received 25 mg/die of prednisone for the initial three weeks of treatment. Before treatment ESR, WBC, and circulating immune-complexes were increased, while C3a, C3c and C4 serum complement components levels were normal. Skin ulcers healed within 4 months. A progressive marked improvement of visceral damages in the first months of therapy have been noted (e.g. blood pressure values in normal range after suspension of concomitant antihypertensive treatment, regression of peripheral neuropathy, etc. etc.). No further ischemic lesions occurred during treatment. Significant decreases of ESR and serum immune-complexes levels were detected. No untoward effects due to cyclophosphamide were observed. These findings support the effectiveness of this drug in polyarteritis. The possibility of association with glucocorticoids during the acute phase of disease is also discussed.

  8. Cyclophosphamide

    MedlinePlus

    ... mention any of the following: allopurinol (Zyloprim®), cortisone acetate, doxorubicin (Adriamycin®, Doxil®), hydrocortisone (Cortef®), or phenobarbital (Luminal® Sodium). Your doctor may need to change the doses ...

  9. Sinuplasty (Balloon Catheter Dilation)

    MedlinePlus

    ... development of the balloon dilating catheter and its adaptation to sinus surgery. In the 1980s, the field ... used in endoscopic sinus surgery. It is the adaptation or application of minimally-invasive balloon technology to ...

  10. Intermittent cyclophosphamide treatment of autoimmune thrombocytopenia

    PubMed Central

    Weinerman, Brian; Maxwell, Ian; Hryniuk, William

    1974-01-01

    Cyclophosphamide was given intermittently rather than daily to 14 patients with autoimmune thrombocytopenic purpura. Eight patients responded and six did not. In those who responded the rise in platelet count was rapid, and in all patients the lack of toxicity was striking. Intermittent cyclophosphamide seems effective in some cases of autoimmune thrombocytopenia and is safe, at least in the short term. Controlled trials would be required to prove that intermittent is better than daily administration. PMID:4473260

  11. Continuous controllable balloon dilation: a novel approach for cervix dilation

    PubMed Central

    2012-01-01

    Background Cervical dilation using mechanical dilators is associated with various complications, such as uterine perforation, cervical laceration, infections and intraperitoneal hemorrhage. To achieve safe and painless cervical dilation, we constructed a new medical device to achieve confident mechanical cervical dilation: a continuous controllable balloon dilator (CCBD). Methods Controlled pumping of incompressible fluid into the CCBD increases the pressure and outer diameter of the CCBD, continuously dilating the cervical canal. The reliability of the CCBD was confirmed in vitro (testing for consistency and endurance, with no detected risk for breakage) and in vivo. A multi-center clinical study was conducted,with 120 pregnant women randomly assigned to one of three groups: Group I,control group, no dilation;Group II,mechanical dilation, Hegar dilator (HeD); and Group III,CCBD. The tissue material for histological evaluation was obtained from the endocervical mucosa before and after dilation using the HeD or CCBD. Results The CCBD dilations were successful and had no complications in all 40 patients of Group III. The cervical tissue was markedly less damaged after CCBD dilation compared with HeD dilation (epithelium damage: 95% (HeD) vs. 45% (CCBD), P <0.001; basal membrane damage: 82.5% (HeD) vs. 27.5% (CCBD), P <0.001; stromal damage: 62.5% (HeD) vs. 37.5% (CCBD), P <0.01). Cervical hemorrhagia was observed in 90% of the patients after HeD dilation versus in 32.5% of the patients after CCBD dilation. Conclusions The CCBD should be used as a replacement for mechanical dilators to prevent uterine and cervical injury during cervical dilation. Trial registration ISRCTN54007498 PMID:23088906

  12. Cyclophosphamide-induced reversible posterior leukoencephalopathy syndrome.

    PubMed

    Abenza-Abildua, Maria Jose; Fuentes, Blanca; Diaz, Domingo; Royo, Aranzazu; Olea, Teresa; Aguilar-Amat, Maria Jose; Diez-Tejedor, Exuperio

    2009-01-01

    Reversible posterior leukoencephalopathy syndrome (RPLS) is a clinical radiological syndrome, characterised by acute headache, altered consciousness, seizures and hypertension. The most frequent causes are hypertensive encephalopathy, eclampsia and some immunosuppressive therapies. The pathogenesis remains unclear, but it appears to be related to altered cerebral circulation, producing oedema that can be seen on MRI, and it resolves in 2 or 3 weeks. In the present report, a possible first reported case of cyclophosphamide-induced RPLS in a 27-year-old man with high blood pressure (HBP) and glomerulonephritis caused by Goodpasture syndrome, treated with cyclophosphamide during the last month and prednisone for glomerulonephritis resulting from Goodpasture syndrome without other immunosuppressive drugs, is described.Symptoms appeared during a hypertensive crisis, but when cyclophosphamide was replaced by rituximab and hypertension was controlled, the patient did not have neurological symptoms. Almost all reported cases induced by immunosuppressive therapy or other causes were associated with hypertension as well.

  13. Cyclophosphamide-induced reversible posterior leukoencephalopathy syndrome

    PubMed Central

    Abenza-Abildua, Maria Jose; Fuentes, Blanca; Diaz, Domingo; Royo, Aranzazu; Olea, Teresa; Aguilar-Amat, Maria Jose; Diez-Tejedor, Exuperio

    2009-01-01

    Reversible posterior leukoencephalopathy syndrome (RPLS) is a clinical radiological syndrome, characterised by acute headache, altered consciousness, seizures and hypertension. The most frequent causes are hypertensive encephalopathy, eclampsia and some immunosuppressive therapies. The pathogenesis remains unclear, but it appears to be related to altered cerebral circulation, producing oedema that can be seen on MRI, and it resolves in 2 or 3 weeks. In the present report, a possible first reported case of cyclophosphamide-induced RPLS in a 27-year-old man with high blood pressure (HBP) and glomerulonephritis caused by Goodpasture syndrome, treated with cyclophosphamide during the last month and prednisone for glomerulonephritis resulting from Goodpasture syndrome without other immunosuppressive drugs, is described. Symptoms appeared during a hypertensive crisis, but when cyclophosphamide was replaced by rituximab and hypertension was controlled, the patient did not have neurological symptoms. Almost all reported cases induced by immunosuppressive therapy or other causes were associated with hypertension as well. PMID:21686794

  14. [Etiopathogenesis of dilated cardiomyopathies].

    PubMed

    Petronio, A S; Manes, M T; Di Meco, F; Nardini, V; Pecori, F; Ceccherini-Nellis, L; Barsotti, A; Mariani, M

    1993-12-01

    This study was carried out on 43 patients affected by dilated cardiomyopathy to investigate some of the etiopathological hypotheses on this illness. The Authors investigated: the persistence of virus genoma (coxsackie, HBV) on endomyocardial biopsies; the pattern of the II class major histocompatibility complex (MHC) were in the blood lymphocytes; the microvascular aspect of coronary circulation in the endomyocardial biopsies. Finally, in a separated group of 19 patients, the microvascular circulation was studied on skin biopsies and correlated with diabetic, valvular and normal subject. The results showed a 14% positivity for the presence of the virus genoma and a significant predominate of DR5 in the II class MHC of patients with a worse ventricular function. Capillary vessels of the coronary microcirculation were dilated in the 48% of the patients, especially in more compromised subjects. Viral myocarditis seem to play a role in the etiopathogenesis of dilated cardiomyopathies (DCM) and the pattern of MHC could influence the progression of the illness. The microcirculation is probably a pathophysiological aspect. No etiological hypothesis seems to predominate.

  15. Low-dose cyclophosphamide-induced acute hepatotoxicity

    PubMed Central

    Subramaniam, S. Ravih; Cader, Rizna Abdul; Mohd, Rozita; Yen, Kong Wei; Ghafor, Halim Abdul

    2013-01-01

    Patient: Male, 48 Final Diagnosis: Low dose cyclophosphamide-induced acute hepatotoxicity Symptoms: Epigastric pain Medication: Withdrawal of cyclophosphamide Clinical Procedure: — Specialty: Nephrology • Hepatology • Gastroenterology • Toxicology Objective: Unexpected drug reaction Background: Cyclophosphamide is commonly used to treat cancers, systemic vasculitides, and kidney diseases (e.g., lupus nephritis and focal segmental glomerulosclerosis). Acute adverse effects include bone marrow suppression, hemorrhagic cystitis, nausea, vomiting, and hair loss. Hepatotoxicity with high dose cyclophosphamide is well recognized but hepatitis due to low dose cyclophosphamide has rarely been described. Case Report: We report the case of a 48-year-old Chinese man with a rapidly progressive glomerulonephritis secondary to granulomatosis with polyangiitis who developed severe acute hepatic failure within 24 hours of receiving low-dose intravenous cyclophosphamide. The diagnosis of granulomatosis with polyangiitis was supported with a positive c-ANCA serology. The patient was treated with high dose methylprednisolone, plasmapheresis, intermittent hemodialysis, and low-dose intravenous cyclophosphamide. Conclusions: Hepatotoxicity may occur even after low-dose intravenous cyclophosphamide treatment. To the best of our knowledge, this is the first report of severe, non-viral, liver inflammation developing within 24 hours of administration of low-dose intravenous cyclophosphamide (200 mg). Physicians should be aware of this serious adverse reaction and should not repeat the cyclophosphamide dose when there is hepatotoxicity caused by the first dose. Initial and follow-up liver function tests should be monitored in all patients receiving cyclophosphamide treatment. PMID:24023976

  16. Bootstrapping Time Dilation Decoherence

    NASA Astrophysics Data System (ADS)

    Gooding, Cisco; Unruh, William G.

    2015-10-01

    We present a general relativistic model of a spherical shell of matter with a perfect fluid on its surface coupled to an internal oscillator, which generalizes a model recently introduced by the authors to construct a self-gravitating interferometer (Gooding and Unruh in Phys Rev D 90:044071, 2014). The internal oscillator evolution is defined with respect to the local proper time of the shell, allowing the oscillator to serve as a local clock that ticks differently depending on the shell's position and momentum. A Hamiltonian reduction is performed on the system, and an approximate quantum description is given to the reduced phase space. If we focus only on the external dynamics, we must trace out the clock degree of freedom, and this results in a form of intrinsic decoherence that shares some features with a proposed "universal" decoherence mechanism attributed to gravitational time dilation (Pikovski et al in Nat Phys, 2015). We note that the proposed decoherence remains present in the (gravity-free) limit of flat spacetime, emphasizing that the effect can be attributed entirely to proper time differences, and thus is not necessarily related to gravity. Whereas the effect described in (Pikovski et al in Nat Phys, 2015) vanishes in the absence of an external gravitational field, our approach bootstraps the gravitational contribution to the time dilation decoherence by including self-interaction, yielding a fundamentally gravitational intrinsic decoherence effect.

  17. High dose cyclophosphamide performs better than monthly dose cyclophosphamide in quality of life measures.

    PubMed

    Dussán, K B; Magder, L; Brodsky, R A; Jones, R J; Petri, M

    2008-12-01

    In spite of current therapies, the overall health status of patients with SLE is poor. High-dose cyclophosphamide (50 mg/kg for 4 days) with or without stem-cell rescue has been introduced as a new therapy for severe SLE, including renal and central nervous system (CNS)-SLE. Long-term durable responses have been found to be 40%. A randomised clinical trial was completed comparing high-dose cyclophosphamide with monthly intravenous cyclophosphamide (750 mg/m squared bovine serum albumin) in patients with SLE who need cyclophosphamide for the first time. The primary outcome of the trial was complete clinical response. In this report, we compare the treatment groups with respect to quality of life. The patients in this study had a mean age of 35.3 +/- 10.1 years, were of Caucasian (35%), African-American (51%), Hispanic (8%) and Asian (6%) people, and 88% were women. The organ leading to treatment was renal lupus in 29%, CNS-lupus in 45% and other organs in 26%. Quality of life was measured at each visit using the Medical Outcome Study Short-Form 36 (SF-36). At 6 months, the patients in the high-dose cyclophosphamide trial arm had significantly greater improvement than patients in the monthly intravenous cyclophosphamide arm (P = 0.026; P = 0.0082, respectively) in the categories of general health and social functioning. At 18 months, the improvement in the role-physical score was significantly greater in the high-dose cyclophosphamide trial arm than in the monthly-dose cyclophosphamide arm (P = 0.025). At the end of the two and a half-year study, there were no significant differences between the groups with respect to changes in SF-36. By pooling the groups, at 30 months, there was a statistically significant (P < 0.05) improvement over baseline in 6 of the 8 SF-36 domains. This study shows earlier improvement in SF-36 measures at 6 months in the high-dose cyclophosphamide group but equal improvement in both arms at two and one and a half years. Eventual improvements

  18. Pulmonary toxicity of cyclophosphamide: a 1-year study

    SciTech Connect

    Morse, C.C.; Sigler, C.; Lock, S.; Hakkinen, P.J.; Haschek, W.M.; Witschi, H.P.

    1985-01-01

    The development of cyclophosphamide-induced pulmonary lesions over a 1-year period was studied in mice. Male BALB/c mice received a single intraperitoneal injection of 100 mg/kg of cyclophosphamide. Within 3 weeks there were scattered foci of intraalveolar foamy macrophages. With time, these foci increased in size and, 1 year later, occupied large areas in all lung lobes. There was also diffuse interstitial fibrosis. Chemical determination done 3, 12, 24, and 52 weeks after cyclophosphamide showed that lungs of animals treated with cyclophosphamide had significantly more hydroxyproline per lung than controls. One year after cyclophosphamide pressure - volume curves measured in vivo were shifted down and to the right and total lung volumes were decreased. A single injection of cyclophosphamide produced an irreversible and progressive pulmonary lesion. 16 references, 5 figures, 3 tables.

  19. Inflammatory dilated cardiomyopathy (DCMI).

    PubMed

    Maisch, Bernhard; Richter, Anette; Sandmöller, Andrea; Portig, Irene; Pankuweit, Sabine

    2005-09-01

    Cardiomyopathies are heart muscle diseases, which have been defined by their central hemodynamics and macropathology and divided in five major forms: dilated (DCM), hypertrophic (HCM), restrictive (RCM), right ventricular (RVCM), and nonclassifiable cardiomyopathies (NCCM). Furthermore, the most recent WHO/WHF definition also comprises, among the specific cardiomyopathies, inflammatory cardiomyopathy as a distinct entity, defined as myocarditis in association with cardiac dysfunction. Idiopathic, autoimmune, and infectious forms of inflammatory cardiomyopathy were recognized. Viral cardiomyopathy has been defined as viral persistence in a dilated heart. It may be accompanied by myocardial inflammation and then termed inflammatory viral cardiomyopathy (or viral myocarditis with cardiomegaly). If no inflammation is observed in the biopsy of a dilated heart (< 14 lymphocytes and macrophages/mm(2)), the term viral cardiomyopathy or viral persistence in DCM should be applied according to the WHF Task Force recommendations. Within the German heart failure net it is the authors' working hypothesis, that DCM shares genetic risk factors with other diseases of presumed autoimmune etiology and, therefore, the same multiple genes in combination with environmental factors lead to numerous different autoimmune diseases including DCM. Therefore, the authors' primary goal is to acquire epidemiologic data of patients with DCM regarding an infectious and inflammatory etiology of the disease. Circumstantial evidence points to a major role of viral myocarditis in the etiology of DCM. The common presence of viral genetic material in the myocardium of patients with DCM provides the most compelling evidence, but proof of causality is still lacking. In addition, autoimmune reactions have been described in many studies, indicating them as an important etiologic factor. Nevertheless, data on the proportion of patients, in whom both mechanisms play a role are still missing.A pivotal role for

  20. Water Intoxication Following Low-Dose Intravenous Cyclophosphamide

    PubMed Central

    Koo, Tai Yeon; Bae, Sang-Cheol; Park, Joon Sung; Lee, Chang Hwa; Park, Moon Hyang; Kang, Chong Myung

    2007-01-01

    Cyclophosphamide is frequently used for the treatment of severe lupus nephritis, but is very rarely associated with dilutional hyponatremia. Recently we experienced a case of water intoxication following low-dose intravenous cyclophosphamide. Five hours after one dose of intravenous pulse cyclophosphamide 750 mg, the patient developed nausea, vomiting, and general weakness. Serum sodium concentration revealed 114 mEq/L and her hyponatremia was initially treated with hypertonic saline infusion. Then her serum sodium concentration rapidly recovered to normal with water restriction alone. During the course of intravenous pulse cyclophosphamide therapy, one must be aware of the possibility of significant water retention. PMID:24459501

  1. Water intoxication following low-dose intravenous cyclophosphamide.

    PubMed

    Koo, Tai Yeon; Bae, Sang-Cheol; Park, Joon Sung; Lee, Chang Hwa; Park, Moon Hyang; Kang, Chong Myung; Kim, Gheun-Ho

    2007-06-01

    Cyclophosphamide is frequently used for the treatment of severe lupus nephritis, but is very rarely associated with dilutional hyponatremia. Recently we experienced a case of water intoxication following low-dose intravenous cyclophosphamide. Five hours after one dose of intravenous pulse cyclophosphamide 750 mg, the patient developed nausea, vomiting, and general weakness. Serum sodium concentration revealed 114 mEq/L and her hyponatremia was initially treated with hypertonic saline infusion. Then her serum sodium concentration rapidly recovered to normal with water restriction alone. During the course of intravenous pulse cyclophosphamide therapy, one must be aware of the possibility of significant water retention.

  2. Microstructural formulation of stress dilatancy

    NASA Astrophysics Data System (ADS)

    Wan, Richard; Guo, Peijun

    2014-03-01

    In this work, we show that the well-known Rowe's stress-dilatancy relation can be readily recovered from a micromechanical analysis of an assembly of rigid particles as a purely dissipative system in the case of a regular packing. When the analysis is extended to a random packing, one can explicitly incorporate the dependence of fabric, density and stress level on dilatancy, a basic aspect of geomaterial behaviour. The resulting microstructurally based stress dilatancy relation can be easily implemented as a non-associated flow rule in any standard elastoplastic model. Some numerical simulations of stress-dilatancy with initial fabric as a controlling variable are presented to illustrate the developed model. xml:lang="fr"

  3. Post-earthquake dilatancy recovery

    NASA Technical Reports Server (NTRS)

    Scholz, C. H.

    1974-01-01

    Geodetic measurements of the 1964 Niigata, Japan earthquake and of three other examples are briefly examined. They show exponentially decaying subsidence for a year after the quakes. The observations confirm the dilatancy-fluid diffusion model of earthquake precursors and clarify the extent and properties of the dilatant zone. An analysis using one-dimensional consolidation theory is included which agrees well with this interpretation.

  4. Esophageal dilation in eosinophilic esophagitis.

    PubMed

    Richter, Joel E

    2015-10-01

    Tissue remodeling with scaring is common in adult EoE patients with long standing disease. This is the major factor contributing to their complaints of solid food dysphagia and recurrent food impactions. The best tests to define the degree of remodeling are barium esophagram, high resolution manometry and endoscopy. Many physicians are fearful to dilate EoE patients because of concerns about mucosal tears and perforations. However, multiple recent case series attest to the safety of esophageal dilation and its efficacy with many patients having symptom relief for an average of two years. This chapter will review the sordid history of esophageal dilation in EoE patients and outline how to perform this procedure safely. The key is graduated dilation over one to several sessions to a diameter of 15-18 mm. Postprocedural pain is to be expected and mucosal tears are a sign of successful dilation, not complications. In some healthy adults, occasional dilation may be preferred to regular use of medications or restricted diets. This approach is now supported by recent EoE consensus statements and societal guidelines.

  5. Dilatational band formation in bone

    PubMed Central

    Poundarik, Atharva A.; Diab, Tamim; Sroga, Grazyna E.; Ural, Ani; Boskey, Adele L.; Gundberg, Caren M.; Vashishth, Deepak

    2012-01-01

    Toughening in hierarchically structured materials like bone arises from the arrangement of constituent material elements and their interactions. Unlike microcracking, which entails micrometer-level separation, there is no known evidence of fracture at the level of bone’s nanostructure. Here, we show that the initiation of fracture occurs in bone at the nanometer scale by dilatational bands. Through fatigue and indentation tests and laser confocal, scanning electron, and atomic force microscopies on human and bovine bone specimens, we established that dilatational bands of the order of 100 nm form as ellipsoidal voids in between fused mineral aggregates and two adjacent proteins, osteocalcin (OC) and osteopontin (OPN). Laser microdissection and ELISA of bone microdamage support our claim that OC and OPN colocalize with dilatational bands. Fracture tests on bones from OC and/or OPN knockout mice (OC−/−, OPN−/−, OC-OPN−/−;−/−) confirm that these two proteins regulate dilatational band formation and bone matrix toughness. On the basis of these observations, we propose molecular deformation and fracture mechanics models, illustrating the role of OC and OPN in dilatational band formation, and predict that the nanometer scale of tissue organization, associated with dilatational bands, affects fracture at higher scales and determines fracture toughness of bone. PMID:23129653

  6. HLA Haplotype Mismatch Transplants and Posttransplant Cyclophosphamide.

    PubMed

    Bacigalupo, Andrea; Sica, Simona

    2016-01-01

    The use of high dose posttransplant cyclophosphamide (PT-CY) introduced by the Baltimore group approximately 10 years ago has been rapidly adopted worldwide and is becoming a standard for patients undergoing unmanipulated haploidentical (HAPLO) transplants. PT-CY has been used following nonmyeloablative as well as myeloablative conditioning regimens, for bone marrow or peripheral blood grafts, for patients with malignant and nonmalignant disorders. Retrospective comparisons of HAPLO grafts with conventional sibling and unrelated donor grafts have been published and suggest comparable outcome. The current questions to be answered include the use of PT-CY for sibling and unrelated donors transplant, possibly in the context of prospective randomized trial.

  7. HLA Haplotype Mismatch Transplants and Posttransplant Cyclophosphamide

    PubMed Central

    Bacigalupo, Andrea; Sica, Simona

    2016-01-01

    The use of high dose posttransplant cyclophosphamide (PT-CY) introduced by the Baltimore group approximately 10 years ago has been rapidly adopted worldwide and is becoming a standard for patients undergoing unmanipulated haploidentical (HAPLO) transplants. PT-CY has been used following nonmyeloablative as well as myeloablative conditioning regimens, for bone marrow or peripheral blood grafts, for patients with malignant and nonmalignant disorders. Retrospective comparisons of HAPLO grafts with conventional sibling and unrelated donor grafts have been published and suggest comparable outcome. The current questions to be answered include the use of PT-CY for sibling and unrelated donors transplant, possibly in the context of prospective randomized trial. PMID:27143973

  8. A Case of Polyarteritis Nodosa Associated with Vertebral Artery Vasculitis Treated Successfully with Tocilizumab and Cyclophosphamide

    PubMed Central

    Watanabe, Kae; Rajderkar, Dhanashree A.; Modica, Renee F.

    2016-01-01

    Pediatric polyarteritis nodosa is rare systemic necrotizing arteritis involving small- and medium-sized muscular arteries characterized by aneurysmal dilatations involving the vessel wall. Aneurysms associated with polyarteritis nodosa are common in visceral arteries; however intracranial aneurysms have also been reported and can be associated with central nervous system symptoms, significant morbidity, and mortality. To our knowledge extracranial involvement of the vertebral arteries has not been reported but has the potential to be deleterious due to fact that they supply the central nervous system vasculature. We present a case of a 3-year-old Haitian boy with polyarteritis nodosa that presented with extracranial vessel involvement of his vertebral arteries. After thorough diagnostic imaging, including a bone scan, ultrasound, Magnetic Resonance Imaging/Angiography, and Computed Tomography Angiography, he was noted to have vertebral artery vasculitis, periostitis, subacute epididymoorchitis, arthritis, and myositis. He met diagnostic criteria for polyarteritis nodosa and was treated with cyclophosphamide, methylprednisolone, and tocilizumab, which resulted in improvement of his inflammatory markers, radiographic findings, and physical symptoms after treatment. To the authors' knowledge, this is the first report of vertebral artery vasculitis in polyarteritis nodosa as well as successful treatment of the condition using the combination cyclophosphamide and tocilizumab for this condition. PMID:27018080

  9. Viral Myocarditis and Dilated Cardiomyopathy: Etiology and Pathogenesis.

    PubMed

    Huber, Sally A

    2016-01-01

    Myocarditis is an inflammation of the myocardium which often follows microbial infections and is a significant cause of sudden unexpected death in the young (<40 years of age) and an underlying cause of dilated cardiomyopathy. Although histologically, the disease is usually associated with infiltration of the myocardium with either eosinophils or leukocytes, use of immunosuppression is controversial outside of giant cell myocarditis and has been found to be of limited value in lymphocytic myocarditis. The relatively limited response might reflect the need for host immunity to control persistent virus infection in the heart which may be the predominant cause of the chronic myocarditis and dilated cardiomyopathy. Treating the persistent virus infection with interferon-beta improved cardiac function in a clinical trial. However, classic immunosuppressive drugs, such as cyclosporine A and cyclophosphamide, are not effective against all types of immunity and experimental myocarditis models have shown that certain immunopathogenic forms of the disease are resistant to these immunosuppressive agents. Understanding the molecular mechanisms underlying the pathogenesis of this disease and the various infectious agents which can cause it will be essential for developing effective therapeutic agents.

  10. Phase I controlled trials of WR-2721 and cyclophosphamide

    SciTech Connect

    Glick, J.H.; Glover, D.; Weiler, C.; Norfleet, L.; Yuhas, J.; Kligerman, M.M.

    1984-09-01

    WR-2721 is an organic thiophosphate compound which in the animal model selectively protects against the hematologic toxicity of cyclophosphamide by factors of 1.5 to 2.0. Controlled Phase I trials of WR-2721 and cyclophosphamide were initiated to determine if WR-2721 protected against cyclophosphamide's hematolgic toxicity. Fifteen patients received WR-2721 prior to cyclophosphamide and were subsequently retreated 4 weeks later with the same cyclophosphamide dose alone. With WR-2721 pretreatment, 11/15 (73%) patients had improved WBC counts. In the second trial, 25 patients received the reverse sequence: an initial dose of cyclophosphamide alone, followed 4 weeks later by WR-2721 prior to the same dose of cyclophosphamide. With WR-2721 pretreatment, 12/25 (48%) patients had improved nadir WBC counts. No patient developed microscopic or gross hematuria or inappropriate antidiuretic hormone secretion. These data suggest that WR-2721 provides significant protection against cyclophosphamide-induced granulocytopenia, but the dose modification factors and degree of clinical benefit remain to be established. The current recommended WR-2721 dose for Phase II trials is 740 mg/m/sup 2/ administered over 15 minutes.

  11. Bioavailability of cyclophosphamide and vincristine after intraperitoneal administration in cats.

    PubMed

    Voorhorst, Marieke J; van Maarseveen, Erik M; van Lankveld, Adriaan J; Teske, Erik

    2014-11-01

    Cyclophosphamide and vincristine are widely used intravenous chemotherapeutic agents in both human and veterinary oncology. Although intravenous administration of these chemotherapeutics is the gold standard in most treatment protocols, this route of administration has several disadvantages (e.g. long infusion times and risk of extravasation). Therefore, alternative routes have been explored in the past. Recently, good clinical results were achieved with intraperitoneal (i.p.) administration of cyclophosphamide and vincristine in cats. However, the bioavailability following i.p. administration of cyclophosphamide and vincristine providing proof of principle has not been investigated and is the focus of the present study. The pharmacokinetics of cyclophosphamide and vincristine after i.p. and intravenous administration was investigated in six cats in a cross-over study by analysis of plasma levels of cyclophosphamide and vincristine after simultaneously administration of 0.6 mg/m vincristine and 200 mg/m cyclophosphamide. The median bioavailability on i.p. administration was 76% for cyclophosphamide and 100% for vincristine. Median areas under the curve for i.p. and intravenous administration were 11.4 and 16.0 ng h/ml for cyclophosphamide and 16.7 and 16.5 ng h/ml for vincristine, respectively. No specific i.p. administration-related adverse events were observed after i.p. administration. The high bioavailability of both cyclophosphamide and vincristine after i.p. administration and the absence of specific i.p. administration-related side effects suggest that i.p. administration is a suitable route of systemic chemotherapy for both chemotherapeutics. These results are promising and may serve as a stepping stone for the investigation of the pharmacology, safety, and efficacy of i.p. administration of cyclophosphamide and vincristine in humans.

  12. Genetic basis of dilated cardiomyopathy.

    PubMed

    Pérez-Serra, Alexandra; Toro, Rocio; Sarquella-Brugada, Georgia; de Gonzalo-Calvo, David; Cesar, Sergi; Carro, Esther; Llorente-Cortes, Vicenta; Iglesias, Anna; Brugada, Josep; Brugada, Ramon; Campuzano, Oscar

    2016-12-01

    Dilated cardiomyopathy is a rare cardiac disease characterized by left ventricular dilatation and systolic dysfunction leading to heart failure and sudden cardiac death. Currently, despite several conditions have been reported as aetiologies of the disease, a large number of cases remain classified as idiopathic. Recent studies determine that nearly 60% of cases are inherited, therefore due to a genetic cause. Progressive technological advances in genetic analysis have identified over 60 genes associated with this entity, being TTN the main gene, so far. All these genes encode a wide variety of myocyte proteins, mainly sarcomeric and desmosomal, but physiopathologic pathways are not yet completely unraveled. We review the recent published data about genetics of familial dilated cardiomyopathy.

  13. Cyclophosphamide administration routine in autoimmune rheumatic diseases: a review.

    PubMed

    Teles, Kaian Amorim; Medeiros-Souza, Patrícia; Lima, Francisco Aires Correa; Araújo, Bruno Gedeon de; Lima, Rodrigo Aires Correa

    2016-09-17

    Cyclophosphamide (CPM) is an alkylating agent widely used for the treatment of malignant neoplasia and which can be used in the treatment of multiple rheumatic diseases. Medication administration errors may lead to its reduced efficacy or increased drug toxicity. Many errors occur in the administration of injectable drugs. The present study aimed at structuring a routine for cyclophosphamide use, as well as creating a document with pharmacotherapeutic guidelines for the patient. The routine is schematized in three phases: pre-chemotherapy (pre-ChT), administration of cyclophosphamide, and post-chemotherapy (post-ChT), taking into account the drugs to be administered before and after cyclophosphamide in order to prevent adverse effects, including nausea and hemorrhagic cystitis. Adverse reactions can alter laboratory tests; thus, this routine included clinical management for changes in white blood cells, platelets, neutrophils, and sodium, including cyclophosphamide dose adjustment in the case of kidney disease. Cyclophosphamide is responsible for other rare-but serious-side effects, for instance, hepatotoxicity, severe hyponatremia and heart failure. Other adverse reactions include hair loss, amenorrhea and menopause. In this routine, we also entered guidelines to post-chemotherapy patients. The compatibility of injectable drugs with the vehicle used has been described, as well as stability and infusion times. The routine aimed at the rational use of cyclophosphamide, with prevention of adverse events and relapse episodes, factors that may burden the health care system.

  14. Imaging enhancement of malignancy by cyclophosphamide: surprising chemotherapy opposite effects

    NASA Astrophysics Data System (ADS)

    Yamauchi, Kensuke; Yang, Meng; Hayashi, Katsuhiro; Jiang, Ping; Xu, Mingxu; Yamamoto, Norio; Tsuchiya, Hiroyuki; Tomita, Katsuro; Moossa, A. R.; Bouvet, Michael; Hoffman, Robert M.

    2008-02-01

    Although side effects of cancer chemotherapy are well known, "opposite effects" of chemotherapy which enhance the malignancy of the treated cancer are not well understood. We have observed a number of steps of malignancy that are enhanced by chemotherapy pre-treatment of mice before transplantation of human tumor cells. The induction of intravascular proliferation, extravasation, and colony formation by cancer cells, critical steps of metastasis was enhanced by pretreatment of host mice with the commonly-used chemotherapy drug cyclophosphamide. Cyclophosphamide appears to interfere with a host process that inhibits intravascular proliferation, extravasation, and extravascular colony formation by at least some tumor cells. Cyclophosphamide does not directly affect the cancer cells since cyclophosphamide has been cleared by the time the cancer cells were injected. Without cyclophosphamide pretreatment, human colon cancer cells died quickly after injection in the portal vein of nude mice. Extensive clasmocytosis (destruction of the cytoplasm) of the cancer cells occurred within 6 hours. The number of apoptotic cells rapidly increased within the portal vein within 12 hours of injection. However, when the host mice were pretreated with cyclophosphamide, the cancer cells survived and formed colonies in the liver after portal vein injection. These results suggest that a cyclophosphamide-sensitive host cellular system attacked the cancer cells. This review describes an important unexpected "opposite effects" of chemotherapy that enhances critical steps in malignancy rather than inhibiting them, suggesting that certain current approaches to cancer chemotherapy should be modified.

  15. Idiopathic dilatation of pulmonary artery

    PubMed Central

    Sharma, Rahul Kumar; Talwar, Deepak; Gupta, Sameer K; Bansal, Shobhit

    2016-01-01

    Idiopathic dilatation of pulmonary arteries (IDPA) is a rare abnormality of pulmonary arteries, the reported incidence in literature being as low as 0.007% in autopsy samples. With the improvement in diagnostic modalities, antemortem diagnosis of IDPA has been increasingly established by excluding diseases that induce pulmonary arterial enlargement. Here, we present a rare case of idiopathic dilatation of the pulmonary artery admitted with shortness of breath where IDPA was diagnosed as an incidental finding using computed tomography pulmonary angiography and cardiac catheterization. PMID:27891002

  16. Cyclophosphamide-associated enteritis: A rare association with severe enteritis

    PubMed Central

    Yang, Linda S; Cameron, Karla; Papaluca, Tim; Basnayake, Chamara; Jackett, Louise; McKelvie, Penelope; Goodman, David; Demediuk, Barbara; Bell, Sally J; Thompson, Alexander J

    2016-01-01

    Cyclophosphamide is a potent cytotoxic agent used in many clinical settings. The main risks of cyclophosphamide therapy include hematological disorders, infertility, hemorrhagic cystitis and malignancies. Gastrointestinal side effects reported to date are often non-specific and not severe. We present the first case of a fatal small bowel enteritis and pan-colitis which appears to be associated with cyclophosphamide. We aim to raise the readers’ awareness of this significant adverse event to facilitate clinical suspicion and early recognition in potential future cases. PMID:27818600

  17. The effect of cyclophosphamide on MSV-H oncogenesis.

    PubMed Central

    Branca, M.; Nicoletti, L.

    1977-01-01

    The effect of cyclophosphamide on MSV-H oncogensis and the immune response of young mice has been investigated. A single, sublethal dose (100 and 50 mg/kg of cyclophosphamide) in 8-day-old mice given 24 h before or after MSV-H infection led to an earlier and lower incidence of tumours in comparison with controls infected only with MSV-H. The protective effect of cyclophosphamide, and the mechanism of action of both cyclophosphamide and MSV-H on the target cells, mesenchymal cells in rapid replication, as well the immunological implications of the findings are discussed. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:201258

  18. Genetics Home Reference: X-linked dilated cardiomyopathy

    MedlinePlus

    ... Conditions X-linked dilated cardiomyopathy X-linked dilated cardiomyopathy Printable PDF Open All Close All Enable Javascript ... the expand/collapse boxes. Description X-linked dilated cardiomyopathy is a form of heart disease. Dilated cardiomyopathy ...

  19. Damage to rat spermatozoal DNA after chronic cyclophosphamide exposure.

    PubMed

    Qiu, J; Hales, B F; Robaire, B

    1995-12-01

    Treatment of male rats with low dosages of cyclophosphamide causes a dramatic increase in early embryo death among their progeny without significantly affecting the general health of the male. It is hypothesized that cyclophosphamide exerts its effects by targeting specific components of spermatozoal nuclei. The purpose of the present studies was to investigate the effects of chronic cyclophosphamide treatment on spermatozoal DNA. Two approaches were pursued. The first was to determine total DNA damage by using the alkaline elution method. The second was to study spermatozoal DNA template function by using an in vitro DNA synthesis system. Adult male rats were treated with saline or cyclophosphamide (6.1 mg/kg/day) daily for 1 or 6 wk. Cauda epididymal spermatozoa were collected and subjected to alkaline elution using DNA-DNA dot hybridization to quantify the fractionated DNA. One week of treatment with cyclophosphamide caused DNA single strand breaks that could be detected only in the presence of proteinase K in the lysis solution; no DNA cross-links were observed in the animals that received 1-wk drug treatment. In contrast, 6 wk of treatment with cyclophosphamide induced a significant increase in both DNA single strand breaks and cross-links in spermatozoal nuclei; the cross-links were attributable primarily to DNA-DNA linkages. The availability of spermatozoal DNA for template function was not affected by 1 wk of treatment with cyclophosphamide but was markedly affected after 6 wk of treatment with this drug. It is proposed that during chromatin transition processes the male genome may be in an open dynamic state with many exposed sites that are vulnerable to alkylating agents. Since there is no DNA repair during spermiogenesis, damage to the genome by alkylation at this stage may be cumulative, resulting in the production of dysfunctional germ cells.

  20. Antarctic Analog for Dilational Bands on Europa

    NASA Technical Reports Server (NTRS)

    Hurford, T. A.; Brunt, K. M.

    2014-01-01

    Europa's surface shows signs of extension, which is revealed as lithospheric dilation expressed along ridges, dilational bands and ridged bands. Ridges, the most common tectonic feature on Europa, comprise a central crack flanked by two raised banks a few hundred meters high on each side. Together these three classes may represent a continuum of formation. In Tufts' Dilational Model ridge formation is dominated by daily tidal cycling of a crack, which can be superimposed with regional secular dilation. The two sources of dilation can combine to form the various band morphologies observed. New GPS data along a rift on the Ross Ice Shelf, Antarctica is a suitable Earth analog to test the framework of Tufts' Dilational Model. As predicted by Tufts' Dilational Model, tensile failures in the Ross Ice Shelf exhibit secular dilation, upon which a tidal signal can be seen. From this analog we conclude that Tufts' Dilational Model for Europan ridges and bands may be credible and that the secular dilation is most likely from a regional source and not tidally driven.

  1. Antarctic analog for dilational bands on Europa

    NASA Astrophysics Data System (ADS)

    Hurford, T. A.; Brunt, K. M.

    2014-09-01

    Europa's surface shows signs of extension, which is revealed as lithospheric dilation expressed along ridges, dilational bands and ridged bands. Ridges, the most common tectonic feature on Europa, comprise a central crack flanked by two raised banks a few hundred meters high on each side. Together these three classes may represent a continuum of formation. In Tufts' Dilational Model ridge formation is dominated by daily tidal cycling of a crack, which can be superimposed with regional secular dilation. The two sources of dilation can combine to form the various band morphologies observed. New GPS data along a rift on the Ross Ice Shelf, Antarctica is a suitable Earth analog to test the framework of Tufts' Dilational Model. As predicted by Tufts' Dilational Model, tensile failures in the Ross Ice Shelf exhibit secular dilation, upon which a tidal signal can be seen. From this analog we conclude that Tufts' Dilational Model for Europan ridges and bands may be credible and that the secular dilation is most likely from a regional source and not tidally driven.

  2. Diagnostic criteria for congenital biliary dilatation 2015.

    PubMed

    Hamada, Yoshinori; Ando, Hisami; Kamisawa, Terumi; Itoi, Takao; Urushihara, Naoto; Koshinaga, Tsugumichi; Saito, Takeshi; Fujii, Hideki; Morotomi, Yoshiki

    2016-06-01

    The Diagnostic Criteria for Pancreaticobiliary Maljunction 2013 were published by the Japanese Study Group on Pancreaticobiliary Maljunction (JSGPM) in 2014. The committee of JSGPM for diagnostic criteria for pancreaticobiliary maljunction has established the standard diameter of the bile duct, and a definition of dilatation of the bile duct was proposed in 2014. The committee of JSGPM prepared the diagnostic criteria for congenital biliary dilatation in 2014, and a final revised version was approved in 2015. Congenital biliary dilatation is defined as a congenital malformation involving both local dilatation of the extrahepatic bile duct, including the common bile duct, and pancreaticobiliary maljunction. However, cases associated with intrahepatic bile duct dilatation can also be included. Various kinds of pathological conditions can occur on hepatobiliary systems and pancreas by bile duct dilatation and pancreaticobiliary maljunction. For a diagnosis of congenital biliary dilatation, both abnormal dilatation of the bile duct and pancreaticobiliary maljunction must be evident by either imaging test or anatomical examination. Acquired or secondary dilatation of the bile duct by obstruction due to biliary stones or malignancy should be strictly excluded. Diagnostic criteria for congenital biliary dilatation 2015 were established from Japan representing a world first. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  3. The use of emoxipin for correction of cyclophosphamide cytotoxicity in experimental animals.

    PubMed

    Siprov, A V; Kinzirskaya, Yu A

    2008-07-01

    In experiments on animals with Lewis lung carcinoma, emoxipin decreased hematotoxicity of cyclophosphamide without reducing its antitumor efficiency (effect on primary tumor node). Combined administration of emoxipin and cyclophosphamide more effectively prevented the development of metastases compared to cytostatic monotherapy.

  4. The pupil dilation response to visual detection

    NASA Astrophysics Data System (ADS)

    Privitera, Claudio M.; Renninger, Laura W.; Carney, Thom; Klein, Stanley; Aguilar, Mario

    2008-02-01

    The pupil dilation reflex is mediated by inhibition of the parasympathetic Edinger-Westphal oculomotor complex and sympathetic activity. It has long been documented that emotional and sensory events elicit a pupillary reflex dilation. Is the pupil response a reliable marker of a visual detection event? In two experiments where viewers were asked to report the presence of a visual target during rapid serial visual presentation (RSVP), pupil dilation was significantly associated with target detection. The amplitude of the dilation depended on the frequency of targets and the time of the detection. Larger dilations were associated with trials having fewer targets and with targets viewed earlier during the trial. We also found that dilation was strongly influenced by the visual task.

  5. [Monitoring cervical dilatation by impedance].

    PubMed

    Salvat, J; Lassen, M; Sauze, C; Baud, S; Salvat, F

    1992-01-01

    Several different physics procedures have been tried to mechanize the recording of partograms. Can a measure of impedance of tissue Z using potential difference V, according to Ohm's law V = Z1, and 1 is a constant, be correlated with a measure of cervical dilatation using vaginal examination? This was our hypothesis. The tissue impedance meter was made to our design and applied according to a bipolar procedure. Our work was carried out on 28 patients. 10 patients were registered before labour started in order to test the apparatus and to record the impedance variations without labour taking place, and 18 patients were registered in labour to see whether there was any correlation. The level of impedance in the cervix without labour was 302.7 Ohms with a deviation of 8.2. Using student's t tests it was found that there was a significant correlation (p less than 0.001) in four measurements between the impedance measure and measures obtained by extrapolating the degrees of dilatation calculated from vaginal examination. This is a preliminary study in which we have defined the conditions that are necessary to confirm these first results and to further develop the method.

  6. Cyclophosphamide and Doxorubicin Induced Melanonychia: A Case Report

    PubMed Central

    Prajapati, Vivek Bhanubhai; Acharya, Raviraj; Gopalaswamy, Vinaya; Doddamani, Akhila

    2017-01-01

    Chemotherapeutic agents may rarely cause discoloration and hyperpigmentation of the nails. We present a patient who developed blackish discoloration of nails also referred as melanonychia during six cycles of R-CHOP chemotherapy regimen (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) for the treatment of Non Hodgkin Lymphoma (NHL) follicular type. The patient developed blackish brown discoloration in all the nails. As suggested by previous literature evidence the melanonychia could be associated with cyclophosphamide and doxorubicin. According to the Naranjo causality assessment scale, we established that there was a ‘probable’ association of nail discoloration with the drug. PMID:28273993

  7. Cyclophosphamide in the treatment of toxic epidermal necrolysis.

    PubMed

    Frangogiannis, N G; Boridy, I; Mazhar, M; Mathews, R; Gangopadhyay, S; Cate, T

    1996-10-01

    A patient with non-small cell lung carcinoma and recent radiotherapy for brain metastases developed toxic epidermal necrolysis (TEN) shortly after therapy with phenytoin was initiated for a seizure. Exfoliation progressed to involve 90% of her body surface despite treatment with high-dose corticosteroids for 5 days, but sloughing and systemic toxicity ceased within 2 days of initiating therapy with intravenous cyclophosphamide (300 mg/day). Reepithelialization rapidly followed. This experience and the reports of others suggest that intravenous cyclophosphamide is helpful in the treatment of TEN.

  8. Teratogenic effects of first-trimester cyclophosphamide therapy.

    PubMed

    Kirshon, B; Wasserstrum, N; Willis, R; Herman, G E; McCabe, E R

    1988-09-01

    Intravenous cyclophosphamide was administered for severe exacerbation of systemic lupus erythematosus to a patient not known to be in the first trimester of pregnancy. The patient received no other medication except prednisone. Her neonate was born with multiple anomalies, including absent thumbs, cleft palate, low-set ears, and multiple eye abnormalities. These anomalies probably reflect teratogenic effects of cyclophosphamide, and indicate that judgment is required before its use in the first trimester. Furthermore, this case illustrates the need for effective contraception and repetitive pregnancy testing when potentially teratogenic agents are administered to presumably nonpregnant women in the reproductive age group.

  9. A randomized trial of cyclophosphamide, doxorubicin, and prednisone versus cyclophosphamide, 5-fluorouracil, and prednisone in patients with metastatic breast cancer.

    PubMed

    Ahmann, D L; Schaid, D J; Ingle, J N; Bisel, H F; Schutt, A J; Buckner, J C; Long, H J; Rubin, J

    1991-06-01

    Ninety-four patients were entered in a clinical trial assessing the clinical activity of cyclophosphamide, doxorubicin, and prednisone (CAP) versus a combination of cyclophosphamide. 5-Fluorouracil, and prednisone (CFP) in patients with advanced breast cancer. Objective response rates were comparable, 49% for CFP and 46% for CAP. There was no statistical difference between the duration of response of the two regimens or in time to progression. Most importantly, survival differences were not apparent. Both regimens were clinically tolerable and toxicities, for the most part, were comparable. Thus, no therapeutic advantage existed for either of these polychemotherapy regimens in patients with advanced breast cancer.

  10. [Percutanous dilation tracheotomy: our experience].

    PubMed

    Domènech, I; Mateu, T; Cisa, E; Juan, A; Gil, E; Palau, M; Dicenta, M

    2004-01-01

    Percutaneous dilation Tracheotomy (PDT) is becoming a popular alternative to surgical tracheotomy. In our hospital, we recently adopted the use of the PDT in intensive care unit patients. The objective [corrected] of this investigation is to characterize and quantify the rate of complications for PDT. A prospective study of 60 PDT performed at different intesive care units, betweem September 2002 to July 2003. The intraoperative time for PDT was 8 minutes. Complications included 6 cases of mild intraoperative hemorrhage, 1 case of moderate intraoperative hemorrhage, 4 cases of mild postoperative hemorrhage and 1 case of subcutaneous emphysema. PDT is a good alternative to surgical tracheotomy and should be added to the otolaryngologists armamentarium of surgical airway procedures.

  11. On turbulence in dilatant dispersions

    NASA Astrophysics Data System (ADS)

    Baumert, Helmut Z.; Wessling, Bernhard

    2016-07-01

    This paper presents a new theory on the behaviour of shear-thickening (dilatant) fluids under turbulent conditions. The structure of a dilatant colloidal fluid in turbulent motion may be characterized by (at least) four characteristic length scales: (i) the ‘statistically largest’ turbulent scale, {λ }0, labeling the begin of the inertial part of the wavenumber spectrum; (ii) the energy-containing scale, { L }; (iii) Kolmogorov’s micro-scale, {λ }{ K }, related with the size of the smallest vortices existing for a given kinematic viscosity and forcing; (iv) the inner (‘colloidal’) micro-scale, {λ }i, typically representing a major stable material property of the colloidal fluid. In particular, for small ratios r={λ }i/{λ }{ K }∼ { O }(1), various interactions between colloidal structures and smallest turbulent eddies can be expected. In the present paper we discuss particularly that for ρ ={λ }0/{λ }{ K }\\to { O }(1) turbulence (in the narrow, inertial sense) is strangled and chaotic but less mixing fluid motions remain. We start from a new stochastic, micro-mechanical turbulence theory without empirical parameters valid for inviscid fluids as seen in publications by Baumert in 2013 and 2015. It predicts e.g. von Karman’s constant correctly as 1/\\sqrt{2 π }=0.399. In its generalized version for non-zero viscosity and shear-thickening behavior presented in this contribution, it predicts two solution branches for the steady state: The first characterizes a family of states with swift (inertial) turbulent mixing and small {λ }{ K }, potentially approaching {λ }i. The second branch characterizes a state family with ρ \\to { O }(1) and thus strangled turbulence, ρ ≈ { O }(1). Stability properties and a potential dynamic commuting between the two solution branches had to be left for future research.

  12. Cardanol: toxicogenetic assessment and its effects when combined with cyclophosphamide

    PubMed Central

    Schneider, Beatriz Ursinos Catelan; Meza, Alisson; Beatriz, Adilson; Pesarini, João Renato; de Carvalho, Pamela Castilho; Mauro, Mariana de Oliveira; Karaziack, Caroline Bilhar; Cunha-Laura, Andréa Luiza; Monreal, Antônio Carlos Duenhas; Matuo, Renata; de Lima, Dênis Pires; Oliveira, Rodrigo Juliano

    2016-01-01

    Abstract Cardanol is an effective antioxidant and is a compound with antimutagenic and antitumoral activity. Here, we evaluated the genotoxic and mutagenic potential of saturated side chain cardanol and its effects in combination with cyclophosphamide in preventing DNA damage, apoptosis, and immunomodulation. Swiss mice were treated with cardanol (2.5, 5 and 10 mg/kg) alone or in combination with cyclophosphamide (100 mg/kg). The results showed that cardanol is an effective chemopreventive compound, with damage reduction percentages that ranged from 18.9 to 31.76% in the comet assay and from 45 to 97% in the micronucleus assay. Moreover, cardanol has the ability to reduce the frequency of apoptosis induced by cyclophosphamide. The compound did not show immunomodulatory activity. A final interpretation of the data showed that, despite its chemoprotective capacity, cardanol has a tendency to induce DNA damage. Hence, caution is needed if this compound is used as a chemopreventive agent. Also, this compound is likely not suitable as an adjuvant in chemotherapy treatments that use cyclophosphamide. PMID:27303909

  13. Effect of afobazole on teratogenic activity of cyclophosphamide in rats.

    PubMed

    Shreder, O V; Smolnikova, N M; Durnev, A D; Seredenin, S B

    2008-04-01

    A new anxiolytic afobazole (1-100 mg/kg perorally, Russia) dose-dependently abolished the embryotoxic and teratogenic effects of cyclophosphamide and reduced the range of induced malformations in outbred albino rats. Our results suggest that afobazole possesses antiteratogenic activity.

  14. Cardanol: toxicogenetic assessment and its effects when combined with cyclophosphamide.

    PubMed

    Schneider, Beatriz Ursinos Catelan; Meza, Alisson; Beatriz, Adilson; Pesarini, João Renato; Carvalho, Pamela Castilho de; Mauro, Mariana de Oliveira; Karaziack, Caroline Bilhar; Cunha-Laura, Andréa Luiza; Monreal, Antônio Carlos Duenhas; Matuo, Renata; Lima, Dênis Pires de; Oliveira, Rodrigo Juliano

    2016-01-01

    Cardanol is an effective antioxidant and is a compound with antimutagenic and antitumoral activity. Here, we evaluated the genotoxic and mutagenic potential of saturated side chain cardanol and its effects in combination with cyclophosphamide in preventing DNA damage, apoptosis, and immunomodulation. Swiss mice were treated with cardanol (2.5, 5 and 10 mg/kg) alone or in combination with cyclophosphamide (100 mg/kg). The results showed that cardanol is an effective chemopreventive compound, with damage reduction percentages that ranged from 18.9 to 31.76% in the comet assay and from 45 to 97% in the micronucleus assay. Moreover, cardanol has the ability to reduce the frequency of apoptosis induced by cyclophosphamide. The compound did not show immunomodulatory activity. A final interpretation of the data showed that, despite its chemoprotective capacity, cardanol has a tendency to induce DNA damage. Hence, caution is needed if this compound is used as a chemopreventive agent. Also, this compound is likely not suitable as an adjuvant in chemotherapy treatments that use cyclophosphamide.

  15. 21 CFR 876.5365 - Esophageal dilator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Esophageal dilator. 876.5365 Section 876.5365 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5365 Esophageal dilator. (a...

  16. 21 CFR 876.5365 - Esophageal dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Esophageal dilator. 876.5365 Section 876.5365 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5365 Esophageal dilator. (a...

  17. 21 CFR 876.5450 - Rectal dilator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Rectal dilator. 876.5450 Section 876.5450 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5450 Rectal dilator. (a) Identification. A rectal...

  18. 21 CFR 876.5450 - Rectal dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rectal dilator. 876.5450 Section 876.5450 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5450 Rectal dilator. (a) Identification. A rectal...

  19. 21 CFR 876.5520 - Urethral dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Urethral dilator. 876.5520 Section 876.5520 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5520 Urethral dilator. (a...

  20. 21 CFR 876.5470 - Ureteral dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ureteral dilator. 876.5470 Section 876.5470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5470 Ureteral dilator. (a...

  1. 21 CFR 876.5520 - Urethral dilator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Urethral dilator. 876.5520 Section 876.5520 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5520 Urethral dilator. (a...

  2. 21 CFR 876.5470 - Ureteral dilator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ureteral dilator. 876.5470 Section 876.5470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GASTROENTEROLOGY-UROLOGY DEVICES Therapeutic Devices § 876.5470 Ureteral dilator. (a...

  3. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A...

  4. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A...

  5. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A...

  6. Long-Term Cyclophosphamide Treatment in a Case with Serpiginous Choroiditis.

    PubMed

    Sahin, Ozlem G

    2010-10-05

    PURPOSE: To report the effect of long-term therapy with the alkylating agent cyclophosphamide in a case with serpiginous choroiditis and thus to contribute to the previously reported few cases showing the beneficial effect of long-term cyclophosphamide therapy for serpiginous choroiditis. PROCEDURES: Oral cyclophosphamide therapy for 12 months in a case with unilateral active serpiginous choroiditis. RESULTS: The active lesion responded well to long-term therapy with cyclophosphamide without recurrences and significant systemic side-effects. CONCLUSIONS: Long-term therapy with cyclophosphamide for serpiginous choroiditis is effective for improving vision and preventing recurrences.

  7. The protective effect of Canova homeopathic medicine in cyclophosphamide-treated non-human primates.

    PubMed

    Leal, Mariana Ferreira; Antunes, Lusânia Maria Greggi; Lamarão, Maria Fernanda Vita; da Silva, Carla Elvira Araújo; da Silva, Ismael Dale Cotrim Guerreiro; Assumpção, Paulo Pimentel; Andrade, Edilson Ferreira; Rezende, Alexandre Pingarilho; Imbeloni, Aline Amaral; Muniz, José Augusto Pereira Carneiro; Pinto, Giovanny Rebouças; Smith, Marília de Arruda Cardoso; Burbano, Rommel Rodríguez

    2012-12-01

    Canova activates macrophages and indirectly induces lymphocyte proliferation. Here we evaluated the effects of Canova in cyclophosphamide-treated non-human primates. Twelve Cebus apella were evaluated. Four animals were treated with Canova only. Eight animals were treated with two doses of cyclophosphamide (50 mg/kg) and four of these animals received Canova. Body weight, biochemistry and hematologic analyses were performed for 40 days. Micronucleus and comet assays were performed for the evaluation of DNA damage. We observed that cyclophosphamide induced abnormal WBC count in all animals. However, the group treated with cyclophosphamide plus Canova presented a higher leukocyte count than that which received only cyclophosphamide. Cyclophosphamide induced micronucleus and DNA damage in all animals. The frequency of these alterations was significantly lower in the Canova group than in the group without this medicine. Our results demonstrated that Canova treatment minimizes cyclophosphamide myelotoxicity in C. apella. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Forceful dilatation under endoscopic control in the treatment of achalasia: a randomised trial of pneumatic versus metallic dilator.

    PubMed Central

    Mearin, F; Armengol, J R; Chicharro, L; Papo, M; Balboa, A; Malagelada, J R

    1994-01-01

    Forceful dilatation under endoscopic control is a well established treatment of achalasia; several different types of dilators can be used. This study prospectively compared the clinical and manometric efficacy of a single dilatation using two different dilators. Forty one patients were randomly assigned to forceful dilatation under endoscopic control with either a pneumatic dilator (n = 17) or a metallic dilator (n = 24). Thereafter, the patients received periodic clinical and manometric evaluation for one year (before and one, six, and 12 months after dilatation). One month after dilatation all but one of the subjects in each group had experienced good to excellent results and their clinical improvement persisted for the one year follow up. Two patients (one in each group) were perforated during the procedure and required surgical treatment. Recovery was uneventful in both cases. Resting lower oesophageal sphincter pressure (mean (SEM)) significantly and similarly decreased after both methods of dilatation (pneumatic dilator: before dilatation 37 (3) mm Hg, one year after dilatation 18 (3) mm Hg; metallic dilator: before dilatation 34 (2) mm Hg, one year after dilatation 17 (3) mm Hg; p < 0.05 for both). It is concluded that in the treatment of achalasia a single dilatation under endoscopic control with either pneumatic or metallic dilator yield comparable clinical and manometric results and similar complication rates. The use of one or other dilator should depend more on the preference and experience of the endoscopist than on the type of device. PMID:7959186

  9. Genetic Variations Leading to Familial Dilated Cardiomyopathy

    PubMed Central

    Cho, Kae Won; Lee, Jongsung; Kim, Youngjo

    2016-01-01

    Cardiomyopathy is a major cause of death worldwide. Based on pathohistological abnormalities and clinical manifestation, cardiomyopathies are categorized into several groups: hypertrophic, dilated, restricted, arrhythmogenic right ventricular, and unclassified. Dilated cardiomyopathy, which is characterized by dilation of the left ventricle and systolic dysfunction, is the most severe and prevalent form of cardiomyopathy and usually requires heart transplantation. Its etiology remains unclear. Recent genetic studies of single gene mutations have provided significant insights into the complex processes of cardiac dysfunction. To date, over 40 genes have been demonstrated to contribute to dilated cardiomyopathy. With advances in genetic screening techniques, novel genes associated with this disease are continuously being identified. The respective gene products can be classified into several functional groups such as sarcomere proteins, structural proteins, ion channels, and nuclear envelope proteins. Nuclear envelope proteins are emerging as potential molecular targets in dilated cardiomyopathy. Because they are not directly associated with contractile force generation and transmission, the molecular pathways through which these proteins cause cardiac muscle disorder remain unclear. However, nuclear envelope proteins are involved in many essential cellular processes. Therefore, integrating apparently distinct cellular processes is of great interest in elucidating the etiology of dilated cardiomyopathy. In this mini review, we summarize the genetic factors associated with dilated cardiomyopathy and discuss their cellular functions. PMID:27802374

  10. Genetic Variations Leading to Familial Dilated Cardiomyopathy.

    PubMed

    Cho, Kae Won; Lee, Jongsung; Kim, Youngjo

    2016-10-01

    Cardiomyopathy is a major cause of death worldwide. Based on pathohistological abnormalities and clinical manifestation, cardiomyopathies are categorized into several groups: hypertrophic, dilated, restricted, arrhythmogenic right ventricular, and unclassified. Dilated cardiomyopathy, which is characterized by dilation of the left ventricle and systolic dysfunction, is the most severe and prevalent form of cardiomyopathy and usually requires heart transplantation. Its etiology remains unclear. Recent genetic studies of single gene mutations have provided significant insights into the complex processes of cardiac dysfunction. To date, over 40 genes have been demonstrated to contribute to dilated cardiomyopathy. With advances in genetic screening techniques, novel genes associated with this disease are continuously being identified. The respective gene products can be classified into several functional groups such as sarcomere proteins, structural proteins, ion channels, and nuclear envelope proteins. Nuclear envelope proteins are emerging as potential molecular targets in dilated cardiomyopathy. Because they are not directly associated with contractile force generation and transmission, the molecular pathways through which these proteins cause cardiac muscle disorder remain unclear. However, nuclear envelope proteins are involved in many essential cellular processes. Therefore, integrating apparently distinct cellular processes is of great interest in elucidating the etiology of dilated cardiomyopathy. In this mini review, we summarize the genetic factors associated with dilated cardiomyopathy and discuss their cellular functions.

  11. Dilational Response of Voided Polycrystals

    NASA Astrophysics Data System (ADS)

    Savage, Daniel J.; Cazacu, Oana; Knezevic, Marko

    2017-05-01

    Finite-element (FE) cell model computations have been used to gain insights into the ductile response of porous polycrystals. Generally, the behavior of the matrix is described by a J 2-plasticity model. In this article, we present a new computational approach to FE cell models for porous polycrystals deforming by slip based on crystal plasticity. The cell provides the homogenized dilational response, where the constitutive response of every integration point is based on a single-crystal visco-plasticity law. The calculations are performed for a body-centered cubic polycrystal with random texture. Axisymmetric tensile and compressive loadings are imposed corresponding to the fixed values of the stress triaxiality and to two possible values of the Lode parameter. The resulting numerical yield points are compared with those obtained using a J 2-FE cell and an analytical model. The predictions confirm the combined effects of the mean stress and third-invariant on yielding recently revealed by the analytical model.

  12. The genetics of dilated cardiomyopathy

    PubMed Central

    Dellefave, Lisa; McNally, Elizabeth M.

    2010-01-01

    Purpose of review More than forty different individual genes have been implicated in the inheritance of dilated cardiomyopathy. For a subset of these genes, mutations can lead to a spectrum of cardiomyopathy that extends to hypertrophic cardiomyopathy and left ventricular noncompaction. In nearly all cases, there is an increased risk of arrhythmias. With some genetic mutations, extracardiac manifestations are likely to be present. The precise genetic etiology can usually not be discerned from the cardiac and/or extracardiac manifestations and requires molecular genetic diagnosis for prognostic determination and cardiac care. Recent findings Newer technologies are influencing genetic testing, especially cardiomyopathy genetic testing, where an increased number of genes are now routinely being tested simultaneously. While this approach to testing multiple genes is increasing the diagnostic yield, the analysis of multiple genes in one test is also resulting in a large amount of genetic information of unclear significance. Summary Genetic testing is highly useful in the care of patients and families, since it guides diagnosis, influences care and aids in prognosis. However, the large amount of benign human genetic variation may complicate genetic results, and often requires a skilled team to accurately interpret the findings. PMID:20186049

  13. Dilated Cardiomyopathy Revealing Cushing Disease

    PubMed Central

    Marchand, Lucien; Segrestin, Bérénice; Lapoirie, Marion; Favrel, Véronique; Dementhon, Julie; Jouanneau, Emmanuel; Raverot, Gérald

    2015-01-01

    Abstract Cardiovascular impairments are frequent in Cushing's syndrome and the hypercortisolism can result in cardiac structural and functional changes that lead in rare cases to dilated cardiomyopathy (DCM). Such cardiac impairment may be reversible in response to a eucortisolaemic state. A 43-year-old man with a medical past of hypertension and history of smoking presented to the emergency department with global heart failure. Coronary angiography showed a significant stenosis of a marginal branch and cardiac MRI revealed a nonischemic DCM. The left ventricular ejection fraction (LVEF) was estimated as 28% to 30%. Clinicobiological features and pituitary imaging pointed toward Cushing's disease and administration of adrenolytic drugs (metyrapone and ketoconazole) was initiated. Despite the normalization of cortisol which had been achieved 2 months later, the patient presented an acute heart failure. A massive mitral regurgitation secondary to posterior papillary muscle rupture was diagnosed as a complication of the occlusion of the marginal branch. After 6 months of optimal pharmacological treatment for systolic heart failure, as well as treatment with inhibitors of steroidogenesis, there was no improvement of LVEF. The percutaneous mitral valve was therefore repaired and a defibrillator implanted. The severity of heart failure contraindicated pituitary surgery and the patient was instead treated by stereotaxic radiotherapy. This is the first case reporting a Cushing's syndrome DCM without improvement of LVEF despite normalization of serum cortisol levels. PMID:26579807

  14. Dilational Response of Voided Polycrystals

    NASA Astrophysics Data System (ADS)

    Savage, Daniel J.; Cazacu, Oana; Knezevic, Marko

    2017-02-01

    Finite-element (FE) cell model computations have been used to gain insights into the ductile response of porous polycrystals. Generally, the behavior of the matrix is described by a J 2-plasticity model. In this article, we present a new computational approach to FE cell models for porous polycrystals deforming by slip based on crystal plasticity. The cell provides the homogenized dilational response, where the constitutive response of every integration point is based on a single-crystal visco-plasticity law. The calculations are performed for a body-centered cubic polycrystal with random texture. Axisymmetric tensile and compressive loadings are imposed corresponding to the fixed values of the stress triaxiality and to two possible values of the Lode parameter. The resulting numerical yield points are compared with those obtained using a J 2-FE cell and an analytical model. The predictions confirm the combined effects of the mean stress and third-invariant on yielding recently revealed by the analytical model.

  15. Clinical significance of main pancreatic duct dilation on computed tomography: Single and double duct dilation

    PubMed Central

    Edge, Mark D; Hoteit, Maarouf; Patel, Amil P; Wang, Xiaoping; Baumgarten, Deborah A; Cai, Qiang

    2007-01-01

    AIM: To study the patients with main pancreatic duct dilation on computed tomography (CT) and thereby to provide the predictive criteria to identify patients at high risk of significant diseases, such as pancreatic cancer, and to avoid unnecessary work up for patients at low risk of such diseases. METHODS: Patients with dilation of the main pancreatic duct on CT at Emory University Hospital in 2002 were identified by computer search. Clinical course and ultimate diagnosis were obtained in all the identified patients by abstraction of their computer database records. RESULTS: Seventy-seven patients were identified in this study. Chronic pancreatitis and pancreatic cancer were the most common causes of the main pancreatic duct dilation on CT. Although the majority of patients with isolated dilation of the main pancreatic duct (single duct dilation) had chronic pancreatitis, one-third of patients with single duct dilation but without chronic pancreatitis had pancreatic malignancies, whereas most of patients with concomitant biliary duct dilation (double duct dilation) had pancreatic cancer. CONCLUSION: Patients with pancreatic double duct dilation need extensive work up and careful follow-up since a majority of these patients are ultimately diagnosed with pancreatic cancer. Patients with single duct dilation, especially such patients without any evidence of chronic pancreatitis, also need careful follow-up since the possibility of pancreatic malignancy, including adenocarcinoma and intraductal papillary mucinous tumors, is still high. PMID:17461473

  16. Glucocorticoid with cyclophosphamide for paraquat-induced lung fibrosis.

    PubMed

    Li, Luying Ryan; Sydenham, Emma; Chaudhary, Bhuwan; Beecher, Deirdre; You, Chao

    2014-08-07

    Paraquat is an effective and widely used herbicide but is also a lethal poison. In many developing countries paraquat is widely available and inexpensive, making poisoning prevention difficult. However most of the people who become poisoned from paraquat have taken it as a means of suicide.Standard treatment for paraquat poisoning both prevents further absorption and reduces the load of paraquat in the blood through haemoperfusion or haemodialysis. The effectiveness of standard treatments is extremely limited.The immune system plays an important role in exacerbating paraquat-induced lung fibrosis. Immunosuppressive treatment using glucocorticoid and cyclophosphamide in combination is being developed and studied. To assess the effects of glucocorticoid with cyclophosphamide on mortality in patients with paraquat-induced lung fibrosis. The most recent search was run on the 15th April 2014. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (Ovid), ISI WOS (SCI-EXPANDED, SSCI, CPCI-S & CPSI-SSH), trials registries, Chinese databases (, , ) and reference lists. RCTs were included in this review. All patients were to receive standard care, plus the intervention or control. The intervention was glucocorticoid with cyclophosphamide in combination versus a control of a placebo, standard care alone or any other therapy in addition to standard care. The mortality risk ratio (RR) and 95% confidence interval (CI) was calculated for each study on an intention-to-treat basis. Data for all-cause mortality at final follow-up were summarised in a meta-analysis using a fixed-effect model. This systematic review includes three trials with a combined total of 164 participants who had moderate to severe paraquat poisoning. Patients who received glucocorticoid with cyclophosphamide in addition to standard care

  17. Nemaline myopathy with dilated cardiomyopathy in childhood.

    PubMed

    Gatayama, Ryohei; Ueno, Kentaro; Nakamura, Hideaki; Yanagi, Sadamitsu; Ueda, Hideaki; Yamagishi, Hiroyuki; Yasui, Seiyo

    2013-06-01

    We present a case of a 9-year-old boy with nemaline myopathy and dilated cardiomyopathy. The combination of nemaline myopathy and cardiomyopathy is rare, and this is the first reported case of dilated cardiomyopathy associated with childhood-onset nemaline myopathy. A novel mutation, p.W358C, in ACTA1 was detected in this patient. An unusual feature of this case was that the patient's cardiac failure developed during early childhood with no delay of gross motor milestones. The use of a β-blocker did not improve his clinical course, and the patient died 6 months after diagnosis of dilated cardiomyopathy. Congenital nonprogressive nemaline myopathy is not necessarily a benign disorder: deterioration can occur early in the course of dilated cardiomyopathy with neuromuscular disease, and careful clinical evaluation is therefore necessary.

  18. An Erupted Dilated Odontoma: A Rare Presentation

    PubMed Central

    Sharma, Gaurav; Nagra, Amritpreet; Singh, Gurkeerat; Nagpal, Archna; Soin, Atul; Bhardwaj, Vishal

    2016-01-01

    A dilated odontoma is an extremely rare developmental anomaly represented as a dilatation of the crown and root as a consequence of a deep, enamel-lined invagination and is considered a severe variant of dens invaginatus. An oval shape of the tooth lacking morphological characteristics of a crown or root implies that the invagination happened in the initial stages of morphodifferentiation. Spontaneous eruption of an odontoma is a rare occurrence and the occurrence of a dilated odontoma in a supernumerary tooth is even rarer with only a few case reports documented in the English literature. We present an extremely rare case of erupted dilated odontoma occurring in the supernumerary tooth in anterior maxillary region in an 18-year-old male, which, to the best of our knowledge, is the first ever case reported in English literature. PMID:26989523

  19. 21 CFR 876.5365 - Esophageal dilator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... and weighted with mercury or a metal olive-shaped weight that slides on a guide, such as a string or... esophageal or gastrointestinal bougies and the esophageal dilator (metal olive). (b) Classification. Class...

  20. 21 CFR 876.5365 - Esophageal dilator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... and weighted with mercury or a metal olive-shaped weight that slides on a guide, such as a string or... esophageal or gastrointestinal bougies and the esophageal dilator (metal olive). (b) Classification. Class...

  1. 21 CFR 876.5365 - Esophageal dilator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... and weighted with mercury or a metal olive-shaped weight that slides on a guide, such as a string or... esophageal or gastrointestinal bougies and the esophageal dilator (metal olive). (b) Classification. Class...

  2. The pathogenesis of proventricular dilatation disease.

    PubMed

    Tizard, Ian; Shivaprasad, H L; Guo, Jianhua; Hameed, Samer; Ball, Judith; Payne, Susan

    2016-12-01

    Bornaviruses cause neurologic diseases in several species of birds, especially parrots, waterfowl and finches. The characteristic lesions observed in these birds include encephalitis and gross dilatation of the anterior stomach - the proventriculus. The disease is thus known as proventricular dilatation disease (PDD). PDD is characterized by extreme proventricular dilatation, blockage of the passage of digesta and consequent death by starvation. There are few clinical resemblances between this and the bornaviral encephalitides observed in mammals. Nevertheless, there are common virus-induced pathogenic pathways shared across this disease spectrum that are explored in this review. Additionally, a review of the literature relating to gastroparesis in humans and the control of gastric mobility in mammals and birds points to several plausible mechanisms by which bornaviral infection may result in extreme proventricular dilatation.

  3. Genetics of hypertrophic and dilated cardiomyopathy.

    PubMed

    Friedrich, Felix W; Carrier, Lucie

    2012-10-01

    Cardiomyopathies are categorized as extrinsic, being caused by external factors, such as hypertension, ischemia, inflammation, valvular dysfunction, or as intrinsic, which correspond to myocardial diseases without identifiable external causes. These so called primary cardiomyopathies can be categorized in four main forms: hypertrophic, dilated, restrictive, and arrhythmogenic right ventricular cardiomyopathy. Cardiomyopathies are diagnosed by clinical expression, echocardiography, electrocardiography, non-invasive imaging, and sometimes by cardiac catheterization to rule out external causes as ischemia. The two main forms of primary cardiomyopathies are the hypertrophic and dilated cardiomyopathies. Most of hypertrophic cardiomyopathy and 20-50% of dilated cardiomyopathy are familial showing a wide genetic and phenotypic heterogeneity. This review presents the current knowledge on the causative genes, molecular mechanisms and the genotype � phenotype relations of hypertrophic and dilated cardiomyopathies.

  4. Aortic dilatation in children with systemic hypertension.

    PubMed

    Gupta-Malhotra, Monesha; Devereux, Richard B; Dave, Archana; Bell, Cynthia; Portman, Ronald; Milewicz, Diana

    2014-04-01

    The aim of the study was to determine the presence of aortic dilatation in hypertensive children, the prevalence of which is 4% to 10% in hypertensive adults. Prospectively enrolled multiethnic children, untreated for their hypertension, underwent an echocardiogram to exclude congenital heart disease and evaluate for end-organ damage and aortic size. The aorta was measured in the parasternal long-axis view at three levels: the sinus of Valsalva, supra-tubular junction, and the ascending aorta. Aortic dilatation was determined by z-score >2 at any one of the levels measured. Hypertension was defined as blood pressure above the 95th percentile based on the Fourth Working Group criteria confirmed by 24-hour ambulatory blood pressure monitoring. Among 142 consecutive hypertensive children (median age, 14 years; 45% females) aortic dilatation was detected in 2.8% (95% confidence interval, 1%-7%; median age, 16 years; 100% females). Children with aortic dilatation, when compared with those without, had significantly more aortic valve insufficiency (P = .005) and left ventricular hypertrophy (P = .018). Prevalence of aortic dilatation was 2.8% and was associated with significantly more aortic insufficiency and left ventricular hypertrophy in comparison to those without aortic dilatation.

  5. Aortic Dilatation in Children with Systemic Hypertension

    PubMed Central

    Gupta-Malhotra, Monesha; Devereux, Richard B.; Dave, Archana; Bell, Cynthia; Portman, Ronald; Milewicz, Diana

    2014-01-01

    Background The aim of the study was to determine presence of aortic dilatation in hypertensive children, the prevalence of which is 4–10% in hypertensive adults. Methods Prospectively enrolled multiethnic children untreated for their hypertension, underwent an echocardiogram to exclude congenital heart disease and evaluate for end-organ damage and aortic size. The aorta was measured in the parasternal long-axis view at 3 levels: the sinus of Valsalva, supra-tubular junction and the ascending aorta. Aortic dilatation was determined by z-score > 2 at any 1 of the levels measured. Hypertension was defined as blood pressure above the 95th percentile based on the Fourth Working Group criteria confirmed by 24-hour ambulatory blood pressure monitoring. Results Among 142 consecutive hypertensive children (median age 14 years, 45% females) aortic dilatation was detected in 2.8% (95% CI 1% to 7%, median age 16 years, 100% females). Children with aortic dilatation, when compared to those without, had significantly more aortic valve insufficiency (p = 0.005) and left ventricular hypertrophy (p = 0.018). Conclusions Prevalence of aortic dilatation was 2.8% and was associated with significantly more aortic insufficiency and left ventricular hypertrophy in comparison to those without aortic dilatation. PMID:24507486

  6. 21 CFR 884.4250 - Expandable cervical dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Expandable cervical dilator. 884.4250 Section 884....4250 Expandable cervical dilator. (a) Identification. An expandable cervical dilator is an instrument with two handles and two opposing blades used manually to dilate (stretch open) the cervical os. (b...

  7. 21 CFR 884.4250 - Expandable cervical dilator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Expandable cervical dilator. 884.4250 Section 884....4250 Expandable cervical dilator. (a) Identification. An expandable cervical dilator is an instrument with two handles and two opposing blades used manually to dilate (stretch open) the cervical os. (b...

  8. 21 CFR 884.4270 - Vibratory cervical dilators.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Vibratory cervical dilators. 884.4270 Section 884....4270 Vibratory cervical dilators. (a) Identification. A vibratory cervical dilator is a device designed to dilate the cervical os by stretching it with a power-driven vibrating probe head. The device is...

  9. 21 CFR 884.4270 - Vibratory cervical dilators.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Vibratory cervical dilators. 884.4270 Section 884....4270 Vibratory cervical dilators. (a) Identification. A vibratory cervical dilator is a device designed to dilate the cervical os by stretching it with a power-driven vibrating probe head. The device is...

  10. 21 CFR 884.4250 - Expandable cervical dilator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Expandable cervical dilator. 884.4250 Section 884....4250 Expandable cervical dilator. (a) Identification. An expandable cervical dilator is an instrument with two handles and two opposing blades used manually to dilate (stretch open) the cervical os. (b...

  11. 21 CFR 884.4250 - Expandable cervical dilator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Expandable cervical dilator. 884.4250 Section 884....4250 Expandable cervical dilator. (a) Identification. An expandable cervical dilator is an instrument with two handles and two opposing blades used manually to dilate (stretch open) the cervical os. (b...

  12. 21 CFR 884.4260 - Hygroscopic Laminaria cervical dilator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Hygroscopic Laminaria cervical dilator. 884.4260... Devices § 884.4260 Hygroscopic Laminaria cervical dilator. (a) Identification. A hygroscopic Laminaria cervical dilator is a device designed to dilate (stretch open) the cervical os by cervical insertion of a...

  13. 21 CFR 884.4260 - Hygroscopic Laminaria cervical dilator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Hygroscopic Laminaria cervical dilator. 884.4260... Devices § 884.4260 Hygroscopic Laminaria cervical dilator. (a) Identification. A hygroscopic Laminaria cervical dilator is a device designed to dilate (stretch open) the cervical os by cervical insertion of a...

  14. 21 CFR 884.4250 - Expandable cervical dilator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Expandable cervical dilator. 884.4250 Section 884....4250 Expandable cervical dilator. (a) Identification. An expandable cervical dilator is an instrument with two handles and two opposing blades used manually to dilate (stretch open) the cervical os. (b...

  15. 21 CFR 884.4270 - Vibratory cervical dilators.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Vibratory cervical dilators. 884.4270 Section 884....4270 Vibratory cervical dilators. (a) Identification. A vibratory cervical dilator is a device designed to dilate the cervical os by stretching it with a power-driven vibrating probe head. The device is...

  16. 21 CFR 884.4270 - Vibratory cervical dilators.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Vibratory cervical dilators. 884.4270 Section 884....4270 Vibratory cervical dilators. (a) Identification. A vibratory cervical dilator is a device designed to dilate the cervical os by stretching it with a power-driven vibrating probe head. The device is...

  17. 21 CFR 884.4270 - Vibratory cervical dilators.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Vibratory cervical dilators. 884.4270 Section 884....4270 Vibratory cervical dilators. (a) Identification. A vibratory cervical dilator is a device designed to dilate the cervical os by stretching it with a power-driven vibrating probe head. The device is...

  18. 21 CFR 884.4260 - Hygroscopic Laminaria cervical dilator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Hygroscopic Laminaria cervical dilator. 884.4260... Devices § 884.4260 Hygroscopic Laminaria cervical dilator. (a) Identification. A hygroscopic Laminaria cervical dilator is a device designed to dilate (stretch open) the cervical os by cervical insertion of a...

  19. 21 CFR 884.4260 - Hygroscopic Laminaria cervical dilator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Hygroscopic Laminaria cervical dilator. 884.4260... Devices § 884.4260 Hygroscopic Laminaria cervical dilator. (a) Identification. A hygroscopic Laminaria cervical dilator is a device designed to dilate (stretch open) the cervical os by cervical insertion of a...

  20. 21 CFR 884.4260 - Hygroscopic Laminaria cervical dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hygroscopic Laminaria cervical dilator. 884.4260... Devices § 884.4260 Hygroscopic Laminaria cervical dilator. (a) Identification. A hygroscopic Laminaria cervical dilator is a device designed to dilate (stretch open) the cervical os by cervical insertion of a...

  1. Protective effect of berberine on cyclophosphamide-induced haemorrhagic cystitis in rats.

    PubMed

    Xu, X; Malavé, A

    2001-05-01

    The urotoxicity of cyclophosphamide and the protective effect of the herb berberine were investigated in this study. Administration of 150 mg/kg cyclophosphamide intraperitoneally caused a serious haemorrhagic cystitis in rats after 12 hr, including bladder oedema, haemorrhage, and dramatic elevation of nitric oxide metabolites (nitrite+nitrate) in urine and in plasma. To explore whether cyclophosphamide-induced cystitis could be prevented by berberine, rats were pretreated with a single dose or two doses of berberine at 50, 100, or 200 mg/kg intraperitoneally then challenged with cyclophosphamide (150 mg/kg, intraperitoneally). The results indicated that pretreatment of rats with berberine could reduce cyclophosphamide-induced cystitis in a dose-dependent manner. Furthermore, we found that two doses of berberine showed greater protection against cyclophosphamide urotoxicity than when given a single dose. In addition, our data shows that a single dose of 200 mg/kg berberine, or two doses of 100, and 200 mg/kg berberine could completely block cyclophosphamide-induced bladder oedema and haemorrhage, as well as nitric oxide metabolites increase in rat urine and plasma. In conclusion, our findings suggest that berberine could be a potential effective drug in the treatment of cyclophosphamide-induced cystitis, and provides us with the bright hope in the prevention and treatment of cyclophosphamide urotoxicity.

  2. Impairment of flow-mediated dilation correlates with aortic dilation in patients with Marfan syndrome.

    PubMed

    Takata, Munenori; Amiya, Eisuke; Watanabe, Masafumi; Omori, Kazuko; Imai, Yasushi; Fujita, Daishi; Nishimura, Hiroshi; Kato, Masayoshi; Morota, Tetsuro; Nawata, Kan; Ozeki, Atsuko; Watanabe, Aya; Kawarasaki, Shuichi; Hosoya, Yumiko; Nakao, Tomoko; Maemura, Koji; Nagai, Ryozo; Hirata, Yasunobu; Komuro, Issei

    2014-07-01

    Marfan syndrome is an inherited disorder characterized by genetic abnormality of microfibrillar connective tissue proteins. Endothelial dysfunction is thought to cause aortic dilation in subjects with a bicuspid aortic valve; however, the role of endothelial dysfunction and endothelial damaging factors has not been elucidated in Marfan syndrome. Flow-mediated dilation, a noninvasive measurement of endothelial function, was evaluated in 39 patients with Marfan syndrome. Aortic diameter was measured at the aortic annulus, aortic root at the sinus of Valsalva, sinotubular junction and ascending aorta by echocardiography, and adjusted for body surface area (BSA). The mean value of flow-mediated dilation was 6.5 ± 2.4 %. Flow-mediated dilation had a negative correlation with the diameter of the ascending thoracic aorta (AscAd)/BSA (R = -0.39, p = 0.020) and multivariate analysis revealed that flow-mediated dilation was an independent factor predicting AscAd/BSA, whereas other segments of the aorta had no association. Furthermore, Brinkman index had a somewhat greater influence on flow-mediated dilation (R = -0.42, p = 0.008). Although subjects who smoked tended to have a larger AscAd compared with non-smokers (AscA/BSA: 17.3 ± 1.8 versus 15.2 ± 3.0 mm/m(2), p = 0.013), there was no significant change in flow-mediated dilation, suggesting that smoking might affect aortic dilation via an independent pathway. Common atherogenic risks, such as impairment of flow-mediated dilation and smoking status, affected aortic dilation in subjects with Marfan syndrome.

  3. Sequential probing and dilatation in canalicular stenosis.

    PubMed

    Park, Jongyeop; Kim, Hochang

    2015-11-01

    To assess the usefulness of sequential probing for diagnosing lacrimal canalicular stenosis, and the effectiveness of bicanalicular silicone intubation after sequential dilatation in treatment. Canalicular stenosis was diagnosed by sequential probing in 22 patients (22 eyes) who were misdiagnosed as canalicular obstruction. The patients were treated by bicanalicular silicone intubation after sequential dilatation. Anatomical improvements and functional relief of epiphora were evaluated. In addition, complications were evaluated. The average age of the 22 patients was 57 years, and the average follow-up period was 13 months. The silicone tube was left in place for an average of 14 weeks. The anatomical success rate was 100 %. Fifty-four percent of patients achieved complete relief of epiphora, 32 % partial relief, and 14 % no relief. There were no complications. Sequential probing is an useful diagnostic method for canalicular stenosis. Bicanalicular silicone intubation after sequential dilatation is a simple and effective treatment, and could be performed as primary procedure for canalicular stenosis before invasive surgery.

  4. Dilated cardiomyopathy and progressive familial intrahepatic cholestasis

    PubMed Central

    James, Stephanie; Waterhouse, Deirdre; McDonald, Kenneth; O'Hanlon, Rory

    2014-01-01

    This case is of a 29-year-old man with progressive familial intrahepatic cholestasis type 1 also known as Byler's disease. At the age of 21, our patient developed non-ischaemic dilated cardiomyopathy. Cardiac MRI demonstrated global wall thinning, with significant areas of myocardial fibrosis in the mid and epicardial walls from base to apex on postgadolinium late contrast enhanced images. No shared genetic loci between dilated cardiomyopathy and Byler's or cholestatic liver disease have yet been found. This presents the first documented case of non-ischaemic dilated cardiomyopathy, with evidence of mid wall fibrosis, in association with an established diagnosis of progressive familial intrahepatic cholestasis type 1 since childhood. PMID:24654243

  5. Apricot Kernel Oil Ameliorates Cyclophosphamide-Associated Immunosuppression in Rats.

    PubMed

    Tian, Honglei; Yan, Haiyan; Tan, Siwei; Zhan, Ping; Mao, Xiaoying; Wang, Peng; Wang, Zhouping

    2016-08-01

    The effects of dietary apricot kernel oil (AKO), which contains high levels of oleic and linoleic acids and lower levels of α-tocopherol, were evaluated in a rat model of cyclophosphamide-induced immunosuppression. Rats had intraperitoneal injection with cyclophosphamide to induce immunosuppression and were then infused with AKO or normal saline (NS) for 4 weeks. Enzyme-linked immunosorbent assays were used to detect antimicrobial factors in lymphocytes and anti-inflammatory factors in hepatocytes. Hematoxylin & eosin staining was conducted prior to histopathological analysis of the spleen, liver, and thymus. Significant differences were observed between the immune functions of the healthy control group, the normal saline group, and the AKO group. Compared to the normal saline-treated group, lymphocytes isolated from rats administered AKO showed significant improvement in immunoglobulin (Ig)A, IgM, IgG, interleukin (IL)-2, IL-12, and tumor necrosis factor-α (TNF-α) levels (p < 0.01). Liver tissue levels of malondialdehyde and activities of superoxide dismutase and glutathione peroxidase indicated reduced oxidative stress in rats treated with AKO (p < 0.01). Dietary AKO positively affected rat growth and inhibited cyclophosphamide-associated organ degeneration. These results suggested that AKO may enhance the immune system in vivo. These effects may reflect the activities of intermediate oleic and linoleic acid metabolites, which play a vital role in the immune system, and the α-tocopherol in AKO may further enhance this phenomenon. Thus, the use of AKO as a nutritional supplement can be proposed to ameliorate chemotherapy-associated immunosuppression.

  6. Effect of cyclophosphamide on selected hematologic parameters of the turkey.

    PubMed

    Ficken, M D; Barnes, H J

    1988-01-01

    The effect of three daily cyclophosphamide (CY) injections (doses of 0-100 mg/kg.day) on selected hematologic parameters in 7-to-8-week-old female Nicholas turkeys was examined. CY induced significant leukopenia, lymphopenia, thrombocytopenia, and heteropenia 24 to 72 hours after the initial injection; time depended on cell type and dose of CY. Significant linear correlation between increasing CY dose and increasing severity of circulating cell depression occurred. CY had no significant effect on circulating numbers of monocytes, packed cell volume, or plasma protein. Changes in basophils and eosinophils could not be identified because of their low numbers.

  7. [Pneumatic dilation in the treatment of achalasia].

    PubMed

    Ruiz Cuesta, Patricia; Hervás Molina, Antonio José; Jurado García, Juan; Pleguezuelo Navarro, María; García Sánchez, Valle; Casáis Juanena, Luis L; Gálvez Calderón, Carmen; Naranjo Rodríguez, Antonio

    2013-10-01

    Pneumatic dilation and surgical myotomy are currently the procedures of choice to treat achalasia. The selection of one or other treatment depends on the experience of each center and patient preferences. To review the experience of pneumatic dilation in patients with achalasia in our center. We included all patients with a clinical, endoscopic and manometric diagnosis compatible with achalasia who underwent pneumatic dilation in a 19-year period. All dilations were routinely performed with a Rigiflex(®) balloon, usually at pressures of 250, 250 and 300mm Hg in three inflations of one minute, each separated by one minute. The success of the dilation was assessed on the basis of the patient's symptoms, the number of sessions, the need for surgery, and the presence of complications. A total of 171 patients were included, 53.2% men and 46.8% women, with a mean age of 51.53±17.78 years (16-87 years), from June 1993 to October 2012. A 35-mm balloon was used in 157 patients, a 30-mm balloon in 9 patients and a 40-mm balloon in 7 patients. A single dilation session was required in 108 patients, two sessions were required in 56 patients, with a mean time between the first and second sessions of 25.23±43.25 months (1-215 months), and 3 sessions were required in 7 patients with a mean time between the second and third sessions of 6.86±5.33 months (1-15 months). Outcome after dilation was successful in 81% of the patients. Of the 140 responders, 121 had complete response (complete disappearance of symptoms without recurrence) and 19 partial response (initial disappearance of symptoms with subsequent reappearance). Surgery (Heller myotomy) was required in 15.8% of the patients. Perforation occurred in 4 of the 171 patients as a complication of the technique; these perforations were satisfactorily resolved, two by conservative treatment and two by surgery. There was no mortality associated with the technique or its complications. In our series, pneumatic dilation had a

  8. Understanding the dilation and dilation relaxation behavior of graphite-based lithium-ion cells

    NASA Astrophysics Data System (ADS)

    Bauer, Marius; Wachtler, Mario; Stöwe, Hendrik; Persson, Jon V.; Danzer, Michael A.

    2016-06-01

    The dilation of lithium-ion cells is sensitive towards swelling phenomena caused by both graphite staging processes and lithium plating on graphite anodes. In this work, the dilation behavior of graphite/NMC pouch cells is studied with a focus on relaxation phenomena occurring after current pulses. In order to prevent misleading interpretations due to thermal effects, thermal expansion is quantified and a method for the thermal compensation of dilation data is developed. Dilation data are recorded for quasi-equilibrium cycling as well as for current pulses at high rates. In the quasi-equilibrium case, the staging behavior is characterized based on dilation and voltage data. By comparison with a graphite half-cell measurement, the major effects in full cell dilation are confirmed to be anode related. In the high rate case, the dilation responses to the actual pulse and the subsequent relaxation phases are recorded systematically. Positive and negative relaxation phenomena are observed depending on the SOC. They are ascribed to both graphite staging and lithium plating processes. A model is presented explaining the unexpected relaxation effects by a temporary coexistence of three or more staging compounds during high rate lithiation and delithiation. Our data thereby confirm the shrinking annuli model introduced by Heβ and Novák.

  9. Randomised comparison of cisplatin with cyclophosphamide/cisplatin and with cyclophosphamide/doxorubicin/cisplatin in advanced ovarian cancer. Gruppo Interegionale Cooperativo Oncologico Ginecologia.

    PubMed

    1987-08-15

    565 patients with stage III-IV epithelial ovarian cancer were randomly assigned to receive cisplatin (P), cyclophosphamide and cisplatin (CP), or cyclophosphamide, doxorubicin, and cisplatin (CAP). Data on 531 patients were analysed. Treatment with CAP resulted in a significantly higher overall (complete and partial) response rate (66 vs 56 vs 49% for CAP, CP, and P, respectively), but the rate of complete surgical response for the three treatment arms was similar (26, 21, and 20%). Size of residual tumour after first surgery and Karnofsky index were the best predictors of complete remission. Survival and disease-free survival were not significantly different in the three arms, although progression-free survival was significantly longer after CAP. However, tumour size, cell type, and Karnofsky index, but not therapy, were independent predictors for survival. Haematological toxicity was highest with CAP. The addition of cyclophosphamide or doxorubicin and cyclophosphamide to cisplatin does not substantially increase the number of potentially curable, advanced ovarian cancer patients.

  10. [Examination of Measures for Preventing Exposure in Nurses Who Handle Cyclophosphamide].

    PubMed

    Suzuki, Kaoru; Ono, Yuki; Suzuki, Yumi; Omori, Keiko; Matsuda, Mikiko; Sato, Hiroko; Omoto, Eijiro

    2015-12-01

    Health hazards due to long-term exposure to anticancer drugs have been reported among health care professionals. In Yamagata Prefectural Central Hospital, constant use of personal protective equipment(gloves and mask with face shield)is mandatory, but there is no clear description of the protective gown. To verify the exposure status of nurses while handling cyclophosphamide and the usefulness of a protective gown as a protective measure, urinary concentration of cyclophosphamide was measured for nurses who handled cyclophosphamide. No cyclophosphamide was detected in the urine samples collected from nurses who handled cyclophosphamide while wearing protective gowns or in the samples collected from nurses who handled cyclophosphamide without protective gowns. This finding suggests that gloves and a mask with a face shield are sufficient for preventing exposure to cyclophosphamide. However, considering that only experienced nurses were included as subjects in this study, we cannot conclude that a protective gown is unnecessary, because inexperienced nurses may be exposed to cyclophosphamide. Our study's findings may be one reference to examine measures for preventing exposure in nurses.

  11. Computed tomography of localized dilatation of the intrahepatic bile ducts

    SciTech Connect

    Araki, T.; Itai Y.; Tasaka, A.

    1981-12-01

    Twenty-nine patients showed localized dilatation of the intrahepatic bile ducts on computed tomography, usually unaccompanied by jaundice. Congenital dilatation was diagnosed when associated with a choledochal cyst, while cholangiographic contrast material was helpful in differentiating such dilatation from a simple cyst by showing its communication with the biliary tract when no choledochal cyst was present. Obstructive dilatation was associated with intrahepatic calculi in 4 cases, hepatoma in 9, cholangioma in 5, metastatic tumor in 5, and polycystic disease in 2. Cholangioma and intrahepatic calculi had a greater tendency to accompany such localized dilatation; in 2 cases, the dilatation was the only clue to the underlying disorder.

  12. Cytochrome P450 Oxidoreductase Influences CYP2B6 Activity in Cyclophosphamide Bioactivation

    PubMed Central

    El-Serafi, Ibrahim; Afsharian, Parvaneh; Moshfegh, Ali; Hassan, Moustapha; Terelius, Ylva

    2015-01-01

    Introduction Cyclophosphamide is commonly used as an important component in conditioning prior to hematopoietic stem cell transplantation, a curative treatment for several hematological diseases. Cyclophosphamide is a prodrug activated mainly by cytochrome P450 2B6 (CYP2B6) in the liver. A high degree of inter- and intra-individual variation in cyclophosphamide kinetics has been reported in several studies. Materials and Methods Hydroxylation of cyclophosphamide was investigated in vitro using three microsomal batches of CYP2B6*1 with different ratios of POR/CYP expression levels. Twenty patients undergoing hematopoietic stem cell transplantation were also included in the study. All patients received an i.v. infusion of cyclophosphamide (60 mg/kg/day, for two days) as a part of their conditioning. Blood samples were collected from each patient before cyclophosphamide infusion, 6 h after the first dose and before and 6 h after the second dose. POR gene expression was measured by mRNA analysis and the pharmacokinetics of cyclophosphamide and its active metabolite were determined. Results A strong correlation between the in vitro intrinsic clearance of cyclophosphamide and the POR/CYP ratio was found. The apparent Km for CYP2B6.1 was almost constant (3-4 mM), while the CLint values were proportional to the POR/CYP ratio (3-34 μL/min/nmol CYP). In patients, the average expression of the POR gene in blood was significantly (P <0.001) up-regulated after cyclophosphamide infusion, with high inter-individual variations and significant correlation with the concentration ratio of the active metabolite 4-hydroxy-cyclophosphamide/cyclophosphamide. Nine patients were carriers for POR*28; four patients had relatively high POR expression. Conclusions This investigation shows for the first time that POR besides CYP2B6 can influence cyclophosphamide metabolism. Our results indicate that not only CYPs are important, but also POR expression and/or activity may influence

  13. Charged dilation black holes as particle accelerators

    NASA Astrophysics Data System (ADS)

    Pradhan, Parthapratim

    2015-03-01

    We examine the possibility of arbitrarily high energy in the center-of-mass (CM) frame of colliding neutral particles in the vicinity of the horizon of a charged dilation black hole (BH). We show that it is possible to achieve the infinite energy in the background of the dilation black hole without fine-tuning of the angular momentum parameter. It is found that the CM energy (Ecm) of collisions of particles near the infinite red-shift surface of the extreme dilation BHs are arbitrarily large while the non-extreme charged dilation BHs have the finite energy. We have also compared the Ecm at the horizon with the ISCO (Innermost Stable Circular Orbit) and MBCO (Marginally Bound Circular Orbit) for extremal Reissner-Nordstrøm (RN) BH and Schwarzschild BH. We find that for extreme RN BH the inequality becomes Ecm|r+ >Ecm|rmb >Ecm|rISCO i.e. Ecm|r+=M :Ecm | rmb =(3 +√{ 5 }/2) M :Ecm| rISCO = 4 M = ∞ : 3.23 : 2.6 . While for Schwarzschild BH the ratio of CM energy is Ecm| r+ = 2 M :Ecm| rmb = 4 M :Ecm| rISCO = 6 M =√{ 5 } :√{ 2 } :√{ 13 }/3 . Also for Gibbons-Maeda-Garfinkle-Horowitz-Strominger (GMGHS) BHs the ratio is being Ecm| r+ = 2 M :Ecm| rmb = 2 M :Ecm| rISCO = 2 M = ∞ : ∞ : ∞ .

  14. Genetics Home Reference: familial dilated cardiomyopathy

    MedlinePlus

    ... 10.1056/NEJMoa1110186. Citation on PubMed or Free article on PubMed Central Hershberger RE, Hedges DJ, Morales A. Dilated cardiomyopathy: the complexity of a diverse genetic architecture. Nat Rev Cardiol. 2013 Sep;10(9):531- ...

  15. Stability under dilations of nonlinear spinor fields

    NASA Astrophysics Data System (ADS)

    Strauss, Walter A.; Vázquez, Luis

    1986-07-01

    The stability problem of the localized solutions for classical Dirac fields with scalar self-interactions is considered in the framework of the Shatah-Strauss formalism. We study the stability and instability under dilations and provide an application to the Soler model.

  16. Stability under dilations of nonlinear spinor fields

    SciTech Connect

    Strauss, W.A.; Va-acute-accentzquez, L.

    1986-07-15

    The stability problem of the localized solutions for classical Dirac fields with scalar self-interactions is considered in the framework of the Shatah-Strauss formalism. We study the stability and instability under dilations and provide an application to the Soler model.

  17. Hypnoanalgesia for Dilatation and Curettage Pain Control

    PubMed Central

    Fathi, Mehdi; Aziz Mohammadi, Susan; Moslemifar, Mehdi; Kamali, Kurosh; Joudi, Marjan; Sabri Benhangi, Azam; Mohaddes, Mojtaba; Joudi, Mona; Mohajeri, Mozhgan

    2017-01-01

    There are many acceptable approaches ranging from light to moderate intravenous sedation or analgesic drugs that are used to provide pain control in dilatation and curettage. We report the use of hypnosis as a nonpharmacologic approach to control pain in this manner. PMID:28824863

  18. Aortic dilation, genetic testing, and associated diagnoses.

    PubMed

    Zarate, Yuri A; Sellars, Elizabeth; Lepard, Tiffany; Tang, Xinyu; Collins, R Thomas

    2016-04-01

    The aims of this study were to determine the genetic diagnoses most frequently associated with aortic dilation in a large population and to describe the results of genetic testing in the same. A retrospective review of records from patients with known aortic dilation identified through an echocardiogram database was performed. During the study period, different chromosomal microarray platforms and molecular diagnostic techniques were used. A total of 715 patients (mean age, 9.7 years; 67% male) met study inclusion criteria. The overall frequency of underlying presumptive or confirmed genetic diagnoses was 17% (125/715). Molecular evaluation for possible underlying aortopathy-related disorders was performed in 9% of patients (66/715). Next-generation sequencing panels were performed in 16 patients, and pathogenic abnormalities were detected in 4 (25%). Microarrays were conducted in 10% of patients (72/715), with a total of 23 pathogenic copy-number variants identified in 19 patients (26%). Marfan syndrome was the most frequently recognized genetic disorder associated with aortic dilation, but other cytogenetic abnormalities and associated diagnoses also were identified. The differential diagnosis in patients with aortic dilation is broad and includes many conditions outside the common connective tissue disorder spectrum. A genetics evaluation should be considered to assist in the diagnostic evaluation.Genet Med 18 4, 356-363.

  19. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A nasal... nasal airflow. The device decreases airway resistance and increases nasal airflow. The external...

  20. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A nasal... nasal airflow. The device decreases airway resistance and increases nasal airflow. The external...

  1. A Symmetry Approach to Time Dilation.

    ERIC Educational Resources Information Center

    Dunne, Peter

    1995-01-01

    Outlines an approach to introduce students to special relativity using a discussion of stopclocks and measurement of the transmission of light pulses to produce a natural derivation of the time dilation factor. Aims at providing a frame of reference from which they can be tempted to explore special relativity at a more sophisticated level. (JRH)

  2. 21 CFR 876.5520 - Urethral dilator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Urethral dilator. 876.5520 Section 876.5520 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... flexibilities. The device may include a mechanism to expand the portion of the device in the urethra...

  3. 21 CFR 876.5520 - Urethral dilator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Urethral dilator. 876.5520 Section 876.5520 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL... flexibilities. The device may include a mechanism to expand the portion of the device in the urethra...

  4. Surface dilatational viscosity of Langmuir monolayers

    NASA Astrophysics Data System (ADS)

    Lopez, Juan; Vogel, Michael; Hirsa, Amir

    2003-11-01

    With increased interest in microfluidic systems, interfacial phenomena is receiving more attention. As the length scales of fluid problems decrease, the surface to volume ratio increases and the coupling between interfacial flow and bulk flow becomes increasingly dominated by effects due to intrinsic surface viscosities (shear and dilatational), in comparison to elastic effects (due to surface tension gradients). The surface shear viscosity is well-characterized, as cm-scale laboratory experiments are able to isolate its effects from other interfacial processes (e.g., in the deep-channel viscometer). The same is not true for the dilatational viscosity, because it acts in the direction of surface tension gradients. Their relative strength scale with the capillary number, and for cm-scale laboratory flows, surface tension effects tend to dominate. In microfluidic scale flows, the scaling favors viscosity. We have devised an experimental apparatus which is capable of isolating and enhancing the effects of dilatational viscosity at the cm scales by driving the interface harmonically in time, while keeping the interface flat. In this talk, we shall present both the theory for how this works as well as experimental measurements of surface velocity from which we deduce the dilatational viscosity of several monolayers on the air-water interface over a substantial range of surface concentrations. Anomalous behavior over some range of concentration, which superficially indicates negative viscosity, maybe explained in terms of compositional effects due to large spatial and temporal variations in concentration and corresponding viscosity.

  5. Ultrastructural Changes in Murine Peritoneal Cells Following Cyclophosphamide Administration

    PubMed Central

    Chin, K. N.; Hudson, G.

    1974-01-01

    Peritoneal cells were studied at intervals of between 6 h and 30 days following a single intravenous injection of a sublethal dose of cyclophosphamide. With the electron microscope, evidence of cell damage and death could be seen at 6 h, and by 12 h large numbers of dead cells were noted, either lying free or within the cytoplasm of macrophages. Most of the damaged cells were lymphocytes but degenerating blast cells, eosinophils, neutrophils and mast cells were also identified. Nuclei were seen in which margination of chromatin had occurred but nuclei of uniform density were also prominent and showed irregular shape and lobulation. Macrophages exhibited all stages of phagocytosis and digestion and a few phagocytes of atypical appearance were noted. By 24 h most of the dead cells lay within the cytoplasm of macrophages which showed many phagocytic inclusions as well as lipid droplets. By 6 days, the peritoneal cells had regained normal appearances although the proportion of lymphoid cells was still reduced. By the 18th day, all features were indistinguishable from normal. The changes observed showed a general similarity to those noted previously in the lymphoreticular cells of the Peyer's patch; they provide no evidence that the environment of the peritoneal cavity protects cells against the action of cyclophosphamide. ImagesFigs. 4-6Figs. 7-9Figs. 10-12Figs. 1-3 PMID:4447790

  6. [Mycophenolate mofetil in lupus nephritis refractory to intravenous cyclophosphamide].

    PubMed

    Daza, Leonel; Pérez, Salvador; Velasco, Ulises; Hernández, Martha

    2006-09-01

    To evaluate the use of mycophenolate mofetil (MMF) in lupus nephritis (LN) patients with prior failure to intravenous cyclophosphamide over a 12-month follow-up. Eleven patients with LN were included. MMF doses ranged from 1.5-2 grams per day. In all patients, 24-h urinary protein excretion, creatinine clearance, and serum creatinine were evaluated. Treatment-related adverse effects were recorded over the 12-month follow-up. Basal proteinuria decreased from 1.63 g/L (95% CI: 0.78-2.5) to 0.93 (95% CI: 0.1-1.62) g/L at the end of the follow-up period (p = 0.04). Creatinine clearance showed a tendency to improve but no statistically significant differences were found, 69.2 (95% CI 51.4- 87.4) vs. 79.29 (IC 95% 49.2-109.3) ml/min, respectively; p = 0.90). No significant differences were found in the remaining variables. Patients without response to MMF had a higher chronicity index than those with good or average response. MMF doses of 1.5-2 grams per day are a good alternative in LN patients without response to intravenous cyclophosphamide and a low chronicity index. No severe adverse effects were found. Copyright © 2006 Elsevier España S.L. Barcelona. Published by Elsevier Espana. All rights reserved.

  7. Arterial microembolisation: an unusual presentation of dilated cardiomyopathy.

    PubMed Central

    Gillespie, R L; Mullen, G M; Costanzo-Nordin, M R

    1990-01-01

    Systemic embolisation is common in patients with dilated cardiomyopathy. Microembolisation as a presenting sign of dilated cardiomyopathy, however, has not been reported before. A 37 year old woman in whom dilated cardiomyopathy presented as arterial microembolisation to the toes is described. Images PMID:2310647

  8. Effects of cyclophosphamide on the kaolin consumption (pica behavior) in five strains of adult male rats.

    PubMed

    Tohei, Atsushi; Kojima, Shu-ichi; Ikeda, Masashi; Hokao, Ryoji; Shinoda, Motoo

    2011-07-01

    It is known that pica, the consumption of non-nutritive substances such as kaolin, can be induced by administration of toxins or emetic agents in rats. In the present study, we examined the effects of intraperitoneal (i.p.) administration of cyclophosphamide on pica behavior and on the concentration of 5-hydroxyindoleacetic acids (5HIAA) in cerebrospinal fluid (CSF) in the following five strains of adult male rats: Sprague Dawley (SD), Wistar, Fischer 344 (F344), Wistar-Imamichi (WI) and Long Evans (LE). Cyclophosphamide (25 mg or 50 mg/kg) was injected (i.p.) into the rats and kaolin and food intake were measured at 24 hr after injection. The animals were anesthetized with urethane (1 g/kg) at 3 hr after injection of cyclophosphamide, and CSF was collected from the cisterna magna. WI and LE rats clearly showed pica behavior as compared with the other strains. In LE rats, the concentration of 5HIAA in CSF also increased in a dose-dependent manner of cyclophosphamide. The pretreatment with ondansetron (5-HT(3) antagonist) restored both changes (kaolin consumption and 5HIAA levels) induced by cyclophosphamide. These results suggest that the LE rat is sensitive to cyclophosphamide, that pica induced by cyclophosphamide mimics many aspects of emesis including the serotonergic response in the central nervous system and that use of the pica model would be a practical method for evaluating the effects of antiemetic drugs in addition to the mechanism of emesis.

  9. Protective Effects of Essential Oils as Natural Antioxidants against Hepatotoxicity Induced by Cyclophosphamide in Mice.

    PubMed

    Sheweita, Salah A; El-Hosseiny, Lobna S; Nashashibi, Munther A

    2016-01-01

    Clinical application of cyclophosphamide (CP) as an anticancer drug is often limited due to its toxicity. CP is metabolized mainly in the liver by cytochrome P450 system into acrolein which is the proximate toxic metabolite. Many different natural antioxidants were found to alleviate the toxic effects of various toxic agents via different mechanisms. Therefore, the present study aimed at investigating the role of essential oils extracted from fennel, cumin and clove as natural antioxidants in the alleviation of hepatotoxicity induced by CP through assessment of hepatotoxicity biomarkers (AST, ALT, ALP), histopathology of liver tissues as well as other biochemical parameters involved in the metabolism of CP. The data of the present study showed that treatment of male mice with cyclophosphamide (2.5 mg/Kg BW) as repeated dose for 28 consecutive days was found to induce hepatotoxicity through the elevation in the activities of AST, ALT, and ALP. Combined administration of any of these oils with CP to mice partially normalized the altered hepatic biochemical markers caused by CP, whereas administration of fennel, clove or cumin essential oils alone couldn't change liver function indices. Moreover, CP caused histological changes in livers of mice including swelling and dilation in sinusoidal space, inflammation in portal tract and hepatocytes, as well as, hyperplasia in Kuppfer cells. However, co-administration of any of the essential oils with CP alleviated to some extent the changes caused by CP but not as the normal liver. CP was also found to induce free radical levels (measured as thiobarbituric acid reactive substances) and inhibited the activities of superoxide dismutase, glutathione reductase, and catalase as well as activities and protein expressions of both glutathione S-transferase (GSTπ) and glutathione peroxidase. Essential oils restored changes in activities of antioxidant enzymes (SOD, CAT, GR, GST, and GPx) caused by CP to their normal levels compared

  10. Protective Effects of Essential Oils as Natural Antioxidants against Hepatotoxicity Induced by Cyclophosphamide in Mice

    PubMed Central

    Sheweita, Salah A.; El-Hosseiny, Lobna S.; Nashashibi, Munther A.

    2016-01-01

    Clinical application of cyclophosphamide (CP) as an anticancer drug is often limited due to its toxicity. CP is metabolized mainly in the liver by cytochrome P450 system into acrolein which is the proximate toxic metabolite. Many different natural antioxidants were found to alleviate the toxic effects of various toxic agents via different mechanisms. Therefore, the present study aimed at investigating the role of essential oils extracted from fennel, cumin and clove as natural antioxidants in the alleviation of hepatotoxicity induced by CP through assessment of hepatotoxicity biomarkers (AST, ALT, ALP), histopathology of liver tissues as well as other biochemical parameters involved in the metabolism of CP. The data of the present study showed that treatment of male mice with cyclophosphamide (2.5 mg/Kg BW) as repeated dose for 28 consecutive days was found to induce hepatotoxicity through the elevation in the activities of AST, ALT, and ALP. Combined administration of any of these oils with CP to mice partially normalized the altered hepatic biochemical markers caused by CP, whereas administration of fennel, clove or cumin essential oils alone couldn’t change liver function indices. Moreover, CP caused histological changes in livers of mice including swelling and dilation in sinusoidal space, inflammation in portal tract and hepatocytes, as well as, hyperplasia in Kuppfer cells. However, co-administration of any of the essential oils with CP alleviated to some extent the changes caused by CP but not as the normal liver. CP was also found to induce free radical levels (measured as thiobarbituric acid reactive substances) and inhibited the activities of superoxide dismutase, glutathione reductase, and catalase as well as activities and protein expressions of both glutathione S-transferase (GSTπ) and glutathione peroxidase. Essential oils restored changes in activities of antioxidant enzymes (SOD, CAT, GR, GST, and GPx) caused by CP to their normal levels compared

  11. Cyclophosphamide promotes breast cancer cell migration through CXCR4 and matrix metalloproteinases.

    PubMed

    Hung, Chao-Ming; Hsu, Yi-Chiang; Chen, Tzu-Yu; Chang, Chi-Chang; Lee, Mon-Juan

    2017-03-01

    Cyclophosphamide is indicated for the treatment of cancerous diseases such as breast cancer and cervical cancer. Recent studies have shown that cyclophosphamide may induce cancer metastasis, but the cause of this unexpected adverse effect is not fully understood. In this study, we investigate the effect of cyclophosphamide on cancer cell migration and its correlation to chemokine (C-X-C motif) receptor 4 (CXCR4), a biomarker for cancer metastasis. Two human cancer cell lines with significant difference in endogenous CXCR4 expression, the breast cancer cell line, MDA-MB-231, and the melanoma cell line, MDA-MB-435S, were treated with various concentrations of cyclophosphamide, followed by the assessment of CXCR4 expression and cell migration. We found that the migration ability of MDA-MB-231 cells was enhanced with increasing concentrations of cyclophosphamide, which induced the cell-surface expression of CXCR4, but had no effect on the overall amount of CXCR4. In MDA-MB-435S cells, in which CXCR4 was barely detectable, cyclophosphamide was unable to activate cell-surface CXCR4, and did not promote cell migration. Studies on the mRNA expression profile of matrix metalloproteinases (MMPs) in MDA-MB-231 cells further indicate that MMP9 and MMP13 may be involved in the action of cyclophosphamide. The protein expression of both MMP9 and MMP13 was increased in the presence of cyclophosphamide. Results from this study provide the molecular basis for the possible pathway of cyclophosphamide to induce cancer metastasis. © 2017 International Federation for Cell Biology.

  12. Assessment of ventricular function in dilated cardiomyopathies.

    PubMed

    Pak, P H; Kass, D A

    1995-05-01

    Regardless of its cause, systolic dysfunction in dilated cardiomyopathy triggers a wide variety of compensatory responses resulting in cardiac dilatation, fluid retention, and systemic vasoconstriction. Standard therapy with vasodilators, digoxin, and diuretics can provide symptomatic relief in many patients. However, many others do not respond adequately, and mortality from heart failure remains high. This has driven the search for novel therapies. To evaluate the efficacy and decipher mechanisms of action of these treatments, accurate assessments of left ventricular function are valuable. In particular, one seeks indexes that are cardiac-specific, in that they are minimally influenced by vascular loading conditions. An increasingly used "gold standard" that can achieve this goal is the invasively measured pressure-volume relation. Newer noninvasive methods have yielded several surrogates that have the key advantage of being applicable to chronic disease assessment. In this report, we review the current state-of-the-art in left ventricular function assessment, and describe recent advances in its noninvasive evaluation.

  13. Electrocardiography during Manual Dilatation of the Anus

    PubMed Central

    Collins, R. E. C.; Fell, R. H.; Lord, P. H.

    1973-01-01

    Manual dilatation of the anus was carried out on 50 unpremedicated outpatients under propanidid, nitrous oxide, and halothane anaesthesia with E.C.G.monitoring. About half of the patients received intravenous atropine with the propanidid. The operation induced a variety of changes in heart rate but in the whole experiment only two isolated cardiac arrhythmic complexes were seen—a single defect of conduction and a solitary ventricular extrasystole. Changes in rate were not modified by atropine. It is concluded that manual dilatation of the anus is a safe procedure when carried out under the anaesthetic described and that prior medication with atropine is not necessary. This work supports the view that propanidid protects patients from most abnormalities of heart action which result from intense visceral stimulation. PMID:4712484

  14. Sheehan syndrome with reversible dilated cardiomyopathy.

    PubMed

    Laway, Bashir A; Alai, Mohammad S; Gojwari, Tariq; Ganie, Mohd A; Zargar, Abdul Hamid

    2010-01-01

    Cardiac abnormalities in patients with Sheehan syndrome are uncommon. A case of Sheehan syndrome with dilated cardiomyopathy is presented in whom hormone replacement with levothyroxine and prednisolone resulted in complete recovery of cardiomyopathy. A 25-year-old woman presented with lactation failure, secondary amenorrhea, features of hypothyroidism and a hypocortisol state following severe postpartum hemorrhage after her last child birth. She also had smear positive pulmonary tuberculosis. After starting antitubercular treatment, she developed shock, suggestive of hypocortisol crisis. Hormonal investigations revealed evidence of panhypopitutarism and magnetic resonance imaging revealed partial empty sella. Meanwhile echocardiography revealed evidence of dilated cardiomyopathy (DCM). The patient was given replacement therapy in the form of glucocorticoids and levothyroxine in addition to antitubercular treatment. She improved and on follow-up over a period of 7 months, the DCM completely reversed. To our knowledge this is the first report of reversible DCM in a patient with Sheehan syndrome.

  15. Recrudescence of Anaplasma marginale induced by immunosuppression with cyclophosphamide.

    PubMed

    Corrier, D E; Wagner, G G; Adams, L G

    1981-01-01

    Eight doses of cyclophosphamide (5 mg/kg), at 2-day intervals between doses, were administered IV to Anaplasma-carrier splenectomized calves. Significant decreases in serum immunoglobulins, diminished complement-fixing antibody response, and transitory leukopenia were associated with the treatment. Recrudescence of clinical Anaplasma infection occurred after the 5th dose of cyclophosphate was given and was characterized by rapid increase in parasitemia, marked decrease in PCV, and mortality. The results of the present study indicated that humoral mediated immunity may contribute to the maintenance of a state of equilibrium in the host-parasite relationship and that suppression of humoral immune responses may alter the course and outcome of infection in Anaplasma carriers.

  16. Potency and stability of compounded cyclophosphamide: a pilot study.

    PubMed

    Robat, C; Budde, J

    2017-09-01

    Compounding of drugs for use in veterinary oncology is becoming increasingly common. We obtained 15 mg cyclophosphamide capsules from five different compounding pharmacies and performed potency analyses at two time points, as well as stability at 60 days. Potency results for four out of five and zero out of five (4/10) samples analysed were inadequate. Stability at 60 days was acceptable for all but one sample. This pilot study raises several important points of concern when compounding chemotherapy in dogs and cats. Further studies are necessary to solidify this data. Collaboration between pharmacists, veterinarians and regulatory bodies is needed to ensure safe and accurate delivery of compounded drugs to client-owned animals. © 2016 John Wiley & Sons Ltd.

  17. Improved Model of Rock Mass Dilatation.

    DTIC Science & Technology

    1985-05-29

    nonlinear partial differential equations of the hyperbolic type is involved. In both cases, the numerical procedures are discussed in detail : Runge-Kutta...34 ... .. .. .. ’ ................... ":"’’t_ . 2 Geometrical interpretation of the coefficient of friction p and the dilatancy factor 9.....9 3 Variable flow rule, characterized by a...increase of the crack space (porosity) but also by sliding along intergranular surfaces (cataclastic flow ). .- .. At high confining pressure

  18. Charged Dilation Black Holes as Particle Accelerators

    NASA Astrophysics Data System (ADS)

    Pradhan, Parthapratim

    2016-07-01

    We examine the possibility of arbitrarily high energy in the Center-of-mass frame of colliding neutral particles in the vicinity of the horizon of a charged dilation black hole(BH). We show that it is possible to achieve the infinite energy in the background of the dilation black hole without fine-tuning of the angular momentum parameter. It is found that the center-of-mass energy (E_{cm}) of collisions of particles near the infinite red-shift surface of the extreme dilation BHs are arbitrarily large while the non-extreme charged dilation BHs have the finite energy. We have also compared the E_{cm} at the horizon with the ISCO(Innermost Stable Circular Orbit) and MBCO (Marginally Bound Circular Orbit) for extremal RN BH and Schwarzschild BH. We find that for extreme RN BH the inequality becomes E_{cm}mid_{r_{+}}>E_{cm}mid_{r_{mb}}> E_{cm}mid_{r_{ISCO}} i.e. E_{cm}mid_{r_{+}=M}: E_{cm}mid_{r_{mb}= ({3+√{5}}/{2})M} : E_{cm}mid_{r_{ISCO}=4M} =∞ : 3.23 : 2.6 . While for Schwarzschild BH the ratio of CM energy is E_{cm}mid_{r_{+}=2M}: E_{cm}mid_{r_{mb}=4M} : E_{cm}mid_{r_{ISCO}=6M} = √{5} : √{2} : {√{13}}/{3}. Also for Gibbons-Maeda-Garfinkle-Horowitz-Strominger (GMGHS) BHs the ratio is being E_{cm}mid_{r_{+}=2M}: E_{cm}mid_{r_{mb}=2M} : E_{cm}mid_{r_{ISCO}=2M}=∞ : ∞ : ∞.

  19. Dilatancy Instability as a Possible Seismic Mechanism

    DTIC Science & Technology

    1976-06-01

    8217’ 1 I I -- I C=0 Department of Mining Engineering South Dakota School of Mines & Technology Rapid City, South DIlkta 57701 8, 01 08105 FINAL REPORT...Title: Dilatancy Instability as a Possible Seismic Mechanism Principal Investigator: James E. Russell Professor of Mining Engineering South Dakota ...School of Mines & Technology Rapid City, South Dakota 57701 Contract Period: April 10, 1972 to November 30, 1973 Sponsored by: The U. S. Geological Survey

  20. Proventricular dilatation syndrome in large psittacine birds.

    PubMed

    Clark, F D

    1984-01-01

    Proventricular dilatation was diagnosed in 16 psittacine birds. Signs included anorexia, lethargy, weight loss, and intermittent vomiting. The proventriculus in all birds was thin-walled and impacted with ingesta and occupied most of the body cavity. Microscopic changes in the proventriculus varied from none to an infiltration of lymphocytes, macrophages, and heterophils. There was no evidence of viral or bacterial infection or lead toxicity.

  1. Treatment of refractory osteosarcoma with fractionated cyclophosphamide and etoposide.

    PubMed

    Rodríguez-Galindo, Carlos; Daw, Najat C; Kaste, Sue C; Meyer, William H; Dome, Jeffrey S; Pappo, Alberto S; Rao, Bhaskar N; Pratt, Charles B

    2002-05-01

    Standard multiagent chemotherapy for osteosarcoma may include platinum compounds, doxorubicin, and high-dose methotrexate. By identifying new chemotherapeutic strategies, the outcome of these patients can be improved and the toxicity of treatment regimens decreased. The authors evaluated the activity of the combination of cyclophosphamide (500 mg/m2 per day for 5 days) and etoposide (100 mg/m2 per day for 5 days) given with granulocyte colony-stimulating factor (G-CSF) to children with osteosarcoma unresponsive to conventional treatment. Fourteen patients with refractory osteosarcoma were treated with this combination. Twelve patients had been previously treated with a multiagent regimen that included carboplatin, ifosfamide, methotrexate, and doxorubicin. Seven of 11 evaluable patients had a poor histologic response in their primary tumor at the time of definitive surgery (Huvos grade 1 or 2). Sites of relapse included lung, bone, and brain. A total of 47 courses were given. An overall response rate of 28.5% was achieved. A complete response was obtained in one patient (7.1%), a partial response was obtained in three patients (21.4%), and stable disease for 1 to 4 months was achieved in five patients (35.7%). Five patients (35.7%) had progressive disease. Grade 4 neutropenia was the primary form of toxicity observed; the median duration of absolute neurophil count less than 500/microL was 4 days. The combination of cyclophosphamide and etoposide resulted in a response rate of 28.5% in patients with refractory or relapsed osteosarcoma, and its incorporation into front-line therapies deserves further evaluation.

  2. Bougie urethral dilators: revival or survival?

    PubMed Central

    Al–Adawi, Mohammad Ahmad

    2013-01-01

    Objectives To present our center's experience in managing bladder outlet obstruction (BOO) conditions using bougie dilators. We described the dilation technique methodically for teaching purpose. Patients and method Retrospectively, a total of 196 medical records over the last four years denoting BOO conditions in men, women, and children were retrieved for analysis. Data reviewed for common complications was namely: perforation, recurrence, urinary tract obstruction (UTI) and inability to overcome the obstruction. Results Among the 196 analyzed cases, 24 (12.2%) cases were cured, whereas 172 (87.8%) cases reported complications. Within the complicated cases analyzed, 134 (68.4%) cases had recurrent obstructions, 13 (6.6%) cases had perforations, 6 (3.0%) cases developed UTI, while in 19 (9.7%) cases, we failed to pass the obstruction. Conclusions In our center where urethral dilation technique has revived four years ago, it turned back to be the standard choice in managing BOO cases. We propose the technique to Urology training program directors, all over the world, to teach it as a compulsory skill for junior urologists to master. PMID:24757552

  3. Formation and interpretation of dilatant echelon cracks.

    USGS Publications Warehouse

    Pollard, D.D.; Segall, P.; Delaney, P.T.

    1982-01-01

    The relative displacements of the walls of many veins, joints, and dikes demonstrate that these structures are dilatant cracks. We infer that dilatant cracks propagate in a principal stress plane, normal to the maximum tensile or least compressive stress. Arrays of echelon crack segments appear to emerge from the peripheries of some dilatant cracks. Breakdown of a parent crack into an echelon array may be initiated by a spatial or temporal rotation of the remote principal stresses about an axis parallel to the crack propagation direction. Near the parent-crack tip, a rotation of the local principal stresses is induced in the same sense, but not necessarily through the same angle. Incipient echelon cracks form at the parent-crack tip normal to the local maximum tensile stress. Further longitudinal growth along surfaces that twist about axes parallel to the propagation direction realigns each echelon crack into a remote principal stress plane. The walls of these twisted cracks may be idealized as helicoidal surfaces. An array of helicoidal cracks sweeps out less surface area than one parent crack twisting through the same angle. Thus, many echelon cracks grow from a single parent because the work done in creating the array, as measured by its surface area decreases as the number of cracks increases. -from Authors

  4. Dilatancy and shear thickening of particle suspensions

    NASA Astrophysics Data System (ADS)

    Bonn, Daniel

    2013-03-01

    Shear thickening is a fascinating subject, as 99.9% of complex fluids are thinning; thickening systems thus are the ``exception to the rule'' that needs to be understood. Moreover, such tunable systems show very promising applications, e.g. to block large underground pores in oil recovery to maintain a constant oil flow by plugging water filled pores (an approach used in oil recovery by e.g. Shell), or to manufacture bulletproof vests that are comfortable to wear, but stop bullets nonetheless. We study the rheology of non-Brownian particle suspensions (notably, cornstarch) that exhibit shear thickening. Using magnetic resonance imaging (MRI), the local properties of the flow are obtained by the determination of local velocity profiles and concentrations in a Couette cell. We also perform macroscopic rheology experiments in different geometries. The results suggest that the shear thickening is a consequence of dilatancy: the system under flow attempts to dilate but instead undergoes a jamming transition, because it is confined. This proposition is confirmed by an independent measurement of the dilation of the suspension as a function of the shear rate.

  5. Dilational surface rheology of polymer solutions

    NASA Astrophysics Data System (ADS)

    Noskov, B. A.; Bykov, A. G.

    2015-06-01

    The review concerns main achievements in dilational rheology of polymer adsorption films at the gas/liquid interfaces reported in the last fifteen years. The theoretical foundations of methods of surface rheology and the key results obtained in studies of solutions of amphiphilic nonionic polymers, polyelectrolytes, proteins and their complexes with low-molecular-mass surfactants are discussed. Interest in the surface dilational rheology is mainly caused by a small number of available experimental methods for investigation of the surface of liquids, by the fact that traditional methods of measurement of the surface tension that are widely used in studies of solutions of low-molecular-mass surfactants provide little information when applied to polymer solutions owing to very slow establishment of equilibrium as well as by weak dependence of the surface tension on the polymer concentration. Progress in the surface rheology is driven by the recent studies of the stability of foams and emulsions that demonstrated a key role of the dilational surface rheological properties in the dynamics of liquid-phase disperse systems. The bibliography includes 191 references.

  6. Time dilation in quantum systems and decoherence

    NASA Astrophysics Data System (ADS)

    Pikovski, Igor; Zych, Magdalena; Costa, Fabio; Brukner, Časlav

    2017-02-01

    Both quantum mechanics and general relativity are based on principles that defy our daily intuitions, such as time dilation, quantum interference and entanglement. Because the regimes where the two theories are typically tested are widely separated, their foundational principles are rarely jointly studied. Recent works have found that novel phenomena appear for quantum particles with an internal structure in the presence of time dilation, which can take place at low energies and in weak gravitational fields. Here we briefly review the effects of time dilation on quantum interference and generalize the results to a variety of systems. In addition, we provide an extended study of the basic principles of quantum theory and relativity that are of relevance for the effects and also address several questions that have been raised, such as the description in different reference frames, the role of the equivalence principle and the effective irreversibility of the decoherence. The manuscript clarifies some of the counterintuitive aspects arising when quantum phenomena and general relativistic effects are jointly considered.

  7. The Effect of Immunosuppression on Viral Encephalitis, with Special Reference to Cyclophosphamide

    PubMed Central

    Zlotnik, I.; Smith, C. E. G.; Grant, D. P.; Peacock, S.

    1970-01-01

    Cyclophosphamide altered not only the pathological picture of virus encephalitis, but also enhanced the invasiveness of viruses and produced fatal forms of disease to which monkeys were otherwise resistant. Normal patas monkeys infected either i.c. or intranasally (i.n.) with louping ill developed clinical encephalitis from which they recovered, but when cyclophosphamide was administered the disease proved fatal. Normal rhesus monkeys inoculated i.n. with virulent western equine encephalitis virus developed neither clinical disease nor CNS lesions, but after treatment with cyclophosphamide they developed fatal encephalitis. The viruses of louping ill, Venezuelan equine encephalitis and Western equine encephalitis when given without an immunosuppressant usually gave rise to acute inflammatory CNS pathology, but when the monkeys were given cyclophosphamide, the inflammatory reaction was replaced by a degenerative process causing both neuronal necrosis and spongy degeneration. ImagesFigs. 1-3 PMID:4991966

  8. Comparison of pneumatic dilation with pneumatic dilation plus botulinum toxin for treatment of achalasia.

    PubMed

    Bakhshipour, Alireza; Rabbani, Romina; Shirani, Shapoor; Soleimani, Hosein A S L; Mikaeli, Javad

    2010-01-01

    Among the therapeutic options for achalasia are pneumatic dilatation (PD), an appropriate long-term therapy, and botulinum toxin injection (BT) that is a relatively short-term therapy. This study aimed to compare therapeutic effect of repetitive pneumatic dilation with a combined method (botulinum toxin injection and pneumatic dilation) in a group of achalasia patients who are low responder to two initial pneumatic dilations. Thirty-four patients with documented primary achalasia that had low response to two times PD (<50% decrease in symptom score and barium height at 5 minute in timed esophagogram after 3 month of late PD) were randomized to receive pneumatic dilation (n=18) or botulinum toxin injection and pneumatic dilation by four weeks interval (n=16), PD and BT+PD groups respectively. Symptom scores were evaluated before and at 1, 6 and 12 months after treatment. Clinical remission was defined as a decrease in symptom score > or = 50% of baseline. There were no significant differences between the two groups in gender, age and achalasia type. Remission rate of patients in BT-PD group in comparison with PD group were 87.5% vs. 67.1% (P = 0.7), 87.5% vs. 61.1% (P = 0.59) and 87.5% vs. 55.5% (P = 0.53) at 1, 6 and 12 months respectively .There were no major complications in either group. The mean symptom score decreased by 62.71% in the BT-PD group (P < 0.002) and 50.77% in the PD group (P < 0.01) at the end of the first year. Despite a better response rate in BT+PD group, a difference was not statistically significant. A difference may be meaningful if a large numbers of patients are included in the study.

  9. Enantioselectivity in the Metabolism of Cyclophosphamide in Patients With Multiple or Systemic Sclerosis.

    PubMed

    de Castro, Francine Attié; Simões, Belinda Pinto; Coelho, Eduardo Barbosa; Lanchote, Vera Lucia

    2017-06-01

    The aim of this study was to evaluate the enantioselective pharmacokinetics of cyclophosphamide and its metabolites 4-hydroxycyclophosphamide and carboxyethylphosphoramide mustard in patients with systemic or multiple sclerosis. Patients with systemic sclerosis (n = 10) or multiple sclerosis (n = 10), genotyped for the allelic variants of CYP2C9*2 and CYP2C9*3 and of the CYP2B6 G516T polymorphism, were treated with 50 mg cyclophosphamide/kg daily for 4 days. Serial blood samples were collected up to 24 hours after administration of the last cyclophosphamide dose. Cyclophosphamide, 4-hydroxycyclophosphamide, and carboxyethylphosphoramide enantiomers were analyzed in plasma samples using liquid chromatography-tandem mass spectrometry coupled to chiral column Chiralcel OD-R or Chiralpak AD-RH. Cytokines IL-2, IL-4, IL-6, IL-8, IL-10, IL- 12p70, IL-17, TNF-α, and INT-δ in the plasma samples collected before cyclophosphamide infusion were analyzed by Milliplex MAP human cytokine/chemokine. Pharmacokinetic parameters showed higher plasma concentrations of (S)-(-)-cyclophosphamide (AUC 215.0 vs 186.2 μg·h/mL for multiple sclerosis patients and 219.1 vs 179.2 μg·h/mL for systemic sclerosis patients) and (R)-4-hydroxycyclophosphamide (AUC 5.6 vs 3.7 μg·h/mL for multiple sclerosis patients and 6.3 vs 5.6 μg·h/mL for systemic sclerosis patients) when compared to their enantiomers in both groups of patients, whereas the pharmacokinetics of the carboxyethylphosphoramide metabolite was not enantioselective. Cytokines' plasma concentrations were similar between multiple and systemic sclerosis groups. The pharmacokinetics of cyclophosphamide is enantioselective in patients with systemic sclerosis and multiple sclerosis, with higher plasma concentrations of the (S)-(-)-cyclophosphamide enantiomer due to the preferential formation of the (R)-4-hydroxycyclophosphamide metabolite. © 2017, The American College of Clinical Pharmacology.

  10. Chlamydia muridarum Induction of Glandular Duct Dilation in Mice

    PubMed Central

    Sun, Xin; Yang, Zhangsheng; Zhang, Hongbo; Dai, Jin; Chen, Jianlin; Tang, Lingli; Rippentrop, Sheena; Xue, Min

    2015-01-01

    Although Chlamydia-induced hydrosalpinx in women and mice has been used as a surrogate marker for tubal infertility, the medical relevance of nontubal pathologies, such as uterine horn dilation, developed in mice following chlamydial infection remains unclear. We now report that the uterine horn dilation correlates with glandular duct dilation detected microscopically following Chlamydia muridarum infection. The dilated glandular ducts pushed the uterine horn lumen to closure or dilation and even broke through the myometrium to develop extrusion outside the uterine horn. The severity scores of uterine horn dilation observed macroscopically correlated well with the number of cross sections of the dilated glandular ducts counted under microscopy. Chlamydial infection was detected in the glandular epithelial cells, potentially leading to inflammation and dilation of the glandular ducts. Direct delivery of C. muridarum into the mouse uterus increased both uterine horn/glandular duct dilation and hydrosalpinx. However, the chlamydial plasmid, which is essential for the induction of hydrosalpinx, was not required for the induction of uterine horn/glandular duct dilation. Screening 12 strains of mice for uterine horn dilation following C. muridarum infection revealed that B10.D2, C57BL/10J, and C57BL/6J mice were most susceptible, followed by BALB/cJ and A/J mice. Deficiency in host genes involved in immune responses failed to significantly alter the C. muridarum induction of uterine horn dilation. Nevertheless, the chlamydial induction of uterine horn/glandular duct dilation may be used to evaluate plasmid-independent pathogenicity of Chlamydia in susceptible mice. PMID:25824829

  11. Hepatoprotective activity of white horehound (Marrubium vulgare) extract against cyclophosphamide toxicity in male rats.

    PubMed

    Ettaya, Amani; Dhibi, Sabah; Samout, Noura; Elfeki, Abdelfettah; Hfaiedh, Najla

    2016-04-01

    The hepatoprotective activity of Marrubium vulgare against cyclophosphamide toxicity in Wistar rats was evaluated. Adult male rats were divided into 4 groups of 6 each: a control group, a group injected with cyclophosphamide (150 mg·kg(-1)) for 3 days, a group orally given a M. vulgare aqueous extract ((500 mg of dry leaves)·kg(-1)·day(-1)) for 30 days then treated with cyclophosphamide, and a group receiving only M. vulgare for 30 days. After 33 days of treatment, activities of alanine amino transferase (ALAT), aspartate amino transferase (ASAT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) were determined in serum. Moreover, lipid peroxidation level and superoxide dismutase (SOD) activities, catalase (CAT) and glutathione peroxidase (GPx) were measured in liver. Alterations of these hepatic biomarkers and increased lipid peroxidation confirmed cyclophosphamide-induced liver toxicity. Cyclophosphamide also decreased the enzymatic defense system against oxidative stress. However, when this drug was administered in rats given M. vulgare extract, all the biological parameters underwent much less alteration. Administration of M. vulgare extract was found to be beneficial by attenuating cyclophosphamide-induced liver damage. The protective effect of the plant is mainly attributed to its antioxidant properties and the existence of phenolic acids and flavonoids, as highlighted by HPLC-based analysis.

  12. Ovarian failure in systemic lupus erythematosus patients treated with pulsed intravenous cyclophosphamide.

    PubMed

    Katsifis, G E; Tzioufas, A G

    2004-01-01

    Pulsed intravenous cyclophosphamide is considered as standard therapy for lupus nephritis and several other severe manifestations of systemic lupus erythematosus (SLE). While the response rate to intravenous cyclophosphamide is substantial, concern has arisen about its toxicity. In addition to increased susceptibility to infection, bone marrow suppression, alopecia, hemorrhagic cystitis and malignancy, ovarian failure is an important side effect associated with the use of cyclophosphamide. Prior research on cyclophosphamide-treated women has consistently demonstrated that the risk of sustained amenorrhea depends on the age of the patient and the cumulative dose received. Sustained amenorrhea is difficult to avoid in women 32 years or older, even with very short intravenous cyclophosphamide courses. Younger women seem to have a substantially lower incidence of ovarian failure, but this side effect may be far more problematic for these patients. In these young women the risk may be modulated by the prior SLE disease duration, the presence of anti-U1RNP antibodies and anti-Ro antibodies. Co-treatment with gonadotropin-releasing hormone agonists may preseserve the future fertility and ovarian function in young women. Ovarian banking before administration of cyclophosphamide should be considered in selected patients.

  13. Effects of carnosine on cyclophosphamide-induced hematopoietic suppression in mice.

    PubMed

    Xu, Meng; He, Rong-Rong; Zhai, Yu-Jia; Abe, Keiichi; Kurihara, Hiroshi

    2014-01-01

    Cyclophosphamide is one of the most widely used chemotherapeutic agents in treating cancers. Chemotherapy drug-induced oxidative stress produces side effects. The severity of myelosuppression increases with a high dose of cyclophosphamide. Chicken soup or chicken essence, a traditional Chinese aliment, is a popular health supplement for patients with cancers or other diseases in Asia. As a major functional component of chicken meat extract, carnosine (beta-alanyl-L-histidine), a dipeptide of the amino acids beta-alanine and histidine, has been shown to have strong antioxidant activities. In the present study, we investigated the effects of carnosine on hematopoietic suppression in mice treated with cyclophosphamide. As expected, we found that cyclophosphamide administration (with a single dose of 150 mg/kg) induced a rapid (within 24 hours) and severe hematopoietic suppression in mice. We further showed that carnosine administration (100 mg/kg/day or 200 mg/kg/day for continuous seven days) could substantially improve suppressed hematopoietic functions and accelerate the recovery of leukocyte counts, bone marrow spontaneous proliferation, colony stimulating activity (CSA) in serum, and production of endogenous cytokines such as interleukin-3 (IL-3) and stem cell factor (SCF). These results indicate that carnosine has the potential to promote the recovery from hematopoietic suppression induced by cyclophosphamide. Our data suggest that carnosine holds a potential in clinical application to minimize the side effects induced by chemotherapeutic agents such as cyclophosphamide and thus will substantially improve the overall anti-tumor effects of the standard chemotherapies.

  14. Protective effect of Zingiber officinale extract on rat testis after cyclophosphamide treatment.

    PubMed

    Mohammadi, F; Nikzad, H; Taghizadeh, M; Taherian, A; Azami-Tameh, A; Hosseini, S M; Moravveji, A

    2014-08-01

    Decreasing the side effects of chemotherapy in testis has been the subjects of many studies. In this study, the protective effects of Zingiber officinale extract on rat testis were investigated after chemotherapy with cyclophosphamide. Histological and biochemical parameters were compared in cyclophosphamide-treated rats with or without ginger extract intake. Wistar male rats were randomly divided into four groups each 10. The control group received a single injection of 1 ml isotonic saline intraperitoneally. The Cyclophosphamide (CP) group received a single dose of cyclophosphamide (100 mg kg(-1) BW) intraperitoneally. CP + 300 and CP + 600 groups received orally 300 or 600 mg of ginger extract, respectively, for a period of 6 weeks after cyclophosphamide injection. The morphologic and histological structure of the testis was compared in different groups of the rats. Also, factors like malondialdehyde, reactive oxygen species, total antioxidant capacity and testosterone level were assessed in blood serum as well. Our results showed that although ginger extract could not change testis weight, malondialdehyde (MDA) and ROS, but antioxidant and testosterone levels in serum were increased significantly. Also, an obvious improved histological change was seen in CP + 300 and CP + 600 groups in comparison with CP group. These protective effects of ginger on rat testis after cyclophosphamide treatment could be attributed to the higher serum level of antioxidants.

  15. Aerobic Capacity and Postprandial Flow Mediated Dilation.

    PubMed

    Ballard, Kevin D; Miller, James J; Robinson, James H; Olive, Jennifer L

    The consumption of a high-fat meal induces transient vascular dysfunction. Aerobic exercise enhances vascular function in healthy individuals. Our purpose was to determine if different levels of aerobic capacity impact vascular function, as measured by flow mediated dilation, following a high-fat meal. Flow mediated dilation of the brachial artery was determined before, two- and four-hours postprandial a high-fat meal in young males classified as highly trained (n = 10; VO2max = 74.6 ± 5.2 ml·kg·min(-1)) or moderately active (n = 10; VO2max = 47.3 ± 7.1 ml·kg·min(-1)). Flow mediated dilation was reduced at two- (p < 0.001) and four-hours (p < 0.001) compared to baseline for both groups but was not different between groups at any time point (p = 0.108). Triglycerides and insulin increased at two- (p < 0.001) and four-hours (p < 0.05) in both groups. LDL-C was reduced at four-hours (p = 0.05) in highly trained subjects, and two- and four-hours (p ≤ 0.01) in moderately active subjects. HDL-C decreased at two- (p = 0.024) and four-hours (p = 0.014) in both groups. Glucose increased at two-hours postprandial for both groups (p = 0.003). Our results indicate that a high-fat meal results in reduced endothelium-dependent vasodilation in highly trained and moderately active individuals with no difference between groups. Thus, high aerobic capacity does not protect against transient reductions in vascular function after the ingestion of a single high-fat meal compared to individuals who are moderately active.

  16. Dilated cardiomyopathy and inclusion body myositis.

    PubMed

    Ballo, Piercarlo; Chiodi, Leandro; Cameli, Matteo; Malandrini, Alessandro; Federico, Antonio; Mondillo, Sergio; Zuppiroli, Alfredo

    2012-04-01

    Inclusion body myositis (IBM) is the most common inflammatory myopathy after 50 years of age. In contrast to polymyositis and dermatomyositis, in which cardiac involvement is relatively common, current evidences indicate that IBM is not associated with cardiac disease. We report the case of a patient with biopsy-proven IBM who developed heart failure and major ventricular arrhythmias secondary to dilated cardiomyopathy few months after the clinical onset of IBM, and in whom no pathophysiologic causes explaining cardiac enlargement and dysfunction were found by laboratory and instrumental investigations. The hypothesis of a pathophysiologic association between the two conditions is discussed.

  17. Superluminality in dilatationally invariant generalized Galileon theories

    NASA Astrophysics Data System (ADS)

    Kolevatov, R. S.

    2015-12-01

    We consider small perturbations about homogeneous backgrounds in dilatationally invariant Galileon models. The issues we address are stability (absence of ghosts and gradient instabilities) and superluminality. We show that in the Minkowski background, it is possible to construct the Lagrangian in such a way that any homogeneous Galileon background solution is stable and small perturbations about it are subluminal. On the other hand, in the case of Friedmann-Lemaitre-Robertson-Walker (FLRW) backgrounds, for any Lagrangian functions there exist homogeneous background solutions to the Galileon equation of motion and time dependence of the scale factor, such that the stability conditions are satisfied, but the Galileon perturbations propagate with superluminal speed.

  18. Congenital Malformations Attributed to Prenatal Exposure to Cyclophosphamide.

    PubMed

    Rengasamy, Padmanabhan

    2016-12-06

    Cyclophosphamide (CPA) remains one of the most widely prescribed anticancer drugs. It is also used in the treatment of rheumatoid arthritis, childhood nephrotic syndrome and systemic lupus erythematosus. It is a potent immunosuppressive agent. It is commonly used in blood and bone marrow transplantation. With the growing trend among women postponing childbearing, the number of women who are diagnosed with breast cancer is also increasing thus escalating the chances of exposure of the unborn child to antineoplastic drugs. A review of the literature provides strong evidence for the teratogenic effects on infants prenatally exposed to CPA. Both sporadic case reports and larger case series have demonstrated that babies with cyclophosphamide embryopathy are afflicted with intrauterine growth restriction, small for gestational age, and craniofacial malformations including eye anomalies, cleft/arched palate, hydrocephaly, micrognathia, low set microtia, hearing defects, craniosynostosis, and facial asymmetry. Also observed in these cases are limb defects such as radial, ulnar and tibial hypoplasia, club foot, digital defects of the hand and feet as well as vertebral fusion, brevicolis, and occasional Sprengel's deformity. These anomalies vary in consistency of occurrence and severity of the phenotype across cases and lack the specificity of thalidomide embryopathy or rubella embryopathy. However, that they do occur is no longer in doubt. First trimester of pregnancy seems to be particularly susceptible to fetal malformations, although CPA effects on fetuses of later stages of gestation (hearing defects, growth restriction for example) are also reported occasionally. One of the major concerns from a mechanistic point of view is our inability to dissect the teratogenic effects of CPA from those of other drugs administered together with CPA as combination therapy. Animal experiments have been of particular value in that they are able to circumvent the numerous extraneous

  19. Risk factors for development of sterile haemorrhagic cystitis in canine lymphoma patients receiving oral cyclophosphamide: a case-control study.

    PubMed

    Gaeta, R; Brown, D; Cohen, R; Sorenmo, K

    2014-12-01

    Sterile haemorrhagic cystitis (SHC) is a known risk of cyclophosphamide treatment; however, most canine reports are case series. This case-control study examined risk factors for SHC in dogs with lymphoma receiving oral cyclophosphamide. Twenty-two dogs with SHC and 66 control dogs were identified. On univariate analysis, SHC risk factors included age (P = 0.041), induction protocol (P = 0.021) and cumulative cyclophosphamide dose (P = 0.002). On multivariate analysis, increasing cumulative cyclophosphamide dose was associated with increased risk of SHC and the 'short' induction protocol (protocol 1) was associated with decreased risk. Controlling for age and induction protocol, odds of SHC increased by 2.21 per 750 mg m(-2) increase in cyclophosphamide dose (P = 0.001). SHC from oral cyclophosphamide is a predominately delayed toxicity resulting from high cumulative doses.

  20. [Preserving autologous heart operation for dilated cardiomyopathy].

    PubMed

    Hoshino, Joji; Fukada, Yasuhisa; Hirota, Masanori; Kondo, Taichi; Isomura, Tadashi

    2013-01-01

    We report non transplant surgical procedure (preserving autologous heart operation) for the patients with dilated cardiomyopathy( DCM), clinical outcomes, and the factor of predict prognosis. Since May 2000, 258 patients received surgical procedure for 11 years. We performed mitral surgery (plasty or replacement) for the patients with more than mild mitral regurgitation (MR). We performed papirally muscule plication since 2005, and we performed 2nd chordal cutting since 2008, for the patients with MR due to mitral tethering. The surgical left ventricular reconstruction( SVR) was performed for the patients with dilated left ventricular. We use spackle tracking echocardiography to decide the type of SVR since 2008. Hospital death was 18.2%, and late cardiac death was 27.5%.Almost the cause of death was congestive heart failure and ventricular arrhythmia. Five years survival was 58%, 10 years survival was 39%. Preoperative condition, emergent operation, inotropic support, intra aortic balloon pumping(IABP),affect the prognosis. But left ventricular size did not affect it. Surgical treatment for the patient with DCM should be performed with stable preoperative condition.

  1. Doxycycline potentiates antitumor effect of cyclophosphamide in mice

    SciTech Connect

    Chhipa, Rishi Raj; Singh, Sandeep; Surve, Sachin V.; Vijayakumar, Maleppillil Vavachan; Bhat, Manoj Kumar . E-mail: manojkbhat@nccs.res.in

    2005-02-01

    Cyclophosphamide (CPA) is a widely used chemotherapeutic drug in neoplasias. It is a DNA and protein alkylating agent that has a broad spectrum of activity against variety of neoplasms including breast cancer. The therapeutic effectiveness of CPA is limited by the high-dose hematopoietic, renal, and cardiac toxicity that accompanies the systemic distribution of liver-derived activated drug metabolites. The present study examines the potential of combining well-tolerated antibiotic doxycycline (DOX) with CPA and understanding the mechanism of cell killing. Interestingly, we found that DOX significantly enhances the tumor regression activity of CPA on xenograft mice model bearing MCF-7 cells. DOX also potentiates MCF-7 cell killing by CPA in vitro. In presence of DOX (3 {mu}g/ml), the IC{sub 50} value of CPA decreased significantly from 10 to 2.5 mM. Additional analyses indicate that the tumor suppressor p53 and p53-regulated proapoptotic Bax were upregulated in vivo and in vitro following CPA treatment in combination with DOX, suggesting that upregulation of p53 may contribute to the enhancement of antitumor effect of CPA by DOX. Furthermore, downregulation of antiapoptotic Bcl-2 was observed in animals treated with CPA and CPA plus DOX when compared to untreated or DOX-treated groups. Our results raise the possibility that this combination chemotherapeutic regimen may lead to additional improvements in treatment of breast cancer.

  2. Inhibition of cyclophosphamide-induced teratogenesis by beta-ionone.

    PubMed

    Gomes-Carneiro, M R; De-Oliveira, A C A X; De-Carvalho, R R; Araujo, I B; Souza, C A M; Kuriyama, S N; Paumgartten, F J R

    2003-03-03

    Beta-ionone (BI) is a degraded (C 13) sesquiterpene found in plant essential oils. It has been used in the synthesis of perfume chemicals and vitamin A. Recently, it was reported that BI is a rather potent in vitro inhibitor of CYP2B1-catalysed reactions in rat liver microsomes. The present study was performed to investigate whether inhibition of CYP2B1 reactions by BI could lead to an attenuation of cyclophosphamide (CP)-induced embryotoxicity in the rat. In a preliminary experiment, a dose-dependent prolongation of pentobarbital sleeping time in male and female Wistar rats suggested that BI inhibits CYP2B1 in vivo as well. In a second experiment, rats were treated by gavage with BI (0, 250, 500, 750 or 1000 mg/kg body wt) 45 min prior to a subcutaneous injection of either CP (7.5 mg/kg body wt) or its vehicle (saline) on day 11 of pregnancy. BI alone, at the highest dose tested, caused a high proportion of resorptions. Lower doses of BI, however, clearly attenuated CP-induced embryolethality and teratogenicity. These results seem to support the view that, as far as rats are concerned, CYP2B1 plays an important role in the conversion of CP into its embryolethal and teratogenic metabolites.

  3. Processed Aloe vera gel ameliorates cyclophosphamide-induced immunotoxicity.

    PubMed

    Im, Sun-A; Kim, Ki-Hyang; Kim, Hee-Suk; Lee, Ki-Hwa; Shin, Eunju; Do, Seon-Gil; Jo, Tae Hyung; Park, Young In; Lee, Chong-Kil

    2014-10-24

    The effects of processed Aloe vera gel (PAG) on cyclophosphamide (CP)-induced immunotoxicity were examined in mice. Intraperitoneal injection of CP significantly reduced the total number of lymphocytes and erythrocytes in the blood. Oral administration of PAG quickly restored CP-induced lymphopenia and erythropenia in a dose-dependent manner. The reversal of CP-induced hematotoxicity by PAG was mediated by the functional preservation of Peyer's patch cells. Peyer's patch cells isolated from CP-treated mice, which were administered PAG, produced higher levels of T helper 1 cytokines and colony-stimulating factors (CSF) in response to concanavalin A stimulation as compared with those isolated from CP-treated control mice. PAG-derived polysaccharides directly activated Peyer's patch cells isolated from normal mice to produce cytokines including interleukin (IL)-6, IL-12, interferon-γ, granulocyte-CSF, and granulocyte-macrophage-CSF. The cytokines produced by polysaccharide-stimulated Peyer's patch cells had potent proliferation-inducing activity on mouse bone marrow cells. In addition, oral administration of PAG restored IgA secretion in the intestine after CP treatment. These results indicated that PAG could be an effective immunomodulator and that it could prevent CP-induced immunotoxic side effects.

  4. Processed Aloe vera Gel Ameliorates Cyclophosphamide-Induced Immunotoxicity

    PubMed Central

    Im, Sun-A; Kim, Ki-Hyang; Kim, Hee-Suk; Lee, Ki-Hwa; Shin, Eunju; Do, Seon-Gil; Jo, Tae Hyung; Park, Young In; Lee, Chong-Kil

    2014-01-01

    The effects of processed Aloe vera gel (PAG) on cyclophosphamide (CP)-induced immunotoxicity were examined in mice. Intraperitoneal injection of CP significantly reduced the total number of lymphocytes and erythrocytes in the blood. Oral administration of PAG quickly restored CP-induced lymphopenia and erythropenia in a dose-dependent manner. The reversal of CP-induced hematotoxicity by PAG was mediated by the functional preservation of Peyer’s patch cells. Peyer’s patch cells isolated from CP-treated mice, which were administered PAG, produced higher levels of T helper 1 cytokines and colony-stimulating factors (CSF) in response to concanavalin A stimulation as compared with those isolated from CP-treated control mice. PAG-derived polysaccharides directly activated Peyer’s patch cells isolated from normal mice to produce cytokines including interleukin (IL)-6, IL-12, interferon-γ, granulocyte-CSF, and granulocyte-macrophage-CSF. The cytokines produced by polysaccharide-stimulated Peyer’s patch cells had potent proliferation-inducing activity on mouse bone marrow cells. In addition, oral administration of PAG restored IgA secretion in the intestine after CP treatment. These results indicated that PAG could be an effective immunomodulator and that it could prevent CP-induced immunotoxic side effects. PMID:25347273

  5. Tranilast ameliorates cyclophosphamide-induced lung injury and nephrotoxicity.

    PubMed

    Said, Eman; Elkashef, Wagdi F; Abdelaziz, Rania R

    2016-04-01

    The world-wide increase in cancer incidence imposes a corresponding significant increase in the use of chemotherapeutic agents. Nephrotoxicity is a side effect frequently encountered with cyclophosphamide (CP), which is also well-known to cause acute and chronic lung toxicities. The current study focuses on the evaluation of the potential protective efficacy of tranilast against acute and subacute CP-induced lung and kidney injuries in male Swiss Albino mice. Intraperitoneal CP significantly impaired oxidant/anti-oxidant balance and increased inflammatory cell count in bronchoalveolar lavage fluid, serum creatinine, blood urea nitrogen (BUN), tumor necrosis factor-α (TNF-α) and lactate dehydrogenase (LDH) levels, with significant impairment of lung and kidney architectures. Tranilast taken orally for 8 and 14 days significantly enhanced mice anti-oxidant defense mechanisms; it increased lung and kidney SOD activity, GSH content and reduced lipid peroxidation. Tranilast significantly reduced serum creatinine and BUN. Furthermore, it decreased accumulation of inflammatory cells in the lungs. Serum TNF-α, LDH, total lung and kidney protein contents significantly declined as well. Histopathological examination revealed concomitant significant tissue recovery. Such results show a significant protective potential of tranilast against deleterious lung and kidney damage induced by CP, probably by enhancing host antioxidant defense mechanism, decreasing cytotoxicity, and decreasing expression of inflammatory cytokines.

  6. Effect of cyclophosphamide and electromagnetic fields on mouse bone marrow

    SciTech Connect

    Cadossi, R.; Zucchini, P.; Emilia, G.; Torelli, G. )

    1990-02-26

    The authors have previously shown that the exposure to low frequency pulsing electromagnetic fields (PEMF) of mice X-ray irradiated resulted in an increased damage to the bone marrow. The series of experiments here reported were designed to investigate the effect of PEMF exposure after intraperitoneum injection of 200mg/kg of cyclophosphamide (CY). Control mice were CY injected only; experimental mice were CY injected and then exposed to PEMF. Exposure to PEMF (24 hours/day) increased the rate of decline of white blood cells in peripheral blood. Spleen weight was statistically higher among control mice than among mice exposed to PEMF at day 6, 8 and 10 after CY injection. Spleen autoradiography proved to be higher among PEMF exposed mice than among controls at day 8 and 9 after CY injection. The grafting efficiency of the bone marrow obtained from control mice was higher than the grafting efficiency of the bone marrow recovered from mice exposed to PEMF. All these data indicate that the exposure to PEMF increases the cytotoxic effect of CY.

  7. Restraint stress augments antibody production in cyclophosphamide-treated mice.

    PubMed

    Karp, J D; Smith, J; Hawk, K

    2000-01-01

    These studies evaluated the effects of a psychological stressor (restraint, RST) on antibody production in male BALB/cByJ mice. In Experiment 1, mice were immunized with keyhole limpet hemocyanin (KLH, 100 microg i.p.) 8 h prior to 15 h of RST or food and water deprivation (FWD). RST mice exhibited higher serum anti-KLH IgM and IgG antibodies than FWD mice. In Experiment 2, mice were given either cyclophosphamide (CY, 15 mg/kg) or saline (SAL) prior to immunization with KLH and RST or FWD. ANOVA revealed serum anti-KLH IgG antibody titers in CY+RST animals to be significantly higher than in CY+FWD, SAL+FWD, and SAL+RST mice. Anti-KLH IgM titers of CY+RST mice were higher than those of other groups before and after a second immunization with KLH. In Experiment 3, we show that these changes in antibody production are not likely to be mediated via CY-induced alterations in the reactivity of the hypothalamo-pituitary-adrenal axis to RST. Together, these results indicate two potentially immunomodulatory parameters (RST and CY) can interact to alter a humoral immune response. In addition, these data support the hypothesis that humoral immune response of mice can be more reactive to stress when the mice are given a low dose of an immunomodulatory drug prior to stressor exposure.

  8. Fertility preservation in patients receiving cyclophosphamide therapy for renal disease.

    PubMed

    Gajjar, Radha; Miller, Steven D; Meyers, Kevin E; Ginsberg, Jill P

    2015-07-01

    Cyclophosphamide continues to have an important role in the treatment of renal disease, including nephrotic syndrome and lupus nephritis, despite known complications of gonadotoxicity and potential infertility in both male and female patients. It is important that the physician recommending this therapy mitigates the effect of the drug on fertility by adhering to recommendations on dosing limits and offering fertility-preserving strategies. In addition to well-established methods, such as sperm banking and embryo cryopreservation, advances in reproductive technology have yielded strategies such as oocyte cryopreservation, resulting in more fertility-preserving options for the pediatric patient. Despite these advances, there continues to be a significant barrier to referral and access to sperm banks and fertility specialists. These issues are further complicated by ethical issues associated with the treatment of pediatric patients. In this review we explore the development of recommended dosing limits and include a discussion of the available fertility-preserving methods, strategies for increasing access to fertility specialists, and the ethical considerations facing the pediatric healthcare provider.

  9. [Effect of cyclophosphamide in experimental histoplasmosis in the rat].

    PubMed

    Gago, J G; Godio, C M; Ochoa, L B; Negroni, R; Nejamkis, M R

    1998-01-01

    Histoplasmosis is a fungal disease caused by the dimorphous fungus Histoplasma capsulatum (Hc). Cyclophosphamide (Cy) was used as an immunomodulator capable of modifying the course of the disease, as well as of regulating the mechanisms involved in T-lymphocyte mediated immune response. Rats were subjected to intracardiac inoculation of Hc followed by a fractionated treatment with a 100 mg/kg body weight dose of Cy on days +4, +5, +6, +7 and +11 pi. Until day 26 pi, treatment with Cy caused 85% mortality whereas no mortality was observed among animals only inoculated with Hc. On day 14 pi, the group of Hc animals showed a delayed hypersensitivity test (DH) of 26.60 + 13.96 as determined by the swelling of the leg. Conversely, DH was significantly depressed in rats inoculated with Hc and treated with Cy: 3.88 +/- 1.00 (p < 0.01). Colony forming units count in this group was 2020 CFU/g of spleen, and 24 CFU/g of spleen (p < 0.01) in controls. A macroscopic study of the organs revealed that the animals in the Hc+Cy group had spleenomegaly and lungs with granuloma and hemorrhagic spots. The controls only presented small lung abscesses. These findings lead to the conclusion that Cy causes a deterioration of cell mediated immune response which results in the manifestation of an acute, fatal experimental mycosis.

  10. Dilatation balloons: polymer selection, balloon design and assembly.

    PubMed

    Crittenden, J F

    1987-01-01

    The current status of coronary dilating instruments is presented from the designer's perspective. Catheter shaft design is considered by important features, common catheter materials and types of catheter construction. Among the seven companies manufacturing balloon dilating instruments, only three types of catheter and four materials are offered. Balloon design is presented by important features and by materials selected. Performance comparisons are made between the three materials used to fabricate dilating balloons: PVC, PE and PET.

  11. Gastric Necrosis due to Acute Massive Gastric Dilatation

    PubMed Central

    Pergel, Ahmet; Yucel, Ahmet Fikret; Sahin, Dursun Ali; Ozer, Ender

    2013-01-01

    Gastric necrosis due to acute massive gastric dilatation is relatively rare. Vascular reasons, herniation, volvulus, acute gastric dilatation, anorexia, and bulimia nervosa play a role in the etiology of the disease. Early diagnosis and treatment are highly important as the associated morbidity and mortality rates are high. In this case report, we present a case of gastric necrosis due to acute gastric dilatation accompanied with the relevant literature. PMID:23983714

  12. Duodenal adenocarcinoma presenting as a mass with aneurismal dilatation.

    PubMed

    Mama, Nadia; Ben Slama, Aïda; Arifa, Nadia; Kadri, Khaled; Sriha, Badreddine; Ksiaa, Mehdi; Jemni, Hela; Tlili-Graiess, Kalthoum

    2014-01-01

    Duodenal adenocarcinoma is frequent. Aneurysmal dilatation of the small bowel is reported to be a lymphoma characteristic imaging finding. A 57-year-old male was found to have a duodenal adenocarcinoma with aneurismal dilatation on imaging which is an exceptional feature. On laparotomy, the wall thickening of the dilated duodenum extended to the first jejunal loop, with multiple mesenteric lymph nodes and ascites. Segmental palliative resection with gastro-entero-anastomosis was done. Histopathology revealed a moderately differentiated adenocarcinoma with neuro-endocrine differentiation foci. Wide areas of necrosis and vascular emboli were responsible for the radiological feature of the dilated duodenum with wall thickening.

  13. Vaginal dilator therapy for women receiving pelvic radiotherapy.

    PubMed

    Miles, Tracie; Johnson, Nick

    2014-09-08

    Vaginal dilation therapy is advocated after pelvic radiotherapy to prevent stenosis (abnormal narrowing of the vagina), but can be uncomfortable and psychologically distressing. To assess the benefits and harms of different types of vaginal dilation methods offered to women treated by pelvic radiotherapy for cancer. Searches included the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 5), MEDLINE (1950 to June week 2, 2013), EMBASE (1980 to 2013 week 24) and CINAHL (1982 to 2013). Comparative data of any type, which evaluated dilation or penetration of the vagina after pelvic radiotherapy treatment for cancer. Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. We found no trials and therefore analysed no data. We identified no studies for inclusion in the original review or for this update. However, we felt that some studies that were excluded warranted discussion. These included one randomised trial (RCT), which showed no improvement in sexual scores associated with encouraging women to practise dilation therapy; a recent small RCT that did not show any advantage to dilation over vibration therapy during radiotherapy; two non-randomised comparative studies; and five correlation studies. One of these showed that objective measurements of vaginal elasticity and length were not linked to dilation during radiotherapy, but the study lacked power. One study showed that women who dilated tolerated a larger dilator, but the risk of objectivity and bias with historical controls was high. Another study showed that the vaginal measurements increased in length by a mean of 3 cm after dilation was introduced 6 to 10 weeks after radiotherapy, but there was no control group; another case series showed the opposite. Three recent studies showed less stenosis associated with prophylactic dilation after radiotherapy. One small case series suggested that dilation years after radiotherapy might restore the

  14. Fluoroscopically Guided Balloon Dilation for Postintubation Tracheal Stenosis

    SciTech Connect

    Lee, Woong Hee; Kim, Jin Hyoung Park, Jung-Hun

    2013-10-15

    Purpose: Little was known about the safety and long-term efficacy of fluoroscopically guided balloon dilation for postintubation tracheal stenosis. The purpose of this study was to evaluate the safety and long-term efficacy of fluoroscopically guided balloon dilation in patients with postintubation tracheal stenosis. Methods: From February 2000 to November 2010, 14 patients underwent fluoroscopically guided balloon dilation for postintubation tracheal stenosis. Technical success, clinical success, and complications were evaluated. Patients were followed up for recurrent symptoms. Results: In all patients, fluoroscopically guided balloon dilation was technically and clinically successful with no major complications. Following the initial procedure, six patients (43 %) remained asymptomatic during a follow-up period. Obstructive symptoms recurred in eight patients (57 %) within 6 months (mean, 1.7 months), who were treated with repeat balloon dilation (n = 4) and other therapies. Of the four patients who underwent repeat balloon dilation, three became asymptomatic. One patient became asymptomatic after a third balloon dilation. On long-term (mean, 74 months) follow-up, 71 % of patients experienced relief of symptoms following fluoroscopically guided balloon dilation. Conclusions: Fluoroscopically guided balloon dilation may be safe, is easy to perform, and resulted in effective treatment in patients with postintubation tracheal stenosis.

  15. Cyclophosphamide Alters the Gene Expression Profile in Patients Treated with High Doses Prior to Stem Cell Transplantation

    PubMed Central

    El-Serafi, Ibrahim; Abedi-Valugerdi, Manuchehr; Potácová, Zuzana; Afsharian, Parvaneh; Mattsson, Jonas; Moshfegh, Ali; Hassan, Moustapha

    2014-01-01

    Background Hematopoietic stem cell transplantation is a curative treatment for several haematological malignancies. However, treatment related morbidity and mortality still is a limiting factor. Cyclophosphamide is widely used in condition regimens either in combination with other chemotherapy or with total body irradiation. Methods We present the gene expression profile during cyclophosphamide treatment in 11 patients conditioned with cyclophosphamide for 2 days followed by total body irradiation prior to hematopoietic stem cell transplantation. 299 genes were identified as specific for cyclophosphamide treatment and were arranged into 4 clusters highly down-regulated genes, highly up-regulated genes, early up-regulated but later normalized genes and moderately up-regulated genes. Results Cyclophosphamide treatment down-regulated expression of several genes mapped to immune/autoimmune activation and graft rejection including CD3, CD28, CTLA4, MHC II, PRF1, GZMB and IL-2R, and up-regulated immune-related receptor genes, e.g. IL1R2, IL18R1, and FLT3. Moreover, a high and significant expression of ANGPTL1 and c-JUN genes was observed independent of cyclophosphamide treatment. Conclusion This is the first investigation to provide significant information about alterations in gene expression following cyclophosphamide treatment that may increase our understanding of the cyclophosphamide mechanism of action and hence, in part, avoid its toxicity. Furthermore, ANGPTL1 remained highly expressed throughout the treatment and, in contrast to several other alkylating agents, cyclophosphamide did not influence c-JUN expression. PMID:24466173

  16. Population Pharmacokinetics of Cyclophosphamide and Metabolites in Children with Neuroblastoma: a Report from the Children’s Oncology Group

    PubMed Central

    McCune, Jeannine S.; Salinger, David H.; Vicini, Paolo; Oglesby, Celeste; Blough, David K.; Park, Julie R.

    2009-01-01

    Cyclophosphamide-based regimens are front-line treatment for numerous pediatric malignancies, however current dosing methods result in considerable interpatient variability in tumor response and toxicity. In this pediatric population, our objectives were to 1. quantify and explain the pharmacokinetic variability of cyclophosphamide, and two of its metabolites, hydroxycyclophosphamide (HCY) and carboxyethylphosphoramide mustard (CEPM); 2. apply a population pharmacokinetic model to describe the disposition of cyclophosphamide and these metabolites. A total of 196 blood samples were obtained from 22 children with neuroblastoma receiving intravenous (IV) cyclophosphamide (400 mg/m2/day) and topotecan. Blood samples were quantitated for concentrations of cyclophosphamide, HCY and CEPM using liquid chromatography-mass spectrometry and analyzed using nonlinear mixed effects modeling with NONMEM software system. After model building was complete, the area under the concentration-time curve (AUC) was computed using NONMEM. Cyclophosphamide elimination was described by noninducible and inducible routes with the latter producing HCY. Glomerular filtration rate (GFR) was a covariate for the fractional elimination of HCY and its conversion to CEPM. Considerable interpatient variability was observed in the AUC of cyclophosphamide, HCY and CEPM. These results represent a critical first step in developing pharmacokinetic-linked pharmacodynamic studies in children receiving cyclophosphamide to determine the clinical relevance of the pharmacokinetic variability in cyclophosphamide and its metabolites. PMID:18927240

  17. Population pharmacokinetics of cyclophosphamide and metabolites in children with neuroblastoma: a report from the Children's Oncology Group.

    PubMed

    McCune, Jeannine S; Salinger, David H; Vicini, Paolo; Oglesby, Celeste; Blough, David K; Park, Julie R

    2009-01-01

    Cyclophosphamide-based regimens are front-line treatment for numerous pediatric malignancies; however, current dosing methods result in considerable interpatient variability in tumor response and toxicity. In this pediatric population, the authors' objectives were (1) to quantify and explain the pharmacokinetic variability of cyclophosphamide and 2 of its metabolites, hydroxycyclophosphamide (HCY) and carboxyethylphosphoramide mustard (CEPM), and (2) to apply a population pharmacokinetic model to describe the disposition of cyclophosphamide and these metabolites. A total of 196 blood samples were obtained from 22 children with neuroblastoma receiving intravenous cyclophosphamide (400 mg/m2/d) and topotecan. Blood samples were quantitated for concentrations of cyclophosphamide, HCY, and CEPM using liquid chromatography-mass spectrometry and analyzed using nonlinear mixed-effects modeling with the NONMEM software system. After model building was complete, the area under the concentration-time curve (AUC) was computed using NONMEM. Cyclophosphamide elimination was described by noninducible and inducible routes, with the latter producing HCY. Glomerular filtration rate was a covariate for the fractional elimination of HCY and its conversion to CEPM. Considerable interpatient variability was observed in the AUC of cyclophosphamide, HCY, and CEPM. These results represent a critical first step in developing pharmacokinetic-linked pharmacodynamic studies in children receiving cyclophosphamide to determine the clinical relevance of the pharmacokinetic variability in cyclophosphamide and its metabolites.

  18. Vaginal dilator therapy for women receiving pelvic radiotherapy

    PubMed Central

    Miles, Tracie; Johnson, Nick

    2014-01-01

    Background Many vaginal dilator therapy guidelines advocate routine vaginal dilation during and after pelvic radiotherapy to prevent stenosis (abnormal narrowing of the vagina). The UK Gynaecological Oncology Nurse Forum recommend dilation “three times weekly for an indefinite time period”. The UK patient charity Cancer Backup advises using vaginal dilators from two to eight weeks after the end of radiotherapy treatment. Australian guidelines recommend dilation after brachytherapy “as soon as is comfortably possible” and “certainly within four weeks and to continue for three years or indefinitely if possible”. However, dilation is intrusive, uses health resources and can be psychologically distressing. It has also caused rare but very serious damage to the rectum. Objectives To review the benefits and harms of vaginal dilation therapy associated with pelvic radiotherapy for cancer. Search methods Searches included the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 4), MEDLINE (1950 to 2008), EMBASE (1980 to 2008) and CINAHL (1982 to 2008). Selection criteria Any comparative randomised controlled trials (RCT) or data of any type which compared dilation or penetration of the vagina after pelvic radiotherapy treatment for cancer. Data collection and analysis The review authors independently abstracted data and assessed risk of bias. We analysed the mean difference in sexual function scores and the risk ratio for non-compliance at six weeks and three months in single trial analyses. No trials met the inclusion criteria. Main results Dilation during or immediately after radiotherapy can, in rare cases, cause damage and there is no persuasive evidence from any study to demonstrate that it prevents stenosis. Data from one RCT showed no improvement in sexual scores in women who were encouraged to practice dilation. Two case series and one comparative study using historical controls suggest that dilation might be

  19. Intraventricular vortex properties in nonischemic dilated cardiomyopathy.

    PubMed

    Bermejo, Javier; Benito, Yolanda; Alhama, Marta; Yotti, Raquel; Martínez-Legazpi, Pablo; Del Villar, Candelas Pérez; Pérez-David, Esther; González-Mansilla, Ana; Santa-Marta, Cristina; Barrio, Alicia; Fernández-Avilés, Francisco; Del Álamo, Juan C

    2014-03-01

    Vortices may have a role in optimizing the mechanical efficiency and blood mixing of the left ventricle (LV). We aimed to characterize the size, position, circulation, and kinetic energy (KE) of LV main vortex cores in patients with nonischemic dilated cardiomyopathy (NIDCM) and analyze their physiological correlates. We used digital processing of color-Doppler images to study flow evolution in 61 patients with NIDCM and 61 age-matched control subjects. Vortex features showed a characteristic biphasic temporal course during diastole. Because late filling contributed significantly to flow entrainment, vortex KE reached its maximum at the time of the peak A wave, storing 26 ± 20% of total KE delivered by inflow (range: 1-74%). Patients with NIDCM showed larger and stronger vortices than control subjects (circulation: 0.008 ± 0.007 vs. 0.006 ± 0.005 m(2)/s, respectively, P = 0.02; KE: 7 ± 8 vs. 5 ± 5 mJ/m, P = 0.04), even when corrected for LV size. This helped confining the filling jet in the dilated ventricle. The vortex Reynolds number was also higher in the NIDCM group. By multivariate analysis, vortex KE was related to the KE generated by inflow and to chamber short-axis diameter. In 21 patients studied head to head, Doppler measurements of circulation and KE closely correlated with phase-contract magnetic resonance values (intraclass correlation coefficient = 0.82 and 0.76, respectively). Thus, the biphasic nature of filling determines normal vortex physiology. Vortex formation is exaggerated in patients with NIDCM due to chamber remodeling, and enlarged vortices are helpful for ameliorating convective pressure losses and facilitating transport. These findings can be accurately studied using ultrasound.

  20. Intraventricular vortex properties in nonischemic dilated cardiomyopathy

    PubMed Central

    Benito, Yolanda; Alhama, Marta; Yotti, Raquel; Martínez-Legazpi, Pablo; del Villar, Candelas Pérez; Pérez-David, Esther; González-Mansilla, Ana; Santa-Marta, Cristina; Barrio, Alicia; Fernández-Avilés, Francisco; del Álamo, Juan C.

    2014-01-01

    Vortices may have a role in optimizing the mechanical efficiency and blood mixing of the left ventricle (LV). We aimed to characterize the size, position, circulation, and kinetic energy (KE) of LV main vortex cores in patients with nonischemic dilated cardiomyopathy (NIDCM) and analyze their physiological correlates. We used digital processing of color-Doppler images to study flow evolution in 61 patients with NIDCM and 61 age-matched control subjects. Vortex features showed a characteristic biphasic temporal course during diastole. Because late filling contributed significantly to flow entrainment, vortex KE reached its maximum at the time of the peak A wave, storing 26 ± 20% of total KE delivered by inflow (range: 1–74%). Patients with NIDCM showed larger and stronger vortices than control subjects (circulation: 0.008 ± 0.007 vs. 0.006 ± 0.005 m2/s, respectively, P = 0.02; KE: 7 ± 8 vs. 5 ± 5 mJ/m, P = 0.04), even when corrected for LV size. This helped confining the filling jet in the dilated ventricle. The vortex Reynolds number was also higher in the NIDCM group. By multivariate analysis, vortex KE was related to the KE generated by inflow and to chamber short-axis diameter. In 21 patients studied head to head, Doppler measurements of circulation and KE closely correlated with phase-contract magnetic resonance values (intraclass correlation coefficient = 0.82 and 0.76, respectively). Thus, the biphasic nature of filling determines normal vortex physiology. Vortex formation is exaggerated in patients with NIDCM due to chamber remodeling, and enlarged vortices are helpful for ameliorating convective pressure losses and facilitating transport. These findings can be accurately studied using ultrasound. PMID:24414062

  1. Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis

    PubMed Central

    Appel, Gerald B.; Contreras, Gabriel; Dooley, Mary Anne; Ginzler, Ellen M.; Isenberg, David; Jayne, David; Li, Lei-Shi; Mysler, Eduardo; Sánchez-Guerrero, Jorge; Solomons, Neil; Wofsy, David

    2009-01-01

    Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m2 in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis. PMID:19369404

  2. Inflammasomes are important mediators of cyclophosphamide-induced bladder inflammation.

    PubMed

    Hughes, Francis M; Vivar, Nivardo P; Kennis, James G; Pratt-Thomas, Jeffery D; Lowe, Danielle W; Shaner, Brooke E; Nietert, Paul J; Spruill, Laura S; Purves, J Todd

    2014-02-01

    Bladder inflammation (cystitis) underlies numerous bladder pathologies and is elicited by a plethora of agents such as urinary tract infections, bladder outlet obstruction, chemotherapies, and catheters. Pattern recognition receptors [Toll-like receptors (TLRs) and Nod-like receptors (NLRs)] that recognize pathogen- and/or damage-associated molecular patterns (PAMPs and/or DAMPs, respectively) are key components of the innate immune system that coordinates the production (TLRs) and maturation (NLRs) of proinflammatory IL-1β. Despite multiple studies of TLRs in the bladder, none have investigated NLRs beyond one small survey. We now demonstrate that NLRP3 and NLRC4, and their binding partners apoptosis-associated speck-like protein containing a COOH-terminal caspase recruitment domain (ASC) and NLR family apoptosis inhibitory protein (NAIP), are expressed in the bladder and localized predominantly to the urothelia. Activated NLRs form inflammasomes that activate caspase-1. Placement of a NLRP3- or NLRC4-activating PAMP or NLRP3-activating DAMPs into the lumen of the bladder stimulated caspase-1 activity. To investigate inflammasomes in vivo, we induced cystitis with cyclophosphamide (CP, 150 mg/kg ip) in the presence or absence of the inflammasome inhibitor glyburide. Glyburide completely blocked CP-induced activation of caspase-1 and the production of IL-1β at 4 h. At 24 h, glyburide reduced two markers of inflammation by 30-50% and reversed much of the inflammatory morphology. Furthermore, glyburide reversed changes in bladder physiology (cystometry) induced by CP. In conclusion, NLRs/inflammasomes are present in the bladder urothelia and respond to DAMPs and PAMPs, whereas NLRP3 inhibition blocks bladder dysfunction in the CP model. The coordinated response of NLRs and TLRs in the urothelia represents a first-line innate defense that may provide an important target for pharmacological intervention.

  3. Rutin Ameliorates Cyclophosphamide-induced Reproductive Toxicity in Male Rats

    PubMed Central

    Abarikwu, S. O.; Otuechere, C. A.; Ekor, M.; Monwuba, K.; Osobu, D.

    2012-01-01

    Cyclophosphamide (CYC) as an anticancer alkylating agent has been known as a male reproductive toxicant. This study was aimed to evaluate the protective effect of rutin (RUT) on CYC-induced reproductive toxicity. Sexually mature Wistar rats (weighing 199 ± 10 g with five animals in each group) were given CYC (15 mg/kg) and/or RUT (30 mg/kg) twice a week via gavage for 4 weeks. The sperm counts, sperm motility, sperm morphology, daily sperm production (DSP), testicular, and epididymal antioxidant systems: superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione reductase (GR), glutathione-S-transferase (GST), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and testicular steroidogenic enzymes (3β-hydroxysteroid dehydrogenase and 17β-HSD and spermatogenesis marker enzymes (lactate dehydrogenase (LDH), sorbitol dehydrogenase (SDH), alkaline phosphatase (ALP), acid phosphatase (ACP) in the testes, epididymis and seminal vesicles were investigated at the end of the fourth week. By the end of the fourth week, RUT prevented lower sperm counts, sperm motility, DSP, and higher abnormal sperm numbers induced by CYC. In testes, RUT decreased SOD, LDH, and SDH and increased CAT, 3β-HSD, 17β-HSD, ALP, and ACP induced by CYC. In epididymis, RUT increased SOD, CAT, GSH, GSH-Px, GR, GST SDH, ALP and ACP and decreased MDA and LDH induced by CYC. In seminal vesicles, marker enzymes were unchanged in rats given CYC alone or in combination with RUT. It appears that RUT ameliorates CYC reproductive toxicity at the investigated dose. PMID:22778522

  4. Con: Cyclophosphamide for the treatment of lupus nephritis.

    PubMed

    Mok, Chi Chiu

    2016-07-01

    Kidney involvement is a major determinant for morbidity and mortality in patients with systemic lupus erythematosus. The treatment target of lupus renal disease is to induce and maintain remission and to minimize disease or treatment-related comorbidities. Cyclophosphamide (CYC), in conjunction with glucocorticoids, has conventionally been used for the initial treatment of lupus nephritis. However, the major concerns of CYC are its toxicities, such as infertility, urotoxicity and oncogenicity, which are particularly relevant in women of childbearing age. As a result, maintenance therapy of lupus nephritis with an extended course of CYC pulses has largely been replaced by other immunosuppressive agents such as mycophenolate mofetil (MMF) and azathioprine. Recent randomized controlled trials have demonstrated non-inferiority of MMF to pulse CYC as induction therapy of lupus nephritis. Although MMF as induction-maintenance therapy has been increasingly used in lupus nephritis, its efficacy in the long-term preservation of renal function remains to be elucidated. MMF is not necessarily less toxic than CYC. Meta-analyses of clinical trials show similar incidence of infective complications and gastrointestinal adverse events in both MMF- and CYC-based regimens. However, considering the reduction in gonadal toxicity and the risk of oncogenicity, MMF may be used as first-line therapy of lupus nephritis. Tacrolimus (TAC) has recently been shown to be equivalent to either MMF or CYC for inducing remission of lupus nephritis and may be considered as another non-CYC alternative. Combined low-dose MMF and TAC appears to be more effective than CYC pulses in Chinese patients with lupus nephritis and has the potential to replace the more toxic CYC regimens in high-risk patients. Currently, CYC still plays an important role in the management of lupus nephritis patients with impaired or rapidly deteriorating renal function, crescentic glomerulonephritis or as salvage therapy for

  5. Nitric oxide synthases and cyclophosphamide-induced cystitis in rats.

    PubMed

    Alfieri, A B; Malave, A; Cubeddu, L X

    2001-03-01

    The role of inducible (iNOS) and neuronal nitric oxide (nNOS) synthases and of tachykinin NK1 receptors on the pathogenesis of cyclophosphamide (CYP)-induced cystitis was investigated, in rats. CYP-induced cystitis was characterized by large increases in bladder-protein plasma extravasation (PPE), increases in the urinary excretion of nitric oxide (NO) metabolites and histological evidences of urothelial damage, edema, extensive white blood cell infiltrates and vascular congestion of the bladder. The specific iNOS inhibitor, S-methylthiourea (MITU), produced marked inhibition (>90%) of CYP-induced increases in PPE associated with amelioration of tissue inflammatory changes. Treatment with 7-nitroindazole (7-NI; 20, 40 and 80 mg/kg), a selective nNOS inhibitor, did not significantly reduce CYP-induced increases in PPE and failed to produce histological improvement. In addition, treatment with MITU, but not with 7-NI, inhibited the increases in the urinary excretion of NO metabolites induced by CYP treatment. WIN 51,708 (17-beta-hydroxy-17-alpha-ethynyl-androstano[3,2-b]pyrimido[1,2-a]benzimidazole; WIN), a selective NK1-receptor antagonist, reduced the increases in EPP and ameliorated the inflammatory changes in the bladder induced by CYP. However, the maximal degree of protection achieved with WIN was significantly less than that produced by MITU. Combined treatment with the iNOS inhibitor and the NK1 antagonist produced no greater effect than that produced by the iNOS inhibitor alone. Our results suggest that NO plays a fundamental role in the production of the cystitis associated with CYP treatment. The iNOS, and not nNOS, seems responsible for the inflammatory changes. Part of the increases in NO may due to activation of NK1 receptors by neuropeptides such as substance P possibly released from primary afferent fibers.

  6. Effect of Cyclophosphamide on Histoplasma capsulatum Infections in Mice

    PubMed Central

    Cozad, George C.; Lindsey, Terri J.

    1974-01-01

    Mice were injected intraperitoneally (i.p.) with 300 mg of cyclophosphamide (CY)/kg of body weight, and 24 h later were injected i.p. with varying dosages of yeast-phase cells of Histoplasma capsulatum. At specific time intervals organs were removed, ground, and cultured to determine the number of viable organisms contained in the spleen, liver, and lungs. Injection of mice with CY was found to cause a dramatic increase in the numbers of parasites isolated from these organs when compared with non-drug-treated controls. Mice given 107 yeast cells showed the largest increase in colony numbers. A greater than fivefold increase in the numbers of organisms isolated from the spleens of CY and 103 yeast cell-treated mice, as compared with non-drug-treated animals, was observed at all time periods. The general trend for infected control animals was a decrease in colony numbers. All mice given CY plus 107 yeast cells intravenously (i.v.) died by day 20 postinfection. Mice given CY and 107 yeast cells i.p. showed no evidence of fatal Histoplasma infection. Deaths occurring by day 5 in CY-treated animals injected with H. capsulatum yeast cells i.v. or i.p. were considered due to bacterial infection or toxicity, or both. Hepatosplenomegaly was observed in mice treated with CY and 107 yeast cells of H. capsulatum. Enlarged lungs were also noted. CY control mouse spleens weighed 30% less than normal spleens. Organs of animals injected with H. capsulatum alone did not vary significantly from those of normal mice. Complete drug-induced suppression of humoral antibody response was achieved for 10 days, as determined by hemagglutination titrations. PMID:4816459

  7. Bronchoalveolar lavage and response to cyclophosphamide in scleroderma alveolitis.

    PubMed

    Colaci, M; Sebastiani, M; Giuggioli, D; Manfredi, A; Spagnolo, P; Luppi, F; Richeldi, L; Ferri, Clodoveo

    2010-03-01

    Systemic sclerosis (SSc) is characterized by abnormal fibrosis of the skin and internal organs, particularly the lungs. Recent reports have revealed a lack of correlation between bronchoalveolar lavage (BAL) variations and response to cyclophosphamide (CYC) in patients with scleroderma-related alveolitis. Our study aimed to evaluate whether the normalization of BAL cellularity correlates with long-term response to CYC. We retrospectively studied 26 consecutive SSc patients with alveolitis diagnosed by BAL and treated with CYC therapy (cumulative dosage 26.5 +/- 11.7 g; 21.1 +/- 8.9 months of treatment). We evaluated high-resolution computed tomography (HRCT), forced vital capacity (FVC), and carbon monoxide diffusing capacity (DLCO) variations before and after CYC. Radiological and functional parameters were re-evaluated in 23 patients after 1-year follow-up. BAL cellularity normalized after CYC therapy in 12/26 (46.2%) patients (group 1), while it remained abnormal in 14/26 (53.8%) (group 2). FVC and DLCO of group 1 slightly increased after CYC (p = 0.014 and p = 0.07, respectively) and remained stable at follow-up, whereas in group 2 they did not change after CYC and at follow-up (p = not significant). Moreover, at the end of CYC, FVC and/or DLCO showed a clinical improvement/stabilization in all patients of group 1 versus 8/14 of group 2, while at the re-evaluation 1 year after completing CYC, 2/11 patients of group 1 worsened versus 5/12 of group 2. HRCT progression was observed in 1/11 of group 1 and 8/12 of group 2 (p = 0.009). BAL fluid normalization after CYC therapy correlated with long-term response to treatment, contrary to what is observed in individuals with persistent alveolitis.

  8. Activation of Nrf2-ARE signaling mitigates cyclophosphamide-induced myelosuppression.

    PubMed

    Que, Linling; He, Liu; Yu, Chenshu; Yin, Wencheng; Ma, Liwen; Cao, Baoshan; Yu, Siwang

    2016-11-16

    Myelosuppression is the most common dose-limiting adverse effect of chemotherapies. In the present study, we investigated the involvement of nuclear erythroid 2-related factor 2 (Nrf2) in cyclophosphamide-induced myelosuppression in mice, and evaluated the potential of activating Nrf2 signaling as a preventive strategy. The whole blood from Nrf2(-/-) mice exhibited decreased antioxidant capacities, while the bone marrow cells, peripheral blood mononuclear cells and granulocytes from Nrf2(-/-) mice were more susceptible to acrolein-induced cytotoxicity than those from wild type mice. Single dosage of cyclophosphamide induced significantly severer acute myelosuppression in Nrf2(-/-) mice than in wild type mice. Furthermore, Nrf2(-/-) mice exhibited greater loss of peripheral blood nucleated cells and recovered slower from myelosuppression nadir upon multiple consecutive dosages of cyclophosphamide than wild type mice did. This was accompanied with decreased antioxidant and detoxifying gene expressions and impaired colony formation ability of Nrf2(-/-) bone marrow cells. More importantly, activation of Nrf2 signaling by CDDO-Me significantly alleviated cyclophosphamide-induced myelosuppression, while this alleviation was diminished in Nrf2(-/-) mice. In conclusion, the present study shows that Nrf2 plays a protective role in cyclophosphamide-induced myelosuppression and activation of Nrf2 is a promising strategy to prevent or treat chemotherapy-induced myelosuppression.

  9. Late effects on gonadal function of cyclophosphamide, total-body irradiation, and marrow transplantation

    SciTech Connect

    Sanders, J.E.; Buckner, C.D.; Leonard, J.M.; Sullivan, K.M.; Witherspoon, R.P.; Deeg, H.J.; Storb, R.; Thomas, E.D.

    1983-09-01

    One hundred thirty-seven patients had gonadal function evaluated 1-11 years after marrow transplantation. All 15 women less than age 26 and three of nine older than age 26 who were treated with 200 mg/kg cyclophosphamide recovered normal gonadotropin levels and menstruation. Five have had five pregnancies resulting in three live births, one spontaneous abortion, and one elective abortion. Three of 38 women who were prepared with 120 mg/kg cyclophosphamide and 920-1200 rad total-body irradiation had normal gonadotropin levels and menstruation. Two had pregnancies resulting in one spontaneous and one elective abortion. Of 31 men prepared with 200 mg/kg cyclophosphamide, 30 had normal luteinizing hormone levels, 20 had normal follicle-stimulating hormone levels, and 10 of 15 had spermatogenesis. Four have fathered five normal children. Thirty-six of 41 men prepared with 120 mg/kg cyclophosphamide and 920-1750 rad total-body irradiation had normal luteinizing hormone levels, ten had normal follicle-stimulating hormone levels, and 2 of 32 studied had spermatogenesis. One has fathered two normal children. It was concluded that cyclophosphamide does not prevent return of normal gonadal function in younger women and in most men. Total-body irradiation prevents return of normal gonadal function in the majority of patients.

  10. Promotion of the Toxic Action of Cyclophosphamide by Digestive Tract Luminal Ammonia in Rats

    PubMed Central

    Ivnitsky, Jury Ju.; Schäfer, Timur V.; Rejniuk, Vladimir L.

    2011-01-01

    To estimate the influence of the digestive tract luminal ammonia pool on acute toxic effects of cyclophosphamide, the dynamics of blood ammonia, glutamine and urea level, symptoms of toxic action and the survival time have been studied in rats, intraperitoneally treated with cyclophosphamide, at the background of the gavage with non-lethal dose of ammonium acetate (12 mmol/kg, i.e., 0.35 LD50). Ammonium acetate enhanced the hyperammonaemic action of cyclophosphamide while promoting its lethal action: the mean survival time decreased 1.5, 2.1, 2.8, or 6.1 times at the background of cyclophosphamide i/p doses 200, 600, 1000, or 1400 mg/kg, respectively. Animals exposed to the combination of toxicants, manifested symptoms which were characteristic of the effect of lethal doses of ammonia salts. These data provide the evidence of the detrimental role of gastrointestinal luminal ammonia in the acute high-dose cyclophosphamide toxicity. PMID:23724282

  11. Acrocomia aculeata prevents toxicogenetic damage caused by the antitumor agent cyclophosphamide.

    PubMed

    Magosso, M F; Carvalho, P C; Shneider, B U C; Pessatto, L R; Pesarini, J R; Silva, P V B; Correa, W A; Kassuya, C A L; Muzzi, R M; Oliveira, R J

    2016-05-06

    Acrocomia aculeata is a plant rich in antioxidant compounds. Studies suggest that this plant has anti-inflammatory, antidiabetic, and diuretic potential. We assessed the antigenotoxic, antimutagenic, immunomodulation, and apoptotic potentials of A. aculeata alone and in combination with an antitumor agent, cyclophosphamide. Swiss male mice (N = 140) were used. The animals were divided into 14 experimental groups as follows: a negative group, a positive group (100 mg/kg cyclophosphamide), groups that only received the oil extracted from the almond (AO) and from the pulp (PO) of A. aculeata at doses of 3, 15, and 30 mg/kg, and the associated treatment groups (oils combined with cyclophosphamide) involving pretreatment, simultaneous, and post-treatment protocols. Data suggest that both oils were chemopreventive at all doses, based on the tested protocols. The highest damage reduction percentages, observed for AO and PO were 88.19 and 90.03%, respectively, for the comet assay and 69.73 and 70.93%, respectively, for the micronucleus assay. Both AO and PO demonstrated immunomodulatory activity. The oils reduced the capacity of cyclophosphamide to trigger apoptosis in the liver, spleen, and kidney cells. These results suggest that A. aculeate AO and PO can be classified as a functional food and also enrich other functional foods and nutraceuticals with chemopreventive features. However, they are not appropriate sources for chemotherapeutic adjuvants, in particular for those used in combination with cyclophosphamide.

  12. Campomanesia adamantium extract induces DNA damage, apoptosis, and affects cyclophosphamide metabolism.

    PubMed

    Martello, M D; David, N; Matuo, R; Carvalho, P C; Navarro, S D; Monreal, A C D; Cunha-Laura, A L; Cardoso, C A L; Kassuya, C A L; Oliveira, R J

    2016-04-26

    Campomanesia adamantium (Cambess.) O. Berg. is originally from Brazil. Its leaves and fruits have medicinal properties such as anti-inflammatory, antidiarrheal and antiseptic properties. However, the mutagenic potential of this species has been reported in few studies. This study describes the mutagenic/antimutagenic, splenic phagocytic, and apoptotic activities of C. adamantium hydroethanolic extract with or without cyclophosphamide in Swiss mice. The animals orally received the hydroethanolic extract at doses of 30, 100, or 300 mg/kg with or without 100 mg/kg cyclophosphamide. Mutagenesis was evaluated by performing the micronucleus assay after treatment for 24, 48, and 72 h, while splenic phagocytic and apoptotic effects were investigated after 72 h. Short-term exposure of 30 and 100 mg/kg extract induced mild clastogenic/aneugenic effects and increased splenic phagocytosis and apoptosis in the liver, spleen, and kidneys. When the extract was administered in combination with cyclophosphamide, micronucleus frequency and apoptosis reduced. Extract components might affect cyclophosphamide metabolism, which possibly leads to increased clearance of this chemotherapeutic agent. C. adamantium showed mutagenic activity and it may decrease the effectiveness of drugs with metabolic pathways similar to those associated with cyclophosphamide. Thus, caution should be exercised while consuming these extracts, especially when received in combination with other drugs.

  13. Balloon catheter dilatation and thrombectomy for acute aortoiliac occlusion

    PubMed Central

    Archie, Joseph P.

    1981-01-01

    A case of acute distal aortic thrombosis in an elderly high-risk patient was successfully managed with intraoperative thrombectomy and balloon catheter dilatation of the common iliac arteries. Balloon catheter dilatation may be indicated prior to bypass grafting in high-risk patients with acute aortoiliac thrombosis. PMID:15216181

  14. Significance of Main Pulmonary Artery Dilation on Imaging Studies

    PubMed Central

    Raymond, Timothy E.; Khabbaza, Joseph E.; Yadav, Ruchi

    2014-01-01

    Proper and early identification of patients who harbor serious occult illness is the first step in developing a disease-management strategy. Identification of illnesses through the use of noninvasive techniques provides assurance of patient safety and is ideal. PA dilation is easily measured noninvasively and is due to a variety of conditions, including pulmonary hypertension (PH). The clinician should be able to thoroughly assess the significance of PA dilation in each individual patient. This involves knowledge of the ability of PA dilation to accurately predict PH, understand the wide differential diagnosis of causes of PA dilation, and reverse its life-threatening complications. We found that although PA dilation is suggestive of PH, data remain inconclusive regarding its ability to accurately predict PH. At this point, data are insufficient to place PA dilation into a PH risk-score equation. Here we review the causes and complications of PA dilation, define normal and abnormal PA measurements, and summarize the data linking its association to PH, while suggesting an algorithm designed to assist clinicians in patient work-up after recognizing PA dilation. PMID:25406836

  15. Endosonography for Pancreatic Duct Dilatation without Definite Pathology on Ultrasonography.

    PubMed

    Chen, Chien-Hua; Yang, Chi-Chieh; Yeh, Yung-Hsiang

    2014-05-01

    Main pancreatic duct dilatation raises concerns about the possibility of pancreatobiliary malignancy. We evaluated the etiologic yield of endosonography (EUS) for main pancreatic duct dilatation without definite pathology on Ultrasonography (US). A retrospective review was conducted in 54 consecutive patients referred for EUS. No pathological finding (37.0%, 20/54), followed by periampullary cancer (35.2%, 19/54), was the most common finding. Elevated alkaline phosphatase (ALK-P) and marked common bile duct (CBD) dilatation (≥ 12 mm) were the predictors of malignancy (p < 0.05). Among the 37 subjects with available ALK-P and CBD diameter, the probability of malignancy was 84.6% (11/13) for both elevated ALK-P and marked CBD dilatation, 16.7% (1/6) for isolated elevated ALK-P, 18.2% (2/11) for isolated marked CBD dilatation, and none (0/7) was for subjects with neither elevated ALK-P nor marked CBD dilatation, respectively. The overall accuracy of EUS for periampullary carcinomas was 94.7% (18/19) and for choledocholithiasis was 100% (7/7), respectively. EUS had a 100.0% (20/20) sensitivity and a 97.1% (33/34) specificity in the diagnosis of no pathological obstruction. EUS is accurate for main pancreatic duct dilatation without definite pathology on US, and the presence of concomitant elevated ALK-P and CBD dilatation highly suggests malignancy.

  16. Dilated Canine Hearts: A Specimen for Teaching Cardiac Anatomy

    ERIC Educational Resources Information Center

    Cope, Lee Anne

    2008-01-01

    Dilated canine hearts were used to teach undergraduate students internal and external cardiac anatomy. The specimens were dilated using hydrostatic pressure and then fixed using 5% formalin. These specimens provided the students with an alternative to prepackaged embalmed hearts and anatomical models for studying the external and internal cardiac…

  17. Dilated Canine Hearts: A Specimen for Teaching Cardiac Anatomy

    ERIC Educational Resources Information Center

    Cope, Lee Anne

    2008-01-01

    Dilated canine hearts were used to teach undergraduate students internal and external cardiac anatomy. The specimens were dilated using hydrostatic pressure and then fixed using 5% formalin. These specimens provided the students with an alternative to prepackaged embalmed hearts and anatomical models for studying the external and internal cardiac…

  18. Gravitational time dilation induced decoherence in spontaneous emission

    NASA Astrophysics Data System (ADS)

    Xie, Dong; Xu, Chunling; Wang, An Min

    2017-08-01

    We investigate decoherence of quantum superpositions induced by gravitational time dilation and spontaneous emission between two atomic levels. It has been shown that gravitational time dilation can be a universal decoherence source by Pikovski et al. Here, we consider the decoherence induced by the gravitational time dilation only in the situation of spontaneous emission. We obtain the analytical results of the coherence of particle’s position state. Then, we obtain that the coherence of particle’s position state depends on reference frame because the time dilation changes the distinguishability of emitted photons from two positions of particle in different reference frames. For observing the decoherence effect induced by the gravitational time dilation, time-delayed feedback can be utilized to increase the decoherence of particle’s superposition state.

  19. Dilation of fusion pores by crowding of SNARE proteins.

    PubMed

    Wu, Zhenyong; Bello, Oscar D; Thiyagarajan, Sathish; Auclair, Sarah Marie; Vennekate, Wensi; Krishnakumar, Shyam S; O'Shaughnessy, Ben; Karatekin, Erdem

    2017-03-27

    Hormones and neurotransmitters are released through fluctuating exocytotic fusion pores that can flicker open and shut multiple times. Cargo release and vesicle recycling depend on the fate of the pore, which may reseal or dilate irreversibly. Pore nucleation requires zippering between vesicle-associated v- and target membrane t-SNAREs, but the mechanisms governing the subsequent pore dilation are not understood. Here, we probed dilation of single fusion pores using v-SNARE-reconstituted ~23 nm diameter discoidal nanolipoprotein particles (vNLPs) as fusion partners with cells ectopically expressing cognate, 'flipped' t-SNAREs. Pore nucleation required a minimum of 2, and reached a maximum above ~4 copies per face, but the probability of pore dilation was far from saturating at 15 copies, the NLP capacity. Our experimental and computational results suggest SNARE availability may be pivotal in determining whether neurotransmitters or hormones are released through a transient (kiss & run) or an irreversibly dilating pore (full fusion).

  20. [Esophageal dilatation by Savary-Guillard bougies in children].

    PubMed

    Asensio Llorente, M; Broto Mangues, J; Gil-Vernet Huguet, J M; Acosta Farina, D; Marhuenda Irastorza, C; Boix-Ochoa, J

    1999-01-01

    Dilatations are considered the election treatment for esophageal stenosis of different etiologies. Different methods of dilatation have been used through the years. Security and effectiveness are the main subjects when we choose a dilatation method. We present the results of the last 3 years that Savary-Guilliard have been used, with a guide wire probe, under endoscopic control. Six patients with postsurgical stenosis and 10 with post lye ingestion stenosis were treated with the above mentioned method. The site of stenosis is localized under flexible endoscopy, and a special guide wire probe is introduced to the stomach. Once the wire is in place, different diameter bougies are introduced until a firm resistance is felt or the desired diameter is reach. In complicated cases the progression of the wire was controlled by X-rays. A total of 208 dilatations have done in 16 patients over the last three years. Six patients with postsurgical stenosis needed from two to six dilatations for their cure. Of the 10 patients who ingest lye, none of them had needed a gastrostomy. Three of them have no dysphagia after 9, 13 and 13 dilatations. The other 7 are under dilatations every 6 weeks in 6 cases and every 4 weeks in one case, been all of them in the second year of treatment. All the dilatations have been performed under general anesthesia, as outpatients. We have not had any complication under this treatment. We have found that the Savary-Guilliard method is adequate for esophageal dilatations in pediatric population. Security and effectiveness are the main points of this procedure, there is no need for a gastrostomy, and the child will have a better quality of life. This procedure is less aggressive, and this will give a shorter postop period, with no complications and the child will have a longer period of normal life between dilatations.

  1. Dietary taurine deficiency and dilated cardiomyopathy in the fox.

    PubMed

    Moise, N S; Pacioretty, L M; Kallfelz, F A; Stipanuk, M H; King, J M; Gilmour, R F

    1991-02-01

    Taurine deficiency has been implicated as a potential cause of dilated cardiomyopathy. However, the relationship between taurine and myocardial function is presently unclear. The purpose of this study was to determine whether dilated cardiomyopathy in the fox is associated with dietary taurine deficiency. A total of 68 foxes from farms with a history of death caused by dilated cardiomyopathy and 14 foxes from a farm with no history of dilated cardiomyopathy were studied. Dilated cardiomyopathy was diagnosed by echocardiography in 48% of the foxes from one farm with a positive history and in none of the foxes from the control farm. Foxes less than 9 months of age were more commonly affected than older foxes (p = 0.03). Plasma taurine concentrations were significantly less (p less than 0.01) in foxes that had dilated cardiomyopathy (26.8 +/- 16.4 nmol/ml) than in the control foxes (99.3 +/- 60.2 nmol/ml). A significantly higher (p less than 0.01) incidence of dilated cardiomyopathy was present in foxes with a history of a sibling or offspring that died of dilated cardiomyopathy than in foxes without a family history of cardiac death. In one fox with dilated cardiomyopathy that was tested, the myocardial taurine concentration was lower (1.7 mumol/gm wet weight) than that of control foxes (7.3 +/- 1.6 mumol/gm wet weight). Hepatic cysteinesulfinic acid decarboxylase activity was significantly less (p less than 0.001) in foxes with dilated cardiomyopathy (0.97 +/- 0.2 nmol/mm.mg protein) than in control foxes (2.11 +/- 0.07 nmol CO2/mm.mg protein).(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Effects of cyclophosphamide on laser immunotherapy for the treatment of metastatic cancer

    NASA Astrophysics Data System (ADS)

    Bahavar, Cody F.; Acquaviva, Joseph T.; Rabei, Sheyla; Sikes, Allie; Nordquist, Robert E.; Hode, Tomas; Liu, Hong; Chen, Wei R.

    2014-02-01

    Laser immunotherapy (LIT) is an innovative cancer modality that uses laser irradiation and immunological stimulation to treat late-stage, metastatic cancers. The current mode of operation in LIT is through interstitial laser irradiation. Although LIT is still in development, recent clinical trials have shown that it can be used to successfully treat patients with late-stage breast cancer and melanoma. Cyclophosphamide is a chemotherapy drug that suppresses regulatory T cells when used in low doses. In this study tumor-bearing rats were treated with LIT using an 805-nm laser with a power of 2.0 W and low-dose cyclophosphamide. Glycated chitosan was used as an immunological stimulant. The goal was to observe the effects of different doses of cyclophosphamide in addition to LIT on the survival of the tumor-bearing rats.

  3. A comparative study of the action of cyclophosphamide and procarbazine on the antibody production in mice

    PubMed Central

    Liske, Rosemaria

    1973-01-01

    The effect of procarbazine and cyclophosphamide on the formation of antibodies to sheep red blood cells in mice is investigated. Cyclophosphamide was found to have the best immunosuppressive effect when given after antigen; recovery from drug treatment was relatively fast; under experimental conditions that favour cyclophosphamide action (antigen prior to drug) IgM formation was found to be depressed and prolonged; IgG formation was markedly depressed or altogether missing. Procarbazine was found to act best when given prior to antigen; recovery was slow; under experimental conditions that favour procarbazine action (drug prior to antigen) the induction period was prolonged. IgM titres were slightly and IgG titres markedly depressed. Under all conditions tested procarbazine had little effect on the onset of IgG production. PMID:4762019

  4. Combined therapy with cyclophosphamide and DNA preparation inhibits the tumor growth in mice

    PubMed Central

    Alyamkina, Ekaterina A; Dolgova, Evgenia V; Likhacheva, Anastasia S; Rogachev, Vladimir A; Sebeleva, Tamara E; Nikolin, Valeriy P; Popova, Nelly A; Orishchenko, Konstantin E; Strunkin, Dmitriy N; Chernykh, Elena R; Zagrebelniy, Stanislav N; Bogachev, Sergei S; Shurdov, Mikhail A

    2009-01-01

    Background When cyclophosphamide and preparations of fragmented exogenous genomic double stranded DNA were administered in sequence, the regressive effect on the tumor was synergic: this combined treatment had a more pronounced effect than cyclophosphamide alone. Our further studies demonstrated that exogenous DNA stimulated the maturation and specific activities of dendritic cells. This suggests that cyclophosphamide, combined with DNA, leads to an immune response to the tumors that were grafted into the subjects post treatment. Methods Three-month old CBA/Lac mice were used in the experiments. The mice were injected with cyclosphamide (200 mkg per 1 kg body weight) and genomic DNA (of human, mouse or salmon sperm origin). The DNA was administered intraperitoneally or subcutaneously. After 23 to 60 days, one million tumor cells were intramuscularly grafted into the mice. In the final experiment, the mice were pre-immunized by subcutaneous injections of 20 million repeatedly thawed and frozen tumor cells. Changes in tumor growth were determined by multiplying the three perpendicular diameters (measured by caliper). Students' t-tests were used to determine the difference between tumor growth and average survival rate between the mouse groups and the controls. Results An analysis of varying treatments with cyclophosphamide and exogenous DNA, followed by tumor grafting, provided evidence that this combined treatment had an immunizing effect. This inhibitory effect in mice was analyzed in an experiment with the classical immunization of a tumor homogenate. The strongest inhibitory action on a transplanted graft was created through the following steps: cyclophosphamide at 200 mg/kg of body weight administered as a pretreatment; 6 mg fragmented exogenous DNA administered over the course of 3 days; tumor homogenate grafted 10 days following the final DNA injection. Conclusion Fragmented exogenous DNA injected with cyclophosphamide inhibits the growth of tumors that are

  5. Cyclophosphamide dose intensification may circumvent anthracycline resistance of p53 mutant breast cancers.

    PubMed

    Lehmann-Che, Jacqueline; André, Fabrice; Desmedt, Christine; Mazouni, Chafika; Giacchetti, Sylvie; Turpin, Elisabeth; Espié, Marc; Plassa, Louis-François; Marty, Michel; Bertheau, Philippe; Sotiriou, Christos; Piccart, Martine; Symmans, W Fraser; Pusztai, Lajos; de Thé, Hugues

    2010-01-01

    The predictive value of p53 for the efficacy of front-line anthracycline-based chemotherapy regimens has been a matter of significant controversy. Anthracyclines are usually combined with widely different doses of alkylating agents, which may significantly modulate tumor response to these combinations. We analyzed three series of de novo stage II-III breast cancer patients treated front line with anthracycline-based regimens of various cyclophosphamide dose intensities: 65 patients with estrogen receptor (ER)(-) tumors treated with anthracyclines alone (Institut Jules Bordet, Brussels), 51 unselected breast cancer patients treated with intermediate doses of cyclophosphamide (MD Anderson Cancer Center, Houston, TX), and 128 others treated with a dose-dense anthracycline-cyclophosphamide combination (St. Louis, Paris). After chemotherapy and surgery, pathologic complete response (pCR) was evaluated. p53 status was determined by a yeast functional assay on the pretreatment tumor sample. In a multivariate analysis of the pooled results, a lack of ER expression and high-dose cyclophosphamide administration were associated with a higher likelihood of pCR. A sharp statistical interaction was detected between p53 status and cyclophosphamide dose intensity. Indeed, when restricting our analysis to patients with ER(-) tumors, we confirmed that a mutant p53 status was associated with anthracycline resistance, but found that p53 inactivation was required for response to the dose-intense alkylating regimen. The latter allowed very high levels of pCR in triple-negative tumors. Thus, our data strongly suggest that cyclophosphamide dose intensification in ER(-) p53-mutated breast cancer patients could significantly improve their response.

  6. Treatment of Acute Antibody-Mediated Renal Allograft Rejection With Cyclophosphamide.

    PubMed

    Waiser, Johannes; Duerr, Michael; Budde, Klemens; Rudolph, Birgit; Wu, Kaiyin; Bachmann, Friederike; Halleck, Fabian; Schönemann, Constanze; Lachmann, Nils

    2017-10-01

    Antibody-mediated rejection (AMR) is a major risk for renal allograft survival. Throughout decades, cyclophosphamide treatment has been proven to be effective in patients with antibody-associated autoimmune diseases. We investigated whether cyclophosphamide combined with plasmapheresis and intravenous immunoglobulins is an option for patients with AMR. Between March 2013 and November 2015, we initiated treatment of 13 consecutive patients with biopsy-proven acute AMR with intravenous cyclophosphamide pulses (15 mg/kg adapted to age and renal function) at 3-week intervals, PPH (6×), and high-dose intravenous immunoglobulin (1.5 g/kg). Treatment was completed after 6 cyclophosphamide pulses or in case of return to baseline serum creatinine together with reduction of donor-specific HLA antibodies (DSA) below 500 mean fluorescence intensity. Eleven of 13 patients completed treatment. Median follow-up was 18 (12-44) months. At the end of follow-up, graft survival was 77% (10/13). The 3 graft losses were caused at least in part by nonadherence and premature termination of treatment. Serum creatinine increased from 1.7±0.4 mg/dL at 3 months before diagnosis to 3.7±2.4 mg/dL at diagnosis (P = 0.01), and decreased to 2.1 ± 0.7 mg/dL at 3 months after diagnosis (P = 0.01). In 7 (64%) of 11 patients, who completed treatment, DSA decreased, in 4 (36%) of 11 DSA were below 500 mean fluorescence intensity after treatment. Dose reductions had to be performed in 3 of 13 patients for leukopenia. We observed 14 hospitalizations in 9 of 13 patients. To our knowledge, this is the first systematic report on cyclophosphamide-based treatment of acute AMR based on modern diagnostics. Treatment was effective and relatively safe. Future studies will show, whether cyclophosphamide proves to be a valuable alternative for the treatment of AMR.

  7. Pemetrexed and cyclophosphamide combination therapy for the treatment of non-small cell lung cancer.

    PubMed

    Li, Dong; He, Song

    2015-01-01

    Lung cancer is the leading cause of cancer-related mortality. This study was undertaken to investigate the efficacy and safety of adding regulatory T cell inhibitor cyclophosphamide to pemetrexed therapy for the second-line treatment of NSCLC with wild-type epidermal growth factor receptor (EGFR). A total of 70 patients were screened between March 2011 and December 2013, out of which 62 patients were enrolled in the study. Patients were randomized to receive 500 mg/m(2) pemetrexed in combination with 20 mg/kg cyclophosphamide in a 21 day cycle (n=30) or 500 mg/m(2) pemetrexed (n=32), and followed up for 30 months. Disease progression was observed in 23 patients in the pemetrexed plus cyclophosphamide arm and 27 patients in the pemetrexed monotherapy arm. Median progression-free survival was 3.6 months (95% confidence interval [CI], 1.3 to 5.9 months) in the pemetrexed plus cyclophosphamide arm and 2.2 months (95% CI, 1.3 to 3.1 months) in the pemetrexed monotherapy arm. The 6-month PFS rates were 22% (95% CI, 10 to 34) and 14.5% (95% CI, 6 to 23) in the pemetrexed plus cyclophosphamide arm and pemetrexed monotherapy arm, respectively. Median overall survival was 9.8 months for the pemetrexed combination therapy arm and 8.8 months for the pemetrexed arm, and the 1-year survival rates were 46% and 33%, respectively. The present study showed that pemetrexed in combination with low-dose cyclophosphamide may be a better treatment approach than pemetrexed monotherapy when considering second-line treatment for wild-type EGFR NSCLC.

  8. Nitric oxide and NK(1)-tachykinin receptors in cyclophosphamide-induced cystitis, in rats.

    PubMed

    Alfieri, A B; Cubeddu, L X

    2000-11-01

    The present study was conducted to investigate the role of NK(1) receptors and of nitric oxide (NO) on the pathogenesis of cyclophosphamide-induced cystitis, in rats. This bladder toxicity was characterized by marked increases in protein plasma extravasation, urothelial damage, edema, white blood cell infiltrates, and vascular congestion. These changes were associated with appearance of Ca(2+)-independent NO-synthase (NOS) activity [characteristic of inducible NOS (iNOS)] in the bladder and with increases in urinary NO metabolites. GR205171, a selective NK(1) antagonist (10-20 mg/kg, i.p.) reduced cyclophosphamide-induced increases in protein plasma extravasation and in the urinary excretion of NO metabolites. N(G)-Nitro-L-arginine (L-NNA) (10 mg/kg, i.p.), a NOS inhibitor, reduced basal and cyclophosphamide-induced increases in NO metabolites and protected against cyclophosphamide-induced protein plasma extravasation. GR205171 had no effect, whereas L-NNA reduced basal NO metabolite excretion. Combined treatment with the NK(1) antagonist and the NO-synthesis inhibitor produced comparable reduction in protein plasma extravasation than that achieved with each drug given separately. Combined drug treatment ameliorated cyclophosphamideinduced urothelial damage, and the extent of edema, vascular congestion, and white blood cell infiltrates in the bladder. In summary, NK(1) receptors and iNOS play a role in NO formation and on cyclophosphamide-induced cystitis. Activation of NK(1) receptors mainly acts through the formation of NO. It is proposed that cyclophosphamide and/or its metabolites would stimulate primary afferent capsaicin-sensitive fibers in the bladder, releasing neuropeptides, which would activate NK(1) receptors. However, additional mechanisms are involved, because neither the NK(1) receptor antagonist nor the NO synthesis inhibitor, either alone or in combination, were able to completely prevent the toxicity.

  9. Cyclosporine A or intravenous cyclophosphamide for lupus nephritis: the Cyclofa-Lune study.

    PubMed

    Zavada, J; Pesickova, Ss; Rysava, R; Olejarova, M; Horák, P; Hrncír, Z; Rychlík, I; Havrda, M; Vítova, J; Lukác, J; Rovensky, J; Tegzova, D; Böhmova, J; Zadrazil, J; Hána, J; Dostál, C; Tesar, V

    2010-10-01

    Intravenous cyclophosphamide is considered to be the standard of care for the treatment of proliferative lupus nephritis. However, its use is limited by potentially severe toxic effects. Cyclosporine A has been suggested to be an efficient and safe treatment alternative to cyclophosphamide. Forty patients with clinically active proliferative lupus nephritis were randomly assigned to one of two sequential induction and maintenance treatment regimens based either on cyclophosphamide or Cyclosporine A. The primary outcomes were remission (defined as normal urinary sediment, proteinuria <0.3 g/24 h, and stable s-creatinine) and response to therapy (defined as stable s-creatinine, 50% reduction in proteinuria, and either normalization of urinary sediment or significant improvement in C3) at the end of induction and maintenance phase. Secondary outcomes were incidence of adverse events, and relapse-free survival. At the end of the induction phase, 24% of the 21 patients treated by cyclophosphamide achieved remission, and 52% achieved response, as compared with 26% and 43%, respectively of the 19 patients treated by the Cyclosporine A. At the end of the maintenance phase, 14% of patients in cyclophosphamide group, and 37% in Cyclosporine A group had remission, and 38% and 58% respectively response. Treatment with Cyclosporine A was associated with transient increase in blood pressure and reversible decrease in glomerular filtration rate. There was no significant difference in median relapse-free survival. In conclusion, Cyclosporine A was as effective as cyclophosphamide in the trial of sequential induction and maintenance treatment in patients with proliferative lupus nephritis and preserved renal function.(ClinicalTrials.gov identifier: NCT00976300)

  10. Cyclophosphamide-induced changes of serum angiotensin converting enzyme activity and pulmonary microvessels ultrastructure.

    PubMed

    Musiatowicz, B; Terlikowski, S; Sulik, M; Famulski, W; Giedrojć, J; Jakubowski, A; Sobaniec-Lotowska, M; Pasztaleniec, L; Baltaziak, M; Jabłońska, E

    1997-01-01

    The effect of cyclophosphamide (CP) on the ultrastructure of the lung tissue and the activity of angiotensin converting enzyme (ACE) in serum was evaluated in rats. The animals were given cyclophosphamide (CP) in a single intraperitoneal dose of 150 mg/kg b.w. ACE activity was evaluated in the blood serum collected from the left ventricle of the heart using the spectrophometric method. In all time subgroups, the CP-receiving animals showed a decrease in ACE activity. Ultrastructural examinations of CP-treated animals revealed increased adhesion of neutrophiles and monocytes to the damage endothelium of the alveolar septa vessels and focally accumulation of the platelets.

  11. Kaposi's sarcoma in an elderly man with Wegener's granulomatosis treated with cyclophosphamide and corticosteroids.

    PubMed

    Erban, S B; Sokas, R K

    1988-05-01

    The association of Kaposi's sarcoma with malignant lymphoreticular diseases and immunosuppressive therapy is well documented. This report describes an elderly man who presented with fulminant Wegener's granulomatosis that responded to treatment with cyclophosphamide and corticosteroids. Rapidly progressing cutaneous Kaposi's sarcoma developed ten weeks after the start of immunosuppressive therapy yet regressed on discontinuation of the corticosteroid therapy, despite continuation of cyclophosphamide therapy. To our knowledge, this is the first reported case of Kaposi's sarcoma occurring in association with Wegener's granulomatosis. The literature on Kaposi's sarcoma in immunosuppressed patients is reviewed.

  12. Does cyclophosphamide still have a role in the treatment of severe inflammatory eye disease?

    PubMed

    Wakefield, Denis

    2014-08-01

    Cyclophosphamide is a highly effective immunosuppressive drug that has proven efficacy in the treatment of patients with severe inflammatory eye disease. It has the advantage of being able to be used either orally or intravenously, has a potent steroid-sparing effect, and is effective in inducing disease remission. The major limitations to the use of this alkylating agent are its frequent side effects. With the increasing availability of alternate forms of therapy it is time to review the therapeutic regimen for cyclophosphamide use in patients with inflammatory eye disease.

  13. Pupil Dilation to Explicit and Non-Explicit Sexual Stimuli.

    PubMed

    Watts, Tuesday M; Holmes, Luke; Savin-Williams, Ritch C; Rieger, Gerulf

    2017-01-01

    Pupil dilation to explicit sexual stimuli (footage of naked and aroused men or women) can elicit sex and sexual orientation differences in sexual response. If similar patterns were replicated with non-explicit sexual stimuli (footage of dressed men and women), then pupil dilation could be indicative of automatic sexual response in fully noninvasive designs. We examined this in 325 men and women with varied sexual orientations to determine whether dilation patterns to non-explicit sexual stimuli resembled those to explicit sexual stimuli depicting the same sex or other sex. Sexual orientation differences in pupil dilation to non-explicit sexual stimuli mirrored those to explicit sexual stimuli. However, the relationship of dilation to non-explicit sexual stimuli with dilation to corresponding explicit sexual stimuli was modest, and effect magnitudes were smaller with non-explicit sexual stimuli than explicit sexual stimuli. The prediction that sexual orientation differences in pupil dilation are larger in men than in women was confirmed with explicit sexual stimuli but not with non-explicit sexual stimuli.

  14. Review article: oesophageal dilation in adults with eosinophilic oesophagitis.

    PubMed

    Bohm, M E; Richter, J E

    2011-04-01

    Eosinophilic oesophagitis is a chronic inflammatory disorder of the oesophagus, characterised by the proton pump inhibitor-refractory accumulation of eosinophils in the oesophageal epithelium (>15 intraepithelial eosinophils/high powered field). Adults present with solid food dysphagia and recurrent food impactions. Oesophageal remodelling produces the characteristic endoscopic feature of adult eosinophilic oesophagitis including strictures, rings and a narrow calibre oesophagus. To evaluate the safety and efficacy of oesophageal dilation as the initial therapy for adults with eosinophilic oesophagitis. Medline search from 1975 to November 2010 for all reports of the treatment of patients with eosinophilic oesophagitis using search words: eosinophilic oesophagitis treatment, dilation and eosinophilic oesophagitis, steroids and eosinophilic oesophagitis. Our systematic review found that 92% of patients treated with oesophageal dilation had improvement in their dysphagia symptoms for up to 1-2 years. Three case series clearly showed clinical resolution of dysphagia symptoms, independent of the degree of eosinophil infiltration, which was unchanged after dilation. Postprocedure pain for several days is common, due to some degree of mucosal tear, but true perforation very rare (<0.1%). Oesophageal dilation is an acceptable option for healthy adult eosinophilic oesophagitis patients with anatomic narrowing, possibly followed by a course of topical steroids to reduce inflammation and retard remodelling. Future studies should include a head-to-head comparison of topical steroids and oesophageal dilation, bougie vs through-the-scope balloon dilation and maintenance topical steroids compared with on-demand treatment. © 2011 Blackwell Publishing Ltd.

  15. Muscles involved in naris dilation and nose motion in rat

    PubMed Central

    Deschênes, Martin; Haidarliu, Sebastian; Demers, Maxime; Moore, Jeffrey; Kleinfeld, David; Ahissar, Ehud

    2016-01-01

    In a number of mammals muscle dilator nasi (naris) is known as a muscle that reduces nasal airflow resistance by dilating the nostrils. Here we show that in rats the tendon of this muscle inserts into the aponeurosis above the nasal cartilage. Electrical stimulation of this muscle lifts the nose and deflects it sideway towards the side of stimulation, but does not change the size of the nares. In the head-fixed alert rat, electromyographic activity of muscle dilator nasi is tightly coupled to nose motion, not to opening of the nares. Yet, contraction of muscle dilator nasi occurs during the pre-inspiratory phase of the respiratory cycle, suggesting a role in sniffing and sampling odorants. We also show that opening of the nares results from contraction of pars maxillaris profunda of the muscle nasolabialis profundus. This muscle attaches to the outer wall of the nasal cartilage and to the plate of the mystacial pad. Contraction of this muscle exerts a dual action: it pulls the lateral nasal cartilage outwardly, thus dilating the naris, and it drags the plate of the mystacial pad rostralward, provoking a slight retraction of the whiskers. On the basis of these results, we propose that muscle dilator nasi of the rat be renamed muscle deflector nasi, and that pars maxillaris profunda of the muscle nasolabialis profundus be named muscle dilator nasi. PMID:25257748

  16. On the Variable Dilatancy Angle in Rocks Around Underground Galleries

    NASA Astrophysics Data System (ADS)

    Salehnia, Fatemeh; Collin, Frédéric; Charlier, Robert

    2017-03-01

    Correct estimation of the dilatant behavior of a rock has an essential role in a realistic numerical simulation of the fracturing threshold during the rock deformation process and its post-failure response, based on experimental and field observations. This importance has been poorly treated in most of the numerical analyses dealing with the rock engineering common problems such as deep excavations. The dilatancy angle as a commonly used parameter for describing the dilatation response of a rock is mostly simplified to be a constant value. Contrarily, a literature review declares the inadequacy of this approach in those rock mechanics applications. In the present paper, a new formula for considering the variable dilatancy angle is presented which relates this parameter to the plastic shear strain in the course of a loading procedure. It is aimed at characterizing an evolution of the dilatant or contracting volumetric response of a rock as well as giving the possibility to simulate a dilatant/contracting transitional behavior. The model is applied to simulate the development of strain localization, in shear band mode, within the inevitable excavation damaged zone created around an underground opening in rock. It is illustrated that using the model of variable dilatancy angle in a deep excavation modeling could help to better reproduce the fractures development around the opening in the course of tunneling.

  17. The dilated bowel: a liability and an asset.

    PubMed

    Bianchi, A; Morabito, A

    2009-11-01

    The gastrointestinal tract responds to significant mechanical or functional obstruction by dilatation and hypertrophy of the segment proximal to the obstruction. Excessive dilatation compromises motility, and absorption and is associated with considerable morbidity (intraluminal stasis, sepsis) such that bowel dilatation represents a major liability that predisposes the patient to intestinal failure. The dilated bowel proximal to an obstruction provides valuable autologous material for reconstruction with "tissue appropriate to the part." Bowel elongation and dilatation are integral to the natural intestinal adaptation response to loss of small bowel and can also be induced through a structured "Bowel Expansion" program. The additional absorptive tissue that is progressively generated is essential for reconstruction of the bowel (tailoring and lengthening), to restore gastrointestinal dynamics (effective propulsion and absorption), and to reduce morbidity (intraluminal stasis, sepsis). In enhancing the prospects for enteral autonomy, dilatation and elongation of the residual autologous bowel are crucial to long-term survival and good quality life, and represent a most welcome asset. This paper reviews the impact and management of bowel dilatation along the gastrointestinal tract.

  18. C-Reactive protein in dilated cardiomyopathy.

    PubMed

    Kaneko, K; Kanda, T; Yamauchi, Y; Hasegawa, A; Iwasaki, T; Arai, M; Suzuki, T; Kobayashi, I; Nagai, R

    1999-01-01

    The prognosis for patients with idiopathic dilated cardiomyopathy (DCM) is poor, although clinical features are variable. Prediction of outcome has been difficult in individual patients based on laboratory data. In some patients with DCM, myocardial damage secondary to viral or immune-mediated myocardial inflammation may persist. To objectively assess inflammation, we measured plasma concentrations of C-reactive protein (CRP) in 188 patients with idiopathic DCM over 5-8 years. All had dyspnea and fatigue at rest; all patients had a left ventricular ejection fraction less than 40% by echocardiography or by contrast or radionuclide ventriculography. We divided these patients into two groups: patients dying within 5 years following admission (n = 49) and the remainder surviving for at least 5 years (n = 139). CRP concentrations in the patients dying early were significantly higher than in the long-term survivors (1. 05 +/- 1.37 vs. 0.49 +/- 1.04 mg/dl, p < 0.05). Sixty-two percent of the patients with CRP>1.0 died within 5 years. In addition to other laboratory tests including electrocardiography and echocardiography, routine CRP measurements proved to be valuable for identifying high-risk patients who require special treatment strategies.

  19. [Nonischemic dilated cardiomyopathy. Parameters of autonomic tone].

    PubMed

    Demming, Thomas; Sandrock, Sarah; Bonnemeier, Hendrik

    2015-03-01

    Nonischemic dilated cardiomyopathies (DCM) are the most common reason for heart failure in developed countries after ischemic disease. They often lead to device therapy. Left ventricular ejection fraction as a single parameter to identify patients at risk for sudden cardiac death revealed inconclusive data in patients with DCM. Autonomic tone, measured by classical and innovative parameters of heart rate variability (HRV), heart rate turbulence or baroreceptor reflex, was demonstrated to give valuable prognostic information especially in patients with ischemic disease and after acute myocardial infarction. In patients with DCM, classical parameters of HRV showed inhomogeneous data in a heterogeneous patient collective caused by unsystematic measurement of single parameters in various patient collectives. Innovative parameters of HRV are promising in patients with DCM and showed prognostic relevance although patient numbers are limited and prospective data are missing. Further studies are needed in this field. Despite the in part convincing evidence for the relevance of autonomic tone as a prognostic marker in patients with DCM, their evaluation is still not part of clinical routine. Additional parameters to estimate the risk of sudden cardiac death are urgently needed.

  20. Dilated cardiomyopathy in dystrophic epidermolysis bullosa

    PubMed Central

    Sidwell, R; Yates, R; Atherton, D

    2000-01-01

    BACKGROUND—Dystrophic epidermolysis bullosa (DEB) is an uncommon genetic disorder of the skin and mucosae. In 1996, we reported the occurrence of lethal dilated cardiomyopathy (DCM) in two affected children.
METHODS—In the past seven years we have routinely screened patients with severe DEB who have been under the care of this hospital by yearly clinical review, echocardiography, and quantification of plasma selenium and carnitine concentrations, as deficiency of these micronutrients is known to be associated with the development of DCM.
RESULTS—Six of 61 children have developed DCM over the seven year period of this study, four of whom have not been previously reported, and three of whom have since died. We compared the concentrations of selenium and free and total carnitine in the children who developed DCM to concentrations in those with severe DEB who did not. The concentrations of free and total carnitine when first measured were significantly lower in the children with DCM, but the selenium concentrations were not.
CONCLUSIONS—We now believe that DCM is a not infrequent complication of severe recessive DEB, and may be related in part to carnitine concentrations, though the exact mechanism remains unclear. We therefore recommend that patients with this condition should undergo regular cardiac review including echocardiography.

 PMID:10869001

  1. Genetic mutations and mechanisms in dilated cardiomyopathy.

    PubMed

    McNally, Elizabeth M; Golbus, Jessica R; Puckelwartz, Megan J

    2013-01-01

    Genetic mutations account for a significant percentage of cardiomyopathies, which are a leading cause of congestive heart failure. In hypertrophic cardiomyopathy (HCM), cardiac output is limited by the thickened myocardium through impaired filling and outflow. Mutations in the genes encoding the thick filament components myosin heavy chain and myosin binding protein C (MYH7 and MYBPC3) together explain 75% of inherited HCMs, leading to the observation that HCM is a disease of the sarcomere. Many mutations are "private" or rare variants, often unique to families. In contrast, dilated cardiomyopathy (DCM) is far more genetically heterogeneous, with mutations in genes encoding cytoskeletal, nucleoskeletal, mitochondrial, and calcium-handling proteins. DCM is characterized by enlarged ventricular dimensions and impaired systolic and diastolic function. Private mutations account for most DCMs, with few hotspots or recurring mutations. More than 50 single genes are linked to inherited DCM, including many genes that also link to HCM. Relatively few clinical clues guide the diagnosis of inherited DCM, but emerging evidence supports the use of genetic testing to identify those patients at risk for faster disease progression, congestive heart failure, and arrhythmia.

  2. The effect of pneumatic dilation in management of postfundoplication dysphagia.

    PubMed

    Sunjaya, D; Podboy, A; Blackmon, S H; Katzka, D; Halland, M

    2017-06-01

    Fundoplication surgery is a commonly performed procedure for gastro-esophageal reflux disease or hiatal hernia repair. Up to 10% of patients develop persistent postoperative dysphagia after surgery. Data on the effectiveness of pneumatic dilation for treatment are limited. The aim of this study was to evaluate clinical outcomes and identify clinical factors associated with successful response to pneumatic dilation among patients with persistent postfundoplication dysphagia (PPFD). We retrospectively evaluated patients who had undergone pneumatic dilation for PPFD between 1999 and 2016. Patients with dysphagia or achalasia prior to fundoplication were excluded. Demographic information, surgical history, severity of dysphagia, and clinical outcomes were collected. Data pertaining to esophagram, manometry, endoscopy, and pneumatic dilation were also collected. We identified 38 patients (82% female, 95% Caucasian, and median age 59 years) with PPFD who completed pneumatic dilation. The median postfundoplication dysphagia score was 2. Eleven patients had abnormal peristalsis on manometry. Seventeen patients reported response (seven complete) with an average decrease of 1 in their dysphagia score. Fifteen patients underwent reoperation due to PPFD. Hiatal hernia repair was the only factor that predicts a higher response rate to pneumatic dilation. Only one patient in our study developed complication (pneumoperitoneum) from pneumatic dilation. We found that pneumatic dilation to be a safe treatment option for PPFD with moderate efficacy. Patients who developed PPFD after a hiatal hernia repair may gain the greatest benefit after pneumatic dilation. We were not able to identify additional clinical, radiological, endoscopic, or manometric parameters that were predictive of response. © 2017 John Wiley & Sons Ltd.

  3. Dilated cardiomyopathy update: infectious-immune theory revisited.

    PubMed

    Kawai, Chuichi; Matsumori, Akira

    2013-11-01

    Dilated cardiomyopathy is characterized by dilatation of the left or right ventricle, or both ventricles. The degree of myocardial dysfunction is not attributable to abnormal loading conditions. The infectious-immune theory has long been hypothesized to explain the pathogenesis of many etiologically unrecognized dilated cardiomyopathies. Inflammations followed by immune reactions, which may be excessive, in the myocardium, evoked by external triggers such as viral infections and/or autoimmune antibodies, continue insidiously, and lead to the process of cardiac remodeling with ventricular dilatation and systolic dysfunction. This ultimately results in dilated cardiomyopathy. Hepatitis C virus-associated heart diseases are good examples of cardiac lesions definitely induced by viral infections in humans that progress to a chronic stage through complicated immune mechanisms. Therapeutic strategies for myocarditis and dilated cardiomyopathy have been obtained through analyses of the acute, subacute, and chronic phases of experimental viral myocarditis in mice. The appropriate modulation of excessive immune reactions during myocarditis, rather than their complete elimination, appears to be a key option in the prevention and treatment of dilated cardiomyopathy. The clinical application of an NF-κB decoy and immune adsorption of IgG3 cardiac autoantibodies have been used as immunomodulating therapies and may provide novel approaches for the treatment of refractory patients with dilated cardiomyopathy. Conventional therapeutic agents for chronic heart failure such as β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and aldosterone antagonists in particular should be re-evaluated on the basis of their anti-inflammatory properties in the treatment of dilated cardiomyopathy.

  4. The influence of the protector thiol L-cystein on the toxic and therapeutic responses of stabilized "activated" cyclophosphamide (4-(S-ethanol)-sulfido-cyclophosphamide).

    PubMed

    Voelcker, G; Laber, P; Rockinger, H; Wientzek, C; Hohorst, H J

    1984-01-01

    The influence of L-cystein on the toxic and therapeutic responses of 4-(S-ethanol)-sulfido-cyclophosphamide (P1), a stabilized "activated" cyclophosphamide, was investigated. Stabilized "activated" cyclophosphamides hydrolyze under physiological conditions to 4-hydroxycyclophosphamide (4-OH-CP). The antitumor activity of P1 was investigated on a heterotransplanted human bladder sarcoma in nude mice and in perfusion experiments carried out on the isolated tumor bearing limb in rats. Due to its rapid hydrolysis to 4-OH-CP, P1 exhibits severe local toxicity which is decreased by the protector thiol L-cystein. Simultaneous application of double molar amounts of L-cystein reduces toxicity in nude mice to approximately one-third. Therapeutic activity is not affected by this ratio of L-cystein so that the protector thiol increases the therapeutic efficacy of P1. Higher amounts of L-cystein reduce both the acute toxicity in nude mice and the therapeutic efficacy against the human xenograft. The perfusion experiments demonstrate that a P1 concentration necessary to cure rats with tumor bearing limb is only tolerated in combination with L-cystein.

  5. Dilatation of the Lower Cervical Esophagus in a Cow

    PubMed Central

    Kasari, T. R.

    1984-01-01

    Acquired megaesophagus of suspected neuromuscular origin was diagnosed in a six year old Holstein cow. The dilatation was restricted to the lower cervical esophagus. Signs included projectile regurgitation of chewed ingesta at variable periods of time after swallowing, nasal discharge of mucus and feed particles, and a cough. A secondary aspiration pneumonia was associated with this condition. The dilated portion of the esophagus was detected utilizing positive contrast radiography and fiberoptic endoscopy. Treatment consisted of feed management and antibiotics. Deglutition in the cow returned to normal over a three month period despite radiographic and fiberoptic endoscopic evidence of a persistent dilatation of the esophagus. ImagesFigure 1. PMID:17422388

  6. Efficacy of Pneumatic Dilatation in Saudi Achalasia Patients

    PubMed Central

    Aljebreen, Abdulrahman M.; Samarkandi, Sara; Al-Harbi, Tahani; Al-Radhi, Haifa; Almadi, Majid A

    2014-01-01

    Background/Aims: Pneumatic dilatation (PD) is one of the effective treatments of achalasia. The aim of this study was to evaluate the efficacy of pneumatic dilation and patient satisfaction in Saudi achalasia patients. Patients and Methods: We have retrospectively recruited patients with confirmed achalasia, who underwent at least one dilatation session from January 1990 to January 2010 at a single tertiary center. Symptoms, including weight loss, dysphagia, retrosternal pain, and regurgitation, were assessed with the use of the Eckardt score (which ranges from 0 to 12, with higher scores indicating more pronounced symptoms). All patients were called and asked about their Eckardt score in addition to their satisfaction score post the dilatation procedure. The primary outcome was therapeutic success (Eckardt score ≤ 3) and patient satisfaction at the time of their calls. The secondary outcomes included the need for retreatment and the rate of complications. Results: A total of 29 patients were included, with a mean age of 40.30 (95% CI: 36.1-44.6) and 55.2% of them were males. The mean of the pre-dilatation Eckardt score was 8.3 (95% CI: 7.2-9.4), which dropped to 2.59 (95% CI: 1.7-3.5) after PD (P < 0.01) with a clinical remission of 76.7% after the first dilatation and a total failure in two patients (7%) after the third dilatation. The mean number of dilatations was 1.3 (95% CI: 1.1-1.5) where 50.7% required one dilatation, 19.2% required two dilatations, and 30.1% required three dilatations. The mean of the symptoms-free period was 53.4 months (SD 52.7, range 1-180) with symptoms recurring in 35% of patients within 2 years. The mean of post-PD patient satisfaction was 7.45 (95% CI: 6.2-8.7). Perforation, which was treated conservatively, occurred in one patient (3.5%), whereas bleeding occurred in two patients (7%). Age or gender was not found to be a predictor of Eckardt score improvement on multivariate linear regression analysis. Conclusion: PD is an

  7. Statistical analysis with dilatation for development process of human fetuses.

    PubMed

    Naito, Kanta; Notsu, Akifumi; Udagawa, Jun; Otani, Hiroki

    2017-02-01

    This paper is concerned with the development process of human fetuses. Though the development process of human fetuses still includes many unknown issues, it is known that a certain harmonious relationship between the organs can be observed. This knowledge is based on our intuition, but we have no theory which clarifies these harmonized developments. The paper aims to give a mathematical understanding of the notion of harmonized development through the use of dilatation, which is a measure of the departure from conformal mapping. The asymptotics for dilatation have been developed using certain efficient models of quasiconformal mapping. The proposed method of dilatation is effectively applied to the human fetus data.

  8. Automated detection of dilated capillaries on optical coherence tomography angiography

    PubMed Central

    Dongye, Changlei; Zhang, Miao; Hwang, Thomas S.; Wang, Jie; Gao, Simon S.; Liu, Liang; Huang, David; Wilson, David J.; Jia, Yali

    2017-01-01

    Automated detection and grading of angiographic high-risk features in diabetic retinopathy can potentially enhance screening and clinical care. We have previously identified capillary dilation in angiograms of the deep plexus in optical coherence tomography angiography as a feature associated with severe diabetic retinopathy. In this study, we present an automated algorithm that uses hybrid contrast to distinguish angiograms with dilated capillaries from healthy controls and then applies saliency measurement to map the extent of the dilated capillary networks. The proposed algorithm agreed well with human grading. PMID:28271005

  9. Characterization and Long-Term Prognosis of Postmyocarditic Dilated Cardiomyopathy Compared With Idiopathic Dilated Cardiomyopathy.

    PubMed

    Merlo, Marco; Anzini, Marco; Bussani, Rossana; Artico, Jessica; Barbati, Giulia; Stolfo, Davide; Gigli, Marta; Muça, Matilda; Naso, Paola; Ramani, Federica; Di Lenarda, Andrea; Pinamonti, Bruno; Sinagra, Gianfranco

    2016-09-15

    Dilated cardiomyopathy (DC) is the final common pathway of different pathogenetic processes and presents a significant prognostic heterogeneity, possibly related to its etiologic variety. The characterization and long-term prognosis of postmyocarditic dilated cardiomyopathy (PM-DC) remain unknown. This study assesses the clinical-instrumental evolution and long-term prognosis of a large cohort of patients with PM-DC. We analyzed 175 patients affected with DC consecutively enrolled from 1993 to 2008 with endomyocardial biopsy (EMB) data available. PM-DC was defined in the presence of borderline myocarditis at EMB or persistent left ventricular dysfunction 1 year after diagnosis of active myocarditis at EMB. Other patients were defined as affected by idiopathic dilated cardiomyopathy (IDC). Analysis of follow-up evaluations was performed at 24, 60, and 120 months. We found 72 PM-DC of 175 enrolled patients (41%). Compared with IDC, patients with PM-DC were more frequently females and less frequently presented a familial history of DC. No other baseline significant differences were found. During the long-term follow-up (median 154, first to third interquartile range 78 to 220 months), patients with PM-DC showed a trend toward slower disease progression. Globally, 18 patients with PM-DC (25%) versus 49 with IDC (48%) experienced death/heart transplantation (p = 0.045). The prognostic advantage for patients with PM-DC became significant beyond 40 months of follow-up. At multivariable time-dependent Cox analysis, PM-DC was confirmed to have a global independent protective role (hazard ratio 0.53, 95% confidence interval 0.28 to 0.97, p = 0.04). In conclusion, PM-DC is characterized by better long-term prognosis compared with IDC. An exhaustive etiologic characterization appears relevant in the prognostic assessment of DC.

  10. Treatment of colonic anastomotic strictures with 'through the scope' balloon dilators.

    PubMed Central

    Dinneen, M D; Motson, R W

    1991-01-01

    Stricture occurs in 1.2-4.2% of colonic anastomoses. Symptomatic strictures have previously been treated by resection and re-anastomosis and more recently by radiographically guided dilatation by a modified Seldinger technique. This paper describes the endoscopic balloon dilatation of five symptomatic cases and three asymptomatic cases. Eight patients underwent balloon dilatation of colonic anastomotic strictures. Four patients had no symptoms post dilatation and the strictures remained patient on follow-up endoscopy. All the remaining patients required re-dilatation at approximately 2 months. One of these patients underwent dilatation but remained symptomatic, the dilatation was repeated and a colonic perforation occurred at this time. Of the other three, two continue to be followed up, and are well and one patient died of disseminated malignancy. Balloon dilatation with 'through the scope' dilators is a simpler technique than radiologically guided dilatation. These early results suggest that endoscopic dilatation may avoid further surgery in some patients with anastomotic stricture. PMID:2041001

  11. Osmotic self-expanding dilation technology for treatment of sinusitis: the Vent-Os sinus dilation system.

    PubMed

    Catalano, Peter; Hester, Jerome; Mandrusov, Evgenia

    2015-01-01

    The Vent-Os Sinus Dilation System is an osmotically driven device that provides a means to access the sinus space and to dilate the maxillary sinus ostia and associated spaces in adults for diagnostic and therapeutic procedures. Unlike balloon dilation devices that use rapid, high-pressure inflation, this self-expanding device is designed to gently and gradually open the maxillary ostia. The procedure can be safely and easily completed in-office with minimal anesthetics and analgesics on board. Clinical results support excellent patency and safety outcomes with the use of this product in patients with chronic rhinosinusitis.

  12. High-dose cyclophosphamide and adriamycin with DTIC maintenance for metastatic soft tissue sarcomas.

    PubMed

    Clamon, G; Sinkey, C; Jochimsen, P

    1983-08-01

    Intensive chemotherapy with high-dose cyclophosphamide and adriamycin with DTIC maintenance was given to 12 patients with metastatic soft tissue sarcomas. A partial response rate of 25% was seen; this is no better than can be achieved with single-agent therapy. Because of substantial toxicity without improved efficacy, the trial of high dose therapy was halted.

  13. A randomized comparison of cyclophosphamide, DTIC with or without piperazinedione in metastatic malignant melanoma.

    PubMed

    Presant, C A; Bartolucci, A A; Balch, C; Troner, M

    1982-04-01

    One hundred and ninety-five patients with metastatic malignant melanoma were randomized to receive either cyclophosphamide 600 mg/m2 IV plus DTIC 600 mg/m2 IV day 1 (CD); or cyclophosphamide 400 mg/m2 IV, DTIC 400 mg/m2 IV, and piperazinedione 4 mg/m2 IV on day 1 (PCD). Therapy was repeated every 21 days. Patient groups were similar regarding pretreatment performance status, evaluability, and site of metastases. The overall response rate was low, 11% on CD and 12% on PCD. Paradoxically, patients with visceral disease responded at least as frequently as patients with skin and lymph node metastases only (12% and 6% respectively for CD, and 15% and 5% for PCD). Survival was identical on each treatment program, with medians of six months. The major dose-limiting toxicity was myelosuppression, which was similar on each treatment program. We conclude that the addition of piperazinedione to cyclophosphamide plus DTIC does not improve the response rate in patients with metastatic malignant melanoma. Both of the treatment programs (CD and PCD) utilizing one-day DTIC produced response rates slightly (but not meaningfully) lower than those previously obtained with cyclophosphamide plus five-day DTIC.

  14. Amelioration of cyclophosphamide induced myelosuppression and oxidative stress by cinnamic acid.

    PubMed

    Patra, Kartick; Bose, Samadrita; Sarkar, Shehnaz; Rakshit, Jyotirmoy; Jana, Samarjit; Mukherjee, Avik; Roy, Abhishek; Mandal, Deba Prasad; Bhattacharjee, Shamee

    2012-02-05

    Cinnamic acid (C9H8O2), is a major constituent of the oriental Ayurvedic plant Cinnamomum cassia (Family: Lauraceae). This phenolic acid has been reported to possess various pharmacological properties of which its antioxidant activity is a prime one. Therefore it is rational to hypothesize that it may ameliorate myelosuppression and oxidative stress induced by cyclophosphamide, a widely used chemotherapeutic agent. Commercial cyclophosphamide, Endoxan, was administered intraperitoneally to Swiss albino mice (50mg/kg) pretreated with 15, 30 and 60mg/kg doses of cinnamic acid orally at alternate days for 15days. Cinnamic acid pre-treatment was found to reduce cyclophosphamide induced hypocellularity in the bone marrow and spleen. This recovery was also reflected in the peripheral blood count. Amelioration of hypocellularity could be correlated with the modulation of cell cycle phase distribution. Cinnamic acid pre-treatment reduced bone marrow and hepatic oxidative stress as evident by lipid peroxidation and activity assays of antioxidant enzymes such as superoxide dismutase, catalase and glutathione-S-transferase. The present study indicates that cinnamic acid pretreatment has protective influence on the myelosuppression and oxidative stress induced by cyclophosphamide. This investigation is an attempt and is the first of its kind to establish cinnamic acid as an agent whose consumption provides protection to normal cells from the toxic effects of a widely used anti-cancer drug. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  15. Modulator effect of watercress against cyclophosphamide-induced oxidative stress in mice.

    PubMed

    Casanova, Natalia A; Simoniello, María Fernanda; López Nigro, Marcela Mabel; Carballo, Marta A

    2017-01-01

    Watercress (Nasturtium officinale, Cruciferae; W. Aiton) is a vegetable widely consumed in our country, with nutritional and potentially chemopreventive properties. Previous reports from our laboratory demonstrated the protective effect of watercress juice against DNA damage induced by cyclophosphamide in vivo. In this study, we evaluated the in vivo effect of cress plant on the oxidative stress in mice. Animals were treated by gavage with different doses of watercress juice (0.5 and 1g/kg body weight) for 15 consecutive days before intraperitoneal injection of cyclophosphamide (100 mg/kg body weight). After 24 h, mice were killed by cervical dislocation. The effect of watercress was investigated by assessing the following oxidative stress biomarkers: catalase activity, superoxide dismutase activity, lipid peroxidation, and glutathione balance. Intake of watercress prior to cyclophosphamide administration enhanced superoxide dismutase activity in erythrocytes with no effect on catalase activity. In bone marrow and liver tissues, watercress juice counteracted the effect of cyclophosphamide. Glutathione balance rose by watercress supplementation and lipid oxidation diminished in all matrixes when compared to the respective control groups. Our results support the role of watercress as a diet component with promising properties to be used as health promoter or protective agent against oxidative damage.

  16. Combination chemotherapy with cyclophosphamide, thalidomide and dexamethasone for patients with refractory, newly diagnosed or relapsed myeloma.

    PubMed

    Sidra, Gamal; Williams, Cathy D; Russell, Nigel H; Zaman, Sonya; Myers, Bethan; Byrne, Jennifer L

    2006-06-01

    We evaluated the combination of thalidomide, pulsed dexamethasone and weekly cyclophosphamide (CTD) for the treatment of patients with newly diagnosed, relapsed or VAD-refractory multiple myeloma. We found that this combination was highly effective in inducing responses in all treatment groups with an overall response rate of 83.8%. CTD was well tolerated and did not impair stem cell mobilization.

  17. Cyclophosphamide for rapid-onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation syndrome.

    PubMed

    Paz-Priel, Ido; Cooke, David W; Chen, Allen R

    2011-02-01

    Patients with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neural crest tumor syndrome have poor long-term outcomes. We report a patient who was treated successfully with high-dose cyclophosphamide immunoablation. This experience offers a novel therapeutic approach and an indirect insight into the underlying pathogenesis of this syndrome. Copyright © 2011 Mosby, Inc. All rights reserved.

  18. Cyclophosphamide for Rapid-Onset Obesity, Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation Syndrome

    PubMed Central

    Paz-Priel, Ido; Cooke, David W.; Chen, Allen R.

    2014-01-01

    Patients with rapid-onset obesity, hypothalamic dysfunction, hypoventilation, autonomic dysregulation, and neural crest tumor syndrome have poor long-term outcomes. We report a patient who was treated successfully with high-dose cyclophosphamide immunoablation. This experience offers a novel therapeutic approach and an indirect insight into the underlying pathogenesis of this syndrome. PMID:20727534

  19. PLasma half-life and urinary excretion of cyclophosphamide in children.

    PubMed

    Sladek, N E; Priest, J; Doeden, D; Mirocha, C J; Pathre, S; Krivit, W

    1980-01-01

    The plasma half-life and urinary excretion of cyclophosphamide were determined in 13 children who had various malignancies and/or who were being prepared for bone marrow transplantation. Disappearance from the plasma following iv infusion over a 1-2 hour period was first-order. Urinary excretion was maximal during the first 8 hours after administration and was essentially complete in 24 hours. The plasma half-life in children not receiving known inducers of hepatic microsomal mixed-function oxygenase activity or cyclophosphamide in the 3-week period prior to each determination ranged from 145 to 390 minutes. These values are lower than those ordinarily found in adult patients. The fraction of the total dose excreted in the urine as the parent compound ranged from 4% to 27%. Repeated administration of cyclophosphamide at approximately 30-60 day intervals did not appear to alter its plasma half-life but did appear to increase its urinary excretion. Daily administration of cyclophosphamide (approximately 50 mg/kg/day x 2 or 4) significantly decreased its plasma half-life and urinary excretion suggesting that it may reversibly induce its own metabolism.

  20. Ovarian toxicity of cyclophosphamide alone and in combination with ovarian irradiation in the rat

    SciTech Connect

    Jarrell, J.; Lai, E.V.; Barr, R.; McMahon, A.; Belbeck, L.; O'Connell, G.

    1987-05-01

    The effects of radiation and chemotherapy on gonadal function are relevant to the morbidity induced by such treatments. Cyclophosphamide given i.p. to rats on Day 30 of age delayed vaginal opening, prevented vaginal cyclicity, and caused a reduction in serum estradiol and progesterone. Antral follicular atresia increased in a dose-dependent fashion in response to cyclophosphamide (0 mg/kg, 53.5%; 1 mg/kg, 67.3%; 50 mg/kg, 65.7%; 100 mg/kg, 73.9%; 150 mg/kg, 92.2%). Despite such alterations in ovarian function, serum gonadotrophins did not rise. The concurrent administration of 0, 20, 30, 40, 50, and 60 Gy of radiation to the exteriorized ovaries in rats receiving 50 mg/kg cyclophosphamide induced widespread loss of primordial, preantral, and healthy antral follicles associated with reduction in serum progesterone and estradiol. Such irradiation induced dose-related increases in serum follicle-stimulating hormone and luteinizing hormone. Parenteral cyclophosphamide and local irradiation appear to induce ovarian toxicity by different mechanisms.

  1. Teratogenic effect of cyclophosphamide and the preventive effects of pyrithinoldehydrochloride monohydrate.

    PubMed

    Reznik, G; Hecht, J

    1979-01-01

    Teratogenic effects were induced in outbred Swiss mice by treatment of 8-week-old pregnant females with one of five different doses (5, 10, 20, 30, 40 mg/kg b.w.) of cyclophosphamide. Because the 11.5th day of pregnancy was the most effective day to induce malformations in mice, animals treated on this day were used for prophylactic studies. A preliminary study had shown that 30 mg/kg b.w. cyclophosphamide was the ideal dose to produce 100% malformations on the 11.5th day of pregnancy. From day 7.5 to 9.5 all fetuses were resorbed with this dosage. Most malformations were induced with 20, 30 or 40 mg/kg b.w., whereas 5 and 10 mg/kg b.w. caused no alterations of the fetuses. The frequency distributions of the various induced malformations and combined malformations of a positive control group (30 mg/kg b.w. of cyclophosphamide on the 11.5th day of pregnancy) were compared to those found in groups receiving different doses of the prophylactic. This substance reduced significantly the rate of malformations; 1/160 LD50 pyrithinoldehydrochloride monohydrate administered 4 times prior to cyclophosphamide treatment was the most effective. However, a complete prevention of teratogenic effects could not be accomplished.

  2. Pharmacodynamic Interaction of Green Tea Extract with Hydrochlorothiazide against Cyclophosphamide-Induced Myocardial Damage.

    PubMed

    Chakraborty, Manodeep; Kamath, Jagadish Vasudev; Bhattacharjee, Ananya

    2014-05-01

    Treatment of ischemic hypertensive patients with hydrochlorothiazide can precipitate cardiac arrhythmias. Green tea by virtue of its antioxidant potential is responsible for cardio-protective activity. The present study was undertaken to evaluate the pharmacodynamic interaction of green tea extract with hydrochlorothiazide against cyclophosphamide-induced myocardial toxicity. Rats were treated with high (500 mg/kg, p.o.) and low (100 mg/kg, p.o.) dose of green tea extract in alone and interactive groups for 10 days. Standard, high, and low dose of interactive groups received hydrochlorothiazide (10 mg/kg, p.o.) for last 7 days. Apart from normal control, all other groups were subjected to cyclophosphamide (200 mg/kg, i.p.) toxicity on day first and the effects of different treatments were evaluated by changes in electrocardiographic parameters, serum biomarkers, and tissue antioxidant levels. Apart from that, lipid profile and histological studies were also carried out. Compared to cyclophosphamide control group, both high and low dose of green tea exhibited significant decrease in serum biomarkers and increase in tissue antioxidant levels. Green tea treatment was also responsible for significant improvement in echocardiography (ECG) parameter, lipid profile, and histological score. Incorporation of high and low dose of green tea with hydrochlorothiazide-exhibited significant protection compared to hydrochlorothiazide-alone-treated group. The present findings clearly suggested that green tea extract dose dependently reduces cyclophosphamide-induced myocardial toxicity. Green tea when combined with hydrochlorothiazide can reduce the associated side effects and exhibits myocardial protection.

  3. Treatment of microperforate hymen with serial dilation: a novel approach.

    PubMed

    Segal, Thalia R; Fried, Wendy B; Krim, Eileen Y; Parikh, Deep; Rosenfeld, David L

    2015-04-01

    Microperforate and imperforate hymens are one of the most common causes of vaginal outflow obstruction in the adolescent population. To date, these hymen anomalies are traditionally treated by hymenectomy with a cruciate excision. We report 2 cases of adolescent women with a microperforate hymen who were successfully and minimally invasively treated with progressive dilation with Hegar cervical dilators until a number 23 dilator was reached under anesthesia in the OR. Minimally invasive treatment of microperforate hymen with the use of progressive cervical dilators may be an alternative technique to the traditional excisional hymenectomy. Our patients reported satisfaction and minimal postoperative pain or scarring at 2 weeks and 6 months after the procedure. This technique can be an additional option for all women, especially those with cultural beliefs in virginity. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  4. Dilated hearts at high altitude: words from on high.

    PubMed

    Lankford, Harvey V; Swenson, Erik R

    2014-12-01

    From the time of the turn of the twentieth century, dilated hearts and presumed cardiac fatigue in expeditionary climbers and scientists have been the subject of much commentary in the medical and mountaineering literature. Although largely attributed by most, but not all, to left heart strain, the description of dilated hearts in these accounts is clearly that of right heart dilation as a consequence of high and sustained hypoxic pulmonary vasoconstriction with hypertensive remodeling. This essay will feature quotations from the writings of high altitude pioneers about dilated, strained, or enlarged hearts. It will give some brief physiology of the right side of the heart as background, but will focus on the words of mountaineers and mountaineering physicians as color commentary.

  5. Perceptual and not physical eye contact elicits pupillary dilation.

    PubMed

    Honma, Motoyasu; Tanaka, Yasuto; Osada, Yoshihisa; Kuriyama, Kenichi

    2012-01-01

    Eye contact is important to share communication during social interactions. However, how accurately humans can perceive the gaze direction of others toward themselves and whether pupils dilate when humans consciously or unconsciously perceive own eyes are looked by others remain unclear. In this study, we examined the relationship between the explicit perception of looking into each other's eyes and the implicit physiological response of pupillary dilation by using an original face-to-face method. We found that humans do not correctly detect the gaze direction of others. Furthermore, one's pupils dilated when one gazed at others' eyes. Awareness of others' gaze on one's eyes, rather than the actual focusing of other's gaze on one's eyes, enhanced pupillary dilation. Therefore, physiological responses are caused not when people actually look into each other's gaze, but when the consciousness of other's gaze is activated, which suggests that eye contact often involves one-way communication.

  6. Human eyes with dilated pupils induce pupillary contagion in infants.

    PubMed

    Fawcett, Christine; Arslan, Melda; Falck-Ytter, Terje; Roeyers, Herbert; Gredebäck, Gustaf

    2017-08-29

    Being sensitive and responsive to others' internal states is critical for social life. One reliable cue to what others might be feeling is pupil dilation because it is linked to increases in arousal. When adults view an individual with dilated pupils, their pupils dilate in response, suggesting not only sensitivity to pupil size, but a corresponding response as well. However, little is known about the origins or mechanism underlying this phenomenon of pupillary contagion. Here we show that 4- to 6-month-old infants show pupillary contagion when viewing photographs of eyes with varying pupil sizes: their pupils dilate in response to others' large, but not small or medium pupils. The results suggest that pupillary contagion is likely driven by a transfer of arousal and that it is present very early in life in human infants, supporting the view that it could be an adaptation fundamental for social and emotional development.

  7. Dilated cardiomyopathy: a preventable presentation of DiGeorge Syndrome.

    PubMed

    Jamieson, A; Smith, C J

    2015-01-01

    Patients with cardiac failure require careful evaluation to determine the precise nature of the cause of their illness. Genetic causes of dilated cardiomyopathy are well known but inherited conditions may lead to unexpected consequences through intermediate mechanisms not readily recognised as a feature of the inherited disorder. We describe a case of dilated cardiomyopathy resulting from prolonged hypocalcaemia due to previously undiagnosed hypoparathyroidism resulting from DiGeorge Syndrome and describe the features of this case and the treatment of hypoparathyroidism.

  8. The effects of Vitamin C on sperm quality parameters in laboratory rats following long-term exposure to cyclophosphamide

    PubMed Central

    Shabanian, Sheida; Farahbod, Farnoosh; Rafieian, Mahmoud; Ganji, Forouzan; Adib, Afshin

    2017-01-01

    Cyclophosphamide is a widely used medication and can cause oxidative stress. This study was conducted to investigate the effects of Vitamin C on reproductive organs' weight and the quality of sperm parameters in laboratory rats. In this experimental study, 40 rats were randomly assigned into five groups of eight each. Distilled water (DW) group received only food and water, Group 2 was administered with drug solvent (DW) by gavage, Group 3 intraperitoneally administered with 1.6 mg/kg cyclophosphamide, Group 4 gavaged Vitamin C at 0.88 mg/kg, and Group 5 administered with effective doses of Vitamin C and cyclophosphamide by gavage with 1-h intervals. Sperm parameters of the samples were taken from distal epididymis and tissues were studied, and the data were analyzed by SPSS version 22. The lowest weight of testicles and epididymis was seen in cyclophosphamide-exposed rats and the highest weight of testicles and epididymis in Vitamin C-exposed rats (P < 0.05). The highest motility, progression, viability, and count of sperm were seen in the Vitamin C-treated group and the lowest in the cyclophosphamide-exposed group. The highest proportion of sperm anomalies was seen in the cyclophosphamide-exposed group. Vitamin C, as an antioxidant, can be effective on some of the sperm parameters and can reduce cyclophosphamide-induced complications in animal model. PMID:28516060

  9. Urinary bladder cancer in Wegener's granulomatosis: risks and relation to cyclophosphamide

    PubMed Central

    Knight, A; Askling, J; Granath, F; Sparen, P; Ekbom, A

    2004-01-01

    Objective: To assess and characterise the risk of bladder cancer, and its relation to cyclophosphamide, in patients with Wegener's granulomatosis. Methods: In the population based, nationwide Swedish Inpatient Register a cohort of 1065 patients with Wegener's granulomatosis, 1969–95, was identified. Through linkage with the Swedish Cancer Register, all subjects in this cohort diagnosed with bladder cancer were identified. Nested within the cohort, a matched case-control study was performed to estimate the association between cyclophosphamide and bladder cancer using odds ratios (ORs) as relative risk. In the cohort the cumulative risk of bladder cancer after Wegener's granulomatosis, and the relative prevalence of a history of bladder cancer at the time of diagnosis of Wegener's granulomatosis, were also estimated. Results: The median cumulative doses of cyclophosphamide among cases (n = 11) and controls (n = 25) were 113 g and 25 g, respectively. The risk of bladder cancer doubled for every 10 g increment in cyclophosphamide (OR = 2.0, 95% confidence interval (CI) 0.8 to 4.9). Treatment duration longer than 1 year was associated with an eightfold increased risk (OR = 7.7, 95% CI 0.9 to 69). The absolute risk for bladder cancer in the cohort reached 10% 16 years after diagnosis of Wegener's granulomatosis, and a history of bladder cancer was (non-significantly) twice as common as expected at the time of diagnosis of Wegener's granulomatosis. Conclusion: The results indicate a dose-response relationship between cyclophosphamide and the risk of bladder cancer, high cumulative risks in the entire cohort, and also the possibility of risk factors operating even before Wegener's granulomatosis. PMID:15130900

  10. Multicenter study of environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in 48 Canadian hospitals.

    PubMed

    Poupeau, Céline; Tanguay, Cynthia; Caron, Nicolas J; Bussières, Jean-François

    2016-10-31

    Oncology workers are occupationally exposed to antineoplastic drugs. This exposure can induce adverse health effects. In order to reduce their exposure, contamination on surfaces should be kept as low as possible. To monitor environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in oncology pharmacy and patient care areas in Canadian hospitals. To describe the impact of some factors that may limit contamination. This is a descriptive study. Twelve standardized sites were sampled in each participating center (six in the pharmacy and six in patient care areas). Samples were analyzed for the presence of cyclophosphamide, ifosfamide, and methotrexate by ultra-performance liquid chromatography tandem mass spectrometry technology. Descriptive statistical analyses were done and results were compared with a Kolmogorov-Smirnov test for independent samples. In 2015, 48 hospitals participated in this study (48/202, 24%). Overall, 34% (181/525) of the samples were positive for cyclophosphamide, 8% (41/525) for ifosfamide, and 6% (31/525) for methotrexate. The 75th percentile value of cyclophosphamide surface concentration was 6.9 pg/cm(2). For ifosfamide and methotrexate, they were lower than the limit of detection. Centers who prepared more antineoplastic drugs per year and centers who used more cyclophosphamide per year showed significantly higher surface contamination (p < 0.0001). Over the years, we observed a reduction in surface contamination. In comparison with other multicenter studies that were conducted in Canada, the concentration of antineoplastic drugs measured on surfaces is decreasing. Regular environmental monitoring is a good practice in order to maintain contamination as low as reasonably achievable. © The Author(s) 2016.

  11. Clinical and echocardiographic determinants in bicuspid aortic dilatation

    PubMed Central

    Peeters, Frederique E.C.M.; Van der Linden, Noreen; Thomassen, Alissa L.L.; Crijns, Harry J.G.M.; Meex, Steven J.R.; Kietselaer, Bas L.J.H.

    2016-01-01

    Abstract Bicuspid aortic valve (BAV) disease is associated with aortic dilatation. Timing of follow-up and surgery is challenging. Hence, there is an unmet clinical need for additional risk stratification. It is unclear whether valve morphology is associated with dilatation rates. Therefore, the objective of this study was to examine the association between clinical and echocardiographic determinants (including valve morphology) and aortic dimension and the progression rate of dilatation. Aortic dimensions were assessed on serial echocardiographic images between 1999 and 2014 in a population of 392 patients with BAVs in a tertiary care center in the Netherlands. Analyses using mixed linear models were performed. Mean age of participants was 48 ± 17 years and 69% were male. BAV morphology was associated with aortic dimensions, as well as age, sex, BSA, and valvular dysfunction. Tubular ascending aorta, sinus of Valsalva, and sinotubular junction showed a dilatation rate of 0.32, 0.18, and 0.06 mm/year, respectively. Dilatation rate was not associated with valve morphology. In the present study, there is no association between BAV morphology and aortic dilatation rates. Therefore, morphology is of limited use in prediction of aortic growth. Discovering fast progressors remains challenging. PMID:28033264

  12. Clusters, deformation, and dilation: Diagnostics for material accumulation regions

    NASA Astrophysics Data System (ADS)

    Huntley, Helga S.; Lipphardt, B. L.; Jacobs, Gregg; Kirwan, A. D.

    2015-10-01

    Clusters of material at the ocean surface have been frequently observed. Such accumulations of material play an important role in a variety of applications, from biology to pollution mitigation. Identifying where clusters will form can aid in locating, for example, hotspots of biological activity or regions of high pollutant concentration. Here cluster strength is introduced as a new metric for defining clusters when all particle positions are known. To diagnose regions likely to contain clusters without the need to integrate millions of particle trajectories, we propose to use dilation, which quantifies area changes of Lagrangian patches. Material deformation is decomposed into dilation and area-preserving stretch processes to refine previous approaches based on finite-time Lyapunov exponents (FTLE) by splitting the FTLE into fundamental kinematic properties. The concepts are developed theoretically and illustrated in the context of a state-of-the-art data-assimilating predictive ocean model of the Gulf of Mexico. Regions of dilation less than one are shown to be much more likely (6 times more likely in the given example) to be visited by particles than those of dilation greater than one. While the relationship is nonlinear, dilation and cluster strength exhibit a fairly good correlation. In contrast, both stretch and Eulerian divergence are found to be uncorrelated with cluster strength. Thus, dilation maps can be used as guides for identifying cluster locations, while saving some of the computational cost of trajectory integrations.

  13. Congenital duodenal web: successful management with endoscopic dilatation

    PubMed Central

    Poddar, Ujjal; Jain, Vikas; Yachha, Surender Kumar; Srivastava, Anshu

    2016-01-01

    Background and study aims: Congenital duodenal web (CDW) is an uncommon cause of duodenal obstruction and endoscopic balloon dilatation has been reported in just eight pediatric cases to date. Here we are reporting three cases of CDW managed successfully with balloon dilatation. Cases and methods: In 2014 we diagnosed three cases of CDW on the basis of typical radiological and endoscopic findings. Endoscopic balloon dilatation was done under conscious sedation with a through-the-scope controlled radial expansion (CRE) balloon. Results: All three children presented late (median age 8 [range 2 – 9] years) with bilious vomiting, upper abdominal distension, and failure to thrive. One of them had associated Down syndrome and another had horseshoe kidney. In all cases, CDW was observed in the second part of the duodenum beyond the ampulla, causing partial duodenal obstruction. After repeated endoscopic dilatation (2 – 4 sessions), all three patients became asymptomatic. None of the patients experienced complications after balloon dilatation. Conclusions: Duodenal diaphragm should be suspected in patients with abdominal distension with bilious vomiting, even in relatively older children. Endoscopic balloon dilatation is a simple and effective method of treating this condition. PMID:27004237

  14. High Dose Cyclophosphamide without Stem Cell Rescue in 207 Patients with Aplastic anemia and other Autoimmune Diseases

    PubMed Central

    DeZern, Amy E.; Petri, Michelle; Drachman, Daniel B.; Kerr, Doug; Hammond, Edward R.; Kowalski, Jeanne; Tsai, Hua-Ling; Loeb, David M.; Anhalt, Grant; Wigley, Fredrick; Jones, Richard J.; Brodsky, Robert A.

    2011-01-01

    High-dose cyclophosphamide has long been used an anticancer agent, a conditioning regimen for hematopoietic stem cell transplantation and as potent immunosuppressive agent in autoimmune diseases including aplastic anemia. High-dose cyclophosphamide is highly toxic to lymphocytes but spares hematopoietic stem cells because of their abundant levels of aldehyde dehydrogenase, the major mechanism of cyclophosphamide inactivation. High dose cyclophosphamide therapy induces durable remissions in most patients with acquired aplastic anemia. Moreover, high-dose cyclophosphamide without hematopoietic stem cell rescue has shown activity in a variety of other severe autoimmune diseases. Here we review the history of cyclophosphamide as is applies to aplastic anemia (AA) and other autoimmune diseases. Included here are the historical data from early patients treated for AA as well as an observational retrospective study in a single tertiary care hospital. This latter component was designed to assess the safety and efficacy of high-dose cyclophosphamide therapy without stem cell rescue in patients with refractory autoimmune diseases. We analyzed fully the 140 patients with severe, progressive autoimmune diseases treated. All patients discussed here received cyclophosphamide, 50 mg/kg per day for 4 consecutive days. Response, relapse and overall survival were measured. Response was defined as a decrease in disease activity in conjunction with a decrease or elimination of immune modulating drugs. Relapse was defined as worsening disease activity and/or a requirement of an increase in dose of, or administration of new, immunosuppressive medications. Hematologic recovery occurred in all patients. The overall response rate of the was 95%, and 44% of those patients remain progression-free with a median follow up time of 36 (range 1–120) months for the 140 patients analyzed together. The overall actuarial and event free survival across all diseases at 60 months is 90.7% and 20

  15. Spectral dilation of L(B,H)-valued measures and its application to stationary dilation for Banach space valued processes

    NASA Technical Reports Server (NTRS)

    Miamee, A. G.

    1989-01-01

    Let B be a Banach space and H and K to Hilbert spaces. The spectral dilation of L(B,H)-valued measures is studied and it is shown that the recent results of Makagon and Salehi (1986) and Rosenberg (1982) on the dilation of L(K,H)-valued measures can be extended to hold for the general Banach space setting of L(B,H)-valued measures. These L(B,H)-valued measures are closely connected to the Banach space valued processes. This connection is recalled and as application of spectral dilation of L(B,H)-valued measures the well known stationary dilation results for scalar valued processes is extended to the case of Banach space valued processes.

  16. Spectral dilation of L(B,H)-valued measures and its application to stationary dilation for Banach space valued processes

    NASA Technical Reports Server (NTRS)

    Miamee, A. G.

    1988-01-01

    Let B be a Banach space and H and K two Hilbert spaces. The spectral dilation of L(B,H)-valued measures is studied and it is shown that the recent results of Makagon and Salehi (1986) and Rosenberg (1982) on the dilation of L(K,H)-valued measures can be extended to hold for the general Banach space setting of L(B,H)-valued measures. These L(B,H)-valued measures are closely connected to the Banach space valued processes. This connection is recalled and as application of spectral dilation of L(B,H)-valued measures the well known stationary dilation results for scalar valued processes is extended to the case of Banach space valued processes.

  17. Hyperoxia, but not thoracic X-irradiation, potentiates bleomycin- and cyclophosphamide-induced lung damage in mice

    SciTech Connect

    Hakkinen, P.J.; Whiteley, J.W.; Witschi, H.R.

    1982-08-01

    The intraperitoneal administration of cyclophosphamide or bleomycin to BALB/c mice resulted in lung cell damage followed by cellular proliferation, which was quantitated by measuring the increase in thymidine incorporation into pulmonary DNA. We have previously shown that administration of the antioxidant butylated hydroxytoluene produces lung damage that can be potentiated by both hyperoxia and thoracic X-irradiation. In the present study we show that hyperoxic exposure also potentiates bleomycin- and cyclophosphamide-induced acute lung damage. However, thoracic X-irradiation does not potentiate bleomycin- and cyclophosphamide-induced lung toxicity.

  18. Randomized study of whole-abdomen irradiation versus pelvic irradiation plus cyclophosphamide in treatment of early ovarian cancer

    SciTech Connect

    Sell, A.; Bertelsen, K.; Andersen, J.E.; Stroyer, I. )

    1990-06-01

    From 1 September 1981 to 1 January 1987, 118 patients with FIGO Stage IB, IC, IIA, IIB, and IIC epithelial ovarian cancer were randomized to abdominal irradiation or pelvic irradiation + cyclophosphamide. There was no difference between the regimens with respect to recurrence-free survival (55%) and 4-year overall survival (63%). At routine second-look laparotomy, 16% of patients without clinical detectable tumor showed recurrence. Twenty-five percent of the patients treated with pelvic irradiation + cyclophosphamide had hemorrhagic cystitis, probably caused by radiation damage and cyclophosphamide cystitis. Eight percent had late gastrointestinal symptoms requiring surgery.

  19. Outcomes of esophageal dilation in eosinophilic esophagitis: Safety, efficacy, and persistence of the fibrostenotic phenotype

    PubMed Central

    Runge, Thomas M.; Eluri, Swathi; Cotton, Cary; Burk, Caitlin M.; Woosley, John T.; Shaheen, Nicholas J.; Dellon, Evan S.

    2016-01-01

    Objectives Esophageal dilation is commonly performed in eosinophilic esophagitis (EoE), but there are few long-term data. The aims of this study were to assess the safety and long-term efficacy of esophageal dilation in a large cohort of EoE cases and determine the frequency and predictors of requiring multiple dilations. Methods We conducted a retrospective cohort study in the University of North Carolina EoE clinicopathological database from 2002-2014. Included subjects met consensus diagnostic criteria for EoE. Clinical, endoscopic, and histologic features were extracted, as were dilation characteristics (dilator type, change in esophageal caliber, total number of dilations) and complications. Patients with EoE who had undergone dilation were compared to those who did not and also stratified by whether they required single or multiple dilations. Results Of 509 EoE patients, 164 were dilated a total of 486 times. Those who underwent dilation had a longer duration of symptoms prior to diagnosis (11.1 vs. 5.4 yrs, p<0.001). 95 patients (58%) required >1 dilation (417 dilations total, mean of 4.4 ± 4.3 per patient). The only predictor of requiring multiple dilations was a smaller baseline esophageal diameter. Dilation was tolerated well, with no major bleeds, perforations, or deaths. The overall complication rate was 5%, primarily due to post-procedural pain. Of 164 individuals dilated, a majority (58%, or 95/164) required a second dilation. Of these individuals, 75% required dilation within 1 year. Conclusions Dilation in EoE is well-tolerated, with a very low risk of serious complications. Patients with long-standing symptoms prior to diagnosis are likely to require dilation. More than half of those dilated will require multiple dilations, often needing a second procedure within one year. These findings can be used to counsel patients with fibrostenotic complications of EoE. PMID:26753894

  20. Dilation Behavior of Thermal Spray Coatings

    NASA Astrophysics Data System (ADS)

    Bejarano Lopez, Miryan Lorena

    Thermal Spray (TS) is a very versatile manufacturing process to deposit thick coatings on a variety of substrates. Coatings are used in protective (i.e. wear, chemical attack, high temperature, etc.) and functional (i.e. sensors) applications. TS coatings have a unique lamellar microstructure as a result of the overlapping of millions of molten and partially-molten particles. During processing, high deformation by impact, high temperature, and rapid solidification lead to a complex hierarchical material system that contains a high amount of microstructural defects. The presence of defects in the microstructure contribute to differences in property values in comparison to bulk materials. Thermal stresses and residual strains arise from processing, thermal gradients and thermal exposure. Evaluation of thermal properties, in this case, the coefficient of thermal expansion (CTE) is of vital importance to enhance coating performance. In this dissertation, expansion measurements of various metals, alloys, ceramics, and cermet coatings; were carried out using various techniques (push rod dilatometry, x-ray diffraction XRD, digital image correlation DIC, and curvature method) to determine the dilation behavior at the atomic, micro- and macro-scale levels. The main results were. 1) Mathematical models (Turner and Kerner) used for composite materials, successfully predicted the CTE property of a TS coating where the primary phase is the coating material and the secondary phases can be oxides, precipitates, etc. (formed as a byproduct of the spraying process). CTE was found not to be affected by porosity. 2) Despite the anisotropic behavior characteristic of TS coatings, the experimental results shown that CTE results to be reasonable isotropic within the scope of this study. 3) The curvature method was found to be an alternative technique to obtain the CTE, as well as the Young's modulus of coating in a bi-material strip, with good approximation. 4) An anomalous expansion

  1. Aortic Valve Adaptation to Aortic Root Dilatation

    PubMed Central

    Kim, Dae-Hee; Handschumacher, Mark D.; Levine, Robert A.; Sun, Byung Joo; Jang, Jeong Yoon; Yang, Dong Hyun; Kang, Joon-Won; Song, Jong-Min; Kang, Duk-Hyun; Lim, Tae-Hwan; Song, Jae-Kwan

    2015-01-01

    Background The 3-dimensional relationship between aortic root and cusp is essential to understand the mechanism of aortic regurgitation (AR) because of aortic root dilatation (ARD). We sought to test the hypothesis that the stretched cusps in ARD enlarge to compensate for ARD. Methods and Results Computed tomography imaged 92 patients (57 with ARD, 29 with moderate to severe AR, 28 without significant AR) and 35 normal controls. Specialized 3-dimensional software measured individual cusp surface areas relative to maximal mid-sinus cross-sectional area and minimal 3-dimensional annular area, coaptation area fraction, and asymmetry of sinus volumes and intercommissural distances. Total open cusp surface area increased (P<0.001) from 7.6±1.4 cm2/m2 in normals to 12.9±2.2 cm2/m2 in AR-negative and 15.2±3.3 cm2/m2 in AR-positive patients. However, the ratio of closed cusp surface area to maximal mid-sinus area, reflecting cusp adaptation, decreased from normals to AR-negative to AR-positive patients (1.38±0.20, 1.15±0.15, 0.88±0.15; P<0.001), creating the lowest coaptation area fraction. Cusp distensibility (closed diastolic versus open area) decreased from 20% in controls and AR-negative patients to 5% in AR-positive patients (P<0.001). Multivariate determinants of AR and coaptation area fraction reflected both sinus size and cusp-to-annular adaptation. ARD was also progressively asymmetrical with root size, and individual cusp surface areas failed to match this asymmetry. Conclusions Aortic cusp enlargement occurs in ARD, but cusp adaptation and distensibility become limited in prominent, asymmetrical ARD, leading to AR. Optimal AR repair tailored to individual patient anatomy can benefit from appreciating valve adaptation and 3-dimensional relationships; understanding cusp adaptation mechanisms may ultimately provide therapeutic opportunities to improve such compensation. PMID:25051951

  2. Treatment of Ureterointestinal Anastomotic Strictures by Diathermal or Cryoplastic Dilatation

    SciTech Connect

    Orsi, Franco; Penco, Silvia Matei, Victor; Bonomo, Guido; Vigna, Paolo Della; Monfardini, Lorenzo; Cobelli, Ottavio De

    2007-09-15

    Background. Ureterointestinal anastomotic strictures (UAS) complicate 10-15% of surgeries for urinary diversion and are the main cause of deterioration in renal function. Treatments are surgical revision, management with autostatic stent, balloon dilatation, endoscopic incision, and percutaneous transrenal diathermy (Acucise). A new option is cryoplastic dilatation (Polar-Cath). Purpose. To assess the feasibility, complications, and preliminary results of UAS treatment using the Acucise and Polar-Cath systems. Methods. Nineteen UAS, diagnosed by ultrasonography or computed tomography and sequential renal scintigraphy, occurred in 15 cancer patients after radical cystectomy and urinary diversion. Fifteen were managed with balloon diathermy and 4 by balloon cryoplasty in a three-stage procedure-percutaneous nephrostomy, diathermal or cryoplastic dilatation, and transnephrostomic control with nephrostomy removal-each separated by 15 days. All patients gave written informed consent. Results. Dilatations were successful in all cases. The procedure is simple and rapid (about 45 min) under fluoroscopic control and sedation. Procedural complications occurred in 1 (5%) patient with UAS after Wallace II uretero-ileocutaneostomy: a common iliac artery lesion was induced by diathermal dilatation, evident subsequently, and required surgical repair. Patency with balloon diathermy was good, with two restenoses developing over 12 months (range 1-22) of follow-up. With balloon cryoplastic dilatation, one restenosis developed in the short term; follow-up is too brief to assess the long-term efficacy. Conclusion. Our short-term results with diathermal and cryoplastic dilatation to resolve UAS are good. If supported by longer follow-up, the techniques may be considered as first-choice approaches to UAS. Surgery should be reserved for cases in which this minimally invasive technique fails.

  3. [Pneumatic dilatation of achalasia: local experience in treating 41 patients].

    PubMed

    Honein, Khalil; Slim, Rita; Yaghi, César; Kheir, Bahaa; Bou Jaoudé, Joseph; Sayegh, Raymond

    2007-01-01

    L'achalasia is the best known primary motor disorder of the esophagus in which the lower esophageal sphincter (LES) has abnormally high resting pressure and incomplete relaxation with swallowing. Pneumatic dilatation (PD) remains the first choice of treatment. Our aim was to report, in a retrospective way, our experience in treating with pneumatic dilatation 41 achalasia patients admitted to the gastroenterology unit at Hôtel-Dieu de France (HDF) hospital between 1994 and 2004. A total of 46 dilatations were performed in 41 patients with achalasia [20 males and 21 females, the mean age was 46.8 years (range, 15-90)]. All patients underwent an initial dilatation by inflating a 35 mm balloon to 7 psi three times successively under fluoroscopic control. The need for subsequent dilatation with the same technique or for surgical treatment was based on symptom assessment. The mean follow-up period was 36.7 months (3 mo-7 years). Among the patients whose follow-up information was available, a satisfactory result was achieved in 29 patients (80.5%) after only one or two sessions of pneumatic dilatation. Esophageal perforation as a short-term complication was observed in one patient (2.17%). Seven patients were referred for surgery (one for esophageal perforation and six for persistent or recurrent symptoms). In conclusion, performing balloon dilatation under fluoroscopic observation is simple, safe and efficacious for treating patients with achalasia. Referral to repeated PD or to surgical myotomy should be discussed in case of no response to a first session of PD.

  4. Fixed and dilated: the history of a classic pupil abnormality.

    PubMed

    Koehler, Peter J; Wijdicks, Eelco F M

    2015-02-01

    The aim of this study was to investigate the development of ideas about the nature and mechanism of the fixed dilated pupil, paying particular attention to experimental conditions and clinical observations in the 19th century. Starting from Kocher's standard review in 1901, the authors studied German, English, and French texts for historical information. Medical and neurological textbooks from the 19th and 20th centuries were reviewed to investigate when and how this information percolated through neurological and neurosurgical practices. Cooper experimented with intracranial pressure (ICP) in a dog in the 1830s, but did not mention the pupils. He described dilated pupils in clinical cases without referring to the effect of light. Bright demonstrated to have some knowledge of the pupil sign (clinical observations). Realizing the unreliability of the pupil sign, Hutchinson in 1867-1868 tried to reason in which cases trepanation would be advisable. Von Leyden's 1866 animal experiments, in which he increased CSF volume by injecting protein solutions intracranially, was the first observation in which the association between fixed dilated pupils and increased ICP was established. Along with bradycardia and motor and respiratory effects, he noticed wide pupils were usually present in a comatose state. Asymmetrical dilation could not always be attributed to increased ICP, but to an oculomotor nerve lesion. Pagenstecher in 1871 extended knowledge by meticulously studying consecutive pupil phenomena with increasing pressure. In 1880, von Bergmann emphasized the significance of the ipsilateral dilation in experiments as well as in clinical cases. He distinguished the extent of pressure increase and its duration. Probably confusing irritation (epileptic head turning to the other side with pupil dilation) and lesion effects, he suggested a cortical area responsible for oculomotor phenomena, indicating what is now known as the frontal eye field. Naunyn and Schreiber (1881

  5. Clinical Effect of Endoscopic Pneumatic Dilation for Achalasia

    PubMed Central

    Cheng, Peng; Shi, Hai; Zhang, Yanjie; Zhou, Huabang; Dong, Jinhua; Cai, Yiting; Hu, Xing; Dai, Qiang; Yang, Wenyan

    2015-01-01

    Abstract Although pneumatic dilation is an accepted method for the treatment of achalasia, this therapy has high recurrence and complication rates, and prolonged follow-up studies on the parameters associated with various outcomes are rare. In this prospective 10-year follow-up study, a satisfactory therapeutic effect was achieved without serious complications. We report the therapeutic experience with pneumatic dilation, having aimed to evaluate the long-term clinical safety and efficacy of pneumatic dilation. In total, 35 consecutive patients with idiopathic achalasia who underwent pneumatic dilation were followed up at regular intervals in person or by a phone interview over a 10-year period. The mean duration of the follow-up was 43.03 ± 26.34 months (range 6–120 months). Remission was assessed by the dysphagia classification and symptom scores. Patients’ clinical symptom scores were calculated before and at 6 to 36 months, 37 to 60 months, and >60 months after therapy. The influence of the patients’ age, gender, and disease duration on the therapeutic effect was analyzed. The success rate of the operation was 97.2% (35/36), without massive hemorrhaging, perforation or other serious complications. Dysphagia after the therapy was significantly eased (P < 0.01). In total, 35 patients have been followed up for 6 to 36 months after therapy, 21 cases for 37 to 60 months, and 5 cases for >60 months, and the patients’ symptom scores separately decreased significantly compared with the pretherapy scores (P < 0.01). For these patients, the 6 to 36 months remission rate was 85.7% (30/35), the 37 to 60 months rate was 61.9% (13/21), and the >60 months rate was 40% (2/5). The dilation effect had no relationship to the patient's age, gender, and disease duration (P > 0.05). The patients in 30 cases (85.7%) were successfully treated with a single dilation, in 4 cases (11.4%) with 2 dilations, and in 1 case (2.9%) with 3 dilations

  6. Pneumatic dilation versus laparoscopic Heller's myotomy for idiopathic achalasia.

    PubMed

    Boeckxstaens, Guy E; Annese, Vito; des Varannes, Stanislas Bruley; Chaussade, Stanislas; Costantini, Mario; Cuttitta, Antonello; Elizalde, J Ignasi; Fumagalli, Uberto; Gaudric, Marianne; Rohof, Wout O; Smout, André J; Tack, Jan; Zwinderman, Aeilko H; Zaninotto, Giovanni; Busch, Olivier R

    2011-05-12

    Many experts consider laparoscopic Heller's myotomy (LHM) to be superior to pneumatic dilation for the treatment of achalasia, and LHM is increasingly considered to be the treatment of choice for this disorder. We randomly assigned patients with newly diagnosed achalasia to pneumatic dilation or LHM with Dor's fundoplication. Symptoms, including weight loss, dysphagia, retrosternal pain, and regurgitation, were assessed with the use of the Eckardt score (which ranges from 0 to 12, with higher scores indicating more pronounced symptoms). The primary outcome was therapeutic success (a drop in the Eckardt score to ≤3) at the yearly follow-up assessment. The secondary outcomes included the need for retreatment, pressure at the lower esophageal sphincter, esophageal emptying on a timed barium esophagogram, quality of life, and the rate of complications. A total of 201 patients were randomly assigned to pneumatic dilation (95 patients) or LHM (106). The mean follow-up time was 43 months (95% confidence interval [CI], 40 to 47). In an intention-to-treat analysis, there was no significant difference between the two groups in the primary outcome; the rate of therapeutic success with pneumatic dilation was 90% after 1 year of follow-up and 86% after 2 years, as compared with a rate with LHM of 93% after 1 year and 90% after 2 years (P=0.46). After 2 years of follow-up, there was no significant between-group difference in the pressure at the lower esophageal sphincter (LHM, 10 mm Hg [95% CI, 8.7 to 12]; pneumatic dilation, 12 mm Hg [95% CI, 9.7 to 14]; P=0.27); esophageal emptying, as assessed by the height of barium-contrast column (LHM, 1.9 cm [95% CI, 0 to 6.8]; pneumatic dilation, 3.7 cm [95% CI, 0 to 8.8]; P=0.21); or quality of life. Similar results were obtained in the per-protocol analysis. Perforation of the esophagus occurred in 4% of the patients during pneumatic dilation, whereas mucosal tears occurred in 12% during LHM. Abnormal exposure to esophageal acid was

  7. Clinical Effect of Endoscopic Pneumatic Dilation for Achalasia.

    PubMed

    Cheng, Peng; Shi, Hai; Zhang, Yanjie; Zhou, Huabang; Dong, Jinhua; Cai, Yiting; Hu, Xing; Dai, Qiang; Yang, Wenyan

    2015-07-01

    Although pneumatic dilation is an accepted method for the treatment of achalasia, this therapy has high recurrence and complication rates, and prolonged follow-up studies on the parameters associated with various outcomes are rare. In this prospective 10-year follow-up study, a satisfactory therapeutic effect was achieved without serious complications. We report the therapeutic experience with pneumatic dilation, having aimed to evaluate the long-term clinical safety and efficacy of pneumatic dilation. In total, 35 consecutive patients with idiopathic achalasia who underwent pneumatic dilation were followed up at regular intervals in person or by a phone interview over a 10-year period. The mean duration of the follow-up was 43.03 ± 26.34 months (range 6-120 months). Remission was assessed by the dysphagia classification and symptom scores. Patients' clinical symptom scores were calculated before and at 6 to 36  months, 37 to 60  months, and >60  months after therapy. The influence of the patients' age, gender, and disease duration on the therapeutic effect was analyzed. The success rate of the operation was 97.2% (35/36), without massive hemorrhaging, perforation or other serious complications. Dysphagia after the therapy was significantly eased (P < 0.01). In total, 35 patients have been followed up for 6 to 36  months after therapy, 21 cases for 37 to 60  months, and 5 cases for >60  months, and the patients' symptom scores separately decreased significantly compared with the pretherapy scores (P < 0.01). For these patients, the 6 to 36  months remission rate was 85.7% (30/35), the 37 to 60  months rate was 61.9% (13/21), and the >60  months rate was 40% (2/5). The dilation effect had no relationship to the patient's age, gender, and disease duration (P > 0.05). The patients in 30 cases (85.7%) were successfully treated with a single dilation, in 4 cases (11.4%) with 2 dilations, and in 1 case (2.9%) with 3 dilations. These

  8. Role of fault gouge dilatancy on aseismic deformation transients

    NASA Astrophysics Data System (ADS)

    Liu, Yajing; Rubin, Allan M.

    2010-10-01

    In the vicinity of episodic aseismic transients in several subduction zones, the presence of interstitial fluids and near-lithostatic pore pressure has been proposed to interpret seismic observations of high P to S wave speed ratio and high Poisson's ratio. Under such conditions, fault stabilization by dilatancy-induced suction during increased shear strain rates becomes very efficient. We analyze the frictional and hydraulic conditions for spontaneous transients on a fluid-infiltrated fault including dilatancy and pore compaction in the framework of rate and state friction with a "membrane diffusion" approximation. In both a simplified spectral model and a 2-D Cascadia-like subduction fault model, the fault response is mainly controlled by three nondimensional parameters: (1) W/h*, the along-dip width of the high pore pressure, velocity-weakening fault relative to a characteristic nucleation size, (2) a drainage parameter U, the relative time scales for fluid diffusion and friction evolution, and (3) a dilatancy parameter E, the relative contributions to stress drop from dilatancy and friction evolution. The incorporation of dilatancy enables aseismic transients at much larger values of W/h* than is possible under conditions of constant pore pressure. An analytic estimate of the maximum slip velocity as a function of W/h*, E, and U is derived and agrees reasonably well with the simulation results. The dependence of the properties of modeled transients on the drainage parameter U is similar to that on the dilatancy parameter E. For U (E) less than 1, maximum velocity decreases, while recurrence period remains relatively constant. For U (E) greater than 1, maximum velocity approaches the steady state velocity, and recurrence period approaches the period at neutral stability. In the subduction fault model using gabbro gouge friction properties, the slip per episode and the recurrence period increase with W/h*, generally following the trend defined without dilatancy

  9. Change in dynamic visual acuity (DVA) by pupil dilation.

    PubMed

    Ueda, Tetsuo; Nawa, Yoshiaki; Yukawa, Eiichi; Taketani, Futoshi; Hara, Yoshiaki

    2006-01-01

    This study was conducted to assess dynamic visual acuity (DVA) under pupil dilation. Pupil dilation may negatively affect driving performance. Thirty healthy young adults (mean age 29.4 years) with pupil dilation participated in this study as the Mydrin P group. In addition to them, 15 healthy young adults (mean age 28.5 years) without pupil dilation were enrolled as the control group. DVA was measured binocularly with free-head viewing at 0, 30, 60, 120, and 360 min after mydriatic drop instillation in both eyes. Pupil size was measured at each time. In the Mydrin P group, DVA significantly improved at 30, 60, and 120 min (ANOVA; p < .01) but returned to the predilation level at 360 min (ANOVA; p = .61). Pupil size changed from 4.1 to 7.8 mm (ANOVA; p < .01) at 30 min after the instillation, and this level was maintained up to 120 min but returned to normal within 360 min. In the control group, DVA did not significantly change at all measured times (ANOVA; p > .9). DVA was significantly (p < .05) correlated with the pupil size at all measured times. The improvement in DVA was related to the enlargement of the pupil. This study suggests that the pupil size is one factor that may affect DVA. Potential applications of this study include useful information to assess the effect of pupil dilation on driving performance.

  10. Relationships between tissue dilatation and differentiation in distraction osteogenesis.

    PubMed

    Morgan, Elise F; Longaker, Michael T; Carter, Dennis R

    2006-03-01

    Mechanical factors modulate the morphogenesis and regeneration of mesenchymally derived tissues via processes mediated by the extracellular matrix (ECM). In distraction osteogenesis, large volumes of new bone are created through discrete applications of tensile displacement across an osteotomy gap. Although many studies have characterized the matrix, cellular and molecular biology of distraction osteogenesis, little is known about relationships between these biological phenomena and the local physical cues generated by distraction. Accordingly, the goal of this study was to characterize the local physical environment created within the osteotomy gap during long bone distraction osteogenesis. Using a computational approach, we quantified spatial and temporal profiles of three previously identified mechanical stimuli for tissue differentiation-pressure, tensile strain and fluid flow-as well as another candidate stimulus-tissue dilatation (volumetric strain). Whereas pressure and fluid velocity throughout the regenerate decayed to less than 31% of initial values within 20 min following distraction, tissue dilatation increased with time, reaching steady state values as high as 43% strain. This dilatation created large reductions and large gradients in cell and ECM densities. When combined with previous findings regarding the effects of strain and of cell and ECM densities on cell migration, proliferation and differentiation, these results indicate two mechanisms by which tissue dilatation may be a key stimulus for bone regeneration: (1) stretching of cells and (2) altering cell and ECM densities. These results are used to suggest experiments that can provide a more mechanistic understanding of the role of tissue dilatation in bone regeneration.

  11. Dilation of fusion pores by crowding of SNARE proteins

    PubMed Central

    Wu, Zhenyong; Bello, Oscar D; Thiyagarajan, Sathish; Auclair, Sarah Marie; Vennekate, Wensi; Krishnakumar, Shyam S; O'Shaughnessy, Ben; Karatekin, Erdem

    2017-01-01

    Hormones and neurotransmitters are released through fluctuating exocytotic fusion pores that can flicker open and shut multiple times. Cargo release and vesicle recycling depend on the fate of the pore, which may reseal or dilate irreversibly. Pore nucleation requires zippering between vesicle-associated v-SNAREs and target membrane t-SNAREs, but the mechanisms governing the subsequent pore dilation are not understood. Here, we probed the dilation of single fusion pores using v-SNARE-reconstituted ~23-nm-diameter discoidal nanolipoprotein particles (vNLPs) as fusion partners with cells ectopically expressing cognate, 'flipped' t-SNAREs. Pore nucleation required a minimum of two v-SNAREs per NLP face, and further increases in v-SNARE copy numbers did not affect nucleation rate. By contrast, the probability of pore dilation increased with increasing v-SNARE copies and was far from saturating at 15 v-SNARE copies per face, the NLP capacity. Our experimental and computational results suggest that SNARE availability may be pivotal in determining whether neurotransmitters or hormones are released through a transient ('kiss and run') or an irreversibly dilating pore (full fusion). DOI: http://dx.doi.org/10.7554/eLife.22964.001 PMID:28346138

  12. A new device for pre-operation cervical dilatation.

    PubMed

    Southern, E M

    1980-06-01

    Direct dilatation of the cervix and surgical evacuation of the uterus is gaining in popularity as a 2nd-trimester method of induced abortion as technical skills improve. Cervical resistance, however, is an important complicating factor in 2nd-trimester procedures. There is general debate concerning the safest and most effective means of effecting nontraumatic dilatation of the cervix. The disadvantages of laminaria tents and metal dilators are cited. It is important to avoid trauma to the cervix which might lead, especially in primiparous women, to future cervico-vaginal fistulae, endangering future fertility. A new dilating device is described and diagrammed. The device combines an accurate, monitored hydrostatic dilatation at the inner os with administration of low dosages of abortifacients into the extra-amniotic space. The device has the advantages of being less traumatic to the cervix, reducing hospital inpatient time, and reducing blood loss at the time of the procedure. The device could be used by nonmedical personnel with little additional training, which would make it useful for developing countries.

  13. Urethral Dilatation in Women: Urologists' Practice Patterns in the UK

    PubMed Central

    Masarani, M; Willis, RG

    2006-01-01

    INTRODUCTION Review of the literature reveals little evidence to prove the efficacy of urethral dilatation for adult women with various lower urinary tract complaints. We conducted a postal survey to ascertain the actual practice of urethral dilatation among urologists in the UK. MATERIALS AND METHODS A questionnaire was mailed to 428 consultant urologists listed as full members of the British Association of Urological Surgeons. The questionnaire consisted of 8 items about urologists' perception of indications, efficacy, and the need for repeated dilatation and anaesthesia. RESULTS The questionnaire response rate was 42%. Although urethral stenosis was the most common indication (97%), the majority of urologists (69%) indicated that fewer than 25% of patients had evidence of stenosis. Overall, 61% of urologists performed dilatation 7 times or more during the last year and 55% believed that less than half of the patients experienced long-term improvement. CONCLUSIONS Despite the lack of strong evidence to support the use of urethral dilatation in women, many urologists continue to find it a useful tool in approaching women with lower urinary tract complaints. PMID:17002859

  14. Apoptosis in Endomyocardial Biopsies from Patients with Dilated Cardiomyopathy.

    PubMed

    Glumac, S; Pejić, S; Kostadinovic, S; Stojšić, Z; Vasiljevic, J

    2016-01-01

    Apoptosis is an active energy-consuming mechanism of cell death, which may contribute to heart failure in patients with dilated cardiomyopathy. Dilated cardiomyopathy is a common clinical outcome of many prolonged cardiac insults, and therefore is considered as the most prevalent form of cardiomyopathy. Loss of heart mass is highly correlated with the heart failure and mortality, thus the purpose of this study was to define the apoptotic index in patients with dilated cardiomyopathy. Apoptosis was detected by the TUNEL method in 30 patients. Biopsies were obtained from the left ventricle, and at least three specimens were taken. TUNEL-positive cardiomyocytes were found in 26 of 30 cases (86.7 %) and the mean apoptotic index for the entire specimen series was 5.41 ± 1.70 %. The analysis showed that patients with dilated cardiomyopathy had significantly higher apoptotic index (P < 0.001) than healthy subjects. One subject (man, 41 years old) had a markedly elevated apoptotic index of 52.2 %. In the remaining subjects, the percentage of cardiomyocyte death ranged from 0 % to 15.5 %. The high percentage of apoptosis found in our study may be in accordance with the clinically manifested cardiac failure in patients with dilated cardiomyopathy since in most patients we recorded the left ventricular ejection fraction values below 30 %.

  15. A Comparative Effectiveness Research of Azathioprine and Cyclophosphamide on the Clinical and Serological Response in Pemphigus Vulgaris

    PubMed Central

    Sardana, Kabir; Agarwal, Pooja; Bansal, Shivani; Uppal, Beena; Garg, Vijay K

    2016-01-01

    Context: A prospective study was carried out to examine the efficacy of cyclophosphamide and azathioprine in pemphigus vulgaris. Aims: To compare the clinical and serological effect of azathioprine and cyclophosphamide in pemphigus patients. Materials and Methods: Prospective, institutional based study was conducted twenty-one patients of pemphigus vulgaris were initiated on either azathioprine (n = 9) or cyclophosphamide (n = 7) in addition to prednisolone and were evaluated clinically (mucosal and cutaneous severity) and serologically enzyme-linked immunosorbent assay (ELISA) at 0, 3 and 6 months. Results: Azathioprine had a slower onset of action with a statistically significant improvement seen by 6 months (P = 0.016). Cyclophosphamide had a faster onset of action (3 months) though there was no statistical difference in the efficacy between the two at the end of 6 months. The (RonT) was 33.3–44.4% for azathioprine and 28.8–42.9% for cyclophosphamide at 6 months. Though ELISA had a high sensitivity and specificity for diagnosis, as a tool for assessing therapeutic response a significant decrease was seen only till 3 months. This was restricted to Dsg1 for the azathioprine group and both Dsg3 and Dsg1 levels for the cyclophosphamide group. There were two deaths, both in the cyclophosphamide group. Conclusions: Azathiorpine and cyclophosphamide are equally effective for mucosal and cutaneous disease in pemphigus after 6 months of therapy. Dsg ELISA is useful for diagnosis of pemphigus but is not a useful tool for monitoring response to therapy. PMID:27512188

  16. Chronodependent effect of interleukin-2 on mouse spleen cells in the model of cyclophosphamide immunosuppression.

    PubMed

    Shurlygina, A V; Mel'nikova, E V; Trufakin, V A

    2015-02-01

    We studied the chronodependent effect of IL-2 in the experimental model of immunodeficiency, cyclophosphamide-induced immunosuppression in mice. IL-2 in a dose of 100 U/ mouse was administered at 10.00 and 16.00 for 3 days after injection of cyclophosphamide. In contrast to the morning treatment with the cytokine, evening administration produced antiapoptotic effect on splenocytes and stimulated proliferation to a greater extent. This was accompanied by an increase in the number of CD4(+), CD25(+) and CD4(+)25(+) cells in the spleen to a level of intact mice. More pronounced effect of the evening mode of IL-2 administration on the proliferation and subpopulation composition of mouse spleen cells in the studied model can be associated with high blood level of CD25(+) cells at this time of the day.

  17. The effect of immunosuppression with cyclophosphamide on an experimental porcine enterovirus infection in piglets.

    PubMed Central

    Derbyshire, J B

    1983-01-01

    Eleven specific pathogen-free, five week old piglets were infected orally with the T80 strain of porcine enterovirus type 2. Three days after infection, five of the piglets were treated with cyclophosphamide, together with two of four uninfected control piglets. The treated, infected piglets developed severe diarrhea, and one showed signs of encephalomyelitis. These piglets showed no virological evidence of recovery from the infection, since the virus persisted throughout the intestinal tract, and they failed to mount a serological response. It was concluded that immunosuppression with cyclophosphamide impaired the normal recovery mechanisms in this infection, providing further evidence that the humoral immune response is an important defence mechanism against porcine enterovirus infection in piglets. PMID:6224548

  18. Analysis of lymphocytes in, and host environment of, mice showing conditioned immunosuppression to cyclophosphamide

    SciTech Connect

    Gorczynski, R.M.

    1987-03-01

    Mice were subjected to repeated exposures to cyclophosphamide: saccharin (conditioned) or cyclophosphamide:saccharin followed by saccharin only (conditioned:extinguished). Animals in the former group but not the latter subsequently showed diminished IgG antibody-forming cells (AFC) after challenge with sheep red blood cells followed by reexposure to immunologically inert cues (saccharin). When these animals were used as irradiated recipients of syngeneic spleen lymphocytes, reconstituted irradiated conditioned mice showed augmented IgG AFC on transfer of naive spleen cells and reexposure to saccharin. The expected diminished IgG AFC response was seen when cells from conditioned mice were transferred. However, the latter cells gave augmented IgG AFC when transferred to naive irradiated mice. Both of the effects seen with cells from conditioned animals (increased IgG AFC in control recipients; decreased IgG AFC in conditioned mice reexposed to saccharin) were regulated by adoptively transferred T cells in the spleen cell population.

  19. Chemotherapy of disseminated seminoma with combination of cis-diamminedichloroplatinum (II) and cyclophosphamide.

    PubMed

    Vugrin, D; Whitemore, W J; Batata, M

    1981-01-01

    Nine patients with metastatic seminoma who had received no prior chemotherapy were induced with a combination containing cis-platinum 120 mg/m2 I.V. and cyclophosphamide 600 mg/m2 I.V. for three to six treatments at 4-6 weeks intervals, and then received maintenance with cyclophosphamide 600 mg/m2 I.V. every 3-4 weeks to complete 2 years of chemotherapy. Eight patients entered complete remission: five with chemotherapy alone and three with chemotherapy and radiation or resection of residual disease. Seven patients remain in CR with a minimum follow up of 17 months. Chemotherapy is effective in treatment of metastatic seminoma.

  20. THE INDUCTION OF GRAFT VERSUS HOST DISEASE IN MICE TREATED WITH CYCLOPHOSPHAMIDE

    PubMed Central

    Owens, Albert H.; Santos, George W.

    1968-01-01

    In these studies adult mice treated with cyclophosphamide and foreign immunologically competent cells developed a graft versus host disease which outwardly resembled that encountered in other experimental systems. Progressively larger doses of cyclophosphamide produced an increasingly severe disease whereas comparable doses of mechlorethamine were ineffective. Increasingly larger cell inocula from parental, allogeneic, and xenogeneic donors resulted in a correspondingly more severe disease. Nucleated cells obtained from the peripheral blood were found to be the most potent inducers of this syndrome, while cells from the spleen, bone marrow, and thymus displayed lesser degrees of reactivity in that order. No such graft versus host disease occurred in mice given saline, lysed, or heat-killed cells in place of viable foreign cells. Neither did the disorder develop when comparable inocula of isogeneic cells were used. PMID:4873022

  1. Cyclophosphamide, doxorubicin, and cisplatin combined in the treatment of advanced sarcomas.

    PubMed

    Edmonson, J H; Hahn, R G; Schutt, A J; Bisel, H F; Ingle, J N

    1983-01-01

    Twenty-five patients with evaluable histologically confirmed inoperable metastatic sarcomas were treated once every four weeks with cyclophosphamide, doxorubicin, and cisplatin in doses of 400, 40, and 60 mg/m2, respectively. Cyclophosphamide and doxorubicin were given by rapid intravenous injection followed immediately by cisplatin by slow intravenous infusion (2-6 hr) in 1 liter of 0.45% saline with mannitol added. Leukopenia, alopecia, and vomiting were common side effects and three patients refused further treatment because of vomiting following their initial courses. No drug-related deaths occurred and we removed no one from the study because of toxicity problems. Among the 9 patients who experienced objective tumor regression were 2 of 2 with hemangiosarcoma, 3 of 5 with malignant fibrous histiocytoma, 3 of 5 with osteosarcoma, and 1 of 1 with pleomorphic liposarcoma of bone. Although not therapeutically gratifying, these results appear to be better than any previously observed at our institution.

  2. Effects of cyclophosphamide and irradiation singly and in combination upon SaI growth in A/J mice

    SciTech Connect

    Anderson, R.E.; Williams, W.L.; Tokuda, S.

    1987-05-01

    The effects of various doses of cyclophosphamide and low-dose (15 rads) radiation upon the size of tumors caused by 10(4) Sarcoma I (SaI) cells was determined. In intact A/Jax (A/J) recipients, the effect of the two agents singly and in combination was found to be dependent especially upon the dosage of cyclophosphamide and the time of its administration in relation to tumor inoculation. In cell transfer experiments to adult thymectomized, lethally irradiated, bone-marrow-restored (ATxXBM) mice, the effects of cyclophosphamide and irradiation appeared to be either overlapping (low dosages of cyclophosphamide) or additive (dosages of cyclophosphamide greater than or equal to 50 mg/kg), suggesting that the two agents exert their influence in dissimilar fashion, perhaps by injuring different cell types with the same basic function. The most pronounced conjoint effects are seen when low dosages of cyclophosphamide are given 3 days after the adoptive transfer of spleen cells from mice pretreated with low-dose irradiation. The implications of this observation with respect to immunotherapy are discussed.

  3. Cyclophosphamide-facilitated adoptive immunotherapy of an established tumor depends on elimination of tumor-induced suppressor T cells

    PubMed Central

    1982-01-01

    On the basis of preceding studies showing that tumor-induced, T cell- mediated immunosuppression serves as an obstacle to adoptive immunotherapy of the Meth A fibrosarcoma, it was predicted that cyclophosphamide treatment of tumor bearers would remove this obstacle and allow passively transferred immune T cells to cause tumor regression. It was found that infusion of immune spleen cells alone had no effect on tumor growth, and cyclophosphamide alone caused a temporary halt in tumor progression. In contrast, combination therapy consisting of intravenous injection of 100 mg/kg of cyclophosphamide followed 1 h later by intravenous infusion of tumor-immune spleen cells caused small, as well as large tumors, to completely and permanently regress. Tumor regression caused by combination therapy was completely inhibited by intravenous infusion of splenic T cells from donors with established tumors, but not by spleen cells from normal donors. These suppressor T cells were eliminated from the spleen by treating the tumor-bearing donors with 100 mg/kg of cyclophosphamide. Immune T cells, in contrast, were resistant to this dose of cyclophosphamide. These results show that failure of intravenously-infused, tumor- sensitized T cells to cause regression of the Meth A fibrosarcoma growing in its syngeneic or semi-syngeneic host is caused by the presence of a tumor-induced population of cyclophosphamide-sensitive suppressor T cells. PMID:6460831

  4. Endoscope-guided pneumatic dilation for treatment of esophageal achalasia

    PubMed Central

    Chuah, Seng-Kee; Wu, Keng-Liang; Hu, Tsung-Hui; Tai, Wei-Chen; Changchien, Chi-Sin

    2010-01-01

    Pneumatic dilation (PD) is considered to be the first line nonsurgical therapy for achalasia. The principle of the procedure is to weaken the lower esophageal sphincter by tearing its muscle fibers by generating radial force. The endoscope-guided procedure is done without fluoroscopic control. Clinicians usually use a low-compliance balloon such as Rigiflex dilator to perform endoscope-guided PD for the treatment of esophageal achalasia. It has the advantage of determining mucosal injury during the dilation process, so that a repeat endoscopy is not needed to assess the mucosal tearing. Previous studies have shown that endoscope-guided PD is an efficient and safe nonsurgical therapy with results that compare well with other treatment modalities. Although the results may be promising, long-term follow-up is required in the near future. PMID:20101764

  5. Pulmonary artery dilatation: an overlooked mechanism for angina pectoris.

    PubMed

    Ginghina, Carmen; Popescu, Bogdan A; Enache, Roxana; Ungureanu, Catalina; Deleanu, Dan; Platon, Pavel

    2008-07-01

    Dilatation of the pulmonary artery may lead to the compression of adjacent structures. Of those, the extrinsic compression of the left main coronary artery is the most worrisome. We present the case of a 48-year-old woman who was diagnosed with pulmonary artery dilatation due to severe, thromboembolic pulmonary hypertension. She also had angina and coronary angiography revealed a 70% ostial stenosis of the left main coronary artery. The presence of this isolated lesion in a young woman without risk factors for atherosclerosis suggests extrinsic compression of the left main coronary artery by the dilated pulmonary artery as the likely mechanism. The patient underwent direct stenting of the left main coronary stenosis with a good result.

  6. Percutaneous dilatational tracheostomy following total artificial heart implantation.

    PubMed

    Spiliopoulos, Sotirios; Dimitriou, Alexandros Merkourios; Serrano, Maria Rosario; Guersoy, Dilek; Autschbach, Ruediger; Goetzenich, Andreas; Koerfer, Reiner; Tenderich, Gero

    2015-07-01

    Coagulation disorders and an immune-altered state are common among total artificial heart patients. In this context, we sought to evaluate the safety of percutaneous dilatational tracheostomy in cases of prolonged need for mechanical ventilatory support. We retrospectively analysed the charts of 11 total artificial heart patients who received percutaneous dilatational tracheostomy. We focused on early and late complications. We observed no major complications and no procedure-related deaths. Early minor complications included venous oozing (45.4%) and one case of local infection. Late complications, including subglottic stenosis, stomal infection or infections of the lower respiratory tract, were not observed. In conclusion, percutaneous dilatational tracheostomy in total artificial heart patients is safe. Considering the well-known benefits of early tracheotomy over prolonged translaryngeal intubation, we advocate early timing of therapy in cases of prolonged mechanical ventilation. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  7. Patient with Eating Disorder, Carnitine Deficiency and Dilated Cardiomyopathy.

    PubMed

    Fotino, A Domnica; Sherma, A

    2015-01-01

    Dilated cardiomyopathy is characterized by a dilated and poorly functioning left ventricle and can result from several different etiologies including ischemic, infectious, metabolic, toxins, autoimmune processes or nutritional deficiencies. Carnitine deficiency-induced cardiomyopathy (CDIM) is an uncommon cause of dilated cardiomyopathy that can go untreated if not considered. Here, we describe a 30-year-old woman with an eating disorder and recent percutaneous endoscopic gastrotomy (PEG) tube placement for weight loss admitted to the hospital for possible PEG tube infection. Carnitine level was found to be low. Transthoracic echocardiogram (TTE) revealed ejection fraction 15%. Her hospital course was complicated by sepsis from a peripherally inserted central catheter (PICC). She was discharged on a beta-blocker and carnitine supplementation. One month later her cardiac function had normalized. Carnitine deficiency-induced myopathy is an unusual cause of cardiomyopathy and should be considered in adults with decreased oral intake or malabsorption who present with cardiomyopathy.

  8. Dilated Cardiomyopathy Induced by Chronic Starvation and Selenium Deficiency

    PubMed Central

    2016-01-01

    Protein energy malnutrition (PEM) has been rarely documented as a cause of cardiovascular abnormalities, including dilated cardiomyopathy. Selenium is responsible for antioxidant defense mechanisms in cardiomyocytes, and its deficiency in the setting of PEM and disease related malnutrition (DRM) may lead to exacerbation of the dilated cardiomyopathy. We report a rare case of a fourteen-year-old boy who presented with symptoms of congestive heart failure due to DRM and PEM (secondary to chronic starvation) along with severe selenium deficiency. An initial echocardiogram showed severely depressed systolic function consistent with dilated cardiomyopathy. Aggressive nutritional support and replacement of selenium and congestive heart failure medications that included diuretics and ACE inhibitors with the addition of carvedilol led to normalization of the cardiac function within four weeks. He continues to have significant weight gain and is currently completely asymptomatic from a cardiovascular standpoint. PMID:27994905

  9. Peripheral neuritis in psittacine birds with proventricular dilatation disease.

    PubMed

    Berhane, Y; Smith, D A; Newman, S; Taylor, M; Nagy, E; Binnington, B; Hunter, B

    2001-10-01

    Necropsies were performed on 14 psittacine birds of various species suspected to have proventricular dilatation disease (PDD). Eight of the birds exhibited neurological signs (seizures, ataxia, tremors and uncoordinated movements) and digestive tract signs (crop stasis, regurgitation, inappetance and presence of undigested food in the faeces). At necropsy, the birds had pectoral muscle atrophy, proventricular and ventricular distention, thinning of the gizzard wall, and duodenal dilation. In addition, five birds had a transparent fluid (0.2 to 1.0 ml) in the subarachnoidal space of the brain, and one bird had dilatation of the right ventricle of the heart. The histological lesions differed from earlier reports of PDD in that peripheral (sciatic, brachial and vagal) neuritis was seen in addition to myenteric ganglioneuritis, myocarditis, adrenalitis, myelitis and encephalitis.

  10. Negative pressure in shear thickening band of a dilatant fluid

    NASA Astrophysics Data System (ADS)

    Nagahiro, Shin-ichiro; Nakanishi, Hiizu

    2016-12-01

    We perform experiments and numerical simulations to investigate spatial distribution of pressure in a sheared dilatant fluid of the Taylor-Couette flow under a constant external shear stress. In a certain range of shear stress, the flow undergoes the shear thickening oscillation around 20 Hz. We find that, during the oscillation, a localized thickened band rotates around the axis with the flow. Based upon experiments and numerical simulations, we show that a major part of the thickened band is under negative pressure even in the case of discontinuous shear thickening, which indicates that the thickening is caused by Reynolds dilatancy; the dilatancy causes the negative pressure in interstitial fluid, which generates contact structure in the granular medium, then frictional resistance hinders rearrangement of the structure and solidifies the medium.

  11. A Tension-Based Model Distinguishes Hypertrophic versus Dilated Cardiomyopathy.

    PubMed

    Davis, Jennifer; Davis, L Craig; Correll, Robert N; Makarewich, Catherine A; Schwanekamp, Jennifer A; Moussavi-Harami, Farid; Wang, Dan; York, Allen J; Wu, Haodi; Houser, Steven R; Seidman, Christine E; Seidman, Jonathan G; Regnier, Michael; Metzger, Joseph M; Wu, Joseph C; Molkentin, Jeffery D

    2016-05-19

    The heart either hypertrophies or dilates in response to familial mutations in genes encoding sarcomeric proteins, which are responsible for contraction and pumping. These mutations typically alter calcium-dependent tension generation within the sarcomeres, but how this translates into the spectrum of hypertrophic versus dilated cardiomyopathy is unknown. By generating a series of cardiac-specific mouse models that permit the systematic tuning of sarcomeric tension generation and calcium fluxing, we identify a significant relationship between the magnitude of tension developed over time and heart growth. When formulated into a computational model, the integral of myofilament tension development predicts hypertrophic and dilated cardiomyopathies in mice associated with essentially any sarcomeric gene mutations, but also accurately predicts human cardiac phenotypes from data generated in induced-pluripotent-stem-cell-derived myocytes from familial cardiomyopathy patients. This tension-based model also has the potential to inform pharmacologic treatment options in cardiomyopathy patients.

  12. Longitudinal shear wave and transverse dilatational wave in solids.

    PubMed

    Catheline, S; Benech, N

    2015-02-01

    Dilatation wave involves compression and extension and is known as the curl-free solution of the elastodynamic equation. Shear wave on the contrary does not involve any change in volume and is the divergence-free solution. This letter seeks to examine the elastodynamic Green's function through this definition. By separating the Green's function in divergence-free and curl-free terms, it appears first that, strictly speaking, the longitudinal wave is not a pure dilatation wave and the transverse wave is neither a pure shear wave. Second, not only a longitudinal shear wave but also a transverse dilatational wave exists. These waves are shown to be a part of the solution known as coupling terms. Their special motion is carefully described and illustrated.

  13. Pupil dilation patterns reflect the contents of consciousness.

    PubMed

    Kang, Olivia; Wheatley, Thalia

    2015-09-01

    The study of human consciousness has historically depended on introspection. However, introspection is constrained by what can be remembered and verbalized. Here, we demonstrate the utility of high temporal resolution pupillometry to track the locus of conscious attention dynamically, over a single trial. While eye-tracked, participants heard several musical clips played diotically (same music in each ear) and, later, dichotically (two clips played simultaneously, one in each ear). During dichotic presentation, participants attended to only one ear. We found that the temporal pattern of pupil dilation dynamics over a single trial discriminated which piece of music was consciously attended on dichotic trials. Deconvolving these pupillary responses further revealed the real-time changes in stimulus salience motivating pupil dilation. Taken together, these results show that pupil dilation patterns during single-exposure to dynamic stimuli can be exploited to discern the contents of conscious attention.

  14. Regulation of secondary antibody responses in rodents. I. Potentiation of IgG production by cyclophosphamide.

    PubMed Central

    Gagnon, R F; MacLennan, I C

    1979-01-01

    This paper describes the effects of a single dose of cyclophosphamide on specific IgG production in rats during an established secondary immune response. (PVG X Agus)F1 rats were immunized twice (days 0 and 28) with chicken erythrocytes (CRBC), received cyclophosphamide (100 mg/m2 of body surface area) on day 33 and were killed 8 days later. The production of anti-CRBC IgG antibodies was assessed by testing the supernatants of spleen cell cultures in a cytotoxicity assay with 51Cr-labelled CRBC as target cells and normal rat spleen cells as effector cells. In observations of fifty-nine pairs of treated and untreated rats from eight separate experiments, the administration of cyclophosphamide resulted in: (1) a decrease in the number of spleen cell to a median of 10(8.63) from a median of 10(8.7) (P less than 0.0025); (2) an increase in the anti-CRBC IgG antibody titre of the supernatants of cultured spleen cells to a median of 10(0.67) from a median of 10(0.27 (P less than 0.0025); and (3) the calculated anti-CRBC. IgG antibody production per spleen to be increased in the drug-treated rats to a median of 10(2.26) from a median of 10(2.0) (P less than 0.005). In a cyclophosphamide dose-response study, it was shown that some enhancement of antibody production was induced by doses between 12.5 and 50 mg/m2 and consistently elevated levels of antibody production were associated with doses between 100 and 400 mg/m2. PMID:487659

  15. Design, synthesis, and evaluation of new cyclophosphamide-based anticancer prodrugs

    SciTech Connect

    Moon, Ki-Young.

    1993-01-01

    Cyclophosphamide (CP,1) is a prodrug that is activated by hepatic microsomal mixed-function oxidase (MFO) catalyzed C[sub 4]-hydroxylation. The resulting 4-hydroxycyclophosphamide (4-OH-CP) undergoes ring opening to aldophosphamide (Aldo), followed by generation of cytotoxic phosphoramide mustard (PDA,2) and acrolein by [beta]-elimination. The cytotoxic activity of CP is attributed to the aziridinium ion species derived from PDA that cross-links interstrand DNA. The aim of this research is to design, synthesize, and evaluate new cyclophosphamide-based alkylating agents to achieve improved therapeutic efficacy against neoplastic cells. Benzyl phosphoramide mustard (Benzyl PDA,4), 2.4-difluorobenzyl phosphoramide mustard (2,4-Difluorobenzyl PDA,5) and methyl phosphoramide mustard (Methyl PDA,6) were examined as lipophilic, chemically stable prodrugs of PDA (2). These phosphorodiamidic esters were designed to undergo biotransformation by hepatic microsomal enzymes to produce 2 without generation of acrolein and to be active against CP-resistant tumor cells. Several N-methyl-4-(alkylthio)cyclophosphamide derivatives were synthesized and examined as chemically stable, biooxidative prodrugs of 4-OH-CP, the activated species of CP. All of the prodrugs underwent N-demethylation in a time-dependent manner when incubated with rat hepatic microsomes, which resulted in formation of formaldehyde as well as alkylating species. Among the prodrugs, N-methyl-4-(diethyldithiocarbamoyl)cyclophosphamide (N-CH[sub 3]-4-DDTC-CP,15) showed exceptional in vitro cytotoxicity against 3T3 cells as well as against a panel of human tumor cell lines, with a particular sensitivity to leukemia and small cell lung cancer cell lines. Preliminary in vivo antitumor evaluation against L1210 leukemia in mice showed that all of the prodrugs were active.

  16. Exclusion of an interactive effect of combined x-irradiation and activated cyclophosphamide in tissue culture

    SciTech Connect

    Byfield, J.E.; Lynch, M.; Kulhanian, F.

    1986-08-01

    The effect of Cyclophosphamide (CY) on the X ray survival of clonogenic tumor cells has been studied in vitro. Two activated derivatives of the drug, Peroxycyclophosphamide and Hydroperoxycyclophosphamide, were employed. Two cell lines, repair-competent human HeLa cells and the repair-deficient rat REQ line, were investigated. Neither form of CY had any effect on the X ray survival curve of either cell line, indicating that any interaction anticipated in vivo could be expected to be additive.

  17. The Effects of Electroacupuncture on Cyclophosphamide-Induced Emesis in Ferrets.

    DTIC Science & Technology

    1996-07-01

    typically left in place for 20-30 minutes. The effects of acupuncture may be augmented with electrical stimulation (EA) and/or heat (e.g. moxibustion). Side...sham acupuncture group, a non- acupuncture point (dummy point) was used at the elbow area (Dundee, 1991), and no electrical stimulation was applied...examine the effects of electro- acupuncture (EA) on the emetogenic effect of cyclophosphamide a commonly used chemo- therapy agent for breast cancer

  18. New anatomical profile of the nasal musculature: dilator naris vestibularis, dilator naris anterior, and alar part of the nasalis.

    PubMed

    Hur, Mi-Sun; Hu, Kyung-Seok; Youn, Kwan-Hyun; Song, Wu-Chul; Abe, Shinichi; Kim, Hee-Jin

    2011-03-01

    The aim of this study was to clarify the morphology and topography of the dilator naris vestibularis, dilator naris anterior, and alar part of the nasalis. Anatomical variations in the topographic relationships are also described to provide critical data for understanding nasal muscular functions. Anatomical and histological examinations were performed on 40 specimens of embalmed Korean adult cadavers. The dilator naris vestibularis muscle (named by the present authors) was located between the external and vestibular skin of the alar lobule. The muscle fibers radiated along the dome-shaped nasal vestibule. The dilator naris anterior muscle originated from the frontal surfaces of the lateral half of the lateral crus and the accessory alar cartilage adjacent to the lateral crus. The extent of the lower insertion of the dilator naris anterior muscle was at the alar groove. The alar part of the nasalis originated with the transverse part of nasalis from the maxilla. It ascended to attach to the alar crease and the adjacent deep surface of external skin of the alar lobule. These findings may provide anatomical knowledge required to understand the structure and function of these nasal muscles such as during rhinoplasty or other surgery of the face. Copyright © 2010 Wiley-Liss, Inc.

  19. A phase III clinical trial comparing the combination cyclophosphamide, adriamycin, cisplatin with cyclophosphamide, 5-fluorouracil, prednisone in patients with advanced breast cancer.

    PubMed

    Creagan, E T; Green, S J; Ahmann, D L; Ingle, J N; Edmonson, J H; Marschke, R F

    1984-11-01

    We assessed the efficacy of a regimen consisting of four cycles of cyclophosphamide, Adriamycin (Adria Laboratories, Inc, Columbus, Ohio), cisplatin (CAP) followed by maintenance with cyclophosphamide, 5-fluorouracil, prednisone (CFP) compared with CFP alone in a randomized trial of 86 patients with advanced breast cancer. The objective regression rates were 46% (CFP) and 49% (CAP with CFP) which included complete regression rates of 7% (CFP) and 4% (CAP with CFP). The median time to progression was nine months for CFP and six months for CAP with CFP. Median survival in the CFP group was 18 months v 11 months in the CAP recipients. Due to the therapeutic trend in favor of patients receiving CFP, we terminated the study before achieving our initially projected accrual. We observed over a twofold excess of substantial nausea and vomiting among patients receiving the platinum-based regimen. In our view, the CAP followed by the CFP regimen is a more toxic program that offers no clinically meaningful improvement over CFP to patients with advanced breast cancer.

  20. Comparison of total body irradiation plus cyclophosphamide with busulfan plus cyclophosphamide as conditioning regimens in patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplant.

    PubMed

    Eroglu, Celalettin; Pala, Cigdem; Kaynar, Leylagül; Yaray, Kadir; Aksozen, M Tarkan; Bankir, Mehmet; Zararsız, Gökmen; Orhan, Okan; Gündog, Mete; Yıldız, Oguz G; Eser, Bülent; Cetin, Mustafa; Unal, Ali

    2013-11-01

    Conditioning regimens used during stem cell transplant provide prolonged control or cure of the disease in patients with acute lymphoblastic leukemia (ALL). In this study, we present a comparison of treatment results for 95 patients with ALL who underwent allogeneic hematopoietic stem cell transplant (AHSCT) with total body irradiation plus cyclophosphamide (TBI + Cy) or busulfan plus cyclophosphamide (Bu + Cy) as conditioning regimen. Median age was 25 (range: 9-54) years. Median follow-up was 24 (range: 3-107) months. Median overall survival (OS) was found to be 29 months. Median event-free survival (EFS) was 9 months. Median OS was 37 months in the TBI + Cy arm, while it was 12 months in the Bu + Cy arm, suggesting a significant advantage favoring the TBI + Cy arm (p = 0.003). Median EFS was 13 months in the TBI + Cy arm, while it was 4 months in the Bu + Cy arm, indicating a significant difference (p = 0.006). In univariate and multivariate analysis, it was found that high OS and EFS were significantly correlated with TBI + Cy conditioning regimen and lack of transplant-related mortality (p < 0.05). The TBI + Cy conditioning regimen was found to be superior to the Bu + Cy regimen in patients with ALL undergoing AHSCT regarding both OS and EFS.

  1. Superior outcome after neoadjuvant chemotherapy with docetaxel, anthracycline, and cyclophosphamide versus docetaxel plus cyclophosphamide: results from the NATT trial in triple negative or HER2 positive breast cancer.

    PubMed

    Chen, Xiaosong; Ye, Guolin; Zhang, Chenfang; Li, Xinzheng; Chen, Yiding; Xie, Xiaohong; Zheng, Hong; Cao, Yali; Wu, Kejin; Ni, Duo; Tang, Jinhai; Wei, Ziguo; Shen, Kunwei

    2013-12-01

    The purpose of this study is to evaluate the efficacy and safety of docetaxel plus cyclophosphamide(TC) compared with docetaxel, anthracycline, and cyclophosphamide(TEC) in neoadjuvant treatment of triple negative or HER2 positive breast cancer. Eligible breast cancer patients were randomized to receive six cycles of TC or TEC. The primary end point was pathological complete remission (pCR). Secondary end points included safety, clinical response rate, and survival outcome. One hundred and two patients were initially randomized and 96 patients were available for efficacy analysis. 96.9 % patients were treated with epirubicin as an anthracycline agent. pCR rates were 6.8 % (3/45) and 17.6 % (9/51) in TC and TEC group, respectively, P = 0.113. After a mean follow up of 20 (3–36) months, non-anthracycline-containing TC regimen treatment resulted in a worse event free survival (adjusted hazard ratio [HR] 2.42; 95 % CI1.11–5.30) and disease-free survival (HR 2.85; 95 % CI1.21–6.74) compared with TEC regimen, which was more apparent in triple negative subtype. Severe adverse event rates were similar, except that patients treated with TEC had a higher rate of neutropenia and leucopenia. TEC treatment had a superior survival outcome and trend of higher pCR rate compared with TC in this trial setting, especially in triple negative subtype, which deserves further validation.

  2. Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies.

    PubMed

    Ware, James S; Li, Jian; Mazaika, Erica; Yasso, Christopher M; DeSouza, Tiffany; Cappola, Thomas P; Tsai, Emily J; Hilfiker-Kleiner, Denise; Kamiya, Chizuko A; Mazzarotto, Francesco; Cook, Stuart A; Halder, Indrani; Prasad, Sanjay K; Pisarcik, Jessica; Hanley-Yanez, Karen; Alharethi, Rami; Damp, Julie; Hsich, Eileen; Elkayam, Uri; Sheppard, Richard; Kealey, Angela; Alexis, Jeffrey; Ramani, Gautam; Safirstein, Jordan; Boehmer, John; Pauly, Daniel F; Wittstein, Ilan S; Thohan, Vinay; Zucker, Mark J; Liu, Peter; Gorcsan, John; McNamara, Dennis M; Seidman, Christine E; Seidman, Jonathan G; Arany, Zoltan

    2016-01-21

    Background Peripartum cardiomyopathy shares some clinical features with idiopathic dilated cardiomyopathy, a disorder caused by mutations in more than 40 genes, including TTN, which encodes the sarcomere protein titin. Methods In 172 women with peripartum cardiomyopathy, we sequenced 43 genes with variants that have been associated with dilated cardiomyopathy. We compared the prevalence of different variant types (nonsense, frameshift, and splicing) in these women with the prevalence of such variants in persons with dilated cardiomyopathy and with population controls. Results We identified 26 distinct, rare truncating variants in eight genes among women with peripartum cardiomyopathy. The prevalence of truncating variants (26 in 172 [15%]) was significantly higher than that in a reference population of 60,706 persons (4.7%, P=1.3×10(-7)) but was similar to that in a cohort of patients with dilated cardiomyopathy (55 of 332 patients [17%], P=0.81). Two thirds of identified truncating variants were in TTN, as seen in 10% of the patients and in 1.4% of the reference population (P=2.7×10(-10)); almost all TTN variants were located in the titin A-band. Seven of the TTN truncating variants were previously reported in patients with idiopathic dilated cardiomyopathy. In a clinically well-characterized cohort of 83 women with peripartum cardiomyopathy, the presence of TTN truncating variants was significantly correlated with a lower ejection fraction at 1-year follow-up (P=0.005). Conclusions The distribution of truncating variants in a large series of women with peripartum cardiomyopathy was remarkably similar to that found in patients with idiopathic dilated cardiomyopathy. TTN truncating variants were the most prevalent genetic predisposition in each disorder.

  3. Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies

    PubMed Central

    Ware, James S.; Li, Jian; Mazaika, Erica; Yasso, Christopher M.; DeSouza, Tiffany; Cappola, Thomas P.; Tsai, Emily J.; Hilfiker-Kleiner, Denise; Kamiya, Chizuko A.; Mazzarotto, Francesco; Cook, Stuart A.; Halder, Indrani; Prasad, Sanjay K.; Pisarcik, Jessica; Hanley-Yanez, Karen; Alharethi, Rami; Damp, Julie; Hsich, Eileen; Elkayam, Uri; Sheppard, Richard; Kealey, Angela; Alexis, Jeffrey; Ramani, Gautam; Safirstein, Jordan; Boehmer, John; Pauly, Daniel F.; Wittstein, Ilan S.; Thohan, Vinay; Zucker, Mark J.; Liu, Peter; Gorcsan, John; McNamara, Dennis M.; Seidman, Christine E.; Seidman, Jonathan G.; Arany, Zoltan

    2016-01-01

    BACKGROUND Peripartum cardiomyopathy shares some clinical features with idiopathic dilated cardiomyopathy, a disorder caused by mutations in more than 40 genes, including TTN, which encodes the sarcomere protein titin. METHODS In 172 women with peripartum cardiomyopathy, we sequenced 43 genes with variants that have been associated with dilated cardiomyopathy. We compared the prevalence of different variant types (nonsense, frameshift, and splicing) in these women with the prevalence of such variants in persons with dilated cardiomyopathy and with population controls. RESULTS We identified 26 distinct, rare truncating variants in eight genes among women with peripartum cardiomyopathy. The prevalence of truncating variants (26 in 172 [15%]) was significantly higher than that in a reference population of 60,706 persons (4.7%, P = 1.3×10−7) but was similar to that in a cohort of patients with dilated cardiomyopathy (55 of 332 patients [17%], P = 0.81). Two thirds of identified truncating variants were in TTN, as seen in 10% of the patients and in 1.4% of the reference population (P = 2.7×10−10); almost all TTN variants were located in the titin A-band. Seven of the TTN truncating variants were previously reported in patients with idiopathic dilated cardiomyopathy. In a clinically well-characterized cohort of 83 women with peripartum cardiomyopathy, the presence of TTN truncating variants was significantly correlated with a lower ejection fraction at 1-year follow-up (P = 0.005). CONCLUSIONS The distribution of truncating variants in a large series of women with peripartum cardiomyopathy was remarkably similar to that found in patients with idiopathic dilated cardiomyopathy. TTN truncating variants were the most prevalent genetic predisposition in each disorder. PMID:26735901

  4. Intravenous immunoglobulins in children with new onset dilated cardiomyopathy.

    PubMed

    Heidendael, Josephine F; Den Boer, Suzanne L; Wildenbeest, Joanne G; Dalinghaus, Michiel; Straver, Bart; Pajkrt, Dasja

    2017-08-11

    Dilated cardiomyopathy is a rare but serious disorder in children. No effective diagnostic or treatment tools are readily available. This study aimed to evaluate the efficacy of intravenous immunoglobulins in children with new onset dilated cardiomyopathy. Methods and results In this retrospective cohort study, 94 children with new onset dilated cardiomyopathy were followed during a median period of 33 months. All patients with secondary dilated cardiomyopathy - for example, genetic, auto-immune or structural defects - had been excluded. Viral tests were performed in all patients and 18 (19%) children met the criteria for the diagnosis "probable or definite viral myocarditis". Intravenous immunoglobulins were administered to 21 (22%) patients. Overall transplant-free survival was 75% in 5 years and did not differ between treatment groups. The treatment was associated with a higher recovery rate within 5 years, compared with non-treated children (70 versus 43%, log rank=0.045). After correction for possible confounders the hazard ratio for recovery with intravenous immunoglobulins was not significant (hazard ratio: 2.1; 95% CI: 1.0-4.6; p=0.056). Administration of intravenous immunoglobulins resulted in a greater improvement in the shortening fraction of the left ventricle. In our population of children with new onset dilated cardiomyopathy, of either viral or idiopathic origin, intravenous immunoglobulins were administered to a minority of the patients and did not influence transplant-free survival, but were associated with better improvement of systolic left ventricular function and with better recovery. Our results support the concept that children with new onset dilated cardiomyopathy might benefit from intravenous immunoglobulins.

  5. Using surface deformation to infer reservoir dilation induced by injection

    NASA Astrophysics Data System (ADS)

    Nanayakkara, Asanga Sanjeewee

    Reservoir dilations occur due to variety of subsurface injection operations including waste disposal, waterflooding, steam injection, CO 2 sequestration and aquifer storage recovery. These reservoir dilations propagate to the surrounding formations and extend up to the ground surface resulting in surface deformations. The surface deformations can be measured by using various technologies such as tiltmeters and interferometric synthetic aperture radar (InSAR) and they can be inverted to infer reservoir dilations by solving an ill-posed inverse problem. This concept forms the basis of the research work presented in this thesis. Initially, the characteristics of the surface and subsurface deformations (induced by the injection operations) and correlations between them were investigated in detail by applying both analytical (based on center of dilatation approach) and numerical methods (fully coupled finite element method). Then, a simple set of guidelines to obtain quick estimates for the surface heave characteristics were proposed. The guidelines are in the form of simple analytical equations or charts and thereby they could be very useful in obtaining preliminary assessment for the surface deformation characteristics induced by the subsurface injection operations. Next, the mathematical aspects of the inverse problem were discussed in detail and the factors affecting the accuracy of the inverse solution were investigated through an extensive parametric study including both two-dimensional and three-dimensional problems. Then, a method was developed to infer reservoir dilation (with high accuracy and high spatial resolution) using a limited number of surface deformation measurements. The proposed method was applied to infer the reservoir dilation induced by a waste disposal operation conducted at Frog Lake, Alberta and the practical issues pertaining to the proposed method were discussed. Finally, guidelines for tiltmeter array design were proposed and

  6. Haploidentical Related Donor Hematopoietic Stem Cell Transplantation for DOCK8 Deficiency Using Post-Transplantation Cyclophosphamide.

    PubMed

    Shah, Nirali N; Freeman, Alexandra F; Su, Helen; Cole, Kristen; Parta, Mark; Moutsopoulos, Niki M; Baris, Safa; Karakoc-Aydiner, Elif; Hughes, Thomas E; Kong, Heidi H; Holland, Steve M; Hickstein, Dennis D

    2017-03-10

    Dedicator-of-Cytokinesis-8 (DOCK8) deficiency, a primary immunodeficiency disease, can be reversed by allogeneic hematopoietic stem cell transplant (HSCT); however, there are few reports describing the use of alternative donor sources for HSCT in DOCK8 deficiency. We describe HSCT for patients with DOCK8 deficiency who lack a matched related or unrelated donor using bone marrow from haploidentical related donors and post-transplantation cyclophosphamide (PT/CY) for GVHD prophylaxis. Seven patients with DOCK8 deficiency (median age 20 years, range 7-25 years) received a haploidentical related donor HSCT. The conditioning regimen included 2 days of low-dose cyclophosphamide, 5 days of fludarabine, three days of busulfan, and 200 cGy TBI. Graft-versus host disease (GVHD) prophylaxis consisted of post-transplant cyclophosphamide (PT/CY) 50 mg/kg/day on days +3 and +4, and tacrolimus and mycophenolate mofetil starting at day +5. The median times to neutrophil and platelet engraftment were 15 and 19 days, respectively. All patients attained >90% donor engraftment by day +30. Four subjects developed acute GVHD (one with maximum grade 3). No patient developed chronic GVHD. With a median follow-up time of 20.6 months (range 9.5 - 31.7 months), 6 of 7 patients are alive and disease-free. Haploidentical related donor HSCT with PT/CY represents an effective therapeutic approach for patients with DOCK8 deficiency who lack a matched related or unrelated donor.

  7. [Cyclophosphamide versus bolus in Wegener's granulomatosis and other ANCA-related vasculitides: advantages and disadvantages].

    PubMed

    Reinhold-Keller, E; Warnatz, K

    2009-06-01

    Cyclophosphamide remains the therapy of choice in severe ANCA positive vasculitis. In order to avoid the considerable side effects of high cumulative doses sometimes manifesting themselves years later, induction therapy with a low cyclophosphamide dose and an early switch to cyclophosphamide-free maintenance regimens should be aimed for. This can be achieved by an induction therapy of 3--6 months of intravenous pulse therapy (pCYC) or oral therapy (oCYC). The metaanalysis of therapeutic trials in ANCA vasculitis demonstrates a slightly higher induction rate of remission, but an increased relapse rate of pCYC compared to oCYC. The incidence of adverse events seems to be higher in oCYC compared to pCYC. The results of the first controlled prospective multicenter trial (CYCLOPS) directly comparing pCYC and oCYC treatment of ANCA-positive vasculitis are eagerly awaited. It will be important to extend the follow-up over several years in order to reach a valid estimate of the incidence of secondary malignancies due to CYC therapy.

  8. Ozone-induced loss of neuronal M2 muscarinic receptor function is prevented by cyclophosphamide.

    PubMed

    Gambone, L M; Elbon, C L; Fryer, A D

    1994-09-01

    We tested the hypothesis that inflammatory cells mediate the loss of neuronal M2 muscarinic receptors in the lung after ozone exposure. Pathogen-free guinea pigs treated with cyclophosphamide (30 mg.kg-1.day-1 i.p. for 7 days) before exposure to ozone were compared with untreated ozone-exposed animals. This dose of cyclophosphamide significantly reduced leukocytes in peripheral blood and bronchoalveolar lavage fluid. Twenty-four hours after ozone, muscarinic receptor function was tested in anesthetized animals. In air-exposed guinea pigs, vagally induced bronchoconstriction was attenuated by the muscarinic agonist pilocarpine (0.1-100 micrograms/kg i.v.) and potentiated by the selective M2 antagonist gallamine (0.1-10 mg/kg i.v.), indicating that the neuronal M2 muscarinic receptors were functioning. These responses were significantly reduced after ozone, indicating loss of neuronal M2 muscarinic receptor function. However, in those animals treated with cyclophosphamide, M2 muscarinic receptor function was not altered by ozone. These data suggest that ozone-induced loss of neuronal muscarinic receptor function is mediated via inflammatory cells and that the link between ozone-induced hyperresponsiveness and inflammation may be the neuronal M2 muscarinic receptor.

  9. Cyclophosphamide pulses with oral prednisolone in the treatment of pemphigus: a pilot study.

    PubMed

    Bhat, Radhakrishna; Sharma, Vinod K; Ramam, M; Kumar, Ashok

    2005-12-01

    An open labeled clinical trial aimed at assessing the efficacy and safety of pulse intravenous cyclophosphamide with daily oral prednisolone in the treatment of pemphigus was carried out. Twenty-six patients (12 men, 14 women; mean age, 48.4 years), comprising 25 cases with pemphigus vulgaris and 1 with pemphigus vegetans (< 10% body surface area involvement) who did not achieve adequate control on corticosteroids with or without other adjuvants were included. After baseline evaluation, monthly intravenous boluses of cyclophosphamide (15 mg/kg) along with daily oral prednisolone (starting dose 1 mg/kg/day, tapered according to clinical response) were administered. Patients were assessed monthly for clinical activity and side-effects. All patients experienced significant clinical improvement within 1 month of starting treatment. Healing of skin and mucosal lesions occurred respectively at mean durations of 2.1 and 3.6 months. Three weeks to 8 months later, 9 patients had recurrences of activity on tapering/withdrawal of prednisolone, mainly in the oral mucosa. Side effects of treatment included amenorrhea (3 patients), microscopic hematuria (3) which cleared with co-administration of mesna, vomiting (1), weight gain (10), gastritis (1), and cataract (2). It is concluded that treatment with monthly intravenous cyclophosphamide boluses along with daily oral prednisolone clears lesions of pemphigus with < 10 percent body surface involvement, and this may be an alternative regimen for pemphigus. Monitoring for adverse effects is essential.

  10. Evaluation of the immunosuppressive effects of cyclophosphamide in patients with multiple sclerosis.

    PubMed Central

    ten Berge, R J; van Walbeek, H K; Schellekens, P T

    1982-01-01

    In a group of eight patients suffering from clinically definite multiple sclerosis, we studied the effects of treatment with cyclophosphamide on the immune reactivity in vitro and in vivo. The results are compared with those obtained in a control group consisting of eight patients who received no drug therapy and who were matched with the former group for age, sex and severity of disease. The results indicate that therapy with cyclophosphamide at a mean dose of 100 mg/day induces a profound lymphocytopenia in peripheral blood involving both T and B cells. Serum levels of immunoglobulins as well as primary and secondary antibody responses were depressed. In tests with standardized cell numbers, proliferative responses of lymphocytes in vitro and cytotoxic T cell function remained normal, whereas K and NK cell activities were diminished. Secondary cellular immune responses in vivo remained intact; however, the primary cellular immune response in vivo was markedly depressed. From these data, it is concluded that therapy with cyclophosphamide in man mainly affects humoral immune functions, but also cellular immunity, although to a lesser extent. PMID:7165996

  11. DNA damage recognition in the rat zygote following chronic paternal cyclophosphamide exposure.

    PubMed

    Barton, Tara S; Robaire, Bernard; Hales, Barbara F

    2007-12-01

    The detrimental effects of preconceptional paternal exposure to the alkylating anticancer agent, cyclophosphamide, include aberrant epigenetic programming, dysregulated zygotic gene activation, and abnormalities in the offspring that are transmitted to the next generation. The adverse developmental consequences of genomic instabilities transmitted via the spermatozoon emphasize the need to elucidate the mechanisms by which the early embryo recognizes DNA damage in the paternal genome. Little information exists on DNA damage detection in the zygote. We assessed the impact of paternal cyclophosphamide exposure on phosphorylated H2AX (gammaH2AX) and poly(ADP-ribose) polymerase-1(PARP-1), biomarkers of DNA damage, to determine the capacity in the rat zygote to recognize genomic damage and initiate a response to DNA lesions. An amplified biphasic gammaH2AX response was triggered in the paternal pronucleus in zygotes sired by drug-treated males; the maternal genome was not affected. PARP-1 immunoreactivity was substantially elevated in both parental genomes, coincident with the second phase of gammaH2AX induction in embryos sired by cyclophosphamide-exposed spermatozoa. Thus, paternal exposure to a DNA damaging agent rapidly activates signals implemental for DNA damage recognition in the zygote. Inefficient repair of DNA lesions may lead to persistent alterations of the histone code and chromatin integrity, resulting in aberrant embryogenesis. We propose that the response of the early embryo to disturbances in spermatozoal genomic integrity plays a vital role in determining its outcome.

  12. Fever after peripheral blood stem cell infusion in haploidentical transplantation with post-transplant cyclophosphamide.

    PubMed

    Arango, Marcos; Combariza, Juan F

    2017-06-01

    Noninfection-related fever can occur after peripheral blood stem cell infusion in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide. The objective of this study was to analyze the incidence of fever and characterize some clinical features of affected patients. A retrospective case-series study with 40 patients who received haploidentical hematopoietic stem cell transplantation was carried out. Thirty-three patients (82.5%) developed fever; no baseline characteristic was associated with its development. Median time to fever onset was 25.5h (range, 9.5-100h) and median peak temperature was 39.0°C (range, 38.1-40.5°C). Not a single patient developed hemodynamic or respiratory compromise that required admission to the intensive care unit. Fever was not explained by infection in any case. Ninety-one percent of the febrile episodes resolved within 96h of cyclophosphamide administration. No significant difference in overall survival, event-free survival, or graft versus host disease-free/relapse-free survival was found in the group of febrile individuals after peripheral blood stem cell infusion. Fever after peripheral blood stem cell infusion in this clinical setting was common; it usually subsides with cyclophosphamide administration. The development of fever was not associated with an adverse prognosis. Copyright © 2017 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

  13. Balloon dilation of congenital supravalvular pulmonic stenosis in a dog

    PubMed Central

    Treseder, Julia R.

    2017-01-01

    Percutaneous balloon valvuloplasty is considered the standard of care for treatment of valvular pulmonic stenosis, a common congenital defect in dogs. Supravalvular pulmonic stenosis is a rare form of pulmonic stenosis in dogs and standard treatment has not been established. Although, there have been reports of successful treatment of supravalvular pulmonic stenosis with surgical and stenting techniques, there have been no reports of balloon dilation to treat dogs with this condition. Here, a case of supravalvular pulmonic stenosis diagnosed echocardiographically and angiographically in which a significant reduction in pressure gradient was achieved with balloon dilation alone is presented. PMID:27297421

  14. Dilated cardiomyopathy after electrical injury: report of two cases.

    PubMed

    Buono, Lee M; DePace, Nicholas L; Elbaum, David M

    2003-05-01

    The specific etiologic factor and pathogenesis of most dilated cardiomyopathies have yet to be described definitively. Hypotheses of the etiologic factor of idiopathic dilated cardiomyopathy (DCM) abound. This report describes two patients with electrical injury in whom DCM developed after the electrical insult in the absence of other precipitating causes. Further histologic examination of myocardial tissue after electrical injury may reveal clues regarding the pathophysiology behind electrically induced DCM. Because electrical injury may be associated with myocardial dysfunction, short- and long-term evaluation of left ventricular function may be warranted.

  15. A new method for measurement of liquid dilatation parameters

    NASA Astrophysics Data System (ADS)

    Ondris, Lubomír; Rusina, Viktor

    1997-04-01

    A new user-friendly method for measuring dilatation parameters of non-volatile liquids, based on an optoelectronic hydrolevelling sensor, is described. The system is capable of measuring a liquid column height with an accuracy of about 0957-0233/8/4/004/img1 and allows determination of the temperature dilatation volume coefficient for transparent liquids with an accuracy that depends on the used thermometer accuracy. The method is also suitable for specific mass or density measurements with an accuracy comparable to that obtained with the pycnometric method.

  16. Improved test of time dilation in special relativity.

    PubMed

    Saathoff, G; Karpuk, S; Eisenbarth, U; Huber, G; Krohn, S; Muñoz Horta, R; Reinhardt, S; Schwalm, D; Wolf, A; Gwinner, G

    2003-11-07

    An improved test of time dilation in special relativity has been performed using laser spectroscopy on fast ions at the heavy-ion storage-ring TSR in Heidelberg. The Doppler-shifted frequencies of a two-level transition in 7Li+ ions at v=0.064c have been measured in the forward and backward direction to an accuracy of Deltanu/nu=1 x 10(-9) using collinear saturation spectroscopy. The result confirms the relativistic Doppler formula and sets a new limit of 2.2 x 10(-7) for deviations from the time dilation factor gamma(SR)=(1-v2/c2)(-1/2).

  17. Compression of Adjacent Anatomical Structures by Pulmonary Artery Dilation

    PubMed Central

    Dakkak, Wael; Tonelli, Adriano R.

    2016-01-01

    Pulmonary hypertension is the commonest condition leading to dilated pulmonary artery. We describe three different types of compression of adjacent anatomical structures by dilated pulmonary arteries. We included involvement of the left main coronary artery, left recurrent laryngeal nerve and tracheobronchial tree. Compression of these structures can cause major complications such as myocardial ischemia, hoarseness and major airway stenosis. We present a case for each scenario and review the literature for each of these complications, focusing on patients’ characteristics and contemporary management. PMID:26898826

  18. Study of action of cyclophosphamide and extract of mycelium of Pleurotus ostreatus in vivo on mice, bearing melanoma B16-F0-GFP

    NASA Astrophysics Data System (ADS)

    Meerovich, Irina G.; Yang, Meng; Jiang, Ping; Hoffman, Robert M.; Gerasimenya, Valery P.; Orlov, Alexander E.; Savitsky, Alexander P.; Popov, Vladimir O.

    2005-04-01

    In this work we studied in vivo the combined action of cyclophosphamide and the extract of mycelium of Pleurotus ostreatus on mice bearing melanoma B16-F0, expressing green fluorescent protein (GFP). This model allows to recognize small-size tumors and metastases, unrecognizable by other methods. It was found that combined administration of cyclophosphamide (300 mg/kg) and the extract of mycelium of Pleurotus ostreatus (100 mg/kg), administered for 10 days after cyclophosphamide injection, as well administration of cyclophosphamide alone, cause inhibition of tumor growth about 97%. It was shown that administration of the extract of mycelium of Pleurotus ostreatus alone leads to inhibition of tumor growth of 61%. It was found that in case of combined administration of cyclophosphamide and the extract of mycelium of Pleurotus ostreatus, leucopenia was less expressed than in case of administration of cyclophosphamide alone.

  19. Effects of multiple doses of cyclophosphamide on mouse testes: accessing the germ cells lost, and the functional damage of stem cells.

    PubMed

    Drumond, Ana Luiza; Weng, Connie C; Wang, Gensheng; Chiarini-Garcia, Helio; Eras-Garcia, Leticia; Meistrich, Marvin L

    2011-12-01

    Spermatogenesis is sensitive to the chemotherapeutic drug cyclophosphamide, which decreases the patients' sperm count. Since the recovery of fertility is dependent on regeneration from stem cells, in the present study we evaluated the ability of cyclophosphamide-exposed stem spermatogonia from mice to regenerate spermatogenesis in situ and after transplantation. When seven doses of cyclophosphamide were given at 4-day intervals, the differentiating germ cells were largely eliminated but ~50% of the undifferentiated type A spermatogonia remained. We monitored the recovery and found that sperm production recovered to 64% of control within the time expected. When the cyclophosphamide-surviving spermatogonia were transplanted into recipient mice, recovery of spermatogenesis from the cyclophosphamide-exposed donor cells was observed, but was reduced when compared to cells from cryptorchid donors. Thus, multidose regimens of cyclophosphamide did not eliminate the stem spermatogonia, but resulted in cell loss and residual damage.

  20. Intermittent self-dilatation for urethral stricture disease in males.

    PubMed

    Jackson, Matthew J; Veeratterapillay, Rajan; Harding, Chris K; Dorkin, Trevor J

    2014-12-19

    Intermittent urethral self-dilatation is sometimes recommended to reduce the risk of recurrent urethral stricture. There is no consensus as to whether it is a clinically effective or cost-effective intervention in the management of this disease. The purpose of this review is to evaluate the clinical effectiveness and cost-effectiveness of intermittent self-dilatation after urethral stricture surgery in males compared to no intervention. We also compared different programmes of, and devices for, intermittent self-dilatation. . We searched the Cochrane Incontinence Group Specialised Register (searched 7 May 2014), CENTRAL (2014, Issue 4), MEDLINE (1 January 1946 to Week 3 April 2014), PREMEDLINE (covering 29 April 2014), EMBASE (1 January 1947 to Week 17 2014), CINAHL (31 December 1981 to 30 April 2014) OpenGrey (searched 6 May 2014), ClinicalTrials.gov (6 May 2014), WHO International Clinical Trials Registry Platform (6 May 2014), Current Controlled Trials (6 May 2014) and the reference lists of relevant articles. Randomised and quasi-randomised trials where one arm was a programme of intermittent self-dilatation for urethral stricture were identified. Studies were excluded if they were not randomised or quasi-randomised trials, or if they pertained to clean intermittent self-catheterisation for bladder emptying. Two authors screened the records for relevance and methodological quality. Data extraction was performed according to predetermined criteria using data extraction forms. Analyses were carried out in Cochrane Review Manager (RevMan 5). The primary outcomes were patient-reported symptoms and health-related quality of life, and risk of recurrence; secondary outcomes were adverse events, acceptability of the intervention to patients and cost-effectiveness. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Eleven trials were selected for inclusion in the review, including a total of 776

  1. Spinal astrocytic activation contributes to mechanical allodynia in a rat model of cyclophosphamide-induced cystitis

    PubMed Central

    Liu, Bolong; Su, Minzhi; Tang, ShaoJun; Zhan, Hailun; Yang, Fei; Li, Wenbiao; Li, Tengcheng; Xie, Juncong

    2016-01-01

    Background Previous studies have demonstrated that glial cells play an important role in the generation and maintenance of neuropathic pain. Activated glial cells produce numerous mediators such as proinflammatory cytokines that facilitate neuronal activity and synaptic plasticity. Similarly, bladder pain syndrome/interstitial cystitis shares many characteristics of neuropathic pain. However, related report on the involvement of spinal glia in bladder pain syndrome/interstitial cystitis-associated pathological pain and the underlying mechanisms are still lacking. The present study investigated spinal glial activation and underlying molecular mechanisms in a rat model of bladder pain syndrome/interstitial cystitis. Results A rat model of bladder pain syndrome/interstitial cystitis was established via systemic injection with cyclophosphamide. Mechanical allodynia was tested with von Frey monofilaments and up-down method. Moreover, Western blots and double immunofluorescence were used to detect the expression and location of glial fibrillary acidic protein, OX42/Iba1, P-P38, NeuN, interleukin (IL)-1β, phosphorylation of N-methyl-D-aspartate receptor 1 (P-NR1), and IL-1 receptor I (IL-1RI) in the L6-S1 spinal cord. We found that glial fibrillary acidic protein rather than OX42/Iba1 or P-P38 was significantly increased in the spinal cord of cyclophosphamide-induced cystitis. L-alpha-aminoadipate but not minocycline markedly attenuated the allodynia. Furthermore, we found that spinal IL-1β was dramatically increased in cyclophosphamide-induced cystitis, and activated astrocytes were the only source of IL-1β release, which contributed to allodynia in cystitis rats. Besides, spinal P-NR1 was statistically increased in cyclophosphamide-induced cystitis and only localized in IL-1RI positive neurons in spinal dorsal horn. Additionally, NR antagonist significantly attenuated the cystitis-induced pain. Interestingly, the time course of the P-NR1 expression paralleled to that

  2. Rapamycin Prevents cyclophosphamide-induced Over-activation of Primordial Follicle pool through PI3K/Akt/mTOR Signaling Pathway in vivo.

    PubMed

    Zhou, Linyan; Xie, Yanqiu; Li, Song; Liang, Yihua; Qiu, Qi; Lin, Haiyan; Zhang, Qingxue

    2017-08-16

    Primordial follicular depletion has thought to be a common adverse effect of chemotherapy especially for female of reproductive age. The study aimed to evaluate the protective effect of rapamycin on the primordial follicles and its potential mechanism for patients receiving chemotherapy. 8-week old BALB/c female mice were randomly assigned into four groups (control; rapamycin; cyclophosphamide; and rapamycin combined with cyclophosphamide). Hematoxylin staining, immunohistochemical, TUNEL, western blotting and ELISA were employed to assess inter-group differences using Student's t-test and Mann-Whitney test. Cyclophosphamide depleted the follicular reserve and induced the phosphorylation of the key proteins of PI3K/Akt/mTOR pathway in mice in a dose-dependent manner. Co-treatment with rapamycin significantly reduced primordial follicle loss at all cyclophosphamide dose groups and prevent the follicle growth wave caused by cyclophosphamide treatment (P < 0.05). TUNEL staining showed that no apoptosis occured in the primordial follicles in all groups and fewer apoptosis in large growing follicles were observed in ovaries from rapamycin + cyclophosphamide group compared to that received cyclophosphamide alone. Serum anti-Müllerian hormone (AMH) was significantly reduced in cyclophosphamide alone group, in contrast to the normal level in rapamycin + cyclophosphamide group. Compared to p-Akt/Akt and p-mtor/mtor, p-rps6/rps6 was significantly decreased in rapamycin + cyclophosphamide group (P < 0.05), indicating that rapamycin attenuated the increased level of phosphorylation of rpS6 after cyclophosphamide treatment. Rapamycin can prevent the primordial follicle activation induced by cyclophosphamide through PI3K/Akt/mTOR signaling pathway and thus plays a role in preserving the follicle pool. These results suggest that rapamycin may be an effective protection for ovarian function during chemotherapy, which means a new nonsurgical application for protection of

  3. Novel Borna Virus in Psittacine Birds with Proventricular Dilatation Disease

    PubMed Central

    Honkavuori, Kirsi S.; Shivaprasad, H.L.; Williams, Brent L.; Quan, Phenix-Lan; Hornig, Mady; Street, Craig; Palacios, Gustavo; Hutchison, Stephen K.; Franca, Monique; Egholm, Michael; Lipkin, W. Ian

    2008-01-01

    Pyrosequencing of cDNA from brains of parrots with proventricular dilatation disease (PDD), an unexplained fatal inflammatory central, autonomic, and peripheral nervous system disease, showed 2 strains of a novel Borna virus. Real-time PCR confirmed virus presence in brain, proventriculus, and adrenal gland of 3 birds with PDD but not in 4 unaffected birds. PMID:19046511

  4. Cytokines and posthemorrhagic ventricular dilation in premature infants.

    PubMed

    Ambalavanan, Namasivayam; Carlo, Waldemar A; McDonald, Scott A; Das, Abhik; Schendel, Diana E; Thorsen, Poul; Hougaard, David M; Skogstrand, Kristin; Higgins, Rosemary D

    2012-10-01

    To determine in extremely low-birth-weight infants if elevated blood interferon-γ (IFN-γ), interleukin (IL)-1β, IL-18, tumor necrosis factor-α (TNF-α), and transforming growth factor-β are associated with need for shunt following severe intraventricular hemorrhage (IVH) or with ventricular dilation following milder grades/no IVH. Whole blood cytokines were measured on postnatal days 1, 3, 7, 14, and 21. Maximum IVH grade in the first 28 days, and shunt surgery or ventricular dilation on subsequent ultrasound (28 days' to 36 weeks' postmenstrual age) were determined. Of 902 infants in the National Institute of Child Health and Human Development Neonatal Research Network Cytokine study who survived to 36 weeks or discharge, 3.1% had shunts. Of the 12% of infants with severe (grade III to IV) IVH, 26% had a shunt associated with elevated TNF-α. None of the infants without IVH (69%) or with grade I (12%) or II (7%) IVH received shunts, but 8.4% developed ventricular dilation, associated with lower IFN-γ and higher IL-18. Statistically significant but clinically nondiscriminatory alterations in blood cytokines were noted in infants with severe IVH who received shunts and in those without severe IVH who developed ventricular dilation. Blood cytokines are likely associated with brain injury but may not be clinically useful as biomarkers for white matter damage. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  5. Aneurysmal dilatation of medium caliber arteries in Turner syndrome.

    PubMed

    Polkampally, Pritam R; Matta, Jatin R; McAreavey, Dorothea; Bakalov, Vladimir; Bondy, Carolyn A; Gharib, Ahmed M

    2011-01-01

    Turner syndrome is the most common chromosomal abnormality in female subjects, affecting 1 in 2000 live births. The condition is associated with a generalized vasculopathy as well as congenital cardiac and other defects. We report aneurysmal dilation of medium caliber arteries involving the celiac axis and coronary vessels in two women with Turner syndrome.

  6. Thrombus formation in a dilated torcula following aneurysmal subarachnoid haemorrhage.

    PubMed

    Haynes, H R; Visca, A; Renowden, S; Malcolm, G

    2013-08-01

    A case of thrombus formation occurring within a dilation of the dural venous sinuses following aneurysmal sub-arachnoid haemorrhage is presented. Acute neurological deterioration accompanied propagation of the thrombus. The patient was anticoagulated on day 5 post-SAH with no haemorrhagic complications and made a full recovery. The optimum time to commence anticoagulation is not clear and is discussed.

  7. Arborescent vascular dilatation mimicking Lichtenberg figures from lightning.

    PubMed

    Tempark, Therdpong; Iwasaki, Julie; Shwayder, Tor

    2014-01-01

    The clinical presentation of arborizing vascular dilatation can resemble Lichtenberg figures from lightning. Both have a feather-like or ferning pattern. We report an interesting case of pressure-induced vasodilatation (PIV) caused by temporary vascular occlusion from jeans buttons.

  8. Operative balloon dilatation for pulmonary atresia with intact ventricular septum.

    PubMed Central

    Hamilton, J R; Fonseka, S F; Wilson, N; Dickinson, D F; Walker, D R

    1987-01-01

    In six infants with pulmonary atresia and intact ventricular septum operative balloon dilatation was used to achieve continuity between the right ventricle and the main pulmonary artery as the initial procedure. Two of the six subsequently needed an aortico pulmonary shunt. All six are alive and well. Images Fig PMID:3676024

  9. Omasal dilation and displacement in 4 Holstein dairy cows

    PubMed Central

    Bicalho, Rodrigo C.; Mayers, Heather M.; Cheong, Soon Hon; Rosa, Brielle V.; Guard, Charles L.

    2009-01-01

    Cases of omasal dilation and displacement in 4 dairy cows are described. The disease was initially diagnosed by a combination of history and clinical signs that included right-sided abdominal distension, rectal palpation, and decreased milk production. The condition was confirmed by laparotomy or necropsy. PMID:19436447

  10. Prolonged idiopathic gastric dilatation following revascularization for chronic mesenteric ischemia.

    PubMed

    Gauci, Julia L; Stoven, Samantha; Szarka, Lawrence; Papadakis, Konstantinos A

    2014-01-01

    A 71-year-old female presented with nausea, emesis, early satiety, and abdominal distension following revascularization for chronic mesenteric ischemia. Computed tomography angiogram showed gastric dilatation. Esophagogastroduodenoscopy, small bowel follow through, and paraneoplastic panel were negative. Gastric emptying was delayed. Despite conservative management, she required a percutaneous endoscopic jejunostomy. The development of a prolonged gastroparetic state has not been previously described.

  11. Cystic Dilatation of the Parotid Duct of a Goat

    PubMed Central

    Slocombe, R. F.

    1980-01-01

    Cystic dilatation of the parotid duct of a goat was diagnosed by exploratory surgery and analysis of cyst contents. The cyst and its associated salivary gland were surgically removed. This case is compared with the more common salivary mucocele. ImagesFigure 1. PMID:7397617

  12. Prolonged idiopathic gastric dilatation following revascularization for chronic mesenteric ischemia

    PubMed Central

    Gauci, Julia L.; Stoven, Samantha; Szarka, Lawrence; Papadakis, Konstantinos A.

    2014-01-01

    A 71-year-old female presented with nausea, emesis, early satiety, and abdominal distension following revascularization for chronic mesenteric ischemia. Computed tomography angiogram showed gastric dilatation. Esophagogastroduodenoscopy, small bowel follow through, and paraneoplastic panel were negative. Gastric emptying was delayed. Despite conservative management, she required a percutaneous endoscopic jejunostomy. The development of a prolonged gastroparetic state has not been previously described. PMID:24975870

  13. Linkage of familial dilated cardiomyopathy to chromosome 9

    SciTech Connect

    Krajinovic, M.; Vatta, M.; Milasin, J.

    1995-10-01

    Idiopathic dilated cardiomyopathy is a heart muscle disease of unknown etiology, characterized by impaired myocardial contractility and ventricular dilatation. The disorder is an important cause of morbidity and mortality and represents the chief indication for heart transplantation. Familial transmission is often recognized (familial dilated cardiomyopathy, or FDC), mostly with autosomal dominant inheritance. In order to understand the molecular genetic basis of the disease, a large six-generation kindred with autosomal dominant FDC was studied for linkage analysis. A genome-wide search was undertaken after a large series of candidate genes were excluded and was then extended to two other families with autosomal dominant pattern of transmission and identical clinical features. Coinheritance of the disease gene was excluded for >95% of the genome, after 251 polymorphic markers were analyzed. Linkage was found for chromosome 9q13-q22, with a maximum multipoint lod score of 4.2. There was no evidence of heterogeneity. The FDC locus was placed in the interval between loci D9S153 and D9S152. Several candidate genes for causing dilated cardiomyopathy map in this region. 33 refs., 3 figs., 1 tab.

  14. Advanced diagnostic approaches and current management of proventricular dilatation disease.

    PubMed

    Gancz, Ady Y; Clubb, Susan; Shivaprasad, H L

    2010-09-01

    Proventricular dilatation disease (PDD) is a fatal inflammatory disease that affects mainly, but not exclusively, psittacine birds (Order: Psittaciformes). PDD has long been suspected to be a viral disease, but its causative agent, a novel Bornavirus, was only identified in 2008. Copyright 2010 Elsevier Inc. All rights reserved.

  15. Novel borna virus in psittacine birds with proventricular dilatation disease.

    PubMed

    Honkavuori, Kirsi S; Shivaprasad, H L; Williams, Brent L; Quan, Phenix Lan; Hornig, Mady; Street, Craig; Palacios, Gustavo; Hutchison, Stephen K; Franca, Monique; Egholm, Michael; Briese, Thomas; Lipkin, W Ian

    2008-12-01

    Pyrosequencing of cDNA from brains of parrots with proventricular dilatation disease (PDD), an unexplained fatal inflammatory central, autonomic, and peripheral nervous system disease, showed 2 strains of a novel Borna virus. Real-time PCR confirmed virus presence in brain, proventriculus, and adrenal gland of 3 birds with PDD but not in 4 unaffected birds.

  16. 21 CFR 870.1310 - Vessel dilator for percutaneous catheterization.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Vessel dilator for percutaneous catheterization. 870.1310 Section 870.1310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Diagnostic Devices § 870.1310...

  17. 21 CFR 870.1310 - Vessel dilator for percutaneous catheterization.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Vessel dilator for percutaneous catheterization. 870.1310 Section 870.1310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Diagnostic Devices § 870.1310...

  18. 21 CFR 870.1310 - Vessel dilator for percutaneous catheterization.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Vessel dilator for percutaneous catheterization. 870.1310 Section 870.1310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Diagnostic Devices § 870.1310...

  19. 21 CFR 870.1310 - Vessel dilator for percutaneous catheterization.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Vessel dilator for percutaneous catheterization. 870.1310 Section 870.1310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Diagnostic Devices § 870.1310...

  20. 21 CFR 870.1310 - Vessel dilator for percutaneous catheterization.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Vessel dilator for percutaneous catheterization. 870.1310 Section 870.1310 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Diagnostic Devices § 870.1310...

  1. Left coronary aneurysmal dilation and subaortic stenosis in a dog.

    PubMed

    Hernandez, Juan L; Bélanger, Marie-Claude; Benoit-Biancamano, Marie-Odile; Girard, Christiane; Pibarot, Philippe

    2008-06-01

    A 6-month-old German shepherd dog was referred for evaluation of a cardiac murmur. Upon physical examination, the auscultated heart rate was 120 beats/min, and a grade IV/VI systolic heart murmur with a point of maximal intensity over the left heart base radiating up the neck was heard. The standard echocardiographic examination showed subaortic stenosis and an anechoic tubular structure extending from the sinus of Valsalva to the left ventricular posterior wall. Aneurysmal left coronary artery (CA) was confirmed by angiography. The dog was euthanized and post-mortem examination showed severe dilatation of the proximal left CA and confirmed the subaortic stenosis. Histopathology did not demonstrate abnormalities in the walls of the CA, aorta or pulmonary artery. The exact cause of the CA aneurysmal dilation remains unknown. Subaortic stenosis, elevated coronary vascular resistance or a congenital anomaly may have contributed to the dilation. To our knowledge, coronary aneurysmal dilation has never been described in dogs. Standard echocardiography provides reliable information on coronary anatomy.

  2. A Phase I Study of Veliparib in Combination with Metronomic Cyclophosphamide in Adults with Refractory Solid Tumors and Lymphomas

    PubMed Central

    Kummar, Shivaani; Ji, Jiuping; Morgan, Robert; Lenz, Heinz-Josef; Puhalla, Shannon L.; Belani, Chandra P.; Gandara, David R.; Allen, Deborah; Kiesel, Brian; Beumer, Jan H.; Newman, Edward M.; Rubinstein, Larry; Chen, Alice; Zhang, Yiping; Wang, Lihua; Kinders, Robert J.; Parchment, Ralph E.; Tomaszewski, Joseph E.; Doroshow, James H.

    2012-01-01

    Purpose Oral administration of the alkylating agent cyclophosphamide at low doses, metronomic dosing, is well tolerated, with efficacy in multiple tumor types. Poly(ADP-ribose) polymerase (PARP) inhibition potentiates effects of cyclophosphamide in preclinical models. We conducted a phase I trial of the PARP inhibitor veliparib and metronomic cyclophosphamide in patients with refractory solid tumors and lymphoid malignancies. Experimental Design Objectives were to establish the safety and maximum tolerated dose (MTD) of the combination; characterize veliparib pharmacokinetics; measure poly(ADP-ribose) (PAR), a product of PARP, in tumor biopsies and peripheral blood mononuclear cells (PBMCs); and measure the DNA-damage marker γH2AX in PBMCs and circulating tumor cells (CTCs). Cyclophosphamide was administered once daily in 21-day cycles in combination with veliparib administered once daily for 7, 14, or 21 days. Results Thirty-five patients were enrolled. The study treatment was well tolerated, and the MTD was established as veliparib 60 mg with cyclophosphamide 50 mg given once daily. Seven patients had partial responses; an additional six patients had disease stabilization for at least six cycles. PAR was significantly decreased in PBMCs (by at least 50%) and tumor biopsies (by at least 80%) across dose levels; γH2AX levels were increased in CTCs from seven of nine patients evaluated after drug administration. Conclusions The combination of veliparib with metronomic cyclophosphamide is well tolerated and shows promising activity in a subset of patients with BRCA mutations. A phase II trial of the combination compared to single-agent cyclophosphamide is ongoing in BRCA-positive ovarian cancer, triple-negative breast cancer, and low-grade lymphoma. PMID:22307137

  3. Severity of mastalgia in relation to milk duct dilatation.

    PubMed

    Peters, Friedolf; Diemer, Petra; Mecks, Olaf; Behnken L, Lütje J

    2003-01-01

    The etiology of mastalgia is poorly understood. Histology cannot detect any distinct characteristics. This investigation therefore applied ultrasonography to mastalgia patients to investigate morphological structures and to obtain further insights into the pathophysiology of mastalgia. The aim of the study was to analyze the significance of milk duct dilatation in patients with mastalgia. A total of 335 premenopausal women participated in a genital and breast cancer screening program. Of these, 123 women were asymptomatic and 212 complained of breast pain (136 had cyclical mastalgia; 76 reported the noncyclical type). The width of milk ducts was measured by ultrasonography and correlated with the intensity of breast pain. The site of the pain was correlated with duct dilatation. Statistical analysis was performed using the t test, the chi(2) test, analysis of variance, and Pearson correlation. In asymptomatic women, the maximum mean width of the milk ducts was 1.8 +/- 0.84 mm, in cyclical mastalgia 2.34 +/- 1.10 mm, and 3.89 +/- 1.26 mm in noncyclical mastalgia (P <.001). The intensity of pain showed a significant, positive correlation with the width of the milk ducts (r =.5008, P <.001). Noncyclical mastalgia patients located the pain at the site where dilated ducts were detected ultrasonographically (P <.001). The results of this study demonstrate that duct ectasia is a major factor in mastalgia. The degree of duct dilatation correlates positively with the intensity of breast pain. In the noncyclical type of pain, there is a positive correlation between the site of duct dilatation and the site of pain.

  4. Development of dilated cardiomyopathy in Bmal1-deficient mice

    PubMed Central

    Lefta, Mellani; Campbell, Kenneth S.; Feng, Han-Zhong; Jin, Jian-Ping

    2012-01-01

    Circadian rhythms are approximate 24-h oscillations in physiology and behavior. Circadian rhythm disruption has been associated with increased incidence of hypertension, coronary artery disease, dyslipidemia, and other cardiovascular pathologies in both humans and animal models. Mice lacking the core circadian clock gene, brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like protein (Bmal1), are behaviorally arrhythmic, die prematurely, and display a wide range of organ pathologies. However, data are lacking on the role of Bmal1 on the structural and functional integrity of cardiac muscle. In the present study, we demonstrate that Bmal1−/− mice develop dilated cardiomyopathy with age, characterized by thinning of the myocardial walls, dilation of the left ventricle, and decreased cardiac performance. Shortly after birth the Bmal1−/− mice exhibit a transient increase in myocardial weight, followed by regression and later onset of dilation and failure. Ex vivo working heart preparations revealed systolic ventricular dysfunction at the onset of dilation and failure, preceded by downregulation of both myosin heavy chain isoform mRNAs. We observed structural disorganization at the level of the sarcomere with a shift in titin isoform composition toward the stiffer N2B isoform. However, passive tension generation in single cardiomyocytes was not increased. Collectively, these findings suggest that the loss of the circadian clock gene, Bmal1, gives rise to the development of an age-associated dilated cardiomyopathy, which is associated with shifts in titin isoform composition, altered myosin heavy chain gene expression, and disruption of sarcomere structure. PMID:22707558

  5. Open versus percutaneous dilatational tracheostomy: efficacy and cost analysis.

    PubMed

    Grover, A; Robbins, J; Bendick, P; Gibson, M; Villalba, M

    2001-04-01

    The economic advantages of percutaneous dilatational tracheostomies versus open tracheostomies in the operating room have been thoroughly evaluated. We are now reporting our comparison of the costs and charges of percutaneous dilatational tracheostomies with those of open bedside tracheostomies at our institution. The current literature comparing the two open techniques and the percutaneous method of placing tracheostomies was reviewed and the charges and costs for these procedures at our institution were compared. Patients were placed into one of three groups for analysis: open tracheostomies in the operating room (Group I), open tracheostomies in the intensive care unit (Group II), and percutaneous dilatational tracheostomies in the intensive care unit (Group III). Based on our own experience and a literature review it is evident that all three approaches to tracheostomies are safe. Economic analysis showed a savings of $180 in cost per procedure and a $658 savings in charges per procedure for the open method at the bedside when compared with the percutaneous method at the bedside. The professional fee for bronchoscopy was not included in this calculation; including this would lead to greater savings with the open method over the percutaneous method. Open tracheostomy in the operating room increased costs over the bedside procedure by $2194 and increased charges by $2871. For the 150 to 180 tracheostomies done each year at our institution utilization of the open technique at the bedside results in a cost savings of approximately $31,500 and a charge savings of $109,000 compared with the percutaneous dilatational tracheostomy. Both the open bedside and percutaneous dilatational methods are reasonable and safe options. However, the open bedside tracheostomy is a better utilization of resources and is more cost effective, and it is the procedure of choice at our institution.

  6. Progression of cervical dilatation in normal human labor is unpredictable.

    PubMed

    Ferrazzi, Enrico; Milani, Silvano; Cirillo, Federico; Livio, Stefania; Piola, Cinzia; Brusati, Valentina; Paganelli, Andrea

    2015-10-01

    The aim of this study was to analyze how the progression of cervical dilatation in active labor can be predicted by digital assessment in low-risk pregnant women, in spontaneous labor at term. This prospective observational study was performed on 328 women with singleton term gestations experiencing midwife-led labor according to local protocols, progressing to full dilatation and spontaneous delivery without any medical intervention. Mixed nonlinear models were adopted to (i) model individual cervical data into centile curves and (ii) calculate the time needed to gain 1 cm in cervical dilatation (TNG1cm ) modeled as a function of current dilatation. We correlated the first and the last TNG1cm on parturients with at least four cervical data points. TNG1cm showed large variations, both before and after 6 cm. This variability of natural progression of cervical curves described by the 10th and 90th centiles exceeded the differences observed in published curves from cohorts homogeneous for parity, weight and ethnicity. There was no significant correlation between the first and the last TNG1cm . Neonatal base excess was not significantly different in women with TNG1cm <10th centile and >90th centile. The rate of cervical dilatation, traced by parsimonious nonlinear mixed models, is largely unpredictable in the case of spontaneous naturally progressing labor, even when possible larger individual variability is excluded by prudent clinical rules. Future research in labor and delivery should be focused on the diagnosis of the causes that lie behind apparently erratic cervical changes. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

  7. Cervical Preparation Before Dilation and Evacuation Using Adjunctive Misoprostol or Mifepristone Compared With Overnight Osmotic Dilators Alone: A Randomized Controlled Trial.

    PubMed

    Goldberg, Alisa B; Fortin, Jennifer A; Drey, Eleanor A; Dean, Gillian; Lichtenberg, E Steve; Bednarek, Paula H; Chen, Beatrice A; Dutton, Caryn; McKetta, Sarah; Maurer, Rie; Winikoff, Beverly; Fitzmaurice, Garrett M

    2015-09-01

    To evaluate operative time after adjunctive misoprostol or mifepristone compared with overnight osmotic dilators alone for cervical preparation before dilation and evacuation at 16-23 6/7 weeks of gestation. This double-blind, three-arm, multicenter, randomized trial compared overnight osmotic dilators alone, dilators plus 400 micrograms buccal misoprostol 3 hours preoperatively, and dilators plus 200 mg oral mifepristone during dilator placement for dilation and evacuation. Our primary outcome was dilation and evacuation operative time within two cohorts: 16-18 6/7 weeks of gestation (N=150) and 19-23 6/7 weeks of gestation (N=150). Three hundred women were required for 80% power to detect a 2-minute difference in operative time. Secondary outcomes included initial cervical dilation, side effects, physician satisfaction by Likert scale, and complications. Between February 2013 and February 2014 we randomized 300 women evenly across treatment arms. Group demographics were similar. We found no difference in operative time in either gestational cohort (early cohort [minutes]: 5.11±3.0 dilators alone, 4.99±3.3 misoprostol, 4.33±2.0 mifepristone, P=.34; late cohort [minutes]: 7.50±3.7 dilators alone, 7.62±5.4 misoprostol, 6.74±3.2 mifepristone, P=.53). In the early cohort, initial dilation was greater with misoprostol than dilators alone (2.4 compared with 2.0 cm, P=.007). Patients given misoprostol had significantly more pain, fever, and chills. In the late cohort, dilation and evacuation procedures were less difficult after mifepristone (4.1%, 95% confidence interval [CI] 0.0-9.6) than misoprostol (18.8%, 95% CI 7.7-29.8) or dilators alone (18.8%, 95% CI 7.7-29.8; P=.04). We had inadequate power to infer differences in complications: dilators alone (10%, 95% CI 4.2-16.0) compared with misoprostol (2%, 95% CI 0-4.7) compared with mifepristone (2%, 95% CI 0-4.8). Despite no difference in operative time, adjunctive mifepristone facilitates later dilation and

  8. Black-white differences in mortality in idiopathic dilated cardiomyopathy: the Washington, DC, dilated cardiomyopathy study.

    PubMed Central

    Coughlin, S. S.; Gottdiener, J. S.; Baughman, K. L.; Wasserman, A.; Marx, E. S.; Tefft, M. C.; Gersh, B. J.

    1994-01-01

    Racial, socioeconomic, and clinical factors were examined as predictors of survival in idiopathic dilated cardiomyopathy using cases from five Washington, DC-area hospitals. One hundred three (80.5%) of the patients were black and 25 (19.5%) were white. The black patients were less likely to have private health insurance, less educated on average, and more likely to have a household income of $15,000 or less (P < or = .05). No racial differences were found in cardiac medication usage, with the exception of beta blockers and antiarrhythmics. The cumulative survival among black patients at 12 and 24 months was 71.5% and 63.6%, respectively, as compared with 92.0% and 86.3% among whites. The 12-month survival of black patients with ventricular arrhythmias or an ejection fraction of less than 25% was particularly poor. Age, ventricular arrhythmias, ejection fraction, and cigarette usage were significant predictors of survival in univariate analysis using the proportional hazards model. The univariate association with black race was of borderline significance (P < or = .07). In multivariate analysis, age and race were statistically significant independent predictors of survival. A strong association with black race was observed with an estimated relative risk of mortality of 5.41 (P < or = .02) after adjustment for age, ejection fraction, ventricular arrhythmias, and educational attainment. Poorer survival among blacks may be caused by a greater severity of disease at the time of diagnosis or by racial differences in cardiac care, comorbid conditions, or biologic factors affecting survival. PMID:7932836

  9. Diagnostic value of hysteroscopy: correlation with histological findings after dilatation and curettage and hysterectomy.

    PubMed

    Piccolboni, G; Arlacchi, E; Cattani, P; Zardini, R; Lavanda, E; Zardini, E

    1991-01-01

    The Authors carried out a comparative assessment of hysteroscopy diagnosis and histological findings obtained by dilatation and curettage and hysterectomy. Analysis of the data shows a good correlation between hysteroscopic diagnosis and histological findings obtained with dilatation and curettage.

  10. Determination of exposure of dispensary drug preparers to cyclophosphamide by passive sampling and liquid chromatography with tandem mass spectrometry.

    PubMed

    Wakui, Nobuyuki; Ookubo, Tetuo; Iwasaki, Yusuke; Ito, Rie; Mitui, Miyuki; Yano, Yuichi; Saito, Koichi; Nakazawa, Hiroyuki

    2013-03-01

    To determine cyclophosphamide exposure to preparers during tablet crushing and subsequent handling by analyzing indoor air collected using a high-performance volatile organic compounds-solvent desorption (VOC-SD) passive air sampler. The passive sampler was taped to the mask over the mouth of the preparer and indoor air was collected during crushing and preparation of cyclophosphamide tablets (Endoxan®). After collection, the carbon molecular sieve adsorbent of the passive sampler was placed in a centrifuge tube, and 1 mL of carbon disulfide was used to elute cyclophosphamide from the adsorbent. Liquid-liquid extraction with 1 mL of water was performed, and the aqueous phase was used as the test solution. Cyclophosphamide concentration was determined by liquid chromatography with ultraviolet and tandem mass spectrometry detection. Cyclophosphamide concentration was detected in the range of 7.6-157.7 ng/sampler. Our results showed that low-level exposure occurred near the mouth of the preparer, which could present risks for long-term exposure, especially if combined with multiple toxic drug exposures. The anticancer drug monitoring methodology described here is a simple exposure assessment that can be used to ensure the safety of hospital pharmacy tablet preparers. Furthermore, since the anticancer drug exposure risk is very high for preparers, preparation should be in hood or with face mask.

  11. Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results

    PubMed Central

    Morgan, Gareth J.; Davies, Faith E.; Gregory, Walter M.; Bell, Sue E.; Szubert, Alexander J.; Navarro Coy, Nuria; Cook, Gordon; Feyler, Sylvia; Johnson, Peter R.E.; Rudin, Claudius; Drayson, Mark T.; Owen, Roger G.; Ross, Fiona M.; Russell, Nigel H.; Jackson, Graham H.; Child, J. Anthony

    2012-01-01

    Background Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation. Design and Methods Oral cyclophosphamide, thalidomide, and dexamethasone was compared with infusional cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma. Results The post-induction overall response rate (≥ partial response) for the intent-to-treat population was significantly higher with cyclophosphamide-thalidomide-dexamethasone (n=555) versus cyclophosphamide-vincristine-doxorubicin-dexamethasone (n=556); 82.5% versus 71.2%; odds ratio 1.91; 95% confidence interval 1.44–2.55; P<0.0001. The complete response rates were 13.0% with cyclophosphamide-thalidomide-dexamethasone and 8.1% with cyclophos-phamide-vincristine-doxorubicin-dexamethasone (P=0.0083), with this differential response being maintained in patients who received autologous stem-cell transplantation (post-transplant complete response 50.0% versus 37.2%, respectively; P=0.00052). Cyclophosphamide-thalidomide-dexamethasone was non-inferior to cyclophosphamide-vincristine-doxorubicin-dexamethasone for progression-free and overall survival, and there was a trend toward a late survival benefit with cyclophosphamide-thalidomide-dexamethasone in responders. A trend toward an overall survival advantage for cyclophosphamide-thalidomide-dexamethasone over cyclophosphamide-vincristine-doxorubicin-dexamethasone was also observed in a subgroup of patients with favorable interphase fluorescence in situ hybridization. Compared with cyclophosphamide-vincristine-doxorubicin-dexamethasone, cyclophosphamide-thalidomide-dexamethasone was associated with more constipation and somnolence, but a lower incidence of cytopenias. Conclusions The cyclophosphamide-thalidomide-dexamethasone regimen showed improved response rates and was not inferior

  12. Joint Symbolic Dynamics Analysis of Heart Rate and Systolic Blood Pressure Interactions in Dilated Cardiomyopathy

    DTIC Science & Technology

    2007-11-02

    Abstract- The dilated cardiomyopathy (DCM) induces important changes in the autonomic control. Measures of heart rate (HR) variability and systolic...rather simple physiological interpretations and seems to be particularly suitable for risk stratification in patients with dilated cardiomyopathy ...Keywords - Symbolic dynamics, heart rate variability, blood pressure variability I. INTRODUCTION Patients suffering from dilated cardiomyopathy

  13. Lung atelectasis secondary to massive esophageal dilation in a patient with scleroderma

    PubMed Central

    St-Arnaud, Charles; Bouchard, Nicole; Lanthier, Luc

    2010-01-01

    Esophageal dilation is a rare complication of scleroderma and CREST syndrome. A case of atelectasis secondary to right inferior bronchus compression by a massively dilated esophagus is described. The authors are unaware of any previous cases of atelectasis secondary to esophageal dilation in scleroderma. PMID:20808981

  14. Reactivity of the immunological system of rats stimulated with Biolex-Beta HP after cyclophosphamide immunosuppression.

    PubMed

    Wójcik, Roman

    2014-01-01

    The objective of this study was to determine the stimulating effect of the Biolex-Beta HP (β-1,3/1,6-D-glucan) dietary supplement on selected parameters of specific and non-specific humoral and cellular immunity in rats immunosuppressed with cyclophosphamide. The experimental material comprised 40 Wistar rats, divided into two equal groups: control and experimental. In the course of 3 successive days, the rats from the experimental group were administered cyclophosphamide intramuscularly at a rate of 50 mg/kg BW per day. On the 8(th) day of the experiment, 10 control and 10 experimental rats were sacrificed, and total protein and γ-globulin levels, lysozyme and ceruloplasmin activity were determined in the blood serum. The proliferative response of blood lymphocytes after stimulation with lipopolysaccharide or concanavalin A, respiratory burst activity and the potential killing activity of phagocytes were determined in whole heparinised blood. Starting on the 8(th) day of the experiment, the feed of the remaining rats from the experimental and control groups was supplemented for 14 consecutive days with Biolex-Beta HP at a rate of 50 mg/kg BW per day. On day 22, arterial blood samples were collected and immune parameters were determined. The results indicate that β-1,3/1,6-D-glucan has a positive effect on the analysed parameters of non-specific cellular and humoral immunity after cyclophosphamide-induced suppression. Nevertheless, the observed effect only marked a return to the norm, as most of the analysed parameters were merely restored to their initial levels, with the exception of lysozyme activity, which considerably exceeded the level noted before immunosuppression.

  15. Effects of phosphoramide mustard and acrolein, cytotoxic metabolites of cyclophosphamide, on mouse limb development in vitro.

    PubMed

    Hales, B F

    1989-07-01

    Phosphoramide mustard and acrolein are toxic and reactive metabolites of the widely used anticancer drug and known teratogen cyclophosphamide. To study the mechanism(s) involved and to determine which of the active metabolites of cyclophosphamide is responsible for the production of limb malformations, the effects of exposure of cultured limb buds to phosphoramide mustard and acrolein were investigated. Fore- and hindlimbs were excised from ICR mice on day 12 of gestation and cultured in roller bottles for 6 days. Limbs were exposed to either phosphoramide mustard or acrolein (10 or 50 micrograms/ml) for the first 20 hours of the culture period. Exposure to phosphoramide mustard produced limb reduction malformations in both the fore- and hindlimbs; total limb bone area was greatly reduced, while the relative contribution of the paw to this area in forelimbs was increased. There was a fourfold reduction in both DNA and RNA; protein content was reduced only by one-half. Alkaline phosphatase activity was significantly decreased in fore- and hindlimbs exposed to phosphoramide mustard, whereas creatine phosphokinase activity was only reduced in hindlimbs in the limbs exposed to the higher concentration of phosphoramide mustard. Exposure to acrolein also produced malformed limbs with a mangled appearance; however, total limb bone area and the relative contribution of the long bones versus paw structures were not altered. Acrolein exposure had little effect on growth parameters such as DNA (decreased only in hindlimbs exposed to 50 micrograms/ml), RNA (increased in hindlimbs exposed to 50 micrograms/ml), or protein content. Alkaline phosphatase and creatine phosphokinase activities were not altered in acrolein-exposed fore- or hindlimbs. Thus, phosphoramide mustard and acrolein have dramatically different effects on developing limbs in vitro; this observation may indicate that they have different targets and/or mechanisms of action as teratogens in the limb. The effects

  16. Cyclophosphamide-induced agenesis of cerebral aqueduct resulting in hydrocephalus in mice.

    PubMed

    Prakash; Singh, Gajendra; Singh, Sukh Mahendra

    2007-07-01

    The present work was undertaken to reveal the mechanism of cerebral aqueduct agenesis found to result in hydrocephalus following intrauterine exposure to model teratogen, cyclophosphamide, in murine fetuses. A single dose of 10-mg/kg body weight cyclophosphamide was injected intaperitoneally to pregnant mice on day 10, 11 or 12 of gestation. Fetuses were collected through abdominal incision on day 18 and studied for various malformations of brain and cranium including hydrocephalus. Incomplete development and failure of canalization of the cerebral aqueduct were detected when serial sections of brain in coronal and transverse planes were studied under the microscope. Biotechnological investigations such as % DNA fragmentation, % viable cell count and cell proliferation assay were carried out on brain cells for further studies. Agenesis and non-canalization of the cerebral aqueduct resulted in increased pressure of CSF, which led to rupture of the aqueduct complicated by leakage and accumulation of CSF in brain substance forming a cavity containing CSF parallel and lateral to the unopened part of the cerebral aqueduct. Incomplete development along with non-canalization of the cerebral aqueduct resulted in blockage of CSF flow through the ventricles that manifest as internal hydrocephalus. External hydrocephalus on the other hand was detected where the CSF accumulated in the cavity formed inside the brain substance and established communication with the CSF in the subarachnoid space. Cyclophosphamide induced inhibition of mitosis and cell differentiation of ependymal cells reflecting a decreased % viable cell count and cell proliferation assay along with augmentation of apoptosis of brain cells quantified as increased % DNA fragmentation count, which were identified as the contributing factors underlying the agenesis and incomplete development of the cerebral aqueduct. The study also suggests that cell survival, proliferation, migration or differentiation of

  17. High-dose cyclophosphamide therapy associated with diffuse alveolar hemorrhage after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Mo, Xiao-Dong; Xu, Lan-Ping; Liu, Dai-Hong; Zhang, Xiao-Hui; Chen, Huan; Chen, Yu-Hong; Han, Wei; Wang, Yu; Wang, Feng-Rong; Wang, Jing-Zhi; Liu, Kai-Yan; Huang, Xiao-Jun

    2013-01-01

    The occurrence of diffuse alveolar hemorrhage (DAH) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is rare but severe. There are few reports that have examined the correlation between pre-HSCT chemotherapeutic exposure and DAH. We examine the role of pre-HSCT chemotherapeutic exposure, conditioning regimens, pre-HSCT comorbidities and transplant-related complications in the development of DAH after allo-HSCT and evaluate the effect of the high-dose corticosteroid strategy on DAH. A retrospective nested case-control study was designed. Cases with DAH and controls matched for year of allo-HSCT and length of follow-up were identified from a cohort of 597 patients who underwent allo-HSCT between 2006 and 2011 for acute leukemia. Twenty-two patients suffered from DAH; the mean age at the time of presentation was 30.4 years (±12.9) and the mean time to presentation was 7.8 months (±8.1) post-HSCT. The pre-HSCT cyclophosphamide exposure and the cumulative cyclophosphamide dose were significantly higher among the DAH cases compared with the controls, and the cumulative cyclophosphamide dose of ≥5 g/m(2) was independently associated with DAH (OR = 3.4, p = 0.030). High-dose corticosteroid treatment did not significantly improve survival. From these results we can identify patients who are at a higher risk of developing DAH after allo-HSCT, and we found that high-dose corticosteroid therapy may not alter the poor outcome associated with this syndrome. Copyright © 2012 S. Karger AG, Basel.

  18. Competitive binding of anticancer drugs 5-fluorouracil and cyclophosphamide with serum albumin: Calorimetric insights.

    PubMed

    Thoppil, Anu A; Choudhary, Sinjan; Kishore, Nand

    2016-05-01

    Isothermal titration calorimetry (ITC) has emerged as an excellent method to characterize drug-protein interactions. 5-Fluorouracil and cyclophosphamide have been used in combination for the treatment of breast carcinoma, though individually these drugs have also been useful in treating other types of cancer. A quantitative understanding of binding of these drugs with the transport protein under different conditions is essential for optimizing recognition by the protein and delivery at the target. The values of binding constant, enthalpy, and entropy of binding have been determined by using ITC. Fluorescence and circular dichroism spectroscopies have been used to obtain further support to calorimetric observations, monitor conformational changes in the protein and establishing stoichiometry of association. The thermodynamic parameters have enabled a quantitative understanding of the affinity of 5-fluorouracil and cyclophosphamide with bovine serum albumin. The nature of binding has been unraveled based on effect of ionic strength, tetrabutyl-ammonium bromide, and sucrose which interfere in ionic, hydrophobic, and hydrogen bonding interactions. The binding site has been identified by using site marker warfarin in combination with 5-fluorouracil and cyclophosphamide. Further, the experiments have been done to establish whether both the drugs share the same binding site, and the effect of antibiotic drug carbenecillin and anti-inflammatory drug naproxen on their association. Tuning optimum association of drugs with the transport vehicles for effective drug delivery requires identification of the nature of interacting groups in terms of energetics of interactions. Such studies employing ITC have direct significance in rational drug design. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Cyclophosphamide, ara-C and topotecan (CAT) for patients with refractory or relapsed acute leukemia.

    PubMed

    Cortes, J; Estey, E; Beran, M; O'Brien, S; Giles, F; Koller, C; Keating, M; Kantarjian, H

    2000-02-01

    Topotecan is a topoisomerase I inhibitor with significant activity in patients with myelodysplastic syndrome and chronic myelomonocytic leukemia. Pre-clinical data suggest a synergistic activity with DNA damaging agents such as cyclophosphamide, where topotecan might prevent the repair of cyclophosphamide-induced DNA damage. We thus designed a combination including cyclophosphamide 500 mg/m2 every 12 hours given on days 1 to 3; topotecan 1.25 mg/m2/day by continuous infusion on days 2 to 6, and cytosine arabinoside (ara-C) 2 g/m2 over 4 hours daily for 5 days on days 2 to 6 (CAT). Sixty six (63 evaluable) patients were treated. Fifty two patients had refractory (n=12) or relapsed (n=40) acute myelogenous leukemia (AML), and eleven had acute lymphocytic leukemia (ALL) (refractory n=3, relapsed n=8); their median age was 57 years (range, 18 to 79 years). Eleven patients (17%) achieved a complete remission (CR), and two patients (3%) had a hematologic improvement (HI; met all criteria for CR except for platelets < 100x10(9)/L), for an overall response rate of 20%. Responses occurred in 12 of 52 AML patients (23%), including 10 CR (19%) and 2 HI (4%), and in 1 of 11 patients with ALL (9%). Myelosuppression was universal; there were 23 episodes of pneumonia or sepsis and 18 episodes of fever of unknown origin complicating 74 courses of CAT. Non-hematologic toxicity was mostly gastrointestinal, including nausea, vomiting, diarrhea and mucositis, but was severe in only 8%. In summary, the CAT regimen is well tolerated and has significant anti-leukemia activity which warrants further investigation.

  20. Slip and Dilation Tendency Analysis of the Tuscarora Geothermal Area

    DOE Data Explorer

    Faulds, James E.

    2013-12-31

    Critically stressed fault segments have a relatively high likelihood of acting as fluid flow conduits (Sibson, 1994). As such, the tendency of a fault segment to slip (slip tendency; Ts; Morris et al., 1996) or to dilate (dilation tendency; Td; Ferrill et al., 1999) provides an indication of which faults or fault segments within a geothermal system are critically stressed and therefore likely to transmit geothermal fluids. The slip tendency of a surface is defined by the ratio of shear stress to normal stress on that surface: Ts = τ / σn (Morris et al., 1996). Dilation tendency is defined by the stress acting normal to a given surface: Td = (σ1-σn) / (σ1-σ3) (Ferrill et al., 1999). Slip and dilation were calculated using 3DStress (Southwest Research Institute). Slip and dilation tendency are both unitless ratios of the resolved stresses applied to the fault plane by ambient stress conditions. Values range from a maximum of 1, a fault plane ideally oriented to slip or dilate under ambient stress conditions to zero, a fault plane with no potential to slip or dilate. Slip and dilation tendency values were calculated for each fault in the focus study areas at, McGinness Hills, Neal Hot Springs, Patua, Salt Wells, San Emidio, and Tuscarora on fault traces. As dip is not well constrained or unknown for many faults mapped in within these we made these calculations using the dip for each fault that would yield the maximum slip tendency or dilation tendency. As such, these results should be viewed as maximum tendency of each fault to slip or dilate. The resulting along-fault and fault-to-fault variation in slip or dilation potential is a proxy for along fault and fault-to-fault variation in fluid flow conduit potential. Stress Magnitudes and directions Stress field variation within each focus area was approximated based on regional published data and the world stress database (Hickman et al., 2000; Hickman et al., 1998 Robertson-Tait et al., 2004; Hickman and Davatzes

  1. Ecotoxicity and genotoxicity of cyclophosphamide, ifosfamide, their metabolites/transformation products and their mixtures.

    PubMed

    Česen, Marjeta; Eleršek, Tina; Novak, Matjaž; Žegura, Bojana; Kosjek, Tina; Filipič, Metka; Heath, Ester

    2016-03-01

    Cyclophosphamide (CP) and ifosfamide (IF) are commonly used cytostatic drugs that repress cell division by interaction with DNA. The present study investigates the ecotoxicity and genotoxicity of CP, IF, their human metabolites/transformation products (TPs) carboxy-cyclophosphamide (CPCOOH), keto-cyclophosphamide (ketoCP) and N-dechloroethyl-cyclophosphamide (NdCP) as individual compounds and as mixture. The two parent compounds (CP and IF), at concentrations up to 320 mg L(-1), were non-toxic towards the alga Pseudokirchneriella subcapitata and cyanobacterium Synecococcus leopoliensis. Further ecotoxicity studies of metabolites/TPs and a mixture of parent compounds and metabolites/TPs performed in cyanobacteria S. leopoliensis, showed that only CPCOOH (EC50 = 17.1 mg L(-1)) was toxic. The measured toxicity (EC50 = 11.5 mg L(-1)) of the mixture was lower from the toxicity predicted by concentration addition model (EC50 = 21.1 mg L(-1)) indicating potentiating effects of the CPCOOH toxicity. The SOS/umuC assay with Salmonella typhimurium revealed genotoxic activity of CP, CPCOOH and the mixture in the presence of S9 metabolic activation. Only CPCOOH was genotoxic also in the absence of metabolic activation indicating that this compound is a direct acting genotoxin. This finding is of particular importance as in the environment such compounds can directly affect DNA of non-target organisms and also explains toxicity of CPCOOH against cyanobacteria S. leopoliensis. The degradation study with UV irradiation of samples containing CP and IF showed efficient degradation of both compounds and remained non-toxic towards S. leopoliensis, suggesting that no stable TPs with adverse effects were formed. To our knowledge, this is the first study describing the ecotoxicity and genotoxicity of the commonly used cytostatics CP and IF, their known metabolites/TPs and their mixture. The results indicate the importance of toxicological evaluation and monitoring of

  2. Alternative Donor Transplantation with High-Dose Post-Transplantation Cyclophosphamide for Refractory Severe Aplastic Anemia

    PubMed Central

    DeZern, Amy E.; Zahurak, Marianna; Symons, Heather; Cooke, Kenneth; Jones, Richard J.; Brodsky, Robert A.

    2017-01-01

    Severe aplastic anemia (SAA) is a life-threatening hematopoietic stem cell disorder that is treated with bone marrow transplantation (BMT) or immunosuppressive therapy (IST). The management of patients with refractory SAA after IST is a major challenge. Alternative donor BMT is the best chance for cure in refractory SAA, but morbidity and mortality from graft failure and complications of graft-versus-host disease (GVHD) have limited enthusiasm for this approach. Here, we employed post-transplantation high-dose cyclophosphamide in an effort to safely expand the donor pool in 16 consecutive patients with refractory SAA who did not have a matched sibling donor. Between July 2011 and August 2016, 16 patients underwent allogeneic (allo) BMT for refractory SAA from 13 haploidentical donors and 3 unrelated donors. The nonmyeloablative conditioning regimen consisted of antithymocyte globulin, fludarabine, low-dose cyclophosphamide, and total body irradiation. Post-transplantation cyclophosphamide 50 mg/kg/day i.v. on days +3 and +4 was administered for GVHD prophylaxis. Additionally, patients received mycophenolate mofetil on days +5 through 35 and tacrolimus from day +5 through 1 year. The median age of the patients at the time of transplantation was 30 (range, 11 to 69) years. The median time to neutrophil recovery over 1000 × 103/mm3 for 3 consecutive days was 19 (range, 16 to 27) days, to red cell engraftment was 25 (range, 2 to 58) days, and to last platelet transfusion to keep platelets counts over 50 × 103/mm3 was 27.5 (range, 22 to 108) days. Graft failure, primary or secondary, was not seen in any of the patients. All 16 patients are alive, transfusion independent, and without evidence of clonality. The median follow-up is 21 (range, 3 to 64) months. Two patients had grade 1 or 2 skin-only acute GVHD. These same 2 also had mild chronic GVHD of the skin/mouth requiring systemic steroids. One of these GVHD patients was able to come off all IST by 15 months and the

  3. Successful treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) in systemic lupus erythematosus (SLE) with oral cyclophosphamide.

    PubMed

    Jasmin, R; Sockalingam, S; Shahrizaila, N; Cheah, T-E; Zain, A A; Goh, K-J

    2012-09-01

    Peripheral neuropathy is a known manifestation of systemic lupus erythematosus. However, the association of primary autoimmune inflammatory neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) with SLE is uncommon. We report a 26-year-old man who simultaneously presented with severe CIDP and photosensitive rash, but was unresponsive to intravenous immunoglobulin infusion and continued to progress. He was found to have underlying SLE and improved with combined corticosteroid and immunosuppressive therapy with oral cyclophosphamide. CIDP with underlying SLE may be more resistant to conventional therapy with IVIG, requiring the addition of other immunosuppressive agents.

  4. Cyclophosphamide and/or Anthracyclines induced Epiphora in breast cancer patients: A rare side-effect.

    PubMed

    Kalra, Ruchika; Chavada, Bhavesh; Madhani, Nishant R; Purohit, Bhargav; Tripathi, C B

    2017-09-19

    Two female breast cancer patients developed epiphora after administration of Cyclophosphamide and/or anthracyclines based 2-day chemotherapy regimen. The ophthalmologist was consulted and no apparent cause was found. Both patients was managed by ciprofloxacin eye drops. Chemotherapy-induced ocular complications are not uncommon, but under-reported. Although epiphora is a mild reaction if severe can interfere with daily activities. Patients receiving anticancer drugs should have a thorough ocular evaluation, in order to prevent, early diagnose and efficiently treat established ocular complications of the chemotherapy treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Radiation-induced lung fibrosis after treatment of small cell carcinoma of the lung with very high-dose cyclophosphamide

    SciTech Connect

    Trask, C.W.; Joannides, T.; Harper, P.G.; Tobias, J.S.; Spiro, S.G.; Geddes, D.M.; Souhami, R.L.; Beverly, P.C.

    1985-01-01

    Twenty-five previously untreated patients with small cell carcinoma of the lung were treated with cyclophosphamide 160 to 200 mg/kg (with autologous bone marrow support) followed by radiotherapy (4000 cGy) to the primary site and mediastinum. No other treatment was given until relapse occurred. Nineteen patients were assessable at least 4 months after radiotherapy; of these, 15 (79%) developed radiologic evidence of fibrosis, which was symptomatic in 14 (74%). The time of onset of fibrosis was related to the volume of lung irradiated. A retrospective analysis was made of 20 consecutive patients treated with multiple-drug chemotherapy and an identical radiotherapy regimen as part of a randomized trial. Radiologic and symptomatic fibrosis was one half as frequent (35%) as in the high-dose cyclophosphamide group. Very high-dose cyclophosphamide appears to sensitize the lung to radiotherapy and promotes the production of fibrosis.

  6. Capacity buffer of the saliva in children and adolescents with cancer: Variations induced by the administration of metotrexate or cyclophosphamide.

    PubMed

    Rojas-Morales, Thais; Lugo, Zulecnys; Santana, Yrma; Navas, Rita; Zambrano, Olga; Viera, Ninoska; García, Isaura

    2005-07-01

    To determine the variations in the levels of capacity buffer of the saliva in children and adolescents with cancer that receiving Metotrexate or cyclophosphamide. A clinical, random-controlled assay was carried out. The sample was composed by 24 children, ages between 2 and 16 years, with diagnostic of Leukemia and Lymphomas attending to The Autonomous Service of University Hospital of Maracaibo and Hospital of Pediatric Specialties. Two groups were conformed to which a sample of saliva was taken before and after the chemotherapy; twelve patients were randomly placed in the G1: patient receiving Metotrexate and twelve in the G2: patient receiving cyclophosphamide. In order to determine the capacity buffer, the CRT Buffer IVOCLAR VIVADENT was used. The capacity salivary buffer did not show significant differences before and after the administration of the cytostatic agents studied. In this study, the Metotrexate or cyclophosphamide administration does not modify the salivary buffer capacity in pediatric patient with cancer.

  7. Measuring cervical dilatation in human parturition using the Hall effect.

    PubMed

    Kriewall, T J; Work, B A

    1977-01-01

    An instrument was developed to continuously measure cervical dilatation in human labor. The instrument utilizes a small magnetic field source, which is attached to one edge of the cervix while a magnetic field sensor is attached to the diametrically opposite edge of the cervix. The sensor, using two Hall generators, measures orthogonal components of the field to minimize the effects of angular orientation between the source and sensor. The instrument's characteristics indicate that it can measure dilation throughout the range of 1-10 cm, but because its clinical reliability is consistent from only 1-7 cm, the equipment needs to be improved in the ways outlined in the text. This measurement, especially when analyzed with the continous measurement of intrauterine pressure, can provide the obstetrician with new insight into the physiology of labor.

  8. Cardiac compression secondary to a massively dilated substernal colon conduit.

    PubMed

    Khan, Babar A; Ionescu, Ruxandra C; Halal, Ahmed M; Kesler, Kenneth A

    2012-11-01

    With the growing success of surgical repairs of congenital defects previously incompatible with life, it is expected of these patients to live longer and experience the complications of these corrective procedures. Esophageal atresia is a congenital defect that occurs in 1 out of 4000 births and is oftentimes a surgical emergency in which colonic conduits are routinely used for esophageal reconstruction. Colonic conduit redundancy and dilatation are well-recognized late complications of colon conduit surgeries for esophageal reconstructions. We report a rare case of symptomatic cardiac compression secondary to a massively dilated substernal colon conduit occurring 44 years after the initial childhood surgery in 1964 with rapid reversal of hemodynamic compromise after conduit removal. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. Clinical management of dilated cardiomyopathy: current knowledge and future perspectives.

    PubMed

    Merlo, Marco; Cannatá, Antonio; Vitagliano, Alice; Zambon, Elena; Lardieri, Gerardina; Sinagra, Gianfranco

    2016-01-01

    Dilated cardiomyopathy (DCM) is a primary heart muscle disease characterized by a progressive dilation and dysfunction of either the left or both ventricles. The management of DCM is currently challenging for clinicians. The persistent lack of knowledge about the etiology and pathophysiology of this disease continues to determine important fields of uncertainty in managing this condition. Molecular cardiology and genetics currently represent the most crucial horizon of increasing knowledge. Understanding the mechanisms underlying the disease allows clinicians to treat this disease more effectively and to further improve outcomes of DCM patients through advancements in etiologic characterization, prognostic stratification and individualized therapy. Left ventricular reverse remodeling predicts a lower rate of major cardiac adverse events independently from other factors. Optimized medical treatment and device implantation are pivotal in inducing left ventricular reverse remodeling. Newly identified targets, such as angiotensin-neprilysin inhibition, phosphodiesterase inhibition and calcium sensitizing are important in improving prognosis in patients affected by DCM.

  10. Data of methylome and transcriptome derived from human dilated cardiomyopathy.

    PubMed

    Jo, Bong-Seok; Koh, In-Uk; Bae, Jae-Bum; Yu, Ho-Yeong; Jeon, Eun-Seok; Lee, Hae-Young; Kim, Jae-Joong; Choi, Murim; Choi, Sun Shim

    2016-12-01

    Alterations in DNA methylation and gene expression have been implicated in the development of human dilated cardiomyopathy (DCM). Differentially methylated probes (DMPs) and differentially expressed genes (DEGs) were identified between the left ventricle (LV, a pathological locus for DCM) and the right ventricle (RV, a proxy for normal hearts). The data in this DiB are for supporting our report entitled "Methylome analysis reveals alterations in DNA methylation in the regulatory regions of left ventricle development genes in human dilated cardiomyopathy" (Bong-Seok Jo, In-Uk Koh, Jae-Bum Bae, Ho-Yeong Yu, Eun-Seok Jeon, Hae-Young Lee, Jae-Joong Kim, Murim Choi, Sun Shim Choi, 2016) [1].

  11. A new device for pupillary dilatation in vitreous surgery.

    PubMed

    Arpa, P

    1992-01-01

    A completely new surgical technique to obtain pupillary dilatation is presented. It permits achievement of a mydriasis sufficient to observe the vitreous cavity in both phakic and aphakic eyes during vitreous surgery. Miotic immobile pupils not dilatable pharmacologically are enlarged by means of a silastic ring with a C-shaped groove on its outer part. This is introduced into the eye through a limbic opening. When in place, the external sulcus of the ring hosts the pupillary rim. Twelve patients (three phakic and nine aphakic) were treated. In two patients operated upon previously with silicone oil tamponade, some difficulties were encountered during the insertion of the device owing to the lubricating effect of the oil. After the removal of the ring, all the pupils returned to a round shape, with no apparent damage to the iris structure.

  12. Peripartum cardiomyopathy and dilated cardiomyopathy: different at heart

    PubMed Central

    Bollen, Ilse A. E.; Van Deel, Elza D.; Kuster, Diederik W. D.; Van Der Velden, Jolanda

    2015-01-01

    Peripartum cardiomyopathy (PPCM) is a severe cardiac disease occurring in the last month of pregnancy or in the first 5 months after delivery and shows many similar clinical characteristics as dilated cardiomyopathy (DCM) such as ventricle dilation and systolic dysfunction. While PPCM was believed to be DCM triggered by pregnancy, more and more studies show important differences between these diseases. While it is likely they share part of their pathogenesis such as increased oxidative stress and an impaired microvasculature, discrepancies seen in disease progression and outcome indicate there must be differences in pathogenesis as well. In this review, we compared studies in DCM and PPCM to search for overlapping and deviating disease etiology, pathogenesis and outcome in order to understand why these cardiomyopathies share similar clinical features but have different underlying pathologies. PMID:25642195

  13. Gastric dilatation and volvulus in a red panda (Ailurus fulgens).

    PubMed

    Neilsen, Colleen; Mans, Christoph; Colopy, Sara A

    2014-11-01

    To describe the successful management of gastric dilatation and volvulus (GDV) in a red panda. Clinical report. Red panda diagnosed with GDV. A 12-year-old male red panda (Ailurus fulgens) was evaluated for acute onset inappetence, staggering, collapse, and tachypnea. Gastric dilatation and volvulus (GDV) was diagnosed by radiography, abdominal ultrasonography, and exploratory celiotomy. Torsion of the stomach was corrected and an incisional gastropexy performed to prevent recurrence. No organs were devitalized, no other abnormalities detected, and the red panda recovered fully within 72 hours. GDV should be considered as a differential diagnosis for red pandas presenting with acute onset of unspecific signs such as collapse, inappetence, and abdominal distension. GDV in red pandas can be diagnosed and successfully treated as described in dogs. © Copyright 2014 by The American College of Veterinary Surgeons.

  14. Reversible dilatancy in entangled single-wire materials.

    PubMed

    Rodney, David; Gadot, Benjamin; Martinez, Oriol Riu; du Roscoat, Sabine Rolland; Orgéas, Laurent

    2016-01-01

    Designing structures that dilate rapidly in both tension and compression would benefit devices such as smart filters, actuators or fasteners. This property however requires an unusual Poisson ratio, or Poisson function at finite strains, which has to vary with applied strain and exceed the familiar bounds: less than 0 in tension and above 1/2 in compression. Here, by combining mechanical tests and discrete element simulations, we show that a simple three-dimensional architected material, made of a self-entangled single long coiled wire, behaves in between discrete and continuum media, with a large and reversible dilatancy in both tension and compression. This unusual behaviour arises from an interplay between the elongation of the coiled wire and rearrangements due to steric effects, which, unlike in traditional discrete media, are hysteretically reversible when the architecture is made of an elastic fibre.

  15. Success of endoscopic pharyngoesophageal dilation after head and neck cancer treatment.

    PubMed

    Chapuy, Claudia I; Annino, Donald J; Tishler, Roy B; Haddad, Robert I; Snavely, Anna; Goguen, Laura A

    2013-12-01

    To assess clinical success and safety of endoscopic pharyngoesophageal dilation after chemoradiation or radiation for head and neck cancer and to identify variables associated with dilation failure. Case series with chart review. Between 2000 and 2008, a total of 111 patients treated with chemoradiation or radiation for head and neck cancer with subsequent pharyngoesophageal stenosis requiring endoscopic dilation were identified. Patients were evaluated for endoscopic dilation technique, severity of stenosis, technical and clinical success, and intra- and postoperative complications. The Diet/GT score (range, 1-5) was utilized to measure swallow success. Variables associated with dilation failure were analyzed by univariate and multivariate logistic regression. There were 271 dilations analyzed, with 42 combined antegrade retrograde dilations, 208 dilations over a guidewire, and 21 dilations without guidewire. Intraoperative patency and successful dilation of the stenotic segment was achieved in 95% of patients. A Diet/GT score of 5 (gastrostomy tube removed and soft/regular diet) was attained in 84 of 111 (76%) patients. Safety analysis showed complications occurred in 9% of all dilations. Perforations were noted in 4% of all procedures, with only two esophageal perforations requiring significant intervention. Multiple dilations were associated with an increased risk for perforations. Further logistic regression analyses revealed that the number of dilations was indicating a poor outcome and low Diet/GT score. Pharyngoesophageal stenosis, occurring after chemoradiation and radiation treatment, can be successfully and safely treated with endoscopic dilation techniques. Patients with restenosis, requiring multiple dilations, have a higher risk of persistent dysphagia. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

  16. Clinical comparison of the efficiency and security of balloon dilators versus fascial dilators in percutaneous nephrolithotripsy (PCNL)

    PubMed Central

    Yang, Lingbo; Lu, Shuaiqi; Han, Xingtao; Wei, Pengtao; Yang, Jinhui; Hao, Tongtong

    2016-01-01

    Objective: To compare the efficiency and security of the balloon dilators versus fascial dilators in percutaneous nephrolithotripsy (PCNL), We compared the difference of intraoperative and postoperative parameters of patients using these two different methods of expansion and having no significant statistic differences in peroperative parameters. Methods: This is a retrospective analysis of 134 patients undergoing PCNL with upper urinary calculi from January 2012 to January 2014 in Luoyang Central Hospital affiliated to Zhengzhou University. These patients meeting the inclusion criteria were divided into two groups: the group of balloon dilators (group A) and the group of fascial dilators (group B). Two groups were compared for success rate of first expansion, clearance of stone, duration of surgery, intraoperative hemorrhage, blood transfusion rate, postoperative hospitalization and the incidence of complications. Result: In Group A, a total of 91 patients (51 men and 40 women, mean age 51.22±8.96 years, ranged from 28 to 68 years, the calculi maximum diameter from 0.9 to 4.5cm, 28 cases with a history of gravel, mean Body mass index 24.20±2.34, 73 cases with hydronephrosis and 26 cases with underlying diseases such as hypertension, diabetes and the like) undergoing PCNL were retrospectively reviewed. Similarly, In Group B, a total of 43 patients (28 men and 15 women, mean age 49.64±10.62 years, ranged from 15 to 70 years, the calculi maximum diameter from 1.1 to 5.2cm, 18 cases with a history of gravel, mean Body mass index 24.40±2.70, 38 cases with hydronephrosis and 14 cases with underlying diseases such as hypertension, diabetes and the like) undergoing PCNL were retrospectively reviewed. Our results showed that there was a statistically significant better outcome in Group A than in Group B in terms of success rate of first exploration, duration of operation, intraoperative hemorrhage, postoperative hospitalization and the incidence of complications

  17. Isolated proximal esophageal injury from blunt trauma: endoscopic stricture dilatation.

    PubMed

    Pineau, Benoit C; Ott, David J

    2003-01-01

    Blunt neck trauma can cause isolated esophageal injuries that may be difficult to recognize. A high index of suspicion is necessary for optimal identification and management of this condition. We report a case of blunt esophageal trauma resulting from a motor vehicle accident that was initially unrecognized until the patient developed a tight stricture of the cervical esophagus. This was successfully dilated endoscopically. Aerodigestive trauma resulting from neck injuries is reviewed with emphasis on the pathophysiology of esophageal trauma.

  18. Clinical Significance of Biliary Dilatation and Cholelithiasis after Subtotal Gastrectomy.

    PubMed

    Yoon, Harry; Kwon, Chang Il; Jeong, Seok; Lee, Tae Hoon; Han, Joung Ho; Song, Tae Jun; Hwang, Jae Chul; Kim, Dae Jung

    2015-07-01

    The well-organized study to support that increased cholelithiasis and bile duct dilatation can occur after gastrectomy has not been reported. The aim of this study was to determine the incidence of cholelithiasis and the degree of common bile duct (CBD) dilatation in patients undergoing subtotal gastrectomy, compared to those undergoing endoscopic treatment for gastric cancer. Patients who diagnosed with gastric cancer and received treatment at six academic referral centers were investigated for the incidence and time of cholelithiasis and the degree of CBD dilatation after treatment by analysis of 5-year follow-up CTs. The operation group underwent subtotal gastrectomy without vagotomy, while in the control group endoscopic treatment was administered for gastric cancer. A total of 802 patients were enrolled in 5-year analysis (735 patients in the operation group and 67 patients in the control group). Cholelithiasis occurred in 47 patients (6.39%) in the operation group and 3 patients (4.48%) in the control group (p=0.7909). The incidences of cholelithiasis were 4.28% in Billoth-I and 7.89% in Billoth-II (p=0.0487). The diameter of proximal CBD and distal CBD increased by 1.11 mm and 1.41 mm, respectively, in the operation group, compared to 0.4 mm and 0.38 mm, respectively, in the control group (pœ0.05). Patients with increased CBD dilatation more than 5 mm showed statistically significant increases in alkaline phosphatase and gamma-glutamyltransferase. The incidence of cholelithiasis was not increased due to subtotal gastrectomy without vagotomy, but the incidence was higher after Billoth-II compared to Billoth-I. In addition, significant change in the CBD diameter was observed after subtotal gastrectomy.

  19. [Tracheotomy-endoscop for dilatational percutaneous tracheotomy (TED)].

    PubMed

    Klemm, Eckart

    2006-09-01

    While surgical tracheotomies are currently performed using state-of-the-art operative techniques, percutaneous dilatational tracheostomy (PDT) is in a rapidly evolving state with regard to its technology and the number of techniques available. This has resulted in a range of new complications that are difficult to quantify on a scientific basis, given the fact that more than half of the patients who are tracheotomized in intensive care units die from their underlying disease. The new Tracheotomy Endoscope (TED) is designed to help prevent serious complications in dilatational tracheotomies and facilitate their management. The endoscope has been specifically adapted to meet the require-ments of percutaneous dilatational tracheotomies. It is fully compatible with all current techniques of PDT. The method is easy to learn. The percutaneous dilatational tracheotomy with the Tracheotomy Endoscope is a seven-step procedure: Advantages of the Tracheotomy Endoscope: Injuries to the posterior tracheal wall ar impossible (tracheoesophageal fistulas, pneumothorax). Minor bleeding sites on the tracheal mucosa can be controlled with a specially curved suction-coagulation tube introudeced through the Tracheotomy Endoscope. In cases with heavy bleeding and a risk of aspiration, the rigid indwelling Tracheotomy Endoscope provides a secure route for reintubating the patient with a cuffed endotracheal tube. It also allows for rapid conversion to an open surgical procedure if necessary. All the parts are easy to clean and are autoclavable. This type of endoscopically guided PDT creates an optimal link between the specialties of intensive care medicine and otorhinolaryngology. The Tracheotomy Endoscope (TED) increases the standard of safety in PDT.

  20. Motor unit number in a small facial muscle, dilator naris.

    PubMed

    Patel-Khurana, Nilam; Fregosi, Ralph F

    2015-10-01

    A loss of functioning motor units underlies many neuromuscular disorders. The facial nerve innervates the muscles of facial expression, including nasal muscles, which also play an important role in the regulation of airflow resistance. It is difficult to accurately assess motor unit number in the facial muscles, because the muscles are difficult to activate in isolation. Here, we apply the manual McComas method to estimate the number of motor units in a nasal dilator muscle. EMG of the dilator naris was recorded during graded stimulation of the zygomatic branch of the facial nerve in 26 subjects (12 males and 14 females), aged 20-41 years. Each subject was studied twice, on separate days, to estimate method reproducibility. As a check on our use of the McComas method, we also estimated motor unit number in the first dorsal interosseus muscle (FDI) of six subjects, as the muscle is also small and has been studied with the McComas method. Reproducibility was evaluated with a rigorous statistical approach, the Bland-Altman procedure. We estimate that dilator naris is composed of 75 ± 15.6 (SD) motor units, compared to 144 ± 35.5 in FDI. The coefficient of variation for test-retest reproducibility of dilator naris motor unit estimates was 29.6 %, similar to separate-day reproducibility reported for other muscles. Recording and stimulation were done with surface electrodes, and the recordings were of high quality and reproducible. This simple technique could be applied clinically to track motor neuron loss and to monitor facial nerve integrity.

  1. Motor unit number in a small facial muscle, dilator naris

    PubMed Central

    Patel-Khurana, Nilam; Fregosi, Ralph F.

    2015-01-01

    A loss of functioning motor units underlies many neuromuscular disorders. The facial nerve innervates the muscles of facial expression, including nasal muscles, which also play an important role in the regulation of airflow resistance. It is difficult to accurately assess motor unit number in the facial muscles, because the muscles are difficult to activate in isolation. Here we apply the manual McComas method to estimate the number of motor units in a nasal dilator muscle. EMG of the dilator naris was recorded during graded stimulation of the zygomatic branch of the facial nerve in 26 subjects (12 M/14 F), aged 20–41 years. Each subject was studied twice, on separate days, to estimate method reproducibility. As a check on our use of the McComas method, we also estimated motor unit number in the first dorsal interosseus muscle (FDI) of 6 subjects, as the muscle is also small, and has been studied with the McComas method. Reproducibility was evaluated with a rigorous statistical approach, the Bland-Altman procedure. We estimate that dilator naris is composed of 75 ±15.6 (SD) motor units, compared to 144 ± 35.5 in FDI. The coefficient of variation for test-retest reproducibility of dilator naris motor unit estimates was 29.6%, similar to separate-day reproducibility reported for other muscles. Recording and stimulation were done with surface electrodes, and the recordings were of high quality and reproducible. This simple technique could be applied clinically to track motor neuron loss, and to monitor facial nerve integrity. PMID:26169101

  2. Psittacine proventricular dilatation syndrome in an umbrella cockatoo.

    PubMed

    Lutz, M E; Wilson, R B

    1991-06-01

    Psittacine proventricular dilatation syndrome (macaw wasting disease) is a fatal disease of the gastrointestinal tract and, sometimes, the CNS. The disease most often affects macaws and is thought to be of viral origin. An Umbrella cockatoo was referred with signs of neurologic dysfunction. Other unusual findings included flaccid crop, distended duodenum, and acute weight loss. Because treatment has not been reported to be effective, the affected cockatoo was euthanatized to limit spread of the disease.

  3. Clinical findings and treatment in cattle with caecal dilatation.

    PubMed

    Braun, Ueli; Beckmann, Christine; Gerspach, Christian; Hässig, Michael; Muggli, Evelyne; Knubben-Schweizer, Gabriela; Nuss, Karl

    2012-07-09

    This retrospective study describes the clinical and laboratory findings, treatment and outcome of 461 cattle with caecal dilatation. The general condition and demeanor were abnormal in 93.1% of cases, and 32.1% of the patients had colic. Ruminal motility was reduced or absent in 78.3% of cattle. In 82.6% of cases, swinging and/or percussion auscultation were positive on the right side, and 82.4% had little or no faeces in the rectum. Caecal dilatation could be diagnosed via rectal palpation in 405 (88.0%) cattle. There was caudal displacement of the dilated caecum in 291 patients, torsion around the longitudinal axis in 20 and retroflexion in 94. The most important laboratory finding was hypocalcaemia, which occurred in 85.1% of cases. Of the 461 cattle, 122 (26.5%) initially received conservative therapy (intravenous fluids, neostigmine, calcium borogluconate) and 329 (71.4%) underwent surgical treatment. Ten patients were slaughtered or euthanased after the initial physical examination. Of the 122 cattle that received conservative treatment, 42 did not respond after one to two days of therapy and required surgical treatment. The final number of cattle that were operated was 371 (80.5%). Because of a grave prognosis, 24 cases were euthanased or slaughtered intraoperatively. Another 24 cattle did not respond to one or more operations and were euthanased or slaughtered. Of the 461 patients, 403 (87.4%) responded to either conservative or surgical treatment and were cured, and 58 were euthanased or slaughtered. Caecal dilatation can usually be diagnosed based on clinical findings and treated conservatively or surgically. Swinging and percussion auscultation as well as rectal examination are important diagnostic tools. Conservative treatment is not rewarding in cattle considered surgical candidates with suspected caecal torsion or retroflexion and surgery should not be delayed in these patients.

  4. Gastric Dilatation and Volvulus in a Red Panda (Ailurus fulgens)

    PubMed Central

    Neilsen, Colleen; Mans, Christoph; Colopy, Sara A.

    2014-01-01

    A 12-year-old male red panda (Ailurus fulgens) was evaluated for acute onset inappetance, staggering, collapse, and tachypnea. Gastric dilatation and volvulus (GDV) was diagnosed by radiography, abdominal ultrasonography, and exploratory celiotomy. Torsion of the stomach was corrected and an incisional gastropexy performed to prevent recurrence. No organs were devitalized, no other abnormalities detected, and the red panda recovered fully within 72 hours. PMID:24467661

  5. Ring cycle for dilating and constricting the nuclear pore

    PubMed Central

    Solmaz, Sozanne R.; Blobel, Günter; Melčák, Ivo

    2013-01-01

    We recently showed that the three “channel” nucleoporins, Nup54, Nup58, and Nup62, interact with each other through only four distinct sites and established the crystal structures of the two resulting “interactomes,” Nup54•Nup58 and Nup54•Nup62. We also reported instability of the Nup54•Nup58 interactome and previously determined the atomic structure of the relevant Nup58 segment by itself, demonstrating that it forms a twofold symmetric tetramer. Here, we report the crystal structure of the relevant free Nup54 segment and show that it forms a tetrameric, helical bundle that is structurally “conditioned” for instability by a central patch of polar hydrogen-bonded residues. Integrating these data with our previously reported results, we propose a “ring cycle” for dilating and constricting the nuclear pore. In essence, three homooligomeric rings, one consisting of eight modules of Nup58 tetramers, and two, each consisting of eight modules of Nup54 tetramers, are stacked in midplane and characterize a constricted pore of 10- to 20-nm diameter. In going to the dilated state, segments of one Nup58 and two Nup54 tetrameric modules reassort into a dodecameric module, eight of which form a single, heterooligomeric midplane ring, which is flexible in a diameter range of 40–50 nm. The ring cycle would be regulated by phenylalanine–glycine regions (“FG repeats”) of channel nups. Akin to ligand-gated channels, the dilated state of the midplane ring may be stabilized by binding of [cargo•transport-factor] complexes to FG repeats, thereby linking the ratio of constricted to dilated nuclear pores to cellular transport need. PMID:23479651

  6. [Hydropneumatic dilatation of the ureter: A technical option in ureteropyeloplasty].

    PubMed

    Gallego-Grijalva, Jorge E; Jaimes-Jiménez, Ricardo; Alvarado-García, Rafael; Terriquez-Rodríguez, Sergio

    2003-01-01

    The pyeloureteric junction (UP) is the site of obstruction commonest in the upper tract urinary. Several surgical techniques exist and the main complication is the stricture by the disproportion between both ends. The hydropneumatic dilatation of the ureteric would increase of the 5:1 to 2:1 the light of the ureter, improving technically anastomosis and reducing complications. They studied 27 patients with diagnose of Estenosis UP in the Paediatric Urologist Service of CMN 20 of November of the ISSSTE, being made dismembered Pyeloplasty pyeloureteric in all, introducing Fogarty catheter in the Ureter carrying out the hydropneumatic dilatation of the same one, introduction of catheter double J in ureter and in the last patient without this, previous one to the anastomosis. All had a pursuit of 6 months. Of the 27 patients, 21 masculine ones (77.78%), 6 feminine ones (22.22%), of the right side 10 (37.04%), left 14 (51.85%) and bilateral 3 (11.11%). In the 27 studied patients postoperating complications did not appear. To all the patients I am made the dilatation to them hydropneumatics of the Ureter during UP plasty, did not present/display postoperating complications, the anastomosis is carried out with greater technical facility since the light of the Ureteric increase from 5:1 in 2:1, and in I complete case without ferulization of the Ureter, I do not present/display complications. DOSCUSSION: The hydropneumatics dilatation of the Ureter is a technical option in the Surgical handling of stricture UP, facilitating the anastomosis, diminishing the postoperating complications, making the ferulization do withoutible of the Ureter.

  7. Allograft pathology in patients transplanted for idiopathic dilated cardiomyopathy.

    PubMed

    Zhang, Mingchang; Tavora, Fabio; Huebner, Thomas; Heath, Jonathan; Burke, Allen

    2012-03-01

    There are few morphologic studies on idiopathic dilated cardiomyopathy (CM) treated with transplant. We prospectively correlated gross, histologic, and clinical findings pertaining to hearts explanted in a 5-year period from patients with a clinical diagnosis of nonischemic CM and also correlated left ventricular diameter with preoperative echocardiographic reports. Of 64 patients with a clinical diagnosis of dilated cardiomyopathy (DC), 42 were men (age, 51 ± 13 y) and 22 were women (age, 42 ± 18 y). The pathologic diagnosis was idiopathic (dilated) cardiomyopathy (DC) in 55 patients (86%) and features of specific CM in 9 patients (14%). Specific diagnoses were fibrofatty change consistent with arrhythmogenic right ventricular cardiomyopathy (n=6), amyloidosis (n=2), and sarcoidosis (n=1), none of which were suspected clinically. The 55 hearts with idiopathic DC had a mean heart weight of 508 (range, 220 to 980) g. Pathologic subsets of the DC group included 4 hearts without enlargement, cavity dilatation, or significant histologic findings (minimal DC); 3 hearts with histologic evidence of healed myocarditis; and 5 hearts with mildly noncompacted left ventricle with hypertrabeculation. Five patients had prior mitral or tricuspid valve replacement/repairs to manage heart failure. There were 7 postpartum DC cases, 1 with a histologic pattern of healed myocarditis and 1 alcoholism-associated DC. Familial DC comprised 16% (9 of 55) of patients. In patients without prior assist device placement, pathologic left ventricular cavity diameter correlated with echocardiographic end-diastolic volume (r , 0.8, P<0.0001). Morphologically, DC is a heterogeneous group. Areas of fibrofatty change and features of noncompaction are not uncommon. Left ventricular measurement at explant correlates well with echocardiographic findings, with a relatively consistent underestimation of the diameter.

  8. Clinical findings and treatment in cattle with caecal dilatation

    PubMed Central

    2012-01-01

    Background This retrospective study describes the clinical and laboratory findings, treatment and outcome of 461 cattle with caecal dilatation. Results The general condition and demeanor were abnormal in 93.1% of cases, and 32.1% of the patients had colic. Ruminal motility was reduced or absent in 78.3% of cattle. In 82.6% of cases, swinging and/or percussion auscultation were positive on the right side, and 82.4% had little or no faeces in the rectum. Caecal dilatation could be diagnosed via rectal palpation in 405 (88.0%) cattle. There was caudal displacement of the dilated caecum in 291 patients, torsion around the longitudinal axis in 20 and retroflexion in 94. The most important laboratory finding was hypocalcaemia, which occurred in 85.1% of cases. Of the 461 cattle, 122 (26.5%) initially received conservative therapy (intravenous fluids, neostigmine, calcium borogluconate) and 329 (71.4%) underwent surgical treatment. Ten patients were slaughtered or euthanased after the initial physical examination. Of the 122 cattle that received conservative treatment, 42 did not respond after one to two days of therapy and required surgical treatment. The final number of cattle that were operated was 371 (80.5%). Because of a grave prognosis, 24 cases were euthanased or slaughtered intraoperatively. Another 24 cattle did not respond to one or more operations and were euthanased or slaughtered. Of the 461 patients, 403 (87.4%) responded to either conservative or surgical treatment and were cured, and 58 were euthanased or slaughtered. Conclusions Caecal dilatation can usually be diagnosed based on clinical findings and treated conservatively or surgically. Swinging and percussion auscultation as well as rectal examination are important diagnostic tools. Conservative treatment is not rewarding in cattle considered surgical candidates with suspected caecal torsion or retroflexion and surgery should not be delayed in these patients. PMID:22656369

  9. Randomized phase II trial of cyclophosphamide and the oral poly (ADP-ribose) polymerase inhibitor veliparib in patients with recurrent, advanced triple-negative breast cancer.

    PubMed

    Kummar, Shivaani; Wade, James L; Oza, Amit M; Sullivan, Daniel; Chen, Alice P; Gandara, David R; Ji, Jiuping; Kinders, Robert J; Wang, Lihua; Allen, Deborah; Coyne, Geraldine O'Sullivan; Steinberg, Seth M; Doroshow, James H

    2016-06-01

    Background In tumors carrying BRCA mutations, DNA damage caused by standard cytotoxic chemotherapy can be potentiated by poly [ADP-ribose] polymerase (PARP) inhibitors, leading to increased cell death through synthetic lethality. Individuals carrying mutations in BRCA have an increased incidence of triple negative breast cancer (TNBC). In order to assess the role of PARP inhibition in the treatment of TNBC, we conducted a randomized phase II trial of the combination of veliparib, a small molecule PARP inhibitor, with the cytotoxic agent cyclophosphamide versus cyclophosphamide alone in patients with refractory TNBC. Methods Adult patients with TNBC were randomized to receive oral cyclophosphamide 50 mg once daily with or without oral veliparib at 60 mg daily in 21-day cycles. Patients on the cyclophosphamide arm could crossover to the combination arm at disease progression. Results Forty-five patients were enrolled; 18 received cyclophosphamide alone and 21 received the combination as their initial treatment regimen. Lymphopenia was the most common grade 3/4 toxicity noted in both arms. One patient in the cyclophosphamide alone arm, and 2 in the combination arm had objective responses. Response rates and median progression free survival did not significantly differ between both treatment arms. Conclusion The addition of veliparib to cyclophosphamide, at the dose and schedule evaluated, did not improve the response rate over cyclophosphamide treatment alone in patients with heavily pre-treated triple-negative breast cancer.

  10. Phase I Trial of Cyclophosphamide as an Immune Modulator for Optimizing Oncolytic Reovirus Delivery to Solid Tumors

    PubMed Central

    Roulstone, Victoria; Khan, Khurum; Pandha, Hardev S.; Rudman, Sarah; Coffey, Matt; Gill, George M.; Melcher, Alan A.; Vile, Richard; Harrington, Kevin J.; de Bono, Johann; Spicer, James

    2016-01-01

    Purpose Reovirus is a wild-type oncolytic virus that is ubiquitous in the environment; most patients are therefore preimmune. Therapeutic administration leads to an increase in neutralizing antireovirus antibody (NARA) titer. We hypothesized that if NARA limited reovirus antitumor activity, the effect might be attenuated by coadministration of cyclophosphamide. Experimental design In a phase I study, patients with advanced cancer received cyclophosphamide 3 days before intravenous reovirus serotype 3 Dearing (RT3D). The primary objective was to reduce the resulting rise in NARA titer. Cyclophosphamide dose was escalated from 25–1,000 mg/m2 through nine cohorts; we aimed to define a well-tolerated immunomodulatory dose. Results The combination was well tolerated in 36 patients, with grade 3/4 toxicities only seen at or above the maximum tolerated dose of cyclophosphamide, which was 800 mg/m2 combined with reovirus. Immunosuppressive effect, defined as maintaining NARA titer rise below a predefined threshold, was observed in only one patient. Furthermore, despite expected myelosuppression seen at higher cyclophosphamide doses, no changes in T-cell subsets, including Tregs, occurred with dose escalation. Viable virus was detected in association with peripheral blood mononuclear cells (PBMC) from 14% of patients 10 days after the last RT3D injection, despite high plasma NARA titer, demonstrating a potential mechanism for prolonged evasion of neutralization by reovirus. Conclusions Coadministration of cyclophosphamide with reovirus is safe, but does not attenuate host antiviral responses. Alternative immunomodulation approaches should be explored, but association with PBMCs may allow reovirus to persist and evade even high levels of neutralizing antibodies. PMID:25424857

  11. Long-Term Follow-Up of Cyclophosphamide Compared with Azathioprine for Initial Maintenance Therapy in ANCA-Associated Vasculitis

    PubMed Central

    Faurschou, Mikkel; Berden, Annelies; Flossmann, Oliver; Bajema, Ingeborg; Hoglund, Peter; Smith, Rona; Szpirt, Wladimir; Westman, Kerstin; Pusey, Charles D.; Jayne, David R.W.

    2014-01-01

    Background and objectives Treatment with azathioprine within 3 months of remission induction with cyclophosphamide is a common treatment strategy for patients with ANCA-associated vasculitis. This study comprised patients undergoing long-term follow-up who were randomly allocated to azathioprine after 3–6 months or after 12 months of cyclophosphamide treatment. Design, setting, participants, & measurements Patients from 39 European centers between 1995 and 1997 with a new diagnosis of ANCA-associated vasculitis that involved the kidneys or another vital organ were eligible. At the time of diagnosis, participants were randomly allocated to convert to azathioprine after 3–6 months (the azathioprine group) or after 12 months of cyclophosphamide (the cyclophosphamide group). Patients who did not achieve a remission within 6 months were excluded. This study assessed relapses, ESRD, and death during long-term follow-up. Results Patients were allocated to the azathioprine group (n=71) and the cyclophosphamide group (n=73). Of these patients, 63 (43.8%) developed a relapse, 35 (24.3%) developed a renal relapse, 13 (9.0%) developed ESRD, and 21 (14.6%) died. Although there were worse outcomes in the azathioprine group, none were statistically significant. The subdistribution hazard ratio [sHR] for relapse was 1.63 (95% confidence interval [95% CI], 0.99 to 2.71), the composite of relapse or death hazard ratio [HR] was 1.59 (95% CI, 1.00 to 2.54), the ESRD sHR was 1.71 (95% CI, 0.56 to 5.19), and the death HR was 0.75 (95% CI, 0.32 to 1.79). Conclusions It remains uncertain whether converting to azathioprine after 3–6 months of induction cyclophosphamide therapy is as effective as converting after 12 months. Outcomes are still poor for this group of patients and further research is required to determine the optimal timing of maintenance therapy. PMID:24970876

  12. Multicenter study of environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in 66 Canadian hospitals: A 2016 follow-up study.

    PubMed

    Roland, C; Caron, N; Bussières, J F

    2017-08-01

    Oncology workers are occupationally exposed to antineoplastic drugs. This exposure can induce adverse health effects. To reduce their exposure, contamination on surfaces should be kept as low as possible. The main objective of this study was to monitor environmental contamination with cyclophosphamide, ifosfamide, and methotrexate in oncology pharmacy and patient care areas in Canadian centers. The secondary objective was to describe the impact of some factors that may limit contamination. This is a descriptive study. Twelve standardized sites were sampled in each participating center (six in the pharmacy and six in patient care areas). Samples were analyzed for the presence of cyclophosphamide, ifosfamide, and methotrexate by ultra-performance liquid chromatography-tandem mass spectrometry technology. Descriptive statistical analyses were done and results were compared with a Kolmogorov-Smirnov test for independent samples. In 2016, 66 centers participated in this study (66/202, 32.7%). Overall, 43.4% (326/752) of the samples were positive for cyclophosphamide, 13.2% (99/752) for ifosfamide and 6.9% (52/752) for methotrexate. The 75th percentile value of cyclophosphamide surface concentration was 6.8 pg/cm(2) and lower than the limit of detection for ifosfamide and methotrexate. Centers who prepared more antineoplastic drugs per year (p < 0.0001), who used more cyclophosphamide per year (p < 0.0001) and who primed antineoplastic IV tubing in patient care unit by nurses (p = 0.004) showed significantly higher surface contamination to cyclophosphamide. Environmental surveillance is one part of a comprehensive approach for minimizing hazardous exposures in healthcare. This study highlights a low level of contamination of three hazardous drugs amongst 66 Canadian centers. Regular environmental monitoring is a good practice to maintain contamination as low as reasonably achievable.

  13. Developing a rat model of dilated cardiomyopathy with improved survival* #

    PubMed Central

    Shen, Li-juan; Lu, Shu; Zhou, Yong-hua; Li, Lan; Xing, Qing-min; Xu, Yong-liang

    2016-01-01

    To compare the continuous infusion and intermittent bolus injection administration protocols of doxorubicin (Dox) under the same cumulative dose (12 mg/kg), and establish a rat dilated cardiomyopathy model with improved survival, a total of 150 Sprague-Dawley (SD) rats were divided into three groups: a control group, administered with normal saline; a Dox 1 group, administration twice a week at 1 mg/kg; a Dox 2, administration once a week at 2 mg/kg. Mortality rates in the Dox 1 and Dox 2 groups were 22% and 48%, respectively (P<0.05). As shown by echocardiography, both Dox groups exhibited significant chamber dilatation and reduced cardiac function (all P<0.05 vs. control). Plasma brain natriuretic peptide and C-reactive protein concentrations were significantly increased (P<0.05) with both Dox regimens. The concentrations of Caspase-3 in myocardial tissues of rats significantly increased in both doxorubicin regimens. Myocardial metabolism imaging by histology and 18F-fluoro-deoxyglucose-positron emission tomography (18FDG-PET) both revealed decreased myocardial viability and necrosis, and even interstitial fibrosis, in left ventricles (LVs) in both Dox groups. Serum creatinine and aspartate aminotransferase concentrations were significantly higher in the Dox 2 model than in the Dox 1 model. Doxorubicin given at both regimens induced dilated cardiomyopathy, while its administration at lower doses with more frequent infusions reduced the mortality rate. PMID:27921402

  14. Dilated Basilar Arteries in Patients with Congenital Central Hypoventilation Syndrome

    PubMed Central

    Kumar, Rajesh; Nguyen, Haidang D.; Macey, Paul M.; Woo, Mary A.; Harper, Ronald M.

    2009-01-01

    Congenital central hypoventilation syndrome (CCHS) patients show hypoventilation during sleep and severe autonomic impairments, including aberrant cardiovascular regulation. Abnormal sympathetic patterns, together with increased and variable CO2 levels, lead to the potential for sustained cerebral vasculature changes. We performed high-resolution T1-weighted imaging in 13 CCHS and 31 control subjects using a 3.0-Tesla magnetic resonance imaging scanner, and evaluated resting basilar and bilateral middle cerebral artery cross-sections. Two T1-weighted image series were acquired; images were averaged and reoriented to common space, and regions containing basilar and both middle cerebral arteries were oversampled. Cross-sections of the basilar and middle cerebral arteries were manually outlined to calculate cross-sectional areas, and differences between and within groups were evaluated. Basilar arteries in CCHS were significantly dilated over control subjects, but both middle cerebral artery cross-sections were similar between groups. No significant differences appeared between left and right middle cerebral arteries within either group. Basilar artery dilation may result from differential sensitivity to high CO2 over other vascular beds, damage to serotonergic or other chemosensitive cells accompanying the artery, or enhanced microvascular resistance, and that dilation may impair tissue perfusion, leading to further neural injury in CCHS. PMID:19822189

  15. Slip and Dilation Tendency Analysis of the Patua Geothermal Area

    DOE Data Explorer

    Faulds, James E.

    2013-12-31

    Critically stressed fault segments have a relatively high likelihood of acting as fluid flow conduits (Sibson, 1994). As such, the tendency of a fault segment to slip (slip tendency; Ts; Morris et al., 1996) or to dilate (dilation tendency; Td; Ferrill et al., 1999) provides an indication of which faults or fault segments within a geothermal system are critically stressed and therefore likely to transmit geothermal fluids. The slip tendency of a surface is defined by the ratio of shear stress to normal stress on that surface: Ts = τ / σn (Morris et al., 1996). Dilation tendency is defined by the stress acting normal to a given surface: Td = (σ1-σn) / (σ1-σ3) (Ferrill et al., 1999). Slip and dilation were calculated using 3DStress (Southwest Research Institute). Slip and dilation tendency are both unitless ratios of the resolved stresses applied to the fault plane by ambient stress conditions. Values range from a maximum of 1, a fault plane ideally oriented to slip or dilate under ambient stress conditions to zero, a fault plane with no potential to slip or dilate. Slip and dilation tendency values were calculated for each fault in the focus study areas at, McGinness Hills, Neal Hot Springs, Patua, Salt Wells, San Emidio, and Tuscarora on fault traces. As dip is not well constrained or unknown for many faults mapped in within these we made these calculations using the dip for each fault that would yield the maximum slip tendency or dilation tendency. As such, these results should be viewed as maximum tendency of each fault to slip or dilate. The resulting along-fault and fault-to-fault variation in slip or dilation potential is a proxy for along fault and fault-to-fault variation in fluid flow conduit potential. Stress Magnitudes and directions Stress field variation within each focus area was approximated based on regional published data and the world stress database (Hickman et al., 2000; Hickman et al., 1998 Robertson-Tait et al., 2004; Hickman and Davatzes

  16. The analysis and modeling of dilatational terms in compressible turbulence

    NASA Technical Reports Server (NTRS)

    Sarkar, S.; Erlebacher, G.; Hussaini, M. Y.; Kreiss, H. O.

    1989-01-01

    It is shown that the dilatational terms that need to be modeled in compressible turbulence include not only the pressure-dilatation term but also another term - the compressible dissipation. The nature of these dilatational terms in homogeneous turbulence is explored by asymptotic analysis of the compressible Navier-Stokes equations. A non-dimensional parameter which characterizes some compressible effects in moderate Mach number, homogeneous turbulence is identified. Direct numerical simulations (DNS) of isotropic, compressible turbulence are performed, and their results are found to be in agreement with the theoretical analysis. A model for the compressible dissipation is proposed; the model is based on the asymptotic analysis and the direct numerical simulations. This model is calibrated with reference to the DNS results regarding the influence of compressibility on the decay rate of isotropic turbulence. An application of the proposed model to the compressible mixing layer has shown that the model is able to predict the dramatically reduced growth rate of the compressible mixing layer.

  17. Case report of a dilated odontome in the posterior mandible

    PubMed Central

    Almeida, Bruno; Silva, António; Pereira, Miguel; Silva, Mariana; Nunes, Stephanie

    2016-01-01

    Introduction Dens invaginatus (dens in dente) is a developmental malformation resulting from an invagination of enamel organ into the dental papilla, beginning at the crown and sometimes extending into the root before calcification occurs. Dilated odontome is the most extreme form of dens invaginatus and it is extremely rare in the posterior mandible. Presentation of case A 47 years old female patient with occasional episodes of diffuse pain and discomfort in the left posterior mandibular region. The extra-oral examination showed slight facial asymmetry. Panoramic and intra-oral X-rays show an intraosseous circular formation with radiopaque external limits and radiolucent interior. Discussion Computerized tomography scan reveals the bone integrity around the formation, as well as the independence of the neuro-vascular structures of the region. The most likely diagnostic option was dilated odontome. The enucleation procedure was carried out, and the fragments were sent to histopathological examination that revealed a diagnosis consistent with a dilated odontome. Conclusion In this case, the conservative surgical approach after planning was effective and predictable in the treatment of the pathology and patient symptoms without major complications. PMID:26780470

  18. Dilatation-dissipation corrections for advanced turbulence models

    NASA Technical Reports Server (NTRS)

    Wilcox, David C.

    1992-01-01

    This paper analyzes dilatation-dissipation based compressibility corrections for advanced turbulence models. Numerical computations verify that the dilatation-dissipation corrections devised by Sarkar and Zeman greatly improve both the k-omega and k-epsilon model predicted effect of Mach number on spreading rate. However, computations with the k-gamma model also show that the Sarkar/Zeman terms cause an undesired reduction in skin friction for the compressible flat-plate boundary layer. A perturbation solution for the compressible wall layer shows that the Sarkar and Zeman terms reduce the effective von Karman constant in the law of the wall. This is the source of the inaccurate k-gamma model skin-friction predictions for the flat-plate boundary layer. The perturbation solution also shows that the k-epsilon model has an inherent flaw for compressible boundary layers that is not compensated for by the dilatation-dissipation corrections. A compressibility modification for k-gamma and k-epsilon models is proposed that is similar to those of Sarkar and Zeman. The new compressibility term permits accurate predictions for the compressible mixing layer, flat-plate boundary layer, and a shock separated flow with the same values for all closure coefficients.

  19. [Optimal indication for surgical ventricular restoration for dilated cardiomyopathy].

    PubMed

    Wakasa, Satoru; Shingu, Yasushige; Kubota, Suguru; Minamida, Taro; Iijima, Makoto; Naito, Yuji; Ooka, Tomonori; Tachibana, Tsuyoshi; Matsui, Yoshiro

    2013-01-01

    In this study, we assessed mid-term results of surgical ventricular restoration (SVR) for dilated cardiomyopathy. The study subjects were 107 patients who underwent SVR for both ischemic (ischemic cardiomyopathy:ICM, n=57) and non-ischemic (dilated cardiomyopathy:DCM, n=50) dilated cardiomyopathy. In 49(86%)patients ICM was associated with New York heart Association(NYHA) class III or more. Preoperative left ventricular ejection fraction (LVEF) and left ventricular end-diastolic dimension(LVDd)were 22±6% and 67±9 mm, respectively. Hospital mortality was 14% and 5-year mortality was 40%. In contrast, 46( 92%) of the DCM patients presented with NYHA class III or more. Preoperative LVEF and LVDd were 20±6% and 74±9 mm, respectively. Hospital mortality was 28% and 5-year mortality was 63%. For NYHA class III or less, however, 5-year mortality rates were 23% and 39% in those with ICM and DCM, respectively. For those with NYHA functional class III or less, SVR was associated with a satisfactory survival rate and is recommended. For those with severe heart failure, however, ventricular assist devices or heart transplantation may have to be indicated.

  20. Regulation of landslide motion by dilatancy and pore pressure feedback

    USGS Publications Warehouse

    Iverson, R.M.

    2005-01-01

    A new mathematical model clarifies how diverse styles and rates of landslide motion can result from regulation of Coulomb friction by dilation or contraction of water-saturated basal shear zones. Normalization of the model equations shows that feedback due to coupling between landslide motion, shear zone volume change, and pore pressure change depends on a single dimensionless parameter ??, which, in turn, depends on the dilatancy angle ?? and the intrinsic timescales for pore pressure generation and dissipation. If shear zone soil contracts during slope failure, then ?? 0, and negative feedback permits slow, steady landslide motion to occur while positive pore pressure is supplied by rain infiltration. Steady state slip velocities v0 obey v0 = -(K/??) p*e, where K is the hydraulic conductivity and p*e is the normalized (dimensionless) negative pore pressure generated by dilation. If rain infiltration and attendant pore pressure growth continue unabated, however, their influence ultimately overwhelms the stabilizing influence of negative p*e. Then, unbounded landslide acceleration occurs, accentuated by an instability that develops if ?? diminishes as landslide motion proceeds. Nonetheless, numerical solutions of the model equations show that slow, nearly steady motion of a clay-rich landslide may persist for many months as a result of negative pore pressure feedback that regulates basal Coulomb friction. Similarly stabilized motion is less likely to occur in sand-rich landslides that are characterized by weaker negative feedback.

  1. Oxytocin enhances pupil dilation and sensitivity to 'hidden' emotional expressions.

    PubMed

    Leknes, Siri; Wessberg, Johan; Ellingsen, Dan-Mikael; Chelnokova, Olga; Olausson, Håkan; Laeng, Bruno

    2013-10-01

    Sensing others' emotions through subtle facial expressions is a highly important social skill. We investigated the effects of intranasal oxytocin treatment on the evaluation of explicit and 'hidden' emotional expressions and related the results to individual differences in sensitivity to others' subtle expressions of anger and happiness. Forty healthy volunteers participated in this double-blind, placebo-controlled crossover study, which shows that a single dose of intranasal oxytocin (40 IU) enhanced or 'sharpened' evaluative processing of others' positive and negative facial expression for both explicit and hidden emotional information. Our results point to mechanisms that could underpin oxytocin's prosocial effects in humans. Importantly, individual differences in baseline emotional sensitivity predicted oxytocin's effects on the ability to sense differences between faces with hidden emotional information. Participants with low emotional sensitivity showed greater oxytocin-induced improvement. These participants also showed larger task-related pupil dilation, suggesting that they also allocated the most attentional resources to the task. Overall, oxytocin treatment enhanced stimulus-induced pupil dilation, consistent with oxytocin enhancement of attention towards socially relevant stimuli. Since pupil dilation can be associated with increased attractiveness and approach behaviour, this effect could also represent a mechanism by which oxytocin increases human affiliation.

  2. Through-the-scope balloon dilatation of benign pyloric stenoses.

    PubMed

    Schmüdderich, W; Harloff, M; Riemann, J F

    1989-01-01

    In 9 patients with benign pyloric stenosis, the stenosis was dilated using through-the-scope (TTS) balloon catheters (diameter 1.5 to 1.8 cm), which can be passed through the biopsy channel of a standard fiberscope under direct vision. In all cases, the stenosis was secondary to fibrous changes in peptic ulcer disease. In addition, all patients had active ulcers. All dilatation treatments were primarily successful: the stenoses were opened for the passage of the fiberscope. There were no complications; even with active ulcers there were no side effects. The treatment was followed by immediate symptomatic relief. On prospective evaluation over a period of 7 months (mean), 6 patients remained asymptomatic, 2 patients had to be dilated again for restenosis and have since been asymptomatic for 1 and 12 months, respectively. One patient had to undergo surgery after 7 months for ulcer perforation into the common bile duct. The TTS technique has considerable advantages over the methods requiring a guide wire. This technique with its easy practicability and low incidence of complications may become a valid alternative to surgical procedures if the good initial results can be confirmed in further studies.

  3. Factors affecting pupil size after dilatation: the Twin Eye Study

    PubMed Central

    Hammond, C.; Snieder, H.; Spector, T.; Gilbert, C.

    2000-01-01

    BACKGROUND/AIMS—Well dilated pupils make eye surgery easier. A classic twin study was established to examine the relative importance of genes and environment in the variance of pupil size after mydriasis, and to examine the effects of other factors such as age, iris colour, and refractive error.
METHODS—506 twin pairs, 226 monozygotic (MZ) and 280 dizygotic (DZ), aged 49-79 (mean age 62.2 years, SD 5.7) were examined. Dilated pupil size was measured using a standardised grid superimposed over digital retroillumination images taken 50-70 minutes after mydriasis using tropicamide 1% and phenylephrine 10%. Univariate maximum likelihood model fitting was used to estimate genetic and environmental variance components.
RESULTS—Dilated pupil size was more highly correlated in MZ compared with DZ twins (intraclass correlation coefficients 0.82 and 0.39 respectively). A model specifying additive genetic and unique environmental factors showed the best fit to the data, yielding a heritability of 78-80%. Individual environmental factors explained 18-19% of the variance in this population. Age only accounted for 2-3% of the variance and refractive error and iris colour did not significantly contribute to the variance.
CONCLUSIONS—Pupil size after mydriasis is largely genetically determined, with a heritability of up to 80%.

 PMID:11004106

  4. Factors affecting pupil size after dilatation: the Twin Eye Study.

    PubMed

    Hammond, C J; Snieder, H; Spector, T D; Gilbert, C E

    2000-10-01

    Well dilated pupils make eye surgery easier. A classic twin study was established to examine the relative importance of genes and environment in the variance of pupil size after mydriasis, and to examine the effects of other factors such as age, iris colour, and refractive error. 506 twin pairs, 226 monozygotic (MZ) and 280 dizygotic (DZ), aged 49-79 (mean age 62.2 years, SD 5.7) were examined. Dilated pupil size was measured using a standardised grid superimposed over digital retroillumination images taken 50-70 minutes after mydriasis using tropicamide 1% and phenylephrine 10%. Univariate maximum likelihood model fitting was used to estimate genetic and environmental variance components. Dilated pupil size was more highly correlated in MZ compared with DZ twins (intraclass correlation coefficients 0.82 and 0.39 respectively). A model specifying additive genetic and unique environmental factors showed the best fit to the data, yielding a heritability of 78-80%. Individual environmental factors explained 18-19% of the variance in this population. Age only accounted for 2-3% of the variance and refractive error and iris colour did not significantly contribute to the variance. Pupil size after mydriasis is largely genetically determined, with a heritability of up to 80%.

  5. Congenital Intrahepatic Bile Duct Dilatation is a Potentially Curable Disease

    PubMed Central

    Mabrut, Jean-Yves; Partensky, Christian; Jaeck, Daniel; Oussoultzoglou, Elie; Baulieux, Jacques; Boillot, Olivier; Lerut, Jan; de Ville de Goyet, Jean; Hubert, Catherine; Otte, Jean-Bernard; Audet, Maxime; Ducerf, Christian; Gigot, Jean-François

    2007-01-01

    Objective: To report clinical presentation, perioperative outcome, and long-term results of surgical management of congenital intrahepatic bile duct (IHBD) dilatations (including Caroli disease) in a multi-institutional setting. Summary Background Data: Congenital IHBD dilatations are a rare congenital disorder predisposing to intrahepatic stones, cholangitis, and cholangiocarcinoma. The management remains difficult and controversial for bilobar forms of the disease or when concurrent congenital hepatic fibrosis is associated. Methods: From 1976 to 2004, 33 patients (range 11 to 79 years) were retrospectively enrolled. Disease extent into the liver was unilobar in 26 patients and bilobar in 7 patients (21%). Cholangiocarcinoma, congenital hepatic fibrosis, and intrahepatic stones were present in 2, 10, and 20 patients, respectively. Transplantations or liver resections were performed in 5 and 27 patients, respectively, whereas 1 asymptomatic patient was managed conservatively. Results: Postoperative mortality was nil. Postoperative complications occurred in 16 of 32 operated patients (50%) and additional procedures for residual stones were required in 5 patients. During a median follow-up of 80 months (1 patient being lost for follow-up) no patient developed metachronous carcinoma. Six patients (30%) developed recurrent intrahepatic stones but satisfactory late outcome was achieved in 27 patients (87%). Conclusions: Partial or total liver resection achieves satisfactory late outcome in congenital IHBD dilatations, when the affection is treated at an early stage and when the extent of liver resection is tailored to intrahepatic disease extent and takes into consideration the presence and severity of underlying chronic liver and renal diseases. PMID:17667502

  6. [Conservative management of esophageal perforation after pneumatic dilatation for achalasia].

    PubMed

    Scatton, Olivier; Gaudric, Marianne; Massault, Pierre-Philippe; Chaussade, Stanislas; Houssin, Didier; Dousset, Bertrand

    2002-10-01

    To assess the results and indications of conservative management of esophageal perforation following pneumatic dilatation for achalasia. Thirteen esophageal perforations complicating 524 dilatations in 412 patients (3%) were diagnosed by esophagogram. Medical treatment consisted of nasogastric succion, antibiotics and pleural drainage, if necessary. Conservative surgical treatment included left thoracophrenotomy, perforation closure, controlateral myotomy and anterior fundoplication. Surgical decision was based upon clinical and radiological parameters. Functional outcome was assessed by the means of the Eckardt's grading score. Six patients were successfully managed by medical treatment. Seven patients underwent conservative surgery, three of whom after failure of medical treatment. The presence of a pneumomediastinum at initial presentation led to immediate (n=2) or delayed (n=2) surgery in all instances. No patients died. In the surgical group, morbidity consisted of one wound infection, one pleural effusion and one venous thrombosis. One severe chest infection occurred in the medical group. Oral feeding was reintroduced after a median of 10 and 11 days in the surgical and medical groups, respectively. Functional results were satisfactory and similar in both groups. Conservative medical or surgical management of oesophageal perforation following pneumatic dilatation is safe, if the diagnosis is done early. Pneumomediastinum at initial presentation seems to predict failure of conservative medical treatment.

  7. Demosaicking using geometric duality and dilated directional differentiation

    NASA Astrophysics Data System (ADS)

    Kim, Joohyeok; Jeon, Gwanggil; Jeong, Jechang

    This paper presents a new demosaicking algorithm which uses two cost terms: the interpolation error of a low resolution image based on geometric duality and the dilated directional differentiation of color differences. Since a given high resolution image and its low resolution image obtained by sampling have similar edge properties, the proposed algorithm computes the interpolation errors for the candidate directions in the low resolution image, and exploits them as a cost term for the direction. In addition, the interpolation direction can be determined accurately even in the vicinity of object boundaries by dilating the directional differentiation of the color difference values. Through dilation, some pixels, which are in the neighborhood of an edge but classified into a flat region by simple edge detection like the Sobel filter, are reclassified. By combining this edge classifier and the weighted sum of the estimates obtained by Taylor approximation, missing pixels are interpolated. Simulation results show that the proposed demosaicking algorithm is superior to other state-of-the-art algorithms in terms of visual and objective qualities. Furthermore, the computational complexity is comparable with the existing algorithms. Therefore, the proposed algorithm is suitable for real-time implementation.

  8. Dilated odontoma: A report of two cases from a radiological perspective.

    PubMed

    Jayachandran, S; Kayal, L; Sharma, Aatman; Priyanka, Khobre

    2016-01-01

    Dilated odontoma is the most extreme form of dens invaginatus. The lesion appears as a roughly spherical mass that does not resemble a tooth but in a way appears tooth - like on radiographs due to somewhat similar radiodensity. The lesion is mostly spherical in appearance and hence the term "dilated." Occasionally, we come across cases of simultaneous pathologies. Here, we report two cases of a dilated odontoma one of which is associated with dentigerous cyst and in other case dilated odontoma pushing the maxillary sinus superiorly. Histologically, the mass was composed of dentinal tubules. These morphological and histological features are compatible with those of a dilated odontoma.

  9. Dilated odontoma: A report of two cases from a radiological perspective

    PubMed Central

    Jayachandran, S.; Kayal, L.; Sharma, Aatman; Priyanka, Khobre

    2016-01-01

    Dilated odontoma is the most extreme form of dens invaginatus. The lesion appears as a roughly spherical mass that does not resemble a tooth but in a way appears tooth - like on radiographs due to somewhat similar radiodensity. The lesion is mostly spherical in appearance and hence the term “dilated.” Occasionally, we come across cases of simultaneous pathologies. Here, we report two cases of a dilated odontoma one of which is associated with dentigerous cyst and in other case dilated odontoma pushing the maxillary sinus superiorly. Histologically, the mass was composed of dentinal tubules. These morphological and histological features are compatible with those of a dilated odontoma. PMID:27041914

  10. Hybrid cutting balloon dilatation for treatment of cor triatriatum sinister in a cat.

    PubMed

    Stern, Joshua A; Tou, Sandra P; Barker, Piers C A; Hill, Kevin D; Lodge, Andrew J; Mathews, Kyle G; Keene, Bruce W

    2013-09-01

    A hybrid surgical approach and balloon dilatation were performed successfully in a cat with cor triatriatum sinister and clinical signs of congestive heart failure. Left lateral thoracotomy was used to access the heart and cutting balloon followed by standard balloon dilatation were utilized to dilate the perforation in the anomalous left atrial membrane. Clinical signs resolved completely after dilation of the anomalous left atrial membrane. Based upon the outcome of this case, balloon dilatation appears to be a viable treatment option for cats affected with cor triatriatum sinister.

  11. Post-transplant cyclophosphamide versus anti-thymocyte globulin as graft- versus-host disease prophylaxis in haploidentical transplant

    PubMed Central

    Ruggeri, Annalisa; Sun, Yuqian; Labopin, Myriam; Bacigalupo, Andrea; Lorentino, Francesca; Arcese, William; Santarone, Stella; Gülbas, Zafer; Blaise, Didier; Messina, Giuseppe; Ghavamzadeh, Ardeshi; Malard, Florent; Bruno, Benedetto; Diez-Martin, Jose Luis; Koc, Yener; Ciceri, Fabio; Mohty, Mohamad; Nagler, Arnon

    2017-01-01

    Severe graft-versus-host disease is a major barrier for non-T-cell-depleted haploidentical stem cell transplantation. There is no consensus on the optimal graft-versus-host disease prophylaxis. This study compared the two most commonly used graft-versus-host disease prophylaxis regimens (post-transplant cyclophosphamide-based vs. the anti-thymocyte globulin-based) in adults with acute myeloid leukemia reported to the European Society for Blood and Bone Marrow Transplantation. A total of 308 patients were analyzed; 193 received post-transplant cyclophosphamide-based regimen and 115 anti-thymocyte globulin-based regimen as anti-graft-versus-host disease prophylaxis. The post-transplant cyclophosphamide-based regimen was more likely to be associated to bone marrow as graft source (60% vs. 40%; P=0.01). Patients in the post-transplant cyclophosphamide-based regimen group had significantly less grade 3–4 acute graft-versus-host disease than those in the anti-thymocyte globulin-based group (5% vs. 12%, respectively; P=0.01), comparable to chronic graft-versus-host disease. Multivariate analysis showed that non-relapse mortality was lower in the post-transplant cyclophosphamide-based regimen group [22% vs. 30%, Hazard ratio (HR) 1.77(95%CI: 1.09–2.86); P=0.02] with no difference in relapse incidence. Patients receiving post-transplant cyclophosphamide-based regimen had better graft-versus-host disease-free, relapse-free survival [HR 1.45 (95%CI: 1.04–2.02); P=0.03] and leukemia-free survival [HR 1.48 (95%CI: 1.03–2.12); P=0.03] than those in the anti-thymocyte globulin-based group. In the multivariate analysis, there was also a trend for a higher overall survival [HR 1.43 (95%CI: 0.98–2.09); P=0.06] for post-transplant cyclophosphamide-based regimen versus the anti-thymocyte globulin-based group. Notably, center experience was also associated with non-relapse mortality and graft-versus-host disease-free, relapse-free survival. Haplo-SCT using a post

  12. Early Gastric Cancer Recurrence Following Curative Resection Presenting as Biliary Tract Dilatation, Pancreatic Duct Dilatation and Intestinal Wall Thickening.

    PubMed

    Kato, Hiroyuki; Ito, Yukiko; Tanaka, Eri; Noguchi, Kensaku; Yamamoto, Shinzo; Taniguchi, Hiroyoshi; Yoshida, Hideo; Kumasaka, Toshio; Nakata, Ryo

    2016-01-01

    Early gastric cancer, especially cancer confined to the mucosa (stage T1a), is known to have a high cure rate with rare recurrence. We herein report the case of a 40-year-old female who initially presented with biliary tract dilatation, pancreatic duct dilatation and intestinal wall thickening 3 years after curative resection of pT1aN0 stage gastric cancer. The intestinal resection specimen revealed tumor cells spreading through the subserosa to the submucosa sparing mucosal membrane, which made exploratory laparotomy the only approach to confirm the diagnosis. It is always important to be aware of malignancy recurrence and clinicians should not hesitate to choose exploratory laparotomy to avoid any delay in the diagnosis and treatment.

  13. Comparative Metabolism of Cyclophosphamide and Ifosfamide in the Mouse Using UPLC-ESI-QTOFMS-Based Metabolomics

    PubMed Central

    Li, Fei; Patterson, Andrew D.; Höfer, Constance C.; Krausz, Kristopher W.; Gonzalez, Frank J.; Idle, Jeffrey R.

    2010-01-01

    Ifosfamide (IF) and cyclophosphamide (CP) are common chemotherapeutic agents. Interestingly, while the two drugs are isomers, only IF treatment is known to cause nephrotoxicity and neurotoxicity. Therefore, it was anticipated that a comparison of IF and CP drug metabolites in the mouse would reveal reasons for this selective toxicity. Drug metabolites were profiled by ultra-performance liquid chromatography-linked electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS), and the results analyzed by multivariate data analysis. Of the total 23 drug metabolites identified by UPLC-ESI-QTOFMS for both IF and CP, five were found to be novel. Ifosfamide preferentially underwent N-dechloroethylation, the pathway yielding 2-chloroacetaldehyde, while cyclophosphamide preferentially underwent ring-opening, the pathway yielding acrolein (AC). Additionally, S-carboxymethylcysteine and thiodiglycolic acid, two downstream IF and CP metabolites, were produced similarly in both IF- and CP-treated mice. This may suggest that other metabolites, perhaps precursors of thiodiglycolic acid, may be responsible for IF encephalopathy and nephropathy. PMID:20541539

  14. Continuous cyclophosphamide, doxorubicin, vincristine, and prednisolone. A new, innovative protocol for diffuse aggressive lymphomas

    SciTech Connect

    Banavali, S.D.; Advani, S.H.; Gopal, R.; Agarwala, S.; Dinshaw, K.A.; Saikia, T.K.; Pai, S.K.; Kurkure, P.; Nair, C.N.; Gonsalves, M. )

    1990-04-15

    One hundred eight patients with aggressive non-Hodgkin's lymphoma (high and intermediate grade) were treated with a new protocol: continuous cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). They were evaluated for long-term survival and pretreatment characteristics predictive of response and survival. Continuous CHOP protocol consists of initial 8 weeks of intensive chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone, followed by local/cranial radiotherapy and maintenance therapy. Complete remission (CR) was achieved in 84 of 108 (78%) patients; seven (6%) had a moderate response and 17 (16%) had a poor response. A statistically significant difference in CR rate was found only in patients with different stages. Seventeen of 84 (20%) complete responders have had a relapse of the disease. The median survival has not been reached. Results show an actuarial disease-free survival (DFS) of 77% for the 84 patients who had a complete response. The overall survival for all patients was 53% at 5 years of follow-up. The difference in DFS at the end of 5 years between different stages, main histologic subgroups, and age groups was not statistically significant. The toxicity observed was acceptable. Thus continuous CHOP appears to be an effective protocol for the treatment of intermediate-grade and high-grade lymphomas.

  15. Crataegus monogyna aqueous extract ameliorates cyclophosphamide-induced toxicity in rat testis: stereological evidences.

    PubMed

    Jalali, Ali Shalizar; Hasanzadeh, Shapour; Malekinejad, Hassan

    2012-01-01

    Cyclophosphamide (CP) is extensively used as an antineoplastic agent for the treatment of various cancers, as well as an immunosuppressive agent. However, despite its wide spectrum of clinical uses, CP is known to cause several adverse effects including reproductive toxicity. Crataegus monogyna is one of the oldest pharmaceutical plants that have been shown to be cytoprotective by scavenging free radicals. The present study was conducted to assess whether Crataegus monogyna fruits aqueous extract with anti-oxidant properties, could serve as a protective agent against reproductive toxicity during CP treatment in a rat model. Male Wistar rats were categorized into four groups. Two groups of rats were administered CP at a dose of 5 mg in 5 ml saline/kg/day for 28 days by oral gavages. One of these groups received Crataegus monogyna aqueous extract at a dose of 20 mg/kg/day orally four hours after cyclophosphamide administration. A vehicle treated control group and a Crataegus monogyna control group were also included. The CP-treated group showed significant decreases in the body, testes and epididymides weights as well as many histological alterations. Stereological parameters and spermatogenic activities (Sertoli cell, repopulation and miotic indices) were also significantly decreased by CP treatment. Notably, Crataegus coadministration caused a partial recovery in above-mentined parameters. These findings indicate that Crataegus monogyna may be partially protective against CP-induced testicular toxicity.

  16. Quantitative prediction of catalepsy induced by amoxapine, cinnarizine and cyclophosphamide in mice.

    PubMed

    Nasu, R; Matsuo, H; Takanaga, H; Ohtani, H; Sawada, Y

    2000-05-01

    Parkinsonism can be a side effect of antipsychotic drugs, and has recently been reported with peripherally acting drugs such as calcium channel blockers, antiarrhythmic agents and so on. In this study, we examined the quantitative prediction of drug-induced catalepsy by amoxapine, cinnarizine and cyclophosphamide, which have been reported to induce parkinsonism. Dose-dependent catalepsy was induced by these drugs in mice. In vivo dopamine D(1), D(2) and muscarinic acetylcholine (mACh) receptor occupancies by these drugs in the striatum were also examined. The in vitro binding affinities (K(i) values) of amoxapine and cinnarizine to dopamine D(1), D(2) and mACh receptors in rat striatal synaptic membrane were 200 and 2900 nM, 58.4 and 76.4 nM and 379 and 290 nM, respectively. Cyclophosphamide did not bind to these receptors at concentrations up to 100 microM. Twenty drugs, including those mentioned above, showed a significant correlation between the observed intensity of catalepsy and the values predicted with a pharmacodynamic model (Haraguchi K, Ito K, Kotaki H, Sawada Y, Iga T. Prediction of drug-induced catalepsy based on dopamine D(1), D(2), and muscarinic acetylcholine receptor occupancies. Drug Metab Disp 1997; 25: 675-684) based on in vivo occupancy of dopamine D(1), D(2) and mACh receptors. We conclude that occupancy of dopamine D(1) and D(2) receptors contributes to catalepsy induction by amoxapine and cinnarizine.

  17. Insulin-induced enhancement of MCF-7 breast cancer cell response to 5-fluorouracil and cyclophosphamide.

    PubMed

    Agrawal, Siddarth; Łuc, Mateusz; Ziółkowski, Piotr; Agrawal, Anil Kumar; Pielka, Ewa; Walaszek, Kinga; Zduniak, Krzysztof; Woźniak, Marta

    2017-06-01

    The study was designed to evaluate the potential use of insulin for cancer-specific treatment. Insulin-induced sensitivity of MCF-7 breast cancer cells to chemotherapeutic agents 5-fluorouracil and cyclophosphamide was evaluated. To investigate and establish the possible mechanisms of this phenomenon, we assessed cell proliferation, induction of apoptosis, activation of apoptotic and autophagic pathways, expression of glucose transporters 1 and 3, formation of reactive oxygen species, and wound-healing assay. Additionally, we reviewed the literature regarding theuse of insulin in cancer-specific treatment. We found that insulin increases the cytotoxic effect of 5-fluorouracil and cyclophosphamide in vitro up to two-fold. The effect was linked to enhancement of apoptosis, activation of apoptotic and autophagic pathways, and overexpression of glucose transporters 1 and 3 as well as inhibition of cell proliferation and motility. We propose a model for insulin-induced sensitization process. Insulin acts as a sensitizer of cancer cells to cytotoxic therapy through various mechanisms opening a possibility for metronomic insulin-based treatments.

  18. In vivo interaction of anti-cancer drugs with misonidazole or metronidazole: cyclophosphamide and BCNU.

    PubMed Central

    Tannock, I. F.

    1980-01-01

    The addition of misonidazole (MISO) or metronidazole (METRO) to treatment with cyclophosphamide (CY) increased delay to regrowth of 2 experimental tumours. The effect was observed for large an small tumours, was present for doses of MISO that are ineffective for killing hypoxic cells, and required that it be given with, or shortly before CY. Mice receiving combined treatment had more weight loss and myelosuppression than those receiving CY alone, and the Therapeutic Index was lower. MISO caused a marked increase in growth delay when combined with BCNU to treat the KHT sarcoma. This effect was observed for small and large tumours, required simultaneous administration of drugs, and also led to increased host toxicity. There was no therapeutic advantage from combined treatment. Survival of aerobic or anoxic Chinese hamster ovary (CHO) cells was assessed after exposure in vitro to serum from mice that had received CY or BCNU alone. MISO alone, or combined treatment. Results of these experiments suggest that (1) MISO delays the excretion or breakdown of active metabolites of CY, and (2) at a dose that does not kill hypoxic cells, it may selectively "sensitize" hypoxic cells (but not aerobic cells) to the action of BCNU. The presence of other undetermined interactions of BCNU and MISO is inferred from the increased toxicity to (aerobic) normal tissue. Misonidazole or metronidazole should be used with caution in patients who are receiving BCNU or cyclophosphamide. PMID:7459221

  19. Cyclophosphamide, fludarabine, alemtuzumab, and rituximab as salvage therapy for heavily pretreated patients with chronic lymphocytic leukemia

    PubMed Central

    Badoux, Xavier C.; Keating, Michael J.; Wang, Xuemei; O'Brien, Susan M.; Ferrajoli, Alessandra; Faderl, Stefan; Burger, Jan; Koller, Charles; Lerner, Susan; Kantarjian, Hagop

    2011-01-01

    Patients with relapsed chronic lymphocytic leukemia (CLL) and high-risk features, such as fludarabine refractoriness, complex karyotype, or abnormalities of chromosome 17p, experience poor outcomes after standard fludaradine-based regimens. Alemtuzumab is a chimeric CD52 monoclonal antibody with activity in CLL patients with fludarabine-refractory disease and 17p deletion. We report the outcome for 80 relapsed or refractory patients with CLL enrolled in a phase 2 study of cyclophosphamide, fludarabine, alemtuzumab, and rituximab (CFAR). All patients were assessed for response and progression according to the 1996 CLL-working group criteria. For the intention-to-treat analysis, the overall response rate was 65%, including 29% complete response. The estimated progression-free survival was 10.6 months and median overall survival was 16.7 months. Although we noted higher complete response in high-risk patients after CFAR compared with a similar population who had received fludarabine, cyclophosphamide, and rituximab as salvage therapy, there was no significant improvement in progression-free survival and overall survival appeared worse. CFAR was associated with a high rate of infectious complications with 37 patients (46%) experiencing a serious infection during therapy and 28% of evaluable patients experiencing late serious infections. Although CFAR produced good response rates in this highly pretreated high-risk group of patients, there was no benefit in survival outcomes. PMID:21670470

  20. Comparative metabolism of cyclophosphamide and ifosfamide in the mouse using UPLC-ESI-QTOFMS-based metabolomics.

    PubMed

    Li, Fei; Patterson, Andrew D; Höfer, Constance C; Krausz, Kristopher W; Gonzalez, Frank J; Idle, Jeffrey R

    2010-10-01

    Ifosfamide (IF) and cyclophosphamide (CP) are common chemotherapeutic agents. Interestingly, while the two drugs are isomers, only IF treatment is known to cause nephrotoxicity and neurotoxicity. Therefore, it was anticipated that a comparison of IF and CP drug metabolites in the mouse would reveal reasons for this selective toxicity. Drug metabolites were profiled by ultra-performance liquid chromatography-linked electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS), and the results analyzed by multivariate data analysis. Of the total 23 drug metabolites identified by UPLC-ESI-QTOFMS for both IF and CP, five were found to be novel. Ifosfamide preferentially underwent N-dechloroethylation, the pathway yielding 2-chloroacetaldehyde, while cyclophosphamide preferentially underwent ring-opening, the pathway yielding acrolein (AC). Additionally, S-carboxymethylcysteine and thiodiglycolic acid, two downstream IF and CP metabolites, were produced similarly in both IF- and CP-treated mice. This may suggest that other metabolites, perhaps precursors of thiodiglycolic acid, may be responsible for IF encephalopathy and nephropathy. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  1. Particulate Matter Exposure Impairs Systemic Microvascular Endothelium-Dependent Dilation

    PubMed Central

    Nurkiewicz, Timothy R.; Porter, Dale W.; Barger, Mark; Castranova, Vincent; Boegehold, Matthew A.

    2004-01-01

    Acute exposure to airborne pollutants, such as solid particulate matter (PM), increases the risk of cardiovascular dysfunction, but the mechanisms by which PM evokes systemic effects remain to be identified. The purpose of this study was to determine if pulmonary exposure to a PM surrogate, such as residual oil fly ash (ROFA), affects endothelium-dependent dilation in the systemic microcirculation. Rats were intratracheally instilled with ROFA at 0.1, 0.25, 1 or 2 mg/rat 24 hr before experimental measurements. Rats intratracheally instilled with saline or titanium dioxide (0.25 mg/rat) served as vehicle or particle control groups, respectively. In vivo microscopy of the spinotrapezius muscle was used to study systemic arteriolar dilator responses to the Ca2+ ionophore A23187, administered by ejection via pressurized micropipette into the arteriolar lumen. We used analysis of bronchoalveolar lavage (BAL) samples to monitor identified pulmonary inflammation and damage. To determine if ROFA exposure affected arteriolar nitric oxide sensitivity, sodium nitroprusside was iontophoretically applied to arterioles of rats exposed to ROFA. In saline-treated rats, A23187 dilated arterioles up to 72 ± 7% of maximum. In ROFA- and TiO2-exposed rats, A23187-induced dilation was significantly attenuated. BAL fluid analysis revealed measurable pulmonary inflammation and damage after exposure to 1 and 2 mg ROFA (but not TiO2 or < 1 mg ROFA), as evidenced by significantly higher polymorphonuclear leukocyte cell counts, enhanced BAL albumin levels, and increased lactate dehydrogenase activity in BAL fluid. The sensitivity of arteriolar smooth muscle to NO was similar in saline-treated and ROFA-exposed rats, suggesting that pulmonary exposure to ROFA affected endothelial rather than smooth muscle function. A significant increase in venular leukocyte adhesion and rolling was observed in ROFA-exposed rats, suggesting local inflammation at the systemic microvascular level. These results

  2. In vivo, synergestic inhibition of MAT-LyLu rat prostatic adenocarcinoma growth by polyamine deprivation and low-dose cyclophosphamide.

    PubMed

    Cipolla, B; Blanchard, Y; Chamaillard, L; Quemener, V; Guillé, F; Havouis, R; Moulinoux, J P

    1996-01-01

    Polyamine deprivation in vivo produces significant tumor growth inhibition of the hormone-resistant, metastatic Dunning Mat-LyLu murine prostatic carcinoma. In order to produce a cytotoxic effect in addition to the cytostatic effect of polyamine deprivation, various chemotherapy regimens, combined with drug-containing polyamine-deficient chow (DC-PDC), were assessed. Triple chemotherapy combining methotrexate, cyclophosphamide and vindesine; and monochemotherapy with high-dose cyclophosphamide (90 mg. kg-1) and low-dose cyclophosphamide (20 mg.kg-1) were studied alone and in combination with DC-PDC. A variant of DC-PDC excluding the polyamine oxidase inhibitor MDL 72527 was also studied in combination with low-dose cyclophosphamide. The triple-chemotherapy regimen alone or in combination with polyamine deprivation was effective on tumor growth inhibition but was also toxic. High-dose cyclophosphamide alone produced significant tumor growth inhibition and an increase in life span. High-dose cyclophosphamide in combination with DC-PDC was also effective on tumor growth but was also toxic. Low-dose cyclophosphamide alone was moderately effective on tumor growth inhibition with a marginal increase in life span. When combined with polyamine deprivation, results with low-dose cyclophosphamide compared favourably with those of high-dose cyclophosphamide alone and prevented the formation of lung metastases. The polyamine oxidase inhibitor does not appear to be mandatory to achieve this effect if DC-PDC is combined with low-dose cyclophosphamide. Polyamine deprivation appears to be an important tool in anticancer therapy, allowing the use of reduced doses of cytotoxic agents with the same antitumoral efficacy.

  3. Cyclophosphamide (Cytoxan)

    MedlinePlus

    ... the classic rash of “shingles”. Pneumocystis carinii pneumonia (“PCP”) — Pneumocystis carinii is a fungus that resides within ... organism can cause a serious type of pneumonia: PCP. A few years ago, PCP was the most ...

  4. Cyclophosphamide Injection

    MedlinePlus

    ... mention any of the following: allopurinol (Zyloprim®), cortisone acetate, doxorubicin (Adriamycin®, Doxil®), hydrocortisone (Cortef®), or phenobarbital (Luminal® Sodium). Your doctor may need to change the doses ...

  5. Adjuvant treatment of breast cancer patients with 1-3 positive lymph nodes: vinorelbine plus epirubicin; vinorelbine plus epirubicin sequential followed up by paclitaxel; epirubicin plus cyclophosphamide; epirubicin plus cyclophosphamide sequential followed up by paclitaxel. A phase II study.

    PubMed

    Elling, D; Eggemann, H; Kümmel, S; Breitbach, P; Kohls, A; Morack, G; Schlosser, H; Krocker, J

    2003-06-01

    The efficacy of anthracyclin-containing adjuvant chemotherapy of node-positive breast cancer can be further improved by adding sequential paclitaxel (T). There is also clinical evidence that replacing cyclophosphamide (C) with vinorelbin (V) might further reduce toxicity. In order to assess the safety of these options, we initiated a clinical cohort study of epirubicin/cyclophoshamide and epirubicin/vinorelbine with or without sequential paclitaxel. Patients with node-positive (1-3) breast cancer were assigned to open-label epirubicin/vinorelbine (EV), epirubicin/vino-relbine and sequential paclitaxel (EV/T), epirubicin/cyclophosphamide (EC) or epirubicin/cyclophosphamide plus sequential paclitaxel (EC/T) therapy. Fifty four outpatients received a total of 304 chemotherapy cycles. There were significant differences in grade III/IV anemia only between the EV/T and EC/T groups, in favor of the EC/T group (P=0.002). The safety of paclitaxel is not impaired when given sequentially after administration of the two anthracyclin-containing regimens. The exchange of cyclophosphamide against vinorelbine leads to deteriorating safety of the EC/T regimen.

  6. PERSONALIZED DOSING OF CYCLOPHOSPHAMIDE IN THE TOTAL BODY IRRADIATION - CYCLOPHOSPHAMIDE CONDITIONING REGIMEN: A PHASE II TRIAL IN PATIENTS WITH HEMATOLOGIC MALIGNANCY

    PubMed Central

    McCune, Jeannine S.; Batchelder, Ami; Guthrie, Katherine A.; Witherspoon, Robert; Appelbaum, Frederick R.; Phillips, Brian; Vicini, Paolo; Salinger, David H.; McDonald, George B.

    2009-01-01

    This study investigates the efficacy and safety of personalized cyclophosphamide (CY) dosing in 50 patients receiving CY with total body irradiation (TBI). Participants received CY 45 mg/kg with subsequent therapeutic drug monitoring with Bayesian parameter estimation to personalize the second CY dose to a target area under the curve for carboxyethylphosphoramide mustard (a reporter for CY-derived toxins) and for hydroxycyclophosphamide (to ensure engraftment). The mean second CY dose was 66 mg/kg; the total dose ranged from 45–145 mg/kg. After completion of this phase II study, we compared participants’ clinical outcomes to those of concurrent controls (N=100) who received TBI with standard CY doses of 120 mg/kg. Patients receiving personalized CY dosing had significantly lower post-conditioning peak total serum bilirubin (p=0.03); a 38% reduction in the hazard of acute kidney injury (p=0.03); and similar non-relapse and overall survival (p=0.70 and 0.63, respectively) despite lower doses of CY in most patients. PMID:19295506

  7. A phase II study of metronomic paclitaxel/cyclophosphamide/capecitabine followed by 5-fluorouracil/epirubicin/cyclophosphamide as preoperative chemotherapy for triple-negative or low hormone receptor expressing/HER2-negative primary breast cancer.

    PubMed

    Masuda, N; Higaki, K; Takano, T; Matsunami, N; Morimoto, T; Ohtani, S; Mizutani, M; Miyamoto, T; Kuroi, K; Ohno, S; Morita, S; Toi, M

    2014-08-01

    Better treatments for triple-negative breast cancer (TNBC) are needed. To address this need, we studied the effects of preoperative metronomic paclitaxel/cyclophosphamide/capecitabine (mPCX) followed by 5-fluorouracil (FU)/epirubicin/cyclophosphamide (FEC) as preoperative chemotherapy in TNBC patients. Forty primary TNBC patients received four cycles of metronomic paclitaxel (80 mg/m(2) on Days 1, 8, and 15), cyclophosphamide (50 mg/body daily), and capecitabine (1,200 mg/m(2) daily), followed by four cycles of 5-FU (500 mg/m(2)), epirubicin (100 mg/m(2)), and cyclophosphamide (500 mg/m(2)) every 3 weeks. The primary end point was the pathological complete response (pCR) rate. Forty patients formed the intent-to-treat population. The median dose intensities of paclitaxel, cyclophosphamide, and capecitabine were 89.7, 92.1, and 89.8%, respectively. Five patients discontinued mPCX and two discontinued FEC, primarily because of adverse events, resulting in a per-protocol population (PPS) of 33 patients. The pCR (ypT0/Tis ypN0) rate was 47.5% (19/40) in the intent-to-treat population and 54.5% (18/33) in the PPS. The clinical response rates were 36/40 (90.0%) and 31/33 (93.9%) in the intent-to-treat and PPS, respectively. The breast conservation rate was 72.7% (24/33), and 5/13 patients underwent partial resection instead of pre-planned total mastectomy. Grade 3-4 adverse events included neutropenia (35%), leukopenia (25%), and hand-foot syndrome (8%). Metronomic PCX followed by FEC chemotherapy was associated with a high pCR rate and low toxicity in TNBC patients. Further studies of this regimen in larger numbers of patients are warranted.

  8. Idiopathic Relapsing Thrombotic Thrombocytopenic Purpura with Persistent ADAMTS13 Inhibitor Activity Treated Sequentially with Plasmapheresis, Rituximab, Cyclophosphamide and Splenectomy.

    PubMed

    Musa, Faisal; Baidas, Said

    2015-01-01

    We here describe a patient with an idiopathic thrombotic thrombocytopenic purpura (TTP) secondary to an ADAMTS13 inhibitor that continued to be dependent on plasmapheresis until the patient was treated with rituximab. TTP manifestations subsided with rituximab treatment in spite of a persistently low ADAMTS13 activity and continued a detectable inhibitor activity until the patient developed an intolerance to rituximab due to an allergic reaction when cyclophosphamide was added; this resulted in a normalization of ADAMTS13 activity and the disappearance of the inhibitor. Later, the patient developed an intolerance to rituximab due to a severe allergic reaction. Soon after stopping rituximab, the ADAMTS13 activity level dipped below 5% in addition to the appearance of the ADAMTS13 inhibitor. The patient had a splenectomy after rituximab and cyclophosphamide treatment; the medication was stopped based on several case reports of a complete remission of TTP after splenectomy. We believe that the reason TTP went into remission in our patient was because of rituximab treatment, in spite of both persistently low ADAMTS13 activity and a detectable inhibitor activity due to reducing the release of von Willebrand factor large multimers from the endothelial cells. We found that ADAMTS13 activity normalized and the inhibitor activity became undetectable when cyclophosphamide was added to rituximab. We suggest adding cyclophosphamide to rituximab for the treatment of patients with persistent ADAMTS13 inhibitors in order to prolong the remission period and lower the rate of relapse.

  9. Dose-Dense Epirubicin and Cyclophosphamide Followed by Docetaxel as Adjuvant Chemotherapy in Node-Positive Breast Cancer

    PubMed Central

    Mirzaei, Hamid Reza; Sabet Rasekh, Parisa; Nasrollahi, Fatemeh; Sabet Rasekh, Parto; Akbari Tirabad, Zahra; Moein, Hamid Reza; Ghaffari Pour, Taban; Hajian, Parastoo

    2013-01-01

    Background. Adding taxanes to anthracycline-based adjuvant chemotherapy has shown significant improvement particularly in node-positive patients, but optimal dose and schedule remain undetermined. Objectives. This study aimed to assess the feasibility of dose-dense epirubicin and cyclophosphamide followed by docetaxel in node-positive breast cancer. Methods. All Patients first received 4 cycles of epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) at 2-week interval then followed by docetaxel (100 mg/m2) at 2-week interval for 4 cycles, with daily Pegfilgrastim (G-CSF) that was administered in all patients on days 3–10 after each cycle of epirubicin and cyclophosphamide infusion. Results. Fifty-eight patients with axillary lymph node-positive breast cancer were enrolled in the study, of whom 42 (72.4%) completed the regimen. There were two toxicity-related deaths, one patient due to grade 4 febrile neutropenia and the other due to congestive heart failure. Grade 3/4 neutropenia and febrile neutropenia were 13.8% and 5.1%. The most common grade 3/4 nonhematological complications were as follows: skin-nail disorders (48.3%), hand-foot syndrome (34.4%), paresthesia (38%), arthralgia (27.5%), and paresis (24.1%). Conclusions. Dose-dense epirubicin and cyclophosphamide followed by docetaxel with G-CSF support are not feasible, and it is not recommended for further investigation. PMID:24187626

  10. The impact of morin, a natural flavonoid, on cyclophosphamide-induced changes in the oxidative stress parameters in rat livers.

    PubMed

    Merwid-Ląd, Anna; Trocha, Małgorzata; Chlebda-Sieragowska, Ewa; Sozański, Tomasz; Szandruk, Marta; Magdalan, Jan; Ksiądzyna, Dorota; Pieśniewska, Małgorzata; Fereniec-Gołębiewska, Lidia; Kwiatkowska, Joanna; Szeląg, Adam

    2014-01-01

    Cyclophosphamide (CPX) has many adverse effects, partly due to oxidative stress induction in various tissues. Morin is one of the natural flavonoids with strong antioxidant properties. The aim of the current research was to estimate the influence of morin on changes in antioxidant parameters in rat livers after cyclophosphamide administration. The study was performed on Wistar rats. The rats in Group C received 0.9% saline; those in Group CX received cyclophosphamide (CPX); and those in Group M-CX received CPX with morin. Cyclophosphamide and morin were given by gastric gavage for 10 consecutive days at doses of 15 mg/kg and 100 mg/kg, respectively. Malondialdehyde (MDA) and glutathione (GSH) concentrations, superoxide dismutase (SOD) activity and catalase (CAT) activity were determined in liver tissue homogenates. CPX caused a significant decrease in SOD activity and GSH levels, but only the latter was fully restored by morin. There were no significant differences in CAT activity in the various groups. CPX also insignificantly decreased MDA levels, which was aggravated by co-administration of morin. The results obtained indicate that morin may exert some protective action on CPX-induced changes in the antioxidant state in rat livers.

  11. Complete Response and Fatigue Improvement With the Combined Use of Cyclophosphamide and Quercetin in a Patient With Metastatic Bladder Cancer

    PubMed Central

    Di Lorenzo, Giuseppe; Pagliuca, Martina; Perillo, Teresa; Zarrella, Aquilino; Verde, Antonio; De Placido, Sabino; Buonerba, Carlo

    2016-01-01

    Abstract Bladder cancer is a major cause of cancer-related mortality, with an estimated 74,000 new cases and 16,000 deaths in the United States in 2015. In patients with metastatic disease, vinflunine and taxanes are the most widely used chemotherapy agents in the second-line setting after failure of platinum-based treatment. Cyclophosphamide has been used in combination with paclitaxel in urothelial carcinoma of the bladder, but there are no data about the effectiveness of cyclophosphamide administered as a single agent. We here describe the first case of an advanced bladder cancer patient suffering from grade 2 fatigue. He benefited from administration of third-line single-agent metronomic oral cyclophosphamide plus oral doses of quercetin. A complete, prolonged radiologic response according to the RECIST criteria 1.1 was achieved with minimal toxicity and an improvement in fatigue. Further studies are required to assess the potential benefits associated with the combined use of cyclophosphamide plus quercetin in advanced bladder cancer patients. PMID:26844468

  12. Renal parenchyma injury after percutaneous nephrolithotomy tract dilatations in pig and cadaveric kidney models

    PubMed Central

    Emiliani, Esteban; Talso, Michele; Baghdadi, Mohammed

    2017-01-01

    Introduction Miniaturization of instruments has changed the paradigms of percutaneous nephrolithotomy (PCNL). To date, however, few studies have analyzed the possible renal trauma generated by PCNL tract dilation. The purpose of this study is to evaluate and compare systematically the renal injury of all PNCL dilation techniques in pork kidneys (PK) and cadaveric kidney models (CK). Material and methods Twelve dilation devices were tested (from 4.8 to 30 French (Fr)) including micro- and mini- PCNL kits, the Alken dilation set, 20 and 30 ATM balloons and the Amplatz set. Each device was tested six times in PK and CK. Morphologic analysis of tract defects of the different models and dilators were made measuring the longest axis and the area of renal parenchymal damage. Results When comparing the PK and CK dilation tract areas to the device areas, major differences were seen with the 20 ATM 30 Fr balloon (p = 0.0001 and 0.008) respectively, the sequential Amplatz dilation to 30 Fr (p = 0.0005 and 0.0006) respectively, and the Alken 30 FR dilation (p = 0.012 and 0.02) respectively. The 30 Fr dilations were 32.76 mm2 (mean) larger than the instruments themselves, while the ≤24 Fr dilations were 11.6 mm2 (mean) larger than the instruments themselves. Conclusions When comparing devices and tract areas, the dilation tract area exceeded device area by 11.6 mm2 at dilations up to 24 Fr vs. 32.76 mm2 with dilations of 30 Fr. Overall, PK had significantly larger injuries than CK models. PMID:28461992

  13. Renal parenchyma injury after percutaneous nephrolithotomy tract dilatations in pig and cadaveric kidney models.

    PubMed

    Emiliani, Esteban; Talso, Michele; Baghdadi, Mohammed; Traxer, Olivier

    2017-01-01

    Miniaturization of instruments has changed the paradigms of percutaneous nephrolithotomy (PCNL). To date, however, few studies have analyzed the possible renal trauma generated by PCNL tract dilation. The purpose of this study is to evaluate and compare systematically the renal injury of all PNCL dilation techniques in pork kidneys (PK) and cadaveric kidney models (CK). Twelve dilation devices were tested (from 4.8 to 30 French (Fr)) including micro- and mini- PCNL kits, the Alken dilation set, 20 and 30 ATM balloons and the Amplatz set. Each device was tested six times in PK and CK. Morphologic analysis of tract defects of the different models and dilators were made measuring the longest axis and the area of renal parenchymal damage. When comparing the PK and CK dilation tract areas to the device areas, major differences were seen with the 20 ATM 30 Fr balloon (p = 0.0001 and 0.008) respectively, the sequential Amplatz dilation to 30 Fr (p = 0.0005 and 0.0006) respectively, and the Alken 30 FR dilation (p = 0.012 and 0.02) respectively. The 30 Fr dilations were 32.76 mm(2) (mean) larger than the instruments themselves, while the ≤24 Fr dilations were 11.6 mm(2) (mean) larger than the instruments themselves. When comparing devices and tract areas, the dilation tract area exceeded device area by 11.6 mm(2) at dilations up to 24 Fr vs. 32.76 mm(2) with dilations of 30 Fr. Overall, PK had significantly larger injuries than CK models.

  14. Specific mitochondrial DNA deletions in idiopathic dilated cardiomyopathy.

    PubMed

    Marin-Garcia, J; Goldenthal, M J; Ananthakrishnan, R; Pierpont, M E; Fricker, F J; Lipshultz, S E; Perez-Atayde, A

    1996-02-01

    Structural changes in human mitochondrial DNA (mtDNA) have been implicated in a number of clinical conditions with dysfunctions in oxidative phosphorylation called OX-PHOS diseases, some of which have cardiac involvement. The objective of this study was to assess the frequency and extent of specific mitochondrial DNA deletions in idiopathic dilated cardiomyopathy. DNA extracted from tissue derived from the left ventricle of 41 patients with idiopathic dilated cardiomyopathy and 17 controls was amplified by polymerase chain reaction using specific primers to assess the incidence and proportion of 5-kb and 7.4-kb deletions in mitochondrial DNA. In reactions using primers to detect the 5-kb deletion, an amplified product of 593 bp was found in low abundance relative to undeleted mitochondrial DNA but with high frequency in a number of controls and patients. A second deletion of 7.4 kb in size was also frequently present in controls and patients. In contrast to previous reports, these deletions were found to be present in both controls and in cardiomyopathic patients, 18 years and younger, including several infants. The 7.4-kb deletion was prominently increased in both frequency and in its proportion relative to undeleted mitochondrial DNA in patients 40 years and older with idiopathic dilated cardiomyopathy. At variance with current literature our study reports a significant presence of both 5 and 7.4-kb deletions in the young and a higher frequency and quantity of the 7.4-kb deletion in the older cardiomyopathic patients in comparison with controls. The increased accumulation of the 7.4-kb deletion as both a function of aging and cardiomyopathy is suggestive that this specific mitochondrial DNA deletion arises more likely as an effect of heart dysfunction rather than as a primary cause of cardiomyopathy.

  15. Discontinuous Shear Thickening and Dilatancy: Frictional Effects in Viscous Suspensions

    NASA Astrophysics Data System (ADS)

    Morris, Jeffrey

    2015-03-01

    Shear thickening in concentrated suspensions has been well-known for quite a long time, yet a firm consensus on the basis for very abrupt or ``discontinuous'' shear thickening (DST) seen in suspensions of large solid fraction, ϕ, has not been reached. This work addresses the DST phenomenon, and proposes a simulation method based in the Stokesian Dynamics algorithm to explore the role of various forces between the particles, including hydrodynamic, conservative potential, and frictional interactions. This work shows that allowance for friction between spherical particles suspended in a viscous liquid causes a significant reduction in the jamming solid fraction of the mixture, ϕmax, taken as the maximum fraction at which the suspension will flow. A consequence of this is a shifting of the singularity in the effective viscosity, η, to smaller ϕmax, and the frictional suspension has a larger viscosity than does the frictionless suspension of the same solid fraction, as is clear from the standard empirical modeling of η (ϕ) =(1 - ϕ /ϕmax) - α , α ~ 2 . When a counterbalancing repulsive force between the particles, representative for example of charge-induced repulsion, is incorporated in the dynamics, the mixture undergoes a transition from frictionless to frictional interactions, and from low to high effective viscosity, at a critical shear rate. Comparison with experimental data shows remarkable agreement in the features of DST captured by the method. The basic algorithm and results of both rate-controlled and stress-controlled simulations will be presented. Like the shear stress, the magnitude of the normal stress exerted by the suspended particles also increases abruptly at the critical shear rate, consistent with the long-standing notion that dilatancy and shear-thickening are synonymous. We will show that considering all shear thickening materials as dilatant is a misconception, but demonstrate the validity of the connection of dilatancy with DST in

  16. Efficacy of reduced dose of pegfilgrastim in Japanese breast cancer patients receiving dose-dense doxorubicin and cyclophosphamide therapy.

    PubMed

    Mizuno, Yoshio; Fuchikami, Hiromi; Takeda, Naoko; Iwai, Masaru; Sato, Kazuhiko

    2017-01-01

    This retrospective study aimed to evaluate the efficacy of a 3.6-mg dose of pegfilgrastim for primary prophylaxis in Japanese breast cancer patients receiving dose-dense chemotherapy. Patients treated with adjuvant or neoadjuvant chemotherapy for early-stage breast cancer at the Tokyo-West Tokushukai Hospital were included in this analysis. Because 6 mg pegfilgrastim has not yet been approved for use in Japan, we compared the outcomes of a dose-dense doxorubicin and cyclophosphamide regimen plus 3.6 mg pegfilgrastim support with a conventional dose epirubicin and cyclophosphamide regimen. The incidence of febrile neutropenia, relative dose intensity, dose delay, dose reduction, regimen change and hospitalization because of neutropenia were assessed. From November 2013 to March 2016, 97 patients with stage I-III invasive breast cancer were analyzed (dose-dense doxorubicin and cyclophosphamide plus 3.6-mg pegfilgrastim group, n  =  41; epirubicin and cyclophosphamide group, n  =  56; median ages, 49.0 and 48.5 years, respectively). Febrile neutropenia occurred during the first chemotherapy cycle in 7 of 56 patients (12.5%) in the epirubicin and cyclophosphamide group and 0 of 41 patients in the dose-dense doxorubicin and cyclophosphamide group (P  =  0.02). The average relative dose intensities were 97.9% and 96.8%, respectively (P  =  0.28), with corresponding dose delay rates of 4.9% (2/41) and 16.1% (9/56), respectively (P  =  0.11) and dose reduction rates of 0% (0/41) and 7.1% (4/56), respectively (P  =  0.16). Our results indicate the efficacy of a 3.6-mg pegfilgrastim dose for the primary prevention of febrile neutropenia in dose-dense doxorubicin- and cyclophosphamide-treated Japanese breast cancer patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Neoadjuvant chemotherapy of breast cancer with pirarubicin versus epirubicin in combination with cyclophosphamide and docetaxel.

    PubMed

    Gu, Xi; Jia, Shi; Wei, Wei; Zhang, Wen-Hai

    2015-07-01

    Breast cancers (BC) are treated with surgery, radiotherapy, and chemotherapy. Neoadjuvant chemotherapy (NACT) is an emerging treatment option in many cancers and is given before primary therapy to shrink tumor size. The efficacy of NACT in varied settings of BC, such as inoperable tumors, borderline resectable tumors, and breast-conserving surgery, has been debated extensively in literature, and the results remain unclear and depended on a wide variety of factors such as cancer type, disease extent, and the specific combination of chemotherapy drugs. This study was performed to examine the efficacy, toxicity, and tolerability of pirarubicin (THP) and epirubicin (EPI) in combination with docetaxel and cyclophosphamide in a NACT setting for BC. A total of 48 patients with stage II or III breast cancers were randomly divided into two groups: THP group and EPI group. The patients in THP group received 2-4 cycles of neoadjuvant chemotherapy with DTC regimen (docetaxel, THP, cyclophosphamide), while patients in the EPI group received 2-4 cycles of DEC regimen (docetaxel, EPI, cyclophosphamide) before surgery. The incidence of adverse reactions and the efficacy of the treatment regimen were compared between the two groups. Prognostic evaluation indexes were estimated by Kaplan-Meier survival analysis, including the 5-year disease-free survival (DFS) and overall survival (OS). The overall response rate in THP group was 83.3 %, and the EPI group showed a response rate of 79.2 %, with no statistically significant difference in response rate between the two groups. The incidence of cardiac toxicity, myelosuppression, nausea, and vomiting in the THP group was significantly lower than the EPI group (all P < 0.05). The incidence of hepatic toxicity, alopecia, and diarrhea in the THP group was also lower than the EPI group, but these differences were not statistically significant. The 5-year DFS and OS in THP versus EPI groups were 80 versus 76 % (DFS) and 86 versus 81 % (OS

  18. Metabolism and binding of cyclophosphamide and its metabolite acrolein to rat hepatic microsomal cytochrome P-450

    SciTech Connect

    Marinello, A.J.; Bansal, S.K.; Paul, B.; Koser, P.L.; Love, J.; Struck, R.F.; Gurtoo, H.L.

    1984-10-01

    The hepatic cytochrome P-450-mediated metabolism and metabolic activation of (chloroethyl-3H)cyclophosphamide (( chloroethyl-3H)CP) and (4-14C)cyclophosphamide (( 4-14C)CP) were investigated in vitro in the reconstituted system containing cytochrome P-450 isolated from phenobarbital-treated rats. In addition, hepatic microsomal binding and the hepatic microsome-mediated metabolism of (14C)acrolein, a metabolite of (4-14C)CP, were also investigated. The metabolism of (chloroethyl-3H)CP and (4-14C)CP to polar metabolites was found to depend on the presence of NADPH and showed concentration dependence with respect to cytochrome P-450 and NADPH:cytochrome P-450 reductase. Km and Vmax values were essentially similar. The patterns of inhibition by microsomal mixed-function oxidase inhibitors, anti-cytochrome P-450 antibody, and heat denaturation of the cytochrome P-450 were essentially similar, with subtle differences between (4-14C)CP and (chloroethyl-3H)CP metabolism. The in vitro metabolic activation of CP in the reconstituted system demonstrated predominant binding of (chloroethyl-3H)CP to nucleic acids and almost exclusive binding of (4-14C)CP to proteins. Gel electrophoresis-fluorography of the proteins in the reconstituted system treated with (4-14C)CP demonstrated localization of the 14C label in the cytochrome P-450 region. To examine this association further, hepatic microsomes were modified with (14C)acrolein in the presence and the absence of NADPH. The results confirmed covalent association between (14C)acrolein and cytochrome P-450 in the microsomes and also demonstrated further metabolism of (14C)acrolein, apparently to an epoxide, which is capable of binding covalently to proteins. The results of these investigations not only confirm the significance of primary metabolism but also emphasize the potential role of the secondary metabolism of cyclophosphamide in some of its toxic manifestations.

  19. Role of Speckle Tracking Echocardiography in Dilated Cardiomyopathy: A Review

    PubMed Central

    Virk, Hafeez Ul Hasan; Khalid, Muhammad; Rahman, Zia; Sitwala, Puja; Schoondyke, Jeffrey; Al-Balbissi, Kais

    2017-01-01

    Dilated cardiomyopathy (DCM) is an important cause of the heart failure. Timely diagnosis and optimal management decrease morbidity and mortality in heart failure patients. Although transthoracic echocardiography is used as the diagnostic test of choice in these patients, new modalities like speckle tracking echocardiography (STE) have promising results in diagnosing these patients in the earlier course of the disease. Advancements in cardiac imaging are expected as more clinical studies on the role of STE in different cardiac diseases that emerge. In this review article, we will discuss the basics of STE and its role in diagnosing DCM. PMID:28744419

  20. Dilational processes accompanying earthquakes in the Long Valley Caldera

    USGS Publications Warehouse

    Dreger, Douglas S.; Tkalcic, Hrvoje; Johnston, M.

    2000-01-01

    Regional distance seismic moment tensor determinations and broadband waveforms of moment magnitude 4.6 to 4.9 earthquakes from a November 1997 Long Valley Caldera swarm, during an inflation episode, display evidence of anomalous seismic radiation characterized by non-double couple (NDC) moment tensors with significant volumetric components. Observed coseismic dilation suggests that hydrothermal or magmatic processes are directly triggering some of the seismicity in the region. Similarity in the NDC solutions implies a common source process, and the anomalous events may have been triggered by net fault-normal stress reduction due to high-pressure fluid injection or pressurization of fluid-saturated faults due to magmatic heating.

  1. Wavelet transforms with discrete-time continuous-dilation wavelets

    NASA Astrophysics Data System (ADS)

    Zhao, Wei; Rao, Raghuveer M.

    1999-03-01

    Wavelet constructions and transforms have been confined principally to the continuous-time domain. Even the discrete wavelet transform implemented through multirate filter banks is based on continuous-time wavelet functions that provide orthogonal or biorthogonal decompositions. This paper provides a novel wavelet transform construction based on the definition of discrete-time wavelets that can undergo continuous parameter dilations. The result is a transformation that has the advantage of discrete-time or digital implementation while circumventing the problem of inadequate scaling resolution seen with conventional dyadic or M-channel constructions. Examples of constructing such wavelets are presented.

  2. ULTRASOUND ASSESSMENT OF FLOW-MEDIATED DILATION: A TUTORIAL

    PubMed Central

    Harris, Ryan A.; Nishiyama, Steven K.; Wray, D. Walter; Richardson, Russell S.

    2010-01-01

    Developed in 1992, the flow-mediated dilation test is now the most commonly utilized non-invasive assessment of vascular endothelial function in humans. Since its inception, scientists have refined their understanding of the physiology, analysis, and interpretation of this measurement. Recently, a significant growth of knowledge has added to our understanding and implementation of this clinically relevant research methodology. Therefore, this tutorial provides timely insight into recent advances and practical information related to the ultrasonic assessment of vascular endothelial function in humans. PMID:20351340

  3. [Asymptomatic or paucisymptomatic CBD dilatation on US after cholecystectomy: management].

    PubMed

    Pilleul, F

    2006-04-01

    In western countries, 10-15% of the population has gallbladder stones with 46,000 cholecystectomies performed in France in 2003. So, daily ultrasonography of the abdomen performed in patients without gallbladder is a routine exam. However, identification of an enlarged common bile duct is frequent and the normal nature of this finding remains uncertain. The purpose of this article is to perform a literature review of the impact of cholecystectomy on the diameter of the common bile duct. Furthermore, it is important not to dismiss common bile duct dilatation after cholecystectomy because it may be the result of post operative complication or secondary to a congenital disease of bile duct.

  4. The dilatant-compactant transition in edifice-forming andesites

    NASA Astrophysics Data System (ADS)

    Heap, Michael; Farquharson, Jamie; Baud, Patrick; Lavallée, Yan; Reuschlé, Thierry

    2015-04-01

    While the mechanical behaviour of rock is often classified as brittle or ductile, ductile behaviour, defined simply as the capacity of a material to deform to a substantial strain without the tendency to localise the flow into faults, can be the result of a variety of microstructural deformation mechanisms, including microcracking (in the case of cataclastic flow); the description of ductility holds no mechanistic connotation. However, due to instances of compaction localisation, and that ductile behaviour can be driven by microcracking (i.e., brittle on the microscale), we have simplified our classification of the failure mode of rock to "dilatant" and "compactant". The failure mode of lava -- dilatant or compactive -- depends on the physical attributes of the lava, primarily the porosity and pore size, and the conditions under which it deforms. The failure mode for edifice host rock has attendant implications for the structural stability of the edifice and the efficiency of sidewall outgassing of the volcanic conduit. In this contribution we present a systematic experimental study on the failure mode of edifice-forming andesitic rocks (porosity from 8 to 25%) from Volcán de Colima, Mexico. The experiments show that, at shallow depths (< 1 km), both low and high porosity lavas dilate and fail by shear fracturing. However, deeper in the edifice (> 1 km), while low porosity (< 10%) lava remains dilatant, the failure of high porosity lava is compactive and driven by cataclastic pore collapse. Although inelastic compaction is typically characterised by the absence of strain localisation, we observe compactive localisation features in our porous andesite lavas manifested as planes of collapsed pores. In terms of volcano stability, faulting in the upper edifice could destabilise the volcano, leading to an increased risk of flank or large-scale dome collapse, while compactive deformation deeper in the edifice emerges as a viable mechanism driving volcano subsidence and

  5. Silo hiccups: Dynamic effects of dilatancy in granular flow

    NASA Astrophysics Data System (ADS)

    Le Pennec, Thierry; Jørgen Ma˚Løy, Knut; Flekkøy, Eirik G.; Messager, Jean Claude; Ammi, Madani

    1998-12-01

    The granular flow through an open silo is investigated experimentally. A mechanism based both on the dilation of the granular medium and an interaction with the interstitial gas causes the flow to stop at regular intervals. The experiments are carried out at different surrounding pressures P0, and it is found that the intermittent flow becomes continuous at sufficiently low P0, showing that the intermittency is linked to the interaction the gas. The scaling of the average flow rate with particle size further supports our view of the gas-grain interaction.

  6. The effect of dilatancy on velocity anisotropy in Westerly granite

    NASA Technical Reports Server (NTRS)

    Soga, N.; Mizutani, H.; Spetzler, H.; Martin, R. J., III

    1978-01-01

    Jacketed samples of Westerly granite were fractured at confining pressures up to 1 kbar, and compressional and horizontally as well as vertically polarized shear velocities were measured in orthogonal directions perpendicular to the compression axis. Changes occurring with increased strain are described, and the velocity data were analyzed by application of the Anderson et al (1974) approach. Observed and calculated velocities are found to be in good agreement, and the degree of dilatancy was determined from the differences between the strains measured perpendicularly to the compression axis and the estimated elastic strains in those directions.

  7. Dilated cardiomyopathy in acromegaly: Case report and anesthesia management

    PubMed Central

    Nair, Abhijit S.; Nirale, Anand M.; Sriprakash, K.; Gopal, T. V. S.

    2013-01-01

    Patients who are diagnosed having acromegaly develop a lot of cardiovascular Complications such as hypertension, arrhythmias, systolic and diastolic dysfunction, valvular dysfunction and heart failure. Dilated cardiomyopathy (DCM) with systolic and diastolic dysfunction is relatively rare but is associated with an increased mortality. We report a case of acromegaly diagnosed at 52 years of age in a known diabetic, non-hypertensive male who had DCM with severe left ventricular dysfunction, global hypokinesia, moderate mitral regurgitation, and grade II diastolic dysfunction who was treated with diuretics, digitalis, and vasodilators. He was diagnosed with a growth hormone secreting pituitary macroadenoma and underwent endoscopic excision of the pituitary tumor under general anesthesia. PMID:25885996

  8. Endoluminal dilation technique to remove "stuck" tunneled hemodialysis catheters.

    PubMed

    Ryan, Stephen E; Hadziomerovic, Adnan; Aquino, Jose; Cunningham, Ian; O'Kelly, Kevin; Rasuli, Pasteur

    2012-08-01

    Most tunneled catheters can be easily removed after the retention cuff is dissected. Occasionally, these catheters can become resistant to removal even after application of potentially hazardous forceful traction. In addition, an infected catheter may cause life-threatening septicemia. Several methods have been described for their extraction, some of which may be available only in tertiary-care facilities. The present report describes the successful extraction of five such "stuck" catheters by using a recently described technique of endoluminal dilation. The technique appears safe and straightforward and can be performed in any interventional suite while allowing preservation of venous access.

  9. Long term survival effect of metoprolol in dilated cardiomyopathy

    PubMed Central

    Di, L; De Maria, R; Gavazzi, A; Gregori, D; Parolini, M; Sinagra, G; Salvatore, L; Longaro, F; Bernobich, E; Camerini, F

    1998-01-01

    Objective—To evaluate the additive effect of metoprolol treatment on long term incidence of fatal and non-fatal cardiac events in idiopathic dilated cardiomyopathy.
Design—586 patients with idiopathic dilated cardiomyopathy were prospectively enrolled in a multicentre registry and followed up for a mean (SD) of 52 (32) months. Metoprolol, carefully titrated to the maximum tolerated dose, was added to conventional heart failure treatment in 175 patients.
Results—Survival and transplant-free survival at seven years were significantly higher in the 175 metoprolol treated patients than in the remaining 411 on standard treatment (81% v 60%, p < 0.001, and 69% v 49%, p < 0.001, respectively). By multivariate analysis, metoprolol independently predicted survival and transplant-free survival (relative risk reduction values for all cause mortality and combined mortality or transplantation 51% (95% confidence interval 21% to 69%), p = 0.002, and 34% (5% to 53%), p = 0.01, respectively). New York Heart Association class, left ventricular end diastolic diameter, and pulmonary wedge pressure were also predictive. Seven year survival (80% v 62%, p = 0.004) and transplant-free survival (68% v 51%, p = 0.005) were significantly higher in 127 metoprolol treated cases than in 127 controls selected from the entire control cohort and appropriately matched. Metoprolol was associated with a 30% reduction in all cause mortality (7% to 48%, p = 0.015) and a 26% reduction in mortality or transplantation (7% to 41%, p = 0.009). 
Conclusions—The addition of metoprolol to standard heart failure treatment, including angiotensin converting enzyme inhibitors, was effective in the long term, reducing both all cause mortality and transplantation in patients with idiopathic dilated cardiomyopathy.

 Keywords: β blockade;  dilated cardiomyopathy;  heart failure PMID:9616339

  10. Multiple Loci are associated with dilated cardiomyopathy in Irish wolfhounds.

    PubMed

    Philipp, Ute; Vollmar, Andrea; Häggström, Jens; Thomas, Anne; Distl, Ottmar

    2012-01-01

    Dilated cardiomyopathy (DCM) is a highly prevalent and often lethal disease in Irish wolfhounds. Complex segregation analysis indicated different loci involved in pathogenesis. Linear fixed and mixed models were used for the genome-wide association study. Using 106 DCM cases and 84 controls we identified one SNP significantly associated with DCM on CFA37 and five SNPs suggestively associated with DCM on CFA1, 10, 15, 21 and 17. On CFA37 MOGAT1 and ACSL3 two enzymes of the lipid metabolism were located near the identified SNP.

  11. Symmetrization of grey-scale images based on dilation

    NASA Astrophysics Data System (ADS)

    Tuzikov, Alexander V.; Krivonos, O. V.

    1996-03-01

    We generalize set symmetrization transformations based on Minkowski addition to symmetrization transformations for numerical functions. For this purpose two types of function representation are used. The first one is umbra representation, when symmetrization transformations are performed to the set of points under the graph of a function. This corresponds to introducing of transformations using gray-scale dilation. The second representation of a function is based on a family of threshold sets. Flat function symmetrization transformations are generated by corresponding set transformations operating on threshold sets.

  12. Metronomic cyclophosphamide eradicates large implanted GL261 gliomas by activating antitumor Cd8(+) T-cell responses and immune memory.

    PubMed

    Wu, Junjie; Waxman, David J

    2015-04-01

    Cancer chemotherapy using cytotoxic drugs can induce immunogenic tumor cell death; however, dosing regimens and schedules that enable single-agent chemotherapy to induce adaptive immune-dependent ablation of large, established tumors with activation of long-term immune memory have not been identified. Here, we investigate this issue in a syngeneic, implanted GL261 glioma model in immune-competent mice given cyclophosphamide on a 6-day repeating metronomic schedule. Two cycles of metronomic cyclophosphamide treatment induced sustained upregulation of tumor-associated CD8(+) cytotoxic T lymphocyte (CTL) cells, natural killer (NK) cells, macrophages, and other immune cells. Expression of CTL- and NK-cell-shared effectors peaked on Day 6, and then declined by Day 9 after the second cyclophosphamide injection and correlated inversely with the expression of the regulatory T cell (Treg) marker Foxp3. Sustained tumor regression leading to tumor ablation was achieved after several cyclophosphamide treatment cycles. Tumor ablation required CD8(+) T cells, as shown by immunodepletion studies, and was associated with immunity to re-challenge with GL261 glioma cells, but not B16-F10 melanoma or Lewis lung carcinoma cells. Rejection of GL261 tumor re-challenge was associated with elevated CTLs in blood and increased CTL infiltration in tumors, consistent with the induction of long-term, specific CD8(+) T-cell anti-GL261 tumor memory. Co-depletion of CD8(+) T cells and NK cells did not inhibit tumor regression beyond CD8(+) T-cell depletion alone, suggesting that the metronomic cyclophosphamide-activated NK cells function via CD8a(+) T cells. Taken together, these findings provide proof-of-concept that single-agent chemotherapy delivered on an optimized metronomic schedule can eradicate large, established tumors and induce long-term immune memory.

  13. Phase 1 and Extension Study of Clofarabine plus Cyclophosphamide in Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)

    PubMed Central

    Faderl, S; Balakrishnan, K; Thomas, DA; Ravandi, F; Borthakur, G; Burger, J; Ferrajoli, A; Cortes, J; O’Brien, S; Kadia, T; Feliu, J; Plunkett, W; Gandhi, V; Kantarjian, HM

    2014-01-01

    Background Clofarabine is a nucleoside analog with activity in children with ALL. Based on the hypothesis that clofarabine inhibits DNA repair following exposure to DNA damaging agents, we designed a phase 1 and extension study to evaluate the combination of clofarabine with cyclophosphamide in adult patients with relapsed/refractory ALL. Methods The continual reassessment method (CRM) was used to define the maximum tolerated dose (MTD). Results Fifty patients with a median age of 30 years (range 21–72 years) were enrolled of whom 30 patients were part of the phase 1 group. Clofarabine 40 mg/m2 iv daily x 3 days and cyclophosphamide 200 mg/m2 iv q 12 hours x 3 days were established as the MTD. Dose limiting toxicities were diarrhea, transaminase elevations, and skin rashes. The response rate of the whole study group was 14% including 10% of patients who achieved complete remission (CR) or CR without platelet recovery. Three responses occurred in patients with primary refractory disease. Early mortality (< 30 days) was 6%. The median response duration was 69 days (range 5–315 days). Median overall survival was about 3 months. Compared to day 1 (cyclophosphamide alone), H2AX phosphorylation was increased on day 2 when clofarabine and cyclophosphamide were administered as a couplet (n = 8). Conclusions The combination of clofarabine plus cyclophosphamide at the doses used in this study and in a group of heavily pretreated patients with ALL is only moderately effective. Other doses, alternative schedules, or a more favorable patient population may achieve better results. (Word count: 248) PMID:24440659

  14. Etoposide in combination with cyclophosphamide and total body irradiation or busulfan as conditioning for marrow transplantation in adults and children

    SciTech Connect

    Spitzer, T.R.; Ortlieb, M.; Tefft, M.C.; Torrisi, J.; Cahill, R.; Deeg, H.J. ); Peters, C.; Gadner, H. ); Urban, C. )

    1994-04-30

    In an attempt to intensify conditioning therapy for bone marrow transplantation of hematologic malignancies, a retrospective three center evaluation of escalating doses of etoposide added to cyclophosphamide and either total body irradiation or busulfan was undertaken. Seventy-six patients who received etoposide (25-65 mg/kg) added to cyclophosphamide (60-120 mg/kg) and either total body irradiation (12.0-13.2 Gy) or busulfan (12-16 mg/kg) were evaluable for toxicity. Fifty-one of the evaluable patients received allogeneic transplants, while twenty-six received autologous transplants. A comparative analysis of toxicities according to conditioning regimen, donor source and etoposide dose was made. Similar toxicities were observed among the treatment groups with the exception of more frequent skin (p = 0.03) and life threatening hepatic toxicities (p = 0.01) in the busulfan treated patients. Life threatening or fatal toxicities were not influenced by donor source, either when analyzed by treatment group or etoposide dose. Etoposide at a dose of 60-65 mg/kg in combination with TBI and cyclophosphamide was associated with a significantly increased incidence of life threatening or fatal toxicities compared with a combination using a dose of 25-50 mg/kg (15 of 24 vs. 5 of 20; p = 0.013). The maximally tolerated dose of etoposide in combination with busulfan and cyclophosphamide cannot be definitively established in this analysis in part due to the heterogeneity of the patient population and treatment schemes. Although toxicities with bone marrow transplant preparative regimens containing etoposide in combination with cyclophosphamide and total body irradiation or busulfan were frequently severe, treatment related mortality risk was believed to be acceptably low. 27 refs., 3 tabs.

  15. Nuclear aberrations in hair follicle cells of patients receiving cyclophosphamide. A possible in vivo assay for human exposure to genotoxic agents.

    PubMed

    Goldberg, M T; Tackaberry, L E; Hardy, M H; Noseworthy, J H

    1990-01-01

    The toxic effect of cyclophosphamide on the proliferative cell population of hair follicles plucked from the human scalp was examined by the in vivo nuclear aberration assay. Patients participating in an independent clinical trial received oral low dose cyclophosphamide, intravenous high dose cyclophosphamide or oral placebo treatment. The percent of cells with nuclear aberrations (indicating apoptosis, a special form of cell death) and the percent of mitotic cells, in the hair matrix, were calculated for each patient before treatment and at several time points following cyclophosphamide or placebo treatment. The mean percentages of nuclear aberrations in both the treated Low dose and High dose cyclophosphamide patients were significantly higher than those for the pre-treatment and Placebo patients. The nuclear aberrations in hair follicle cells increased from pre-treatment (and Placebo) to treated Low dose and finally to treated High dose patients. The average percentage for pre-treatment samples from all patients was 0.06 +/- 0.03 SE. For 1 week and 1 month samples from Low dose patients it was 0.35 +/- 0.08 SE, and for combined 2,3 and 4 day samples from High dose patients it was 1.08 +/- 0.12 SE. Cyclophosphamide also had a significant effect on mitosis. A decrease in mitotic activity was observed at 1 month following the initial low dose cyclophosphamide treatment and at 24 +/- 2 h following each of the first two high dose cyclophosphamide treatments. The observed increase in nuclear aberrations following low dose as well as high dose cyclophosphamide suggests that it is feasible to use the nuclear aberration assay for in vivo human genotoxicity testing, using proliferating hair follicle cells.

  16. Successful treatment of metastatic sarcomas with cyclophosphamide, adriamycin, and DTIC (CAD).

    PubMed

    Blum, R H; Corson, J M; Wilson, R E; Greenberger, J S; Canellos, G P; Frei, E

    1980-10-15

    Fifty consecutive adults with sarcoma were treated with Adriamycin (45 mg/m2) on day 1, cyclophosphamide (500 mg/m2) on day 2, and DTIC (400 mg/m2) on days 1 and 2 (CAD). Of the 23 patients with measurable metastatic disease, 4 patients (17%) had a complete response, 9 patients (39%) had a partial response, 5 patients (22%) had stabilization, but 5 patients (22%) did not respond. The actuarial survival of complete and partial responders was 31.5 months compared to 5.5 months for non-responders (P < .005). Chemotherapy doses were escalated to a median lowest white count of 700 cells/mm3. Acute gastrointestinal toxicity and alopecia occurred in all patients. CAD differed from previously reported combinations by omission of vincristine, a two-day dose schedule and dose rate intensification. CAD is recommended for patients with metastatic sarcoma.

  17. Virgin coconut oil supplementation ameliorates cyclophosphamide-induced systemic toxicity in mice.

    PubMed

    Nair, S S; Manalil, J J; Ramavarma, S K; Suseela, I M; Thekkepatt, A; Raghavamenon, A C

    2016-02-01

    Virgin coconut oil (VCO) is an unrefined kernal oil, prepared from Cocos nucifera L., having substantial nutritional and medicinal value. Experimental studies have suggested its antioxidant, anti-inflammatory, immunostimulatory and hypolipidemic effects. The present study assesses its effect on formalin-induced chronic inflammation and cyclophosphamide (CTX)-induced systemic toxicity in murine models. Oral administration of VCO effectively reduced formalin-induced paw oedema in mice with more or less similar efficacy as that of diclofenac. The CTX-induced hike in blood urea, creatinine, thiobarbituric acid reactive substances (TBARS) and liver marker enzymes in mice was marginally decreased by VCO (8 g/kg body weight) ingestion orally. The liver and kidney catalase, superoxide dismutase and glutathione peroxidase activities, together with cellular glutathione and TBARS levels, were found to be improved in these animals. Overall the study reveals the protective efficacy of VCO against secondary toxicity induced by CTX possibly through its antioxidant and anti-inflammatory properties.

  18. Chemotherapy with cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP) in childhood acute lymphoblastic leukemia (ALL).

    PubMed

    Sallan, S E; Camitta, B M; Chan, D M; Traggis, D; Jaffe, N

    1977-01-01

    Three groups of children with acute lymphoblastic leukemia (ALL) were treated with intermittent cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP). Group A (no prior relapse) and Group B (prior single-agent relapse) received COAP after 12 months on another chemotherapy regimen. Children in Group C (prior relapse on multiagent regimens) received COAP following A-COAP (asparaginase plus COAP) reinduction. Median disease-free survival after beginning COAP was not reached for Group A, but was only 7 months for Groups B and C. As of November 1976, there were 8 of 15 Group A patients, 1 of 12 Group B patients, and 1 of 28 Group C patients who had remained disease-free from 38 to 60 (median 54.5) months and were off chemotherapy. COAP has activity in childhood ALL. However, effectiveness is markedly diminished in patients with prior bone marrow relapse.

  19. [Soothing effect of Ganoderma lucidum antlered form on cyclophosphamide-induced adverse reaction].

    PubMed

    Nonaka, Yuji; Ishibashi, Hiroko; Nakai, Masaaki; Shibata, Hiroshi; Kiso, Yoshinobu; Abe, Shigeru

    2005-10-01

    The immunological functions of Ganoderma lucidum antlered form (AF) (Rokkaku-Reishi in Japanese), a variant type of Ganoderma lucidum, were investigated in C57BL/6 mice treated with cyclophosphamide (CY). Ganoderma lucidum AF alleviated CY-induced decrease in body weight and abnormal increase in blood neutrophil level, when the mice were fed a diet containing 2.5% Ganoderma lucidum AF starting one week before CY treatment (150 mg/kg, ip). The recovery of CD8+ and NK1.1+ cells in the spleen was accelerated in Ganoderma lucidum AF group compared to the control group. Ganoderma lucidum AF also both alleviated CY-induced splenic lymphopenia and suppressed the abnormal increase in splenocytes 7 days after CY treatment. These results suggest that ingestion of Ganoderma lucidum AF is beneficial for improvement of quality of life reduced by anti-cancer chemotherapeutic drugs such as CY.

  20. Tumor xenotransplantation in Wistar rats after treatment with cyclophosphamide and total lymphoid irradiation. [X-ray

    SciTech Connect

    Hoogenhout, J.; Kazem, I.; Jerusalem, C.R.; Bakkeren, J.A.J.; de Jong, J.; Kal, H.B.; van Munster, P.J.J.

    1982-10-01

    Three-month-old male Wistar rats were treated with cyclophosphamide and total lymphoid irradiation, and C22LR mouse osteosarcoma was transplanted into the rats. The effects of immunosuppression were monitored by lymphocyte counts, serum IgG determinations, phytohemagglutinin (PHA) and concanavalin A (Con A) responses, measurement of the proportion of B cells, and histopathological studies of the lymphoid organs. At eight days after treatment, the lymphocyte counts, IgG levels, and PHA and Con A values were decreased. Mitotic activity started in the depleted B and T cell areas of the peripheral lymphatic organs two weeks after treatment. There was a 94% graft take of the osteosarcoma. It was determined that the optimum time for tumor xenograft transplantation is 4 days after treatment. The duration of growth was 11 days, and this was followed by regression up to day 21.

  1. Tumor xenotransplantation in Wistar rats after treatment with cyclophosphamide and total lymphoid irradiation

    SciTech Connect

    Hoogenhout, J.; Kazem, I.; Jerusalem, C.R.; Bakkeren, J.A.; de Jong, J.; Kal, H.B.; van Munster, P.J.

    1982-10-01

    Three-month-old male Wistar rats were treated with cyclophosphamide and total lymphoid irradiation, and C22LR mouse osteosarcoma was transplanted into the rats. The effects of immunosuppression were monitored by lymphocyte counts, serum IgG determinations, phytohemagglutinin (PHA) and concanavalin A (Con A) responses, measurement of the proportion of B cells, and histopathological studies of the lymphoid organs. At eight days after treatment, the lymphocyte counts, IgG levels, and PHA and Con A values were decreased. Mitotic activity started in the depleted B and T cell areas of the peripheral lymphatic organs two weeks after treatment. There was a 94% graft take of the osteosarcoma. It was determined that the optimum time for tumor xenograft transplantation is 4 days after treatment. The duration of growth was 11 days, and this was followed by regression up to day 21.

  2. Antihepatotoxic efficacy of Mangifera indica L. polysaccharides against cyclophosphamide in rats.

    PubMed

    Fahmy, Sohair R; Amien, Ahmed I; Abd-Elgleel, Fathi M; Elaskalany, Sara M

    2016-01-25

    The present study aims to evaluate the possible protective role of polysaccharides extracted from the Egyptian mango Mangifera indica L. (MPS) and/or silymarine against cyclophosphamide (CP) toxicity in male albino rats. The MPS and/or silymarin significantly decreased the activities of serum ASAT and ALAT. However, MPS (1000 mg/kg) normalized their activities towards the normal levels recording 28.75 and 78.75 U/ml respectively. The recorded data also showed the antioxidant effect of MPS by decreasing the level of malondialdehyde (MDA) and increasing the level of reduced glutathione (GSH) as well as normalized the activities of the antioxidant enzyme GST and SOD. Histopathological examinations also confirmed the protective efficacy of MPS against liver toxicity of CP. In conclusion, the recorded results of the present study support the protective role of MPS and/or silymarin against CP-induced hepatic damage.

  3. [Association of genotoxic and teratogenic effects induced by cyclophosphamide and their modification with afobazole].

    PubMed

    Shreder, O V; Shreder, E D; Durnev, A D; Seredenin, S B

    2011-01-01

    Intact rat embryonic and placental tissues were found to have a characteristic ratio of cells with different degrees of DNA fragmentation. The genotoxic effect of cyclophosphamide was shown to be accompanied by a quantitative deviation from the control group established ratio of different cell types. A relationship was found between the abnormal ratio of different cell types in the embryonic and placental tissues and the occurrence of embryonic morphological abnormalities. The antimutagen afobazole (1, 10, and 100 mg/kg) was ascertained to be able to lower genotoxic effects in the embryonic and placental tissues and their related malformations. It is presumed that it is promising to use DNA damage index in the embryonic and placental cells as a biomarker of the course of embryogenesis and as a basis for devising an indicator test for rapid screening of potential teratogens.

  4. The effect of cyclophosphamide and gamma irradiation on adenosine deaminase and purine nucleoside phosphorylase in mice

    SciTech Connect

    Hosek, B.; Bohaecek, J.; Sikulova, J. )

    1991-01-01

    Changes in ADA and PNP activities in the spleens and thymuses of mice were studied after a single administration of cyclophosphamide and after whole-body gamma irradiation, applied alone or three days after CY application, In the first days after the treatment the enzyme activities were significantly depressed with the exception of ADA in the spleen, where a high elevation in relation to controls was observed. During the regeneration period a pronounced rise of PNP activity in the spleen occurred mainly after a combined application of CY and irradiation. In the thymus the regeneration was manifested by a mild increase of both ADA and PNP activities towards control values. The findings suggest that the expressive changes of ADA and PNP activities, participating in the purine salvage pathway, may, after a cytotoxic treatment, influence the nucleotide pool and DNA synthesis in lymphoid organs.

  5. Treatment of Goodpasture syndrome with cyclophosphamide, prednisone and plasma exchange transfusions.

    PubMed Central

    Rossen, R D; Duffy, J; McCredie, K B; Reisberg, M A; Sharp, J T; Hersh, E M; Eknoyan, G; Suki, W N

    1976-01-01

    Repeated plasm exchanges were performed in a 44-year-old man with Goodpasture syndrome, also treated with cyclophosphamide and prednisone. Improvement was observed within 3 weeks of starting the protocol, and by the 76th week, endogenous creatinine clearance had increased from 30 to 56 ml/min/1.73 M2 and serum albumin from 2.7 to 3.7 g/dl. Prior treatment with immunosuppressive drugs had not significantly influenced circulating antibody levels. But sustained suppression of antibody was achieved after the plasma exchanges were begun, suggesting that physical removal of circulating antibody combined with antiproliferative drug treatment may be a useful way to control undesirable humoral immune responses. PMID:949874

  6. Complete remission of Schnitzler syndrome and Waldenström macroglobulinemia under rituximab-cyclophosphamide-dexamethasone.

    PubMed

    Aouba, Achille; Pressiat, Claire; Pricopi, Maria; Georgin-Lavialle, Sophie; Boue, François; Lievre-Castilla, Maria-Angela; Marfaing-Koka, Anne; Prevot, Sophie; Decottignies, Audrey

    2015-01-01

    In Schnitzler syndrome, which is mostly diagnosed with a low and asymptomatic monoclonal peak, anakinra has always exhibited a complete but only transient control of the auto-inflammatory signs, which are induced by interleukin (IL)-1 auto-activation. We focused on the treatment of a case of Schnitzler syndrome with moderate macroglobulinemia peak. Anakinra failed to improve the severe inflammatory anaemia and the dysglobulinemia, but rituximab-dexamethasone-cyclophosphamide chemotherapy alone allowed a complete response. The correlation between the clinical, pro-inflammatory cytokines and dysglobulinemia complete controls with chemotherapy proves the following: (1) the dual action of this treatment in both the auto-inflammatory and dysglobulinemia components of the syndrome and (2) a different but entangled cytokine network in the pathogenesis of the auto-inflammatory and dysglobulinemia components of the syndrome.

  7. Effect of Chuanminshen violaceum polysaccharides and its sulfated derivatives on immunosuppression induced by cyclophosphamide in mice

    PubMed Central

    Zhao, Xinghong; Zhang, Yuetian; Song, Xu; Yin, Zhongqiong; Jia, Renyong; Zhao, Xingfang; Lai, Xin; Wang, Guangxi; Liang, Xiaoxia; He, Changliang; Yin, Lizi; Lv, Cheng; Zhao, Ling; Shu, Gang; Ye, Gang; Shi, Fei

    2015-01-01

    One hundred mice were randomly divided into five groups. The mice in one group were injected with physiological saline as the normal control group. The mice in the other four groups were injected with physiological saline, sulfated Chuanminshen violaceum polysaccharides (SCVP), Chuanminshen violaceum polysaccharide (CVP) and astragalus polysaccharide (AP) once daily for 7 d and then with cyclophosphamide (CY) in the last 3 d. The serum cytokine level, apoptosis protein expressions, spleen lymphocyte proliferation, changes in peripheral blood T-cell subsets, and immune organ index were then measured. Results showed that SCVP and CVP can overcome CY-induced immunosuppression by promoting spleen lymphocyte proliferation, raising serum IFN-γ and IL-2 levels, enlarging immune organ indexes, and decreasing excessive apoptosis. Moreover, SCVP and CVP showed the potential to treat autoimmune diseases based on CD4+/CD8+ ratios. Results suggested that SCVP and CVP exhibited the potential to treat autoimmune and immunosuppression diseases. PMID:25785030

  8. [Effects of sex hormone on the dilatation of urinary tubule and acidophil body in NON mice].

    PubMed

    Sahata, H; Suzuki, S; Ago, A; Mifune, H; Sakamoto, H

    1994-10-01

    The influences of sex hormones on the dilatation of the urinary tubules and acidophil bodies were histologically investigated in NON (Non-Obese Non-diabetic) mice. Although the dilatation of the proximal tubules and acidophil bodies in NON mice were observed only in female but not in male, a slight dilatation and a few bodies were also observed in castrated male NON mice. Moreover, in ovariectomized female NON mice the dilatation and bodies were less compared with intact female NON mice. Estradiol administration induced prominent dilatation and numerous acidophil bodies, while the administration of testosterone showed a complete preventive effect. Therefore, it is suggested that the dilatation of the tubules and the acidophil bodies can be profoundly influenced by sex hormones.

  9. Vincristine, cisplatin, teniposide, and cyclophosphamide combination in the treatment of recurrent or metastatic adrenocortical cancer.

    PubMed

    Khan, Tanweera S; Sundin, Anders; Juhlin, Claes; Wilander, Erik; Oberg, Kjell; Eriksson, Barbro

    2004-01-01

    The efficacy and tolerability of a combination of vincristine, cisplatin, teniposide, and cyclophosphamide (OPEC) in 11 patients (median age, 45 yr) with recurrent and/or metastatic adrenocortical cancer (ACC) (seven functional and four nonfunctional) were evaluated. All patients received this regimen after the failure of streptozocin and o,p'-DDD (SO) combination therapy. The regimen comprised cyclophosphamide, 600 mg/m2, and vincristine, 1.5 mg/m2, maximum dose 2.0 mg (d 1); cisplatin, 100 mg/m2 (d 2) and teniposide, 150 mg/m2 (d 4). Cycles were repeated every 4 wk. One to eight cycles (median, six cycles) of OPEC were administered to each patient. The median duration of treatment was 6 mo. The overall 2-yr survival rate was 82% and the median survival since diagnosis was 44 mo while it was 21 mo since start of OPEC therapy. Responses were obtained in nine patients: partial response in two patients, and stable disease in seven patients. The median duration of response was 6.75 mo. A total of 60 cycles of chemotherapy were given to all patients; grade 1-2 toxicity occurred in 57 cycles, while grade 3 toxicity was observed only in two cycles, according to NCI's Common Toxicity Criteria. We conclude that the OPEC regimen may be considered in recurrent or metastatic ACC as a second-line medical treatment. However, the combination is accompanied by considerable side effects and dose modifications are necessary in order to be able to recommend the treatment. This regimen needs further evaluation compared with SO therapy preferably in a randomized multicenter trial.

  10. L-Carnitine Protect against Cyclophosphamide Induced Skeletal and Neural Tube Malformations in Rat Fetuses.

    PubMed

    Khaksary Mahabady, Mahmood; Najafzadeh Varzi, Hossein; Zareyan Jahromi, Saeedeh

    2015-11-01

    Cyclophosphamide (CP) is a mustard alkylating agent used in the treatment of a number of neoplastic diseases and as an immunosuppressant for the prevention of xenograft rejection. There are many reports that the teratogenic effects of cyclophosphamide can be prevented by application of antioxidant drugs and stimulation of the maternal immune system. Also, there is some evidence that L-carnitine is antioxidant. Therefore, in this study, the prophylactic effect of L-carnitine on teratogenic effects of CP was evaluated. This study was performed on 31 pregnant rats divided into 5 groups. Control group received normal saline and test groups received L-carnitine (500 mg/kg), CP (15 mg/kg), CP (15 mg/kg) plus L-carnitine (250 mg/kg) and CP (15 mg/kg) plus L-carnitine (500 mg/kg) intraperitoneally at 9th day of gestation. Fetuses were collected at 20th day of gestation and after determination of weight and length; they were stained by Alizarin red-Alcian blue method. Cleft palate, spina bifida, and exencephaly incidence were 55.55%, 33.34% and 27.77% in fetuses of mice that received only CP. Cleft palate, spina bifida, exencephaly incidence were 21.42%, 4.76% and 9.52% in the group which received CP plus L-carnitine (250 mg/kg), respectively. However, cleft palate, spina bifida, and exencephaly incidence were 8%, 0% and 8% range in the group received CP plus L-carnitine (500 mg/kg), respectively. In addition, skeletal anomalies incidence including limbs, vertebrae, and sternum defects were decreased by L-carnitine. The mean of weight and length of animals' fetuses received L-carnitine were significantly greater than those received only CP. In conclusion, L-carnitine significantly decreased teratogenicity induced by CP; but this subject needs more detailed evaluation.

  11. Chemotherapeutic (cyclophosphamide) effects on rat breast tumor hemodynamics monitored by multi-channel NIRS

    NASA Astrophysics Data System (ADS)

    Kim, Jae G.; Zhao, Dawen; Mason, Ralph P.; Liu, Hanli

    2005-04-01

    We previously suggested that the two time constants quantified from the increase of tumor oxyhemoglobin concentration, ▵ [HbO2], during hyperoxic gas intervention are associated with two blood flow/perfusion rates in well perfused and poorly perfused regions of tumors. In this study, our hypothesis is that when cancer therapy is applied to a tumor, changes in blood perfusion will occur and be detected by the NIRS. For experiments, systemic chemotherapy, cyclophosphamide (CTX), was applied to two groups of rats bearing syngeneic 13762NF mammary adenocarcinomas: one group received a single high dose i. p. (200 mg/kg CTX) and the other group continuous low doses (20 mg/kg CTX i. p. for 10 days). Time courses of changes in tumor ▵ [HbO2] were measured at four different locations on the breast tumors non-invasively with an inhaled gas sequence of air-oxygen-air before and after CTX administration. Both rat body weight and tumor volume decreased after administration of high dose CTX, but continuous low doses showed decrease of tumor volume only. Baselines (without any therapy) intra- and inter-tumor heterogeneity of vascular oxygenation during oxygen inhalation were similar to our previous observations. After CTX treatment, significant changes in vascular hemodynamic response to oxygen inhalation were observed from both groups. By fitting the increase of ▵ [HbO2] during oxygen inhalation, we have obtained changes of vascular structure ratio and also of perfusion rate ratio before and after chemotherapy. The preliminary results suggest that cyclophosphamide has greatest effect on the well perfused tumor vasculature. Overall, our study supports our earlier hypothesis, proving that the effects of chemotherapy in tumor may be monitored non-invasively by using NIRS to detect changes of hemodynamics induced with respiratory challenges.

  12. Metastatic Intracerebral Plasmacytoma Treated with Radiation and Thalidomide, Dexamethasone with Cyclophosphamide Chemotherapy.

    PubMed

    Kim, Tae-Shin; Ko, Seok-Jin; Park, Kyung-Jae; Kang, Shin-Hyuk

    2017-07-01

    Intracerebral plasmacytoma is an extremely rare disease for which no treatment protocol has been established. The authors present a case of metastatic intracerebral plasmacytoma that was partially resected and treated with radiation therapy. For tumor recurrence, a combination chemotherapy regimen was initiated. A 48-year-old male patient presented with dizziness and memory loss. Conventional magnetic resonance imaging (MRI) of the brain revealed a multilobulated mass with enhancing cystic and solid components measuring 7 × 7 × 6 cm in the left frontal lobe. The patient had undergone subtotal gastrectomy and transverse colectomy 8 years before admission and had been diagnosed with extraosseous plasmacytoma. At the time of the current presentation, the patient underwent craniotomy for the parenchymal lesion. Partial tumor resection was performed. Histologic and immunohistochemical examinations confirmed the diagnosis of plasmacytoma. Fractionated radiotherapy was administered, and no enhancing mass was observed on follow-up MRI. One year after radiotherapy, tumor recurrence was observed in a different area of the cerebral parenchyma. Combination thalidomide, dexamethasone, and cyclophosphamide chemotherapy was administered. After three cycles of chemotherapy, the tumor was well controlled on MRI. Hereafter, two more times of tumor recurrence occurred in the other sites of the cerebral parenchyma, but with chemoradiation therapy, the tumor was well suppressed. The findings of this case suggest that the cerebral parenchyma can be one of the metastatic sites for extraosseous plasmacytoma. In addition, combination chemotherapy with thalidomide, dexamethasone, and cyclophosphamide may be a useful treatment option for intracerebral plasmacytoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Haploidentical transplant with posttransplant cyclophosphamide vs matched unrelated donor transplant for acute myeloid leukemia

    PubMed Central

    Zhang, Mei-Jie; Bacigalupo, Andrea A.; Bashey, Asad; Appelbaum, Frederick R.; Aljitawi, Omar S.; Armand, Philippe; Antin, Joseph H.; Chen, Junfang; Devine, Steven M.; Fowler, Daniel H.; Luznik, Leo; Nakamura, Ryotaro; O’Donnell, Paul V.; Perales, Miguel-Angel; Pingali, Sai Ravi; Porter, David L.; Riches, Marcie R.; Ringdén, Olle T. H.; Rocha, Vanderson; Vij, Ravi; Weisdorf, Daniel J.; Champlin, Richard E.; Horowitz, Mary M.; Fuchs, Ephraim J.; Eapen, Mary

    2015-01-01

    We studied adults with acute myeloid leukemia (AML) after haploidentical (n = 192) and 8/8 HLA-matched unrelated donor (n = 1982) transplantation. Haploidentical recipients received calcineurin inhibitor (CNI), mycophenolate, and posttransplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis; 104 patients received myeloablative and 88 received reduced intensity conditioning regimens. Matched unrelated donor transplant recipients received CNI with mycophenolate or methotrexate for GVHD prophylaxis; 1245 patients received myeloablative and 737 received reduced intensity conditioning regimens. In the myeloablative setting, day 30 neutrophil recovery was lower after haploidentical compared with matched unrelated donor transplants (90% vs 97%, P = .02). Corresponding rates after reduced intensity conditioning transplants were 93% and 96% (P = .25). In the myeloablative setting, 3-month acute grade 2-4 (16% vs 33%, P < .0001) and 3-year chronic GVHD (30% vs 53%, P < .0001) were lower after haploidentical compared with matched unrelated donor transplants. Similar differences were observed after reduced intensity conditioning transplants, 19% vs 28% (P = .05) and 34% vs 52% (P = .002). Among patients receiving myeloablative regimens, 3-year probabilities of overall survival were 45% (95% CI, 36-54) and 50% (95% CI, 47-53) after haploidentical and matched unrelated donor transplants (P = .38). Corresponding rates after reduced intensity conditioning transplants were 46% (95% CI, 35-56) and 44% (95% CI, 0.40-47) (P = .71). Although statistical power is limited, these data suggests that survival for patients with AML after haploidentical transplantation with posttransplant cyclophosphamide is comparable with matched unrelated donor transplantation. PMID:26130705

  14. Cardiomyopathy in patients after posttransplant cyclophosphamide-based hematopoietic cell transplantation.

    PubMed

    Lin, Chien-Jung; Vader, Justin M; Slade, Michael; DiPersio, John F; Westervelt, Peter; Romee, Rizwan

    2017-05-15

    The use of posttransplant cyclophosphamide (PT-Cy) has contributed significantly to the success of haploidentical hematopoietic cell transplantation (HCT). Furthermore, several studies have shown promising results in the human leukocyte antigen-matched setting. However, the use of high-dose cyclophosphamide has been associated with the development of cardiomyopathy. There is a paucity of data concerning posttransplant cardiac complications in patients undergoing PT-Cy-based HCT. A retrospective analysis of 176 patients undergoing HCT with PT-Cy was performed. The overall survival, left ventricular ejection fractions, brain natriuretic peptide levels, and cardiac comorbidities were reviewed. The associations between comorbidities and the onset of heart failure were assessed with a Cox proportional hazards model. Pretransplant cardiomyopathy was found in 16 patients (9.1%) but had no effect on their posttransplant overall survival. Thirty-five patients (21.9%) developed posttransplant cardiomyopathy, which correlated with increased mortality, but this was not statistically different from the frequency-matched non-PT-Cy cohort. The majority of these cardiomyopathies occurred in the setting of an infectious milieu. An age greater than 60 years and an HCT comorbidity index score equal to or greater than 4 were the only risk factors that correlated with posttransplant cardiomyopathy. The presence of pretransplant cardiomyopathy does not negatively affect overall survival for patients who undergo HCT with PT-Cy. Furthermore, cardiomyopathy in PT-Cy patients is not caused by PT-Cy but is mostly concurrent with infectious complications and is associated with reduced overall survival. Traditional cardiovascular risk factors do not fully predict the occurrence of posttransplant cardiomyopathy. Future research is required to unravel predictive factors for cardiomyopathy after PT-Cy-based HCT. Cancer 2017;123:1800-1809. © 2017 American Cancer Society. © 2017 American Cancer

  15. Cyclophosphamide followed by intravenous targeted busulfan for allogeneic hematopoietic cell transplantation: pharmacokinetics and clinical outcomes

    PubMed Central

    Rezvani, Andrew R.; McCune, Jeannine S.; Storer, Barry E.; Batchelder, Ami; Kida, Aiko; Deeg, H. Joachim; McDonald, George B.

    2013-01-01

    Targeted busulfan/cyclophosphamide (TBU/CY) for allogeneic hematopoietic cell transplantation (HCT) carries a high risk of sinusoidal obstruction syndrome (SOS) in patients transplanted for myelofibrosis. We tested the hypothesis that reversing the sequence of administration (from TBU/CY to CY/TBU) will reduce SOS and day +100 non-relapse mortality (NRM). We enrolled 51 patients with myelofibrosis (n=20), acute myeloid leukemia (AML, n=20), or myelodysplastic syndrome (MDS, n=11) in a prospective trial of CY/TBU conditioning for HCT. Cyclophosphamide 60 mg/kg/day IV for two days was followed by daily IV BU for four days, targeted to a concentration at steady state (Css) of 800–900 ng/mL. CY/TBU-conditioned patients had higher exposure to CY (p<0.0001) and lower exposure to 4-hydroxyCY (p<0.0001) compared to TBU/CY-conditioned patients. Clinical outcomes were compared with controls (n=271) conditioned with TBU/CY for the same indications. In patients with myelofibrosis, CY/TBU conditioning was associated with a significantly reduced incidence of SOS (0% vs. 30% after TBU/CY, p=0.006), while SOS incidence was low in both cohorts with AML/MDS. Day +100 mortality was significantly lower in the CY/TBU cohort (2% vs. 13%, p=0.01). CY/TBU conditioning markedly impacted CY pharmacokinetics and was associated with significantly lower incidences of SOS and day +100 mortality, suggesting that CY/TBU is superior to TBU/CY as conditioning for patients with myelofibrosis. PMID:23583825

  16. Protein adsorption and interfacial rheology interfering in dilatational experiment

    NASA Astrophysics Data System (ADS)

    Rühs, P. A.; Scheuble, N.; Windhab, E. J.; Fischer, P.

    2013-05-01

    The static and dilatational response of β-lactoglobulin fibrils and native β-lactoglobulin (monomers) at water-air and water-oil interfaces (pH 2) was measured using the pendant drop method. The resulting adsorption behavior and viscoelasticity is dependent of concentration and adsorption time. The interfacial pressure of the β-lactoglobulin fibrils obtained in static measurements was 16-18 mN/m (against air) and 7 mN/m (against oil) for all concentrations. With higher concentrations, faster adsorption kinetics and slightly higher interfacial and surface pressure is achieved but did not lead to higher viscoelastic moduli. The transient saturation of the interface is similar for both the fibril solution and the monomers, however the fibril solution forms a strong viscoelastic network. To evaluate the superimposed adsorption behavior and rheological properties, the formed interfacial layer was subjected to dilatational experiments, which were performed by oscillating the surface area of the drop in sinusoidal and sawtooth (diagonal) deformation manner. The sinusoidal oscillations (time depended area deformation rate) result in a complex interfacial tension behavior against air and oil interfaces and show remarkable differences during compression and expansion as emphasized by Lissajous figures. For diagonal (constant area deformation rate) experiments, a slight bending of the interfacial tension response was observed at low frequencies emphasizing the influence of protein adsorption during rheological measurements.

  17. [Expansion dilatation balloons for cervical ripening in obstetric practice].

    PubMed

    Ducarme, G; Grange, J; Vital, M

    2016-02-01

    During recent decades, mechanical devices have been substituted by pharmacological methods. Their place in the therapeutic arsenal remains important with a renewed obstetrical interest for these devices. Due to a lack of data they are still not recommended as first-line. This review thus attempted to examine the use of expansion dilatation balloons (Foley catheter and double-balloons) to analyze their effectiveness in case of native uterus and previous cesarean section. Twenty-seven clinical trials had compared balloons catheter and prostaglandins in patients without a history of uterine scar. The risk of cesarean section did not differ. Mechanical methods seemed to be more effective in achieving delivery within 24hours, with fewer episodes of excessive uterine contractions, but they necessitated more oxytocin during labor. Ten clinical trials analyzed dilatation balloons in patients with previous cesarean section. More than 70% women had favorable cervical ripening (Bishop score>6), and vaginal delivery was reported between 35 and 70% of patients. The risk of uterine rupture was low between 0.64 and 0.72%, with neither increased risk of severe neonatal and maternal morbidity nor increased risk of infectious morbidity. Mechanical methods are effective and safe for third trimester cervical ripening, mainly in women with previous cesarean section. Potential advantages may include wide availability and reduction of some of the side effects.

  18. Surface dilational rheological properties in the nonlinear domain.

    PubMed

    Bykov, A G; Liggieri, L; Noskov, B A; Pandolfini, P; Ravera, F; Loglio, G

    2015-08-01

    The interfacial tension response to dilational deformation of interfacial area exhibits a (more or less) nonlinear behavior, depending on the amplitude of the deformation. Studies of such observable interfacial properties in the nonlinear domain suggest valuable information about the two-dimensional microstructure of the interfacial layer, as well as about the structure time-evolution. In this article, the emphasis is centered on the available mathematical methods for quantitatively analyzing and describing the magnitude and the characteristics of the nonlinear interfacial viscoelastic properties. Specifically, in periodic oscillation experiments the nonlinear behavior can be represented by the combination of a linear part (the surface dilational modulus), with an additional complementary Fourier analysis parameterizing the nonlinearity. Also asymmetric Lissajous plots, of interfacial tension versus deformation, are useful tools for expanding the response nonlinearity into four distinct components relevant to significant points of the cyclic loop. In connection with the mathematical methods, nonequilibrium thermodynamic formulations provide a powerful theoretical framework for investigating the interfacial dynamic properties of multiphase systems. Experimental results for adsorption layers of complex components, available in the literature, show notable nonlinear interfacial viscoelastic behavior. In particular in this review, data are illustrated for solutions of polymers and of polyelectrolyte/surfactant complexes. The observed nonlinear findings reveal formation of complexes, patches, and other different interfacial structures.

  19. Ventricular dilation as an instability of intracranial dynamics

    NASA Astrophysics Data System (ADS)

    Bouzerar, R.; Ambarki, K.; Balédent, O.; Kongolo, G.; Picot, J. C.; Meyer, M. E.

    2005-11-01

    We address the question of the ventricles’ dilation as a possible instability of the intracranial dynamics. The ventricular system is shown to be governed by a dynamical equation derived from first principles. This general nonlinear scheme is linearized around a well-defined steady state which is mapped onto a pressure-volume model with an algebraic effective compliance depending on the ventricles’ geometry, the ependyma’s elasticity, and the cerebrospinal fluid (CSF) surface tension. Instabilities of different natures are then evidenced. A first type of structural instability results from the compelling effects of the CSF surface tension and the elastic properties of the ependyma. A second type of dynamical instability occurs for low enough values of the aqueduct’s conductance. This last case is then shown to be accompanied by a spontaneous ventricle’s dilation. A strong correlation with some active hydrocephalus is evidenced and discussed. The transfer function of the ventricles, compared to a low-pass filter, are calculated in both the stable and unstable regimes and appear to be very different.

  20. Finite-temperature corrections in the dilated chiral quark model

    SciTech Connect

    Kim, Y.; Lee, Hyun Kyu |; Rho, M. |

    1995-03-01

    We calculate the finite-temperature corrections in the dilated chiral quark model using the effective potential formalism. Assuming that the dilaton limit is applicable at some short length scale, we interpret the results to represent the behavior of hadrons in dense and hot matter. We obtain the scaling law, f{sub {pi}}(T)/f{sub {pi}} = m{sub Q}(T)/m{sub Q} {approx_equal} m{sub {sigma}}(T)/m{sub {sigma}}while we argue, using PCAC, that pion mass does not scale within the temperature range involved in our Lagrangian. It is found that the hadron masses and the pion decay constant drop faster with temperature in the dilated chiral quark model than in the conventional linear sigma model that does not take into account the QCD scale anomaly. We attribute the difference in scaling in heat bath to the effect of baryonic medium on thermal properties of the hadrons. Our finding would imply that the AGS experiments (dense and hot matter) and the RHIC experiments (hot and dilute matter) will ``see`` different hadron properties in the hadronization exit phase.

  1. Central Vein Dilatation Prior to Concomitant Port Implantation

    SciTech Connect

    Krombach, Gabriele A. Plumhans, Cedric; Goerg, Fabian; Guenther, Rolf W.

    2010-04-15

    Implantation of subcutaneous port systems is routinely performed in patients requiring repeated long-term infusion therapy. Ultrasound- and fluoroscopy-guided implantation under local anesthesia is broadly established in interventional radiology and has decreased the rate of complications compared to the surgical approach. In addition, interventional radiology offers the unique possibility of simultaneous management of venous occlusion. We present a technique for recanalization of central venous occlusion and angioplasty combined with port placement in a single intervention which we performed in two patients. Surgical port placement was impossible owing to occlusion of the superior vena cava following placement of a cardiac pacemaker and occlusion of multiple central veins due to paraneoplastic coagulopathy, respectively. In both cases the affected vessel segments were dilated with balloon catheters and the port systems were placed thereafter. After successful dilatation, the venous access was secured with a 25-cm-long, 8-Fr introducer sheath, a subcutaneous pocket prepared, and the port catheter tunneled to the venipuncture site. The port catheter was introduced through the sheath with the proximal end connected to a 5-Fr catheter. This catheter was pulled through the tunnel in order to preserve the tunnel and, at the same time, allow safe removal of the long sheath over the wire. The port system functioned well in both cases. The combination of recanalization and port placement in a single intervention is a straightforward alternative for patients with central venous occlusion that can only be offered by interventional radiology.

  2. Adaptive pseudo dilation for gestalt edge grouping and contour detection.

    PubMed

    Papari, Giuseppe; Petkov, Nicolai

    2008-10-01

    We consider the problem of detecting object contours in natural images. In many cases, local luminance changes turn out to be stronger in textured areas than on object contours. Therefore, local edge features, which only look at a small neighborhood of each pixel, cannot be reliable indicators of the presence of a contour, and some global analysis is needed. We introduce a new morphological operator, called adaptive pseudo-dilation (APD), which uses context dependent structuring elements in order to identify long curvilinear structure in the edge map. We show that grouping edge pixels as the connected components of the output of APD results in a good agreement with the gestalt law of good continuation. The novelty of this operator is that dilation is limited to the Voronoi cell of each edge pixel. An efficient implementation of APD is presented. The grouping algorithm is then embedded in a multithreshold contour detector. At each threshold level, small groups of edges are removed, and contours are completed by means of a generalized reconstruction from markers. The use of different thresholds makes the algorithm much less sensitive to the values of the input parameters. Both qualitative and quantitative comparison with existing approaches prove the superiority of the proposed contour detector in terms of larger amount of suppressed texture and more effective detection of low-contrast contours.

  3. Multiple Genetic Associations with Irish Wolfhound Dilated Cardiomyopathy

    PubMed Central

    Dunning, Mark D.; Brownlie, Serena

    2016-01-01

    Cardiac disease is a leading cause of morbidity and mortality in dogs and humans, with dilated cardiomyopathy being a large contributor to this. The Irish Wolfhound (IWH) is one of the most commonly affected breeds and one of the few breeds with genetic loci associated with the disease. Mutations in more than 50 genes are associated with human dilated cardiomyopathy (DCM), yet very few are also associated with canine DCM. Furthermore, none of the identified canine loci explain many cases of the disease and previous work has indicated that genotypes at multiple loci may act together to influence disease development. In this study, loci previously associated with DCM in IWH were tested for associations in a new cohort both individually and in combination. We have identified loci significantly associated with the disease individually, but no genotypes individually or in pairs conferred a significantly greater risk of developing DCM than the population risk. However combining three loci together did result in the identification of a genotype which conferred a greater risk of disease than the overall population risk. This study suggests multiple rather than individual genetic factors, cooperating to influence DCM risk in IWH. PMID:28070514

  4. The locus for bovine dilated cardiomyopathy maps to chromosome 18.

    PubMed

    Guziewicz, K E; Owczarek-Lipska, M; Küffer, J; Schelling, C; Tontis, A; Denis, C; Eggen, A; Leeb, T; Dolf, G; Braunschweig, M H

    2007-06-01

    Bovine dilated cardiomyopathy (BDCMP) is a severe and terminal disease of the heart muscle observed in Holstein-Friesian cattle over the last 30 years. There is strong evidence for an autosomal recessive mode of inheritance for BDCMP. The objective of this study was to genetically map BDCMP, with the ultimate goal of identifying the causative mutation. A whole-genome scan using 199 microsatellite markers and one SNP revealed an assignment of BDCMP to BTA18. Fine-mapping on BTA18 refined the candidate region to the MSBDCMP06-BMS2785 interval. The interval containing the BDCMP locus was confirmed by multipoint linkage analysis using the software loki. The interval is about 6.7 Mb on the bovine genome sequence (Btau 3.1). The corresponding region of HSA19 is very gene-rich and contains roughly 200 genes. Although telomeric of the marker interval, TNNI3 is a possible positional and a functional candidate for BDCMP given its involvement in a human form of dilated cardiomyopathy. Sequence analysis of TNNI3 in cattle revealed no mutation in the coding sequence, but there was a G-to-A transition in intron 6 (AJ842179:c.378+315G>A). The analysis of this SNP using the study's BDCMP pedigree did not conclusively exclude TNNI3 as a candidate gene for BDCMP. Considering the high density of genes on the homologous region of HSA19, further refinement of the interval on BTA18 containing the BDCMP locus is needed.

  5. Cognitive effort and pupil dilation in controlled and automatic processes.

    PubMed

    Querino, Emanuel; Dos Santos, Lafaiete; Ginani, Giuliano; Nicolau, Eduardo; Miranda, Débora; Romano-Silva, Marco; Malloy-Diniz, Leandro

    2015-01-01

    The Five Digits Test (FDT) is a Stroop paradigm test that aims to evaluate executive functions. It is composed of four parts, two of which are related to automatic and two of which are related to controlled processes. It is known that pupillary diameter increases as the task's cognitive demand increases. In the present study, we evaluated whether the pupillary diameter could distinguish cognitive effort between automated and controlled cognitive processing during the FDT as the task progressed. As a control task, we used a simple reading paradigm with a similar visual aspect as the FDT. We then divided each of the four parts into two blocks in order to evaluate the differences between the first and second half of the task. Results indicated that, compared to a control task, the FDT required higher cognitive effort for each consecutive part. Moreover, the first half of every part of the FDT induced dilation more than the second. The differences in pupil dilation during the first half of the four FDT parts were statistically significant between the parts 2 and 4 (p=0.023), and between the parts 3 and 4 (p=0.006). These results provide further evidence that cognitive effort and pupil diameter can distinguish controlled from automatic processes.

  6. Cognitive effort and pupil dilation in controlled and automatic processes

    PubMed Central

    Querino, Emanuel; dos Santos, Lafaiete; Ginani, Giuliano; Nicolau, Eduardo; Miranda, Débora; Romano-Silva, Marco; Malloy-Diniz, Leandro

    2015-01-01

    The Five Digits Test (FDT) is a Stroop paradigm test that aims to evaluate executive functions. It is composed of four parts, two of which are related to automatic and two of which are related to controlled processes. It is known that pupillary diameter increases as the task’s cognitive demand increases. In the present study, we evaluated whether the pupillary diameter could distinguish cognitive effort between automated and controlled cognitive processing during the FDT as the task progressed. As a control task, we used a simple reading paradigm with a similar visual aspect as the FDT. We then divided each of the four parts into two blocks in order to evaluate the differences between the first and second half of the task. Results indicated that, compared to a control task, the FDT required higher cognitive effort for each consecutive part. Moreover, the first half of every part of the FDT induced dilation more than the second. The differences in pupil dilation during the first half of the four FDT parts were statistically significant between the parts 2 and 4 (p=0.023), and between the parts 3 and 4 (p=0.006). These results provide further evidence that cognitive effort and pupil diameter can distinguish controlled from automatic processes. PMID:28123801

  7. Percutaneous transluminal balloon dilatation of the mitral valve in pregnancy.

    PubMed Central

    Smith, R; Brender, D; McCredie, M

    1989-01-01

    Pregnancy can cause life threatening complications in women with mitral stenosis, and there is a substantial risk of fetal death if valvotomy under cardiopulmonary bypass is required. A patient is described in whom pulmonary oedema developed after delivery of her first child by caesarean section 13 months previously. Subsequent cardiac catheterisation showed severe mitral stenosis (valve area 0.96 cm2, valve gradient 12 mm Hg, pulmonary artery pressure 30/16 mm Hg). Before valvotomy could be performed the patient again became pregnant and presented in pulmonary oedema at twenty two weeks' gestation. Medical treatment was unsuccessful and she underwent percutaneous transluminal balloon dilatation of the mitral valve. This increased the valve area to 1.78 cm2 and reduced the transmitral gradient to 6 mm Hg. The procedure was uncomplicated, and she remained symptom free on no medication. She delivered vaginally at 37 weeks' gestation. Percutaneous transluminal balloon dilatation of the mitral valve is a safe and effective alternative to mitral valvotomy in pregnancy. PMID:2757867

  8. Quantum to classical transition induced by gravitational time dilation

    NASA Astrophysics Data System (ADS)

    Sokolov, Boris; Vilja, Iiro; Maniscalco, Sabrina

    2017-07-01

    We study the loss of quantumness caused by time dilation [I. Pikovski, M. Zych, F. Costa, and Č. Brukner, Nat. Phys. 11, 668 (2015), 10.1038/nphys3366] for a Schrödinger cat state. We give a holistic view of the quantum to classical transition by comparing the dynamics of several nonclassicality indicators, such as the Wigner function interference fringe, the negativity of the Wigner function, the nonclassical depth, the Vogel criterion, and the Klyshko criterion. Our results show that only two of these indicators depend critically on the size of the cat, namely, on how macroscopic the superposition is. Finally we compare the gravitation-induced decoherence times to the typical decoherence times due to classical noise originating from the unavoidable statistical fluctuations in the characteristic parameters of the system [J. Trapani, M. Bina, S. Maniscalco, and M. G. A. Paris, Phys. Rev. A 91, 022113 (2015), 10.1103/PhysRevA.91.022113]. We show that the experimental observation of decoherence due to time dilation imposes severe limitations on the allowed levels of classical noise in the experiments.

  9. Fatal dilated cardiomyopathy associated with a mitochondrial DNA deletion.

    PubMed

    Moslemi, A R; Selimovic, N; Bergh, C H; Oldfors, A

    2000-01-01

    A 27-year-old man was admitted to hospital because of severe cardiac failure. Investigation revealed dilated cardiomyopathy with a left ventricular ejection fraction of 15-20%. During adolescence the patient had been investigated for growth retardation and he also had progressive external ophthalmoplegia. There had been no symptoms of cardiac disease until 2 weeks before admittance. An endomyocardial biopsy showed cardiomyocytes deficient in cytochrome c oxidase (COX) in a mosaic pattern. A skeletal muscle biopsy showed mitochondrial myopathy with COX-deficient ragged-red fibers. Molecular genetic analysis revealed a heteroplasmic, 3.8-kb, mitochondrial DNA (mtDNA) deletion in heart and muscle. PCR-based quantification of the proportion of mtDNA with deletion showed 47% mutated mtDNA in the myocardial biopsy and 68% in muscle. In spite of treatment, the condition deteriorated and the patient died 5 days after admittance. This case demonstrates that mtDNA deletions may occasionally be the cause of severe dilated cardiomyopathy, and that morphological and molecular genetic diagnosis may be obtained by endomyocardial biopsy. Copyright 2000 S. Karger AG, Basel.

  10. Effect of sand dilation on core expansion during steel casting

    NASA Astrophysics Data System (ADS)

    Galles, D.; Beckermann, C.

    2015-06-01

    The thermo-mechanical behavior of the bonded sand used for molds and cores has a strong effect on dimensions of steel castings. Experiments are conducted in which a thick- walled hollow carbon steel cylinder is cast using a silica sand core. The temporal evolution of the inner diameter of the cylinder is measured in-situ during solidification and cooling by utilizing quartz rods connected to LVDTs (Linear Variable Differential Transformers). It is found that the inner diameter increases significantly during the initial stages of solidification when the steel offers little restraint to core expansion. Without accurately modeling this initial core expansion, the final cylinder dimensions at room temperature cannot be predicted. Preliminary simulations using the measured linear thermal expansion coefficient of the core considerably under-predict the measurements, which suggests that shear induced sand dilation also contributes to core expansion. The Drucker-Prager Cap model, which can predict dilative behavior, is used to simulate the mechanical behavior of the core. Utilizing this model in conjunction with an elasto-visco-plastic constitutive law for the steel, the stress simulations successfully predict the observed dimensional changes in the casting during solidification.

  11. Dilated cardiomyopathy secondary to chronic cocaine abuse: a case report.

    PubMed

    Cooper, Chad J; Said, Sarmad; Alkhateeb, Haider; Rodriguez, Emmanuel; Trien, Remi; Ajmal, Shajeea; Blandon, Pedro A; Hernandez, German T

    2013-12-17

    Cocaine is a potent sympathomimetic agent associated with the development of possible fatal cardiovascular complications. Dysrhythmias, acute myocardial infarction, hypertension and dilated cardiomyopathy are just some of many cardiovascular effects related to the abuse of cocaine. A 38-year-old Hispanic male with a past medical history of hypertension presented with a chief complaint of progressive shortness of breath. The patient confessed to the use of cocaine for almost 18 years once per week. On examination he was hypertensive and tachycardic with a systolic murmur over the 5th intercostal space at the level of the left mid-clavicular line. Laboratory workup revealed an elevated Brain natriuretic peptide; urine toxicology was positive for cocaine. 2D-echocardiogram showed dilated cardiomyopathy. Cardiac catheterization excluded angioischemic cause. He was managed medically and subsequently discharged with drug rehabilitation. On follow-up diagnostic evaluation after 5 months of cocaine cessation, his ejection function improved significantly. The exact incidence of cocaine related cardiomyopathy is unknown and likely underreported. The clinical course is abrupt and comparatively similar to other types of cardiomyopathy. The management is like other forms of cardiomyopathy; however β-blockers should be avoided. The myocardial dysfunction is reversible with abstaining from additional cocaine ingestion. Non-invasive testing should be performed after several months to re-evaluate the treatment response.

  12. Japanese clinical practice guidelines for congenital biliary dilatation.

    PubMed

    Ishibashi, Hiroki; Shimada, Mitsuo; Kamisawa, Terumi; Fujii, Hideki; Hamada, Yoshinori; Kubota, Masayuki; Urushihara, Naoto; Endo, Itaru; Nio, Masaki; Taguchi, Tomoaki; Ando, Hisami

    2017-01-01

    Until now, there have been no practical clinical guidelines for congenital biliary dilatation (CBD). In this review article, the Japanese Study Group on Congenital Biliary Dilatation (JSCBD) propose to establish clinical practice guidelines for CBD. Because the evidence-based literature is relatively small, we decided to create guidelines based on the consensus of experts, using the medical literature for reference. A total of 20 clinical questions (CQs) were considered by the members of the editorial committee responsible for the guidelines. The CQs included the distinct aspects of CBD: (1) Concepts and Pathology (three CQs); (2) Diagnosis (six CQs); (3) Pancreaticobiliary Complications (three CQs); Treatments and Prognosis (eight CQs). Each statements and comments for CQs were made by the guidelines committee members. CQs were finally approved after review by members of the editorial committee and the guidelines evaluation board of CBD. These guidelines were created to provide assistance in the clinical practice of CBD management; their contents focus on clinical utility, and they include general information on CBD to make this disease more widely recognized. © 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  13. Dilated cardiomyopathy: the complexity of a diverse genetic architecture.

    PubMed

    Hershberger, Ray E; Hedges, Dale J; Morales, Ana

    2013-09-01

    Remarkable progress has been made in understanding the genetic basis of dilated cardiomyopathy (DCM). Rare variants in >30 genes, some also involved in other cardiomyopathies, muscular dystrophy, or syndromic disease, perturb a diverse set of important myocardial proteins to produce a final DCM phenotype. Large, publicly available datasets have provided the opportunity to evaluate previously identified DCM-causing mutations, and to examine the population frequency of sequence variants similar to those that have been observed to cause DCM. The frequency of these variants, whether associated with dilated or hypertrophic cardiomyopathy, is greater than estimates of disease prevalence. This mismatch might be explained by one or more of the following possibilities: that the penetrance of DCM-causing mutations is lower than previously thought, that some variants are noncausal, that DCM prevalence is higher than previously estimated, or that other more-complex genomics underlie DCM. Reassessment of our assumptions about the complexity of the genomic and phenomic architecture of DCM is warranted. Much about the genomic basis of DCM remains to be investigated, which will require comprehensive genomic studies in much larger cohorts of rigorously phenotyped probands and family members than previously examined.

  14. The computational power of time dilation in special relativity

    NASA Astrophysics Data System (ADS)

    Biamonte, Jacob

    2014-03-01

    The Lorentzian length of a timelike curve connecting both endpoints of a classical computation is a function of the path taken through Minkowski spacetime. The associated runtime difference is due to time-dilation: the phenomenon whereby an observer finds that another's physically identical ideal clock has ticked at a different rate than their own clock. Using ideas appearing in the framework of computational complexity theory, time-dilation is quantified as an algorithmic resource by relating relativistic energy to an nth order polynomial time reduction at the completion of an observer's journey. These results enable a comparison between the optimal quadratic Grover speedup from quantum computing and an n=2 speedup using classical computers and relativistic effects. The goal is not to propose a practical model of computation, but to probe the ultimate limits physics places on computation. Parts of this talk are based on [J.Phys.Conf.Ser. 229:012020 (2010), arXiv:0907.1579]. Support is acknowledged from the Foundational Questions Institute (FQXi) and the Compagnia di San Paolo Foundation.

  15. Dilated cerebral venous system observed in growth restricted fetuses.

    PubMed

    Baron, Joel; Mastrolia, Salvatore Andrea; Shelef, Ilan; Tirosh, Dan; Daniel-Spiegel, Etty; Hershkovitz, Reli

    2017-04-03

    The dilation of the fetal cerebral veins is a rare phenomena that may be associated to a bad obstetric outcome, and is usually connected to antenatal thrombosis of the posterior dural venous sinuses. There are several descriptions of cerebral vein distension on magnetic resonance imaging (MRI), but all of them are detected postnatally. We present herein two cases of fetal antenatal cerebral dilation of the venous system, without any association to any sign of vein thrombosis, and a systematic review of literature regarding pathogenesis, diagnosis and outcomes associated to the antenatal detection of this condition with the use of MRI. To identify potentially eligible studies, we searched PubMed, Scopus, Cochrane Library (all from inception to October 20(th), 2016) and applied no language restrictions. The electronic database search provided a total of 22843 results. After the exclusion of duplicates, manuscripts that resulted not relevant to the review based on title and abstract screening, and analysis of manuscripts eligible for full-text assessment, no papers were found related to the subject reported in the present manuscript.

  16. Reversible transition from a hypertrophic to a dilated cardiomyopathy

    PubMed Central

    Spillmann, Frank; Kühl, Uwe; Van Linthout, Sophie; Dominguez, Fernando; Escher, Felicitas; Schultheiss, Heinz‐Peter; Pieske, Burkert

    2015-01-01

    Abstract We report the case of a 17‐year‐old female patient with known hypertrophic cardiomyopathy and a Wolff‐Parkinson‐White syndrome. She came to our department for further evaluation of a new diagnosed dilated cardiomyopathy characterized by an enlargement of the left ventricle and a fall in ejection fraction. Clinically, she complained about atypical chest pain, arrhythmic episodes with presyncopal events, and dyspnea (NYHA III) during the last 6 months. Non‐invasive and invasive examinations including magnetic resonance imaging, electrophysiological examinations, and angiography did not lead to a conclusive diagnosis. Therefore, endomyocardial biopsies (EMBs) were taken to investigate whether a specific myocardial disease caused the impairment of the left ventricular function. EMB analysis resulted in the diagnosis of a virus‐negative, active myocarditis. Based on this diagnosis, an immunosuppressive treatment with prednisolone and azathioprine was started, which led to an improvement of cardiac function and symptoms within 3 months after initiating therapy. In conclusion, we show that external stress triggered by myocarditis can induce a reversible transition from a hypertrophic cardiomyopathy to a dilated cardiomyopathy phenotype. This case strongly underlines the need for a thorough and invasive examination of heart failure of unknown causes, including EMB investigations as recommend by the actual ESC position statement. PMID:27774273

  17. Surface dilational moduli of polymer and blended polymer monolayers spread at air-water interfaces.

    PubMed

    Morioka, Takako; Kawaguchi, Masami

    2014-10-16

    Surface dilational moduli of polymer monolayers, blended polymer monolayers, and polymer particle monolayers spread at air-water interfaces are reviewed, focusing on measurements using surface pressure isotherm, surface pressure relaxation, and oscillating barrier methods. Differences between the surface dilational moduli of condensed polymer monolayers and expanded polymer monolayers are explored. Moreover, the features of the surface dilational moduli in blended polymer monolayers are discussed in terms of their miscibility. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Cyclophosphamide: As bad as its reputation? Long-term single centre experience of cyclophosphamide side effects in the treatment of systemic autoimmune diseases.

    PubMed

    Dan, Diana; Fischer, Rahel; Adler, Sabine; Förger, Frauke; Villiger, Peter M

    2014-01-01

    Despite new treatment modalities, cyclophosphamide (CYC) remains a cornerstone in the treatment of organ or life-threatening vasculitides and connective tissue disorders. We aimed at analysing the short- and long-term side-effects of CYC treatment in patients with systemic autoimmune diseases. Chart review and phone interviews regarding side effects of CYC in patients with systemic autoimmune diseases treated between 1984 and 2011 in a single university centre. Adverse events were stratified according to the "Common Terminology Criteria for Adverse Events" version 4. A total of 168 patients were included. Cumulative CYC dose was 7.45 g (range 0.5-205 g). Gastro-intestinal side effects were seen in 68 events, hair loss occurred in 38 events. A total of 58 infections were diagnosed in 44/168 patients (26.2%) with 9/44 suffering multiple infections. Severity grading of infections was low in 37/58 cases (63.8%). One CYC-related infection-induced death (0.6%) was registered. Amenorrhoea occurred in 7/92 females (7.6%) with 5/7 remaining irreversible. In females with reversible amenorrhoea, prophylaxis with nafarelin had been administered. Malignancy was registered in 19 patients after 4.7 years (median, range 0.25-22.25) presenting as 4 premalignancies and 18 malignancies, 3 patients suffered 2 premalignancies/malignancies each. Patients with malignancies were older with a higher cumulative CYC dose. Death was registered in 28 patients (16.6%) with 2/28 probably related to CYC. Considering the organ or life-threatening conditions which indicate the use of CYC, severe drug-induced health problems were rare. Our data confirm the necessity to follow-up patients long-term for timely diagnosis of malignancies. CYC side-effects do not per se justify prescription of newer drugs or biologic agents in the treatment of autoimmune diseases.

  19. Mechanism of aortic root dilation and cardiovascular function in tetralogy of Fallot.

    PubMed

    Seki, Mitsuru; Kuwata, Seiko; Kurishima, Clara; Nakagawa, Ryo; Inuzuka, Ryo; Sugimoto, Masaya; Saiki, Hirofumi; Iwamoto, Yoichi; Ishido, Hirotaka; Masutani, Satoshi; Senzaki, Hideaki

    2016-05-01

    The aortic root dilation in tetralogy of Fallot (TOF) is a long-term clinical problem, because a severely dilated aorta can lead to aortic regurgitation, dissection, or rupture, which can be fatal, necessitating surgical intervention. The details of the mechanism of aortic root dilation, however, are unclear. We have shown that aortic stiffness is increased in patients with repaired TOF, and may mirror the histological abnormality of elastic fiber disruption and matrix expansion. This aortic stiffness is related closely to the aortic dilation, indicating that aortic stiffness may be a predictor of outcome of aortic dilation. Furthermore, the aortic volume overload is a very important determinant of aortic diameter in TOF patients before corrective surgery. In addition, a chromosomal abnormality and the transforming growth factor-β signaling pathway, a major contributor to aortic dilation in Marfan syndrome, also affect this mechanism. In this way, aortic dilation in TOF patients is suggested to be a multifactorial disorder. The aim of this review was therefore to clarify the mechanism of aortic dilation in TOF, focusing on recent research findings. Studies linking histopathology, mechanical properties, molecular/cellular physiology, and clinical manifestations of aortic dilation facilitate appropriate treatment intervention and improvement of long-term prognosis of TOF. © 2016 Japan Pediatric Society.

  20. Percutaneous balloon dilatation of calcific aortic valve stenosis: anatomical and haemodynamic evaluation.

    PubMed Central

    Commeau, P; Grollier, G; Lamy, E; Foucault, J P; Durand, C; Maffei, G; Maiza, D; Khayat, A; Potier, J C

    1988-01-01

    Two groups of elderly patients with calcified aortic stenosis were treated by balloon dilatation. In group 1, the valve was dilated just before surgical replacement of the valve. The valvar and annular changes occurring during dilatation were examined visually. In 20 of the 26 patients in this group there was no change. In the six remaining patients mobilisation of friable calcific deposits (1 case), slight tearing of the commissure (4 cases), or tearing of the aortic ring (1 case) were seen. Dilatation did not appear to alter valvar rigidity. In 14 patients (group 2) the haemodynamic gradient across the aortic valve was measured before and immediately after dilatation and one week after the procedure. Dilatation produced an immediate significant decrease of the aortic mean gradient and a significant increase of the aortic valve area. Eight days later the mean gradient had increased and the aortic valve area had decreased. Nevertheless there was a significant difference between the initial gradient and the gradient eight days after dilatation. The initial aortic valve area was also significantly larger than the area eight days after dilatation. The aortic valve gradient rose significantly in the eight days after dilatation and at follow up the gradients were those of severe aortic stenosis. Images Fig 1 Fig 2 Fig 3 Fig 4 Fig 5 Fig 6 Fig 7 PMID:3342163