tbuckley/cabot-search huggingface dataset:
Cellular effects of cannabinoids.
Authors: B R Martin
Journal: Pharmacological Reviews (1986)

The many studies that have been included in this review suggest that cannabinoids have ubiquitous effects on biological systems. These results also underscore the intensity to which cannabinoids have been studied. While there are numerous reasons for the prodigious amount of cannabinoid research, a major stimulus has been the desire to identify a specific biochemical event or pathway that is responsible for the expression of delta 9-THC's unique psychoactivity. It is the hope that delta 9-THC, as with all centrally acting drugs, might serve as an important tool for achieving a better understanding of the central nervous system. As discussed in this review, the psychoactivity of cannabinoids might best be described as a composite of numerous effects. If that is indeed the case, then it would seem logical that these centrally mediated effects do not arise from a single biochemical alteration, but rather from multiple actions. Of course, a major problem arises when one attempts to establish a relationship between cause and effect when multiple mechanisms and effects are involved. An initial approach to reducing the complexity of elucidation of mechanism of action should involve attempts to distinguish those cannabinoid actions which result in specific effects (psychoactivity) from those which produce non-psychoactive effects (such as general depression). There are several fundamental principles that can be used to assess specificity, including concentration or dose of the drug that is required to produce a given effect. Low doses of delta 9-THC are capable of producing the psychoactivity that is unique to cannabinoids, whereas higher doses may produce effects that are both specific and nonspecific for cannabinoids. Unfortunately, establishing this basic tenet for delta 9-THC has proven to be difficult. It has not been possible to establish the concentration of delta 9-THC at its site of action that is necessary to produce a given pharmacological effect. While it is a simple matter to measure the concentration of cannabinoids in either a whole tissue or an incubation medium, the hydrophobicity of cannabinoids dramatically affects their affinity for, and hence concentration in, the biochemical components of the tissue. If the concentration of delta 9-THC could be measured at its site of action, then the relevance of many of its pharmacological effects could be adequately determined. Two possible mechanisms by which cannabinoids might produce psychoactivity are membrane perturbation and receptor interactions, and indeed, both mechanisms have received considerable attention.(ABSTRACT TRUNCATED AT 400 WORDS)
Cerebral venous thrombosis in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma during induction chemotherapy with <scp>l</scp>‐asparaginase: The <scp>GRAALL</scp> experience
Authors: Marie-Anne Couturier, Françoise Huguet, Patrice Chevallier, Felipe Suarez, Xavier Thomas, Martine Escoffre-Barbe, Victoria Cacheux, Jean-Michel Pignon, Caroline Bonmati, Laurence Sanhes, Pierre Bories, Etienne Daguindau, Véronique Dorvaux, Oumedaly Reman, Jamile Frayfer, Corentin Orvain, Véronique Lhéritier, Norbert Ifrah, Hervé Dombret, Mathilde Hunault-Berger, Aline Tanguy-Schmidt
Journal: American Journal of Hematology (2015)

Central nervous system (CNS) thrombotic events are a well-known complication of acute lymphoblastic leukemia (ALL) induction therapy, especially with treatments including l-asparaginase (l-ASP). Data on risk factors and clinical evolution is still lacking in adult patients. We report on the clinical evolution of 22 CNS venous thrombosis cases occurring in 708 adults treated for ALL or lymphoblastic lymphoma (LL) with the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-induction protocol, which included eight L-ASP (6,000 IU/m(2) ) infusions. The prevalence of CNS thrombosis was 3.1%. CNS thrombosis occurred after a median of 18 days (range: 11-31) when patients had received a median of three l-ASP injections (range: 2-7). Patients with CNS thrombosis exhibited a median antithrombin (AT) nadir of 47.5% (range: 36-67%) at Day 17 (range: D3-D28), and 95% of them exhibited AT levels lower than 60%. There were no evident increase in hereditary thrombotic risk factors prevalence, and thrombosis occurred despite heparin prophylaxis which was performed in 90% of patients. Acquired AT deficiency was frequently detected in patients with l-ASP-based therapy, and patients with CNS thrombosis received AT prophylaxis (45%) less frequently than patients without CNS thrombosis (83%), P = 0.0002). CNS thrombosis was lethal in 5% of patients, while 20% had persistent sequelae. One patient received all planned l-ASP infusions without recurrence of CNS thrombotic whereas l-ASP injections were discontinued in 20 patients during the management of thrombosis without a significant impact on overall survival (P = 0.4).
STUDIES IN EXPERIMENTAL ANEMIA
Authors: George Draper, Alvan L. Barach
Journal: Journal of Clinical Investigation (1927)

In this study the genesis of pernicious anemia has been investigated from several points of view.The first two papers are concerned with the hypothesis that pernicious anemia is perhaps caused by an intoxication arising in the intestinal canal.Experimental anemia was produced in the first instance by the hemolytic toxin of the Welch bacillus and in the second by the use of stool extracts from pernicious anemia patients and from normal individuals.The third paper is con- cerned with immunologic differences between pernicious anemia and anemia due to the Welch bacillus toxin.In a fourth paper experiments will be reported dealing with a change in atmospheric environ- ment in which rabbits were exposed to three times the normal oxygen concentration in the inspired air. HISTORYDuring the past twenty-five years there has been presented a good deal of evidence pointing to the intestinal origin of pernicious anemia.Hunter (1) (1903) first definitely advanced the theory that pernicious anemia was due to a chronic infection of the gastro-intestinal tract, believing that this view was indicated by the specific glossitis, the gastric achylia and the intestinal symptoms characteristic of the disease.Kulbs (2), discovering that the intestinal contents of patients with chronic intestinal disorders contained hemolytic substances, believed the disease to be associated with hemolytic products of in- testinal putrefaction.Herter (3) found that the stools of pernicious anemia patients contained greatly increased numbers of B. Welchii Red blood cells and hemoglobin after TABLE 2 five intravenous injections of Welch bacillus toxin Date
Possible mechanisms of worsening bronchial asthma coexisting with thyroid gland pathology
Authors: Irina Kamaeva, Natalia Shaporova
Journal: European Respiratory Journal (2013)

We tested serum IgE levels, IL4/IL1 and IL4/INFγ ratio in 17 patients with BA, 14 with hypothyroidism (hypoT), 15 with hyperthyroidism (hyperT), 14 with BA+hypoT and 14 with BA+hyperT. Spirometry was performed. BA remission duration and BA attack frequency per year were assessed. Data are shown as mean±SEM, difference assayed as t-test p   Results : Thyropathology increases BA attack’s frequency (4.5±0.5 in BA vs 6.25±0.65 in BA+hypoT group,  p=0.04;  and 5.08±0.4 in BA+hyperT,  p=0.06 ) and decreases the remission duration (12.08±0.88 weeks/year in BA group vs 8.63±0.88 in BA+hypoT,  p=0.02,  and 9.33±0.76 in BA+hyperT,  p=0.03).  Patients with BA+hyperT had serum IgE levels grater than patients with BA and with BA+hypoT (266.7±17.3 IU/L vs 159.4±3.8 IU/L,  p=0.01,  and 122.5±9,8 IU/L,  p=0.001,  respectively). Serum IL4/IL1 ratio in BA+hyperT group was increased (36.16±1.21 BA+hyperT vs 27.02±0.79 BA,  p=0.001 ), while in BA+hypoT lessened (12.76±0.93 BA+hypoT,  p  vs BA). Ratio IL4/INFγ was decreased in BA+hypoT group (1.1±0.1 BA+hypoT vs 2.21±0.37 BA,  p=0.01 ); between BA+hyperT and BA groups there was no difference.  FEV1 showed no difference between groups. Patients with BA+hypoT had FEF50 and FEF75 reduction versus BA (48.91±3.02% vs 58.45±2.53% , p=0.04 , and 35.24±1.78% vs 47.23±1.78%  p=0.03,  respectively).   Conclusions : Hypothyroidism increases BA attacks, reduces BA remission, FEF50 and FEF75 values and Th2-activity. The possible pathway of BA worsening may concerns not with immunology but myxedema due to lack of thyroid hormones. Hyperthyroidism reduces BA remission, increases serum IgE and IL4/IL1 ratio. The possible BA worsening mechanism may be Th2-response excessive stimulation.
Bronchodilatory effect of inhaled zardaverine, a phosphodiesterase III and IV inhibitor, in patients with asthma
Authors: T Brunnee, R Engelstatter, VW Steinijans, G Kunkel
Journal: European Respiratory Journal (1992)

Zardaverine is a newly developed selective phosphodiesterase III and IV inhibitor. This study investigates the bronchodilatory properties of zardaverine, administered by inhalation. Twelve patients with reversible bronchial obstruction (increase in forced expiratory volume in one second (change FEV1 % predicted) at least 15% after 200 micrograms salbutamol, median age 31 yrs, range 21-54 years) entered the double-blind, crossover study. Four puffs of either zardaverine (total dose 6 mg) or placebo were inhaled at 15 min intervals. Pulmonary function (specific airway conductance (sGaw) and FEV1 was measured by body plethysmography at regular intervals (5 and 12 min after each puff and, in addition, 30, 60, 120, 180 and 240 min after the last puff). Compared to placebo, sGaw and FEV1 increased significantly during the first hour of repeated inhalations, but not during the entire observation period of almost 5 h. The maximum mean difference between zardaverine and placebo for FEV1 was 0.3 l or 12% and occurred approximately 1 h after inhalation of the first puff. In seven patients FEV1 increased by > 15%. The duration of action varied considerably between patients. Three patients complained of side-effects (headache, drowsiness, vertigo, nausea), and one of these dropped out of the study due to vomiting. We conclude that inhalational administration of zardaverine has a modest and short-lasting bronchodilating activity.
Predictive factors of persistent infantile atopic dermatitis up to 6 years old in Taiwan: a prospective birth cohort study
Authors: M. M.-H. Guo, W.-N. Tseng, C.-Y. Ou, T.-Y. Hsu, H.-C. Kuo, K. D. Yang
Journal: Allergy (2015)

Atopic dermatitis affects 15-30% of children worldwide. Onset of disease usually occurs within the first year of life, over half of which regress by 6 years of age. The aim of this study was to investigate the risk factors related to the persistence of infantile atopic dermatitis.In this birth cohort study, patients were enrolled prenatally and followed until 6 years of age; 246 patients had infantile atopic dermatitis at 6 months of age. Family history, maternal and paternal total and specific Immunoglobulin E (IgE) levels, and cord blood IgE were recorded. Clinical examination, questionnaire survey, and blood samples for total and specific IgE of the children were collected at each follow-up visit.Of the 246 patients with infantile atopic dermatitis at 6 months of age, 48 patients had persisted atopic dermatitis at 6 years of age (19.5%). Risk factors associated with persistent infantile atopic dermatitis included egg white sensitization (odds ratio: 3.801, P = 0.020), and atopic dermatitis involving two or more areas at 6 months old (odds ratio: 2.921, P = 0.018) after multivariate analysis with logistic regression. Patients with persistent infantile atopic dermatitis had a higher risk of asthma before 6 years old (39.6% vs 24.2%, P = 0.032).Egg white sensitization and the initial involvement of two or more areas at 6 months of age were associated with the persistent infantile atopic dermatitis. Patients with persistent infantile atopic dermatitis are more likely to develop asthma by 6 years of age.
Extended mantle radiation therapy for pathologic stage I and II Hodgkin's disease.
Authors: R Farah, J Ultmann, M Griem, H Golomb, U Kalokhe, R Desser, R Blough, R Weichselbaum
Journal: Journal of Clinical Oncology (1988)

Between 1968 and 1983, 135 patients with pathologic stage (PS) I and II Hodgkin's disease were treated with extended mantle radiation technique (EMRT) at Michael Reese Hospital and the University of Chicago Center for Radiation Therapy. EMRT combines both standard mantle and para-aorta fields (M-PA) in one port. Actuarial disease-free survival at 5 and 10 years was 82.5%. Actuarial overall survival was 96% and 83% at 5 and 10 years, respectively. Acute complications were evaluated in 112 patients available for analysis. Severe nausea and vomiting occurred in 13%, weight loss of greater than 10% of body weight in 19%, and acute hematologic toxicity in 4% of patients. Bone marrow suppression was transient and did not interfere with subsequent delivery of salvage treatment with either chemotherapy or radiation therapy in 22 patients who relapsed. The cost of EMRT is 40% lower than the cost of treatment with M-PA. The median treatment time was 38 days, 33% less than the 56 days for M-PA field assuming no interruptions. These results suggest that the EMT is a safe and effective treatment tolerated by most patients. The advantages of this method are eliminating the possibility of technical error of matching between mantle and para-aortic field, decreasing overall treatment time, and reducing the cost.
Relationship between obstructive sleep apnoea syndrome (OSAS) and the levels of endothelial progenitor cells (EPC) in patients with acute stroke
Authors: Anna Mola, Ana Mª Fortuna, Rosa Mª Miralda, Raquel Delgado, Joan Martí, Javier Crespo, Mercedes Mayos
Journal: European Respiratory Journal (2011)

OSAS is a cardiovascular risk factor that has a high prevalence in patients with stroke. Endothelial progenitor cells (EPC) are an endogenous repair mechanism of endothelium, which could be altered in OSA and contribute to endothelial dysfunction. The aim of this prospective study is to assess the relationship of OSAS and circulating EPC levels in acute stroke patients. The patients underwent a respiratory polygraphic (RP) evaluation on the 7th day of stroke (acute phase). EPC were measured by flow cytometry at inclusion and were repeated at the 7th day. EPC were considered those that were positive for three markers: CD34, CD133 and KDR (VEGF receptor). 42 of 52 patients were included (age 69±12.5 years, 54.8% male, BMI 27±4 kg/m 2 , Epworth 7±3.6). OSA prevalence in the acute phase of stroke was 54.76% (AHI>20) and 35.71% (AHI>30) with a predominant hypopnoea pattern. Significant differences between EPC levels on inclusion and on the 7th day (0.0004762% ± 0.00175636 vs 0.0034857% ± 0.0061183 (p=0.005) were found. There were no differences between non-OSAS patients and the group with AHI>10, except for age 59,73±15,58 vs 72,61±9,41 (p = 0,013). Patients with AHI>10 had lower EPC baseline levels but the analysis showed no significant differences compared to non-OSA patients. Neither AIH nor EPC values were significantly associated with neurological variables in acute stroke. The results suggest that EPC show a peak on the 7th day of acute stroke, which can express the endothelial repair capacity of the organism. OSA patients showed a lower baseline EPC values but failed to demonstrate significant differences regarding non-OSA population.
Combined Antihaemophilic Globulin and Christmas Factor Deficiency in Haemophilia
Authors: M. Verstraete, J. Vandenbroucke
Journal: BMJ (1955)

ASPIRIN AND GASTRIC HAEMORRHAGE BOURNAL 1533 evacuated, but no true calculi were found.She was well when last seen as an out-patient on November 22, 1951.During her first admission to hospital she was given 2 codeine compound tablets (N.F.) crushed, with a little water, on three successive days after admission, without knowing that she was being given aspirin.In the past all aspirin preparations, including codeine compound tablets and also the " soluble " brands of the drug, had made her sick within a few hours, even when taken crushed and with a cupful of water.She vomited several times in the first few days in hospital, but not after the haematemesis.In view of the equivocal findings of the opaque meal, it is suggested that there is strong presumptive evidence that the bleeding in this case was caused by the administration of aspirin.
Practical Monitoring of Chronic Myelogenous Leukemia: When to Change Treatment
Authors: Giuseppe Saglio, Carmen Fava
Journal: Journal of the National Comprehensive Cancer Network (2012)

In patients with chronic myelogenous leukemia (CML) treated at diagnosis with the standard therapy consisting of imatinib, 400 mg once daily, the failure to achieve a complete cytogenetic response (CCyR) within 12 months from the start of therapy has been shown to be associated with an increased risk of progression and an overall inferior survival. Experts of the European LeukemiaNet and NCCN have indicated what degrees of hematologic, cytogenetic, and molecular responses should be expected at definite time points for patients with CML to have the highest probability of experiencing the final optimal response, defined as the achievement of at least a complete hematologic response with a minor cytogenetic response after 3 months; at least a partial cytogenetic response after 6 months; at least a CCyR after 12 months; and a major molecular response after 18 months of therapy. The last opportunity for a CCyR has been established at 18 months. Because the residual probability of attaining a CCyR is reduced for patients who do not experience a complete hematologic response by 3 months, any cytogenetic response by 6 months, or a major cytogenetic response by 12 months, these conditions are considered treatment failures. At this point, a change in therapy is highly recommended, such as second-line treatment with the second-generation tyrosine kinase inhibitors nilotinib or dasatinib and, in specific situations, a stem cell transplant. The loss of any grade of previously achieved cytogenetic response at any time point is also considered an imatinib failure demanding a change of therapy. Finally, intermediate gradations of response exist between optimal response and failure in which, although not totally compromised, the possibilities of achieving an optimal response later are decreased. The best therapeutic strategies to be followed in these intermediate situations, called suboptimal responses, have not been clearly established and are still under clinical investigation, but for the moment, a change of therapy is not required.
Brief Communication: R-Type Virus-Like Particles in Avian Sarcoma Virus-Induced Rat Central Nervous System Tumors 2
Authors: Miles W. Cloyd, Peter C. Burger, Darell D. Bigner
Journal: JNCI Journal of the National Cancer Institute (1975)

Morphologically distinct virus-like particles (VLP), similar to R-type VLP, were observed by electron microscopy in experimental rat central nervous system tumors induced with the B-77-C strain of avian sarcoma virus (ASV). R-type VLP have a characteristic internal radial structure and were observed previously only in hamster cells and in an established bovine cell line. They were not observed in the B-77 ASV inoculum used to induce the rat tumors or in the B-77 induced hamster glioma cells from which the B-77 was rescued. Nevertheless, the genome of an endogenous hamster R-type particle also might have been rescued and carried in the B-77 inoculum. Alternatively, R-type VLP may exist in a number of animal species, including the rat, and may be expressed in certain conditions such as neoplastic transformation.
Tissue Changes in Mice With Persistent Vaginal Cornification Induced by Early Postnatal Treatment With Estrogen2
Authors: Noboru Takasugi, Howard A. Bern
Journal: JNCI Journal of the National Cancer Institute (1964)

Journal Article Tissue Changes in Mice With Persistent Vaginal Cornification Induced by Early Postnatal Treatment With Estrogen Get access Noboru Takasugi, Noboru Takasugi Search for other works by this author on: Oxford Academic PubMed Google Scholar Howard A. Bern Howard A. Bern Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 33, Issue 5, November 1964, Pages 855–865, https://doi.org/10.1093/jnci/33.5.855 Published: 01 November 1964 Article history Received: 01 May 1964 Published: 01 November 1964
Systemic Inflammatory Disease and Its Association With Type II Endoleak and Late Interventions After Endovascular Aneurysm Repair
Authors: Sherif Y. Shalaby, Trenton R. Foster, Michael R. Hall, Kirstyn E. Brownson, Penny Vasilas, Daniel G. Federman, Hamid R. Mojibian, Alan Dardik
Journal: JAMA Surgery (2015)

Abdominal aortic aneurysms are associated with chronic inflammation within the aortic wall, and previous studies have suggested that chronic inflammation may be a consequence of a dysregulated and persistent autoimmune response. Persistent aortic remodeling after aneurysm repair could place the patient at risk for endoleak or sac rupture.To determine whether patients with systemic inflammatory disease and large aneurysms have persistent aortic remodeling after endovascular aneurysm repair (EVAR).The records of all patients who underwent EVAR between July 2002 and June 2011 at the Veterans Affairs Connecticut Healthcare System were included in this retrospective review. Patients were considered to have a systemic inflammatory disease when confirmed by a referring specialist. Post-EVAR surveillance was performed by yearly imaging.Endovascular aneurysm repair.Significant endoleak, defined as endoleak and sac diameter increase of 0.5 cm or greater.A total of 51 of 79 patients (65%) had a systemic inflammatory disease. These patients had similar comorbid conditions compared with patients without inflammation but significantly greater numbers of major postoperative complications after EVAR (23.5% vs 3.6%; P = .02) and overall postoperative complications after EVAR (27.5% vs 7.1%; P = .03). Patients with a history of systemic inflammatory disease developed more endoleaks (45.1% vs 17.9%; P = .02) and late sac expansion (51.0% vs 21.4%; P = .01) and required more interventions (21.6% vs 3.6%; P = .03) during long-term follow-up. Systemic inflammatory disease was significantly associated with significant endoleak (odds ratio, 5.18; 95% CI, 1.56-17.16; P = .007).Patients with systemic inflammatory disease are at high risk for postoperative complications, type II endoleak, sac expansion, and additional interventions after EVAR. Additional strategies for improving the efficacy of EVAR in these patients may be warranted.