Low psychopathology scores in the prognosis of breast cancer. A preliminary report

BACKGROUND: Research findings regarding the influence of psychopathology on cancer progression are not yet clear. This preliminary report investigates the severity of psychopathology assessed before biopsy in patients with invasive breast carcinoma (IBC) and its association with two follow-up outcomes: disease-free (to first recurrence) and survival periods. METHOD: The psychiatric assessment of 80 patients under 70 years old was established by means of an interview before biopsy. The DSM-IV criteria were used to establish the past and current psychiatric diagnoses. The Present State Examination (PSE)-Index of Definition (ID)-computer program (CATEGO) was used to define total PSE score, clusters of psychiatric symptoms (psychiatric syndromes) and current clinical severity (ID). The independent influence of biological prognostic factors and psychiatric variables on first recurrence or survival period was tested using Cox's proportional hazards regression model. RESULTS: After biopsy, 38 IBC patients were followed up for 3 to 8-1/3 years. During this period, 8 patients died from IBC and 7 were alive with metastatic disease. Cox's proportional hazards regression analyses showed that tumor diameter and low ID were independent significant predictors of early recurrence, whereas tumor diameter, negative estrogen receptors and low ID were independent significant predictors of survival. CONCLUSIONS: A low prebiopsy psychopathology score in IBC is a predictor of early recurrence and short survival.     

Angioedema in pediatric liver transplant recipients under tacrolimus immunosuppression

BACKGROUND: The authors report on their experience with food-induced angioedema in tacrolimus-immunosuppressed pediatric liver recipients. METHODS: Among 121 children treated with tacrolimus after liver transplantation, those who presented with angioedema are reported. RESULTS: Twelve children (10%) experienced angioedema related to food allergy while on tacrolimus. Mean ages at transplantation and angioedema were 1.3 years and 3.75 years, respectively. Angioedema occurred within a mean of 28 months from onset of tacrolimus. Eleven children experienced two or more angioedema attacks without consequences. One child presented with anaphylactic shock that caused postischemic cerebral damage. Besides eviction of food allergens, eight children were switched from tacrolimus to cyclosporine, whereas tacrolimus dosage was decreased in four. Reintroduction of food allergens was successfully performed only in those who were switched to cyclosporine. CONCLUSION: A causal relationship between tacrolimus and the occurrence of food-induced angioedema is suggested. The switch from tacrolimus to cyclosporine should be considered.     

Apoptotic susceptibility of cancer cells selected for camptothecin resistance: gene expression profiling,functional analysis,and molecular interaction mapping

To study the molecular mechanisms by which drug resistance develops, we compared DU145 humanprostate cancer cells with a subline selected for resistance to camptothecin.Differences in gene expression level were assessed by hybridizing the two cell types against each other using quadruplicate "Oncochip" cDNA microarrays that included 1648 cancer-related genes. Expression levels differing by a factor of >1.5 were detected for 181 of the genes. These differences were judged statistically reliable on the basis of a stratum-adjusted Kruskal-Wallis test, after taking into account a dye-dependent variable. The 181 expression-altered genes included a larger than expected number of the "apoptosis-related" genes (P = 0.04). To assess whether this observation reflected a generalized resistance of RCO.1 to apoptosis, we exposed the cells to a range of stresses (cisplatin, staurosporine, UV, ionizing radiation, and serum starvation) and found greatly reduced apoptotic responses for RC0.1 (relative to DU145) using flow cytometric Annexin V and terminal deoxynucleotidyl transferase-mediated nick end labeling assays. We next examined the apoptosis-related genes in the context of a molecular interaction map and found expression differences in the direction "expected" on the basis of the apoptosis-resistance of RC0.1 for BAD, caspase-6, and genes that signal via the Akt pathway. Exposure of the cells to wortmannin, an inhibitor of the Akt effector phosphatidylinositol 3-kinase, provided functional support for involvement of the Akt pathway. However, closer examination of the molecular interaction map revealed a paradox: many of the expression differences observed for apoptosis-related genes were in the direction "contrary" to that expected given the resistance of RC0.1. The map indicated that most of these unexpected expression differences were associated with genes involved in the nuclear factor kappa B and transforming growth factor beta pathways. Overall, the patterns that emerged suggested a two-step model for the selection process that led to resistance in RC0.1 cells. The first hypothesized step would involve a decrease in apoptotic susceptibility through changes in the apoptosis-control machinery associated with the Bcl-2 and caspase gene families, and also in antiapoptotic pathways operating through Akt/PKB. The second step would involve changes in multifunctional upstream genes (including some genes in the nuclear factor kappa B and transforming growth factor beta pathways) that can facilitate apoptosis but that would also tend to contribute to cell proliferation in the presence of drug. Thus, we propose that a downstream blockade of apoptosis was "permissive" for the selection of upstream pathway changes that would otherwise have induced apoptosis. This model is analogous to one suggested previously for the relationship between oncogene function and apoptosis in carcinogenesis.     

High sequence divergence in the 5' non-coding region of reference Coxsackie B and ECHO viral strains and clinical isolates revealed by restriction fragment length polymorphism analysis

We report the restriction fragment length polymorphism (RFLP) patterns of a 440-bp-long 5' non-coding region (5' NCR) amplification target of all 34 reference Coxsackie B and ECHO (enteric cytopathic human orphan) enterovirus strains and a total of 42 serotypically pre-assigned clinical isolates, in order to afford meaningful comparisons among these patterns and those of polioviruses. The RFLP patterns of reference Coxsackie B strains differed from one another and from those of polio and ECHO reference enteroviruses except from Coxsackie B1 and B2, which, although they differed from one another, had identical RFLP patterns with ECHO 17 and 13, respectively. The 28 ECHO reference strains formed a more variable viral group including strains with RFLP patterns distinct from one another and from those of polio and Coxsackie B enteroviruses, and others with RFLP pattern identities common to other ECHO viruses and Coxsackie B1 and B2 but not polioviruses. The RFLP patterns of the clinical isolates and their corresponding serotypically assigned reference Coxsackie B and ECHO strains presented the most notable variations. The observed differences between serotype and genotype-dependent assignments within the 440-bp long 5' NCR target sequence of Coxsackie B and ECHO enteroviruses were in sharp contrast to the analogous situation with polioviruses. These findings support the specificity of the described method for clinical diagnostic genotyping of polioviruses and demonstrate that the 440-bp-long target sequence follows a different evolutionary process in polio and non-polio enteroviruses that is particularly prominent between reference non-polio strains and their serotypically assigned clinical isolates.     

Partial excision of discoid meniscus: Arthroscopic operation of 10 patients

10 patients underwent arthroscopic removal of the central and torn portions of the lateral discoid meniscus, leaving a semilunar-shaped peripheral portion. All but one of the knees were asymptomatic at follow-up.     

Does focal destruction of the thoracic aorta wall by Staphylococcus aureus lead to the development of infected aneurysms? An experimental study.

Objective: The infrequency of infected aneurysms suggests that either infection of segments of the aortic wall is uncommon, or that infections do not always lead top infected aneurysm formation. The purpose of the study was to determine whether focal Staphylococcus aureus infection of aortic wall segments leads consistently to the development of infected aneurysms and to evaluate the segments in which infection did not lead to the infected aneurysm formation. Methods: Twenty pigs were inoculated with 0.1 ml of a Staphylococcus aureus inoculum in three segments of the thoracic aorta wall (study group). In another 10 pigs, 0.1 ml of saline solution was injected in three segments of the thoracic aorta wall (control group). Study group: histological abnormalities and bacterial culture of the inoculation sites were evaluated at 10 days (n=5 pigs), 30 days (n=5 pigs), and 90 days (n=10 pigs). Control group: histological abnormalities were evaluated at 10 days (n=5 pigs) and 90 days (n=5 pigs). Results: Study group: infected aneurysms developed in only two animals killed at 30 days. At 90 days, destruction of the elastic tissue, scar tissue and neointima formation were found in all the aortic segments studied. Control group: no significant changes were found in any of the segments evaluated. Conclusion: In our experimental model, acute local infection by S. aureus caused the development of infected aortic aneurysm in only 10% of the animals. In the remaining 90%, healing of the site of infection followed resolution of the infection.     

Effective immunomodulatory treatment of Escherichia coli experimental sepsis with thalidomide

Thalidomide, an agent which inhibits biosynthesis of tumor necrosis factor alpha (TNF-alpha) and which is used to treat a variety of chronic inflammatory conditions, was investigated as therapy for experimental sepsis. Sepsis was induced by intraperitoneal injection of 10(7) CFU of Escherichia coli per kg of body weight to 80 Wistar rats divided into four groups. Group A consisted of 24 control animals that did not receive any pretreatment, group B consisted of 18 vehicle-treated control animals pretreated with seed oil, group C consisted of 30 rats administered thalidomide diluted in seed oil at a dose of 50 mg/kg 30 min before bacterial challenge, and group D consisted of eight animals that were not challenged with E. coli but that were used for white blood cell count determination. Sepsis was determined by measurement of vital signs before and 6 h after bacterial challenge. After 6 h the animals were killed and blood was sampled for culture; white blood cell count determination; and determination of endotoxin (lipopolysaccharide), TNF-alpha, interleukin-1beta (IL-1beta), and IL-6 levels. The levels of these cytokines were also estimated in the supernatants of human monocytes pretreated with thalidomide after exposure to the isolate. Sepsis developed in all vehicle-treated control animals and controls by 6 h after bacterial challenge but in only 10 animals (33.3%) pretreated with thalidomide (P < 0.0001). Six hours after bacterial challenge all animals had similar levels of endotoxemia, IL-1beta, and IL-6. The mean white blood cell count for groups A, B, and C were 5,631.1, 2,638.9, and 8,169.3 cells/ micro l, respectively (P value between groups, <0.0001); the TNF-alpha levels were 77.3, 107.2, and 26.1 pg/ml, respectively (P values between groups, <0.0001). Pretreatment of human monocytes with thalidomide prevented the secretion of TNF-alpha and IL-1beta but not that of IL-6. It is concluded that thalidomide exerts a considerable anti-inflammatory effect by preventing evolution to sepsis and by decreasing the level of production of TNF-alpha and therefore deserves to be further evaluated in research for the therapy of sepsis.     

Chios Mastic Gum: A Plant-produced Resin Exhibiting Numerous Diverse Pharmaceutical and Biomedical Properties

Chios mastic gum (CMG) is a resin produced by the plant Pistacia lentiscus var. chia. CMG is used to extract the mastic gum essential oil (MGO). CMG and MGO consist of nearly 70 constituents and have demonstrated numerous and diverse biomedical and pharmacological properties including (a) eradication of bacteria and fungi that may cause peptic ulcers, tooth plaque formation and malodor of the mouth and saliva; (b) amelioration or dramatic reduction of symptoms of autoimmune diseases by inhibiting production of pro-inflammatory substances by activated macrophages, production of cytokines by peripheral blood mononuclear cells in patients with active Crohn's disease, and suppression of production of inflammatory cytokines and chemokines in an asthma model in mice; (c) protection of the cardiovascular system by effectively lowering the levels of total serum cholesterol, low-density lipoprotein and triglycerides in rats, and protection of low-density lipoprotein from oxidation in humans; (d) induction of apoptosis in human cancer cells in vitro and extensive inhibition of growth of human tumors xenografted in immunodeficient mice; and (e) improvement of symptoms in patients with functional dyspepsia. Collectively taken, these numerous and diverse medical and pharmaceutical properties of CMG and MGO warrant further research in an effort to enhance specific properties and identify specific constituent(s) that might be associated with each property.