Improving the international prognostic index score using peripheral blood counts: Results of a large multicenter study involving 520 patients with diffuse large B cell lymphoma

The main purpose of this study was to assess whether it is possible to improve the prognostic impact of international prognostic index (IPI) score by combining it with peripheral blood counts. Thus, we evaluated the prognostic power of lymphocyte, neutrophil, and monocyte counts in 520 patients with diffuse large B cell lymphoma treated with R-CHOP, confirming that these parameters have a strong impact on overall survival (OS). Using revised IPI (R-IPI), 44% of patients were categorized as poor-risk and showed an OS at 5 years of 46%. As OS at 5 years of the 520 patients is 67%, it is clearly evident that R-IPI tends to overestimate the proportion of patients with poor prognosis. Accordingly, in an attempt to improve the discriminating power of R-IPI, we evaluated and compared three different scores by combining the neutrophil lymphocyte ratio (NLR) and absolute monocyte count (AMC) with the following values: (a) IPI score 3-5, (b) age > 60 years and performance status, (c) age ≥ 65 years and LDH > ULN. The three indexes studied, had a similar 5 years OS for the high-risk group (46%-52%), but the proportion of patients classified as poor-risk were 37%, 20%, and 32%, respectively, which are lower than 44% identified with R-IPI. Thus, while R-IPI overestimates the number of high-risk patients, after applying our models, it is possible to recognize patients who are truly at high-risk. Of the three scores, the most accurate appears to be that based on NLR, AMC, LDH > ULN and age ≥ 65 years, which identifies 32% of high-risk patients, correlating well with what is seen in clinical practice.     

Maternal obesity and long-term neuropsychiatric morbidity of the offspring

Archives of Gynecology and Obstetrics - To evaluate the long-term pediatric neuropsychiatric morbidity of children born to obese patients. A population-based cohort analysis was performed comparing...     

Similar outcome for cryopreserved embryo transfer following GnRH-antagonist/GnRH-agonist, GnRH-antagonist/HCG or long protocol ovarian stimulation

The pregnancy rates after triggering of final oocyte maturation with gonadotrophin-releasing hormone (GnRH) agonist in GnRH-antagonist ovarian stimulation protocols are lower than those following triggering with human chorionic gonadotrophin (HCG). Furthermore, lower pregnancy rates following GnRH-antagonist protocols compared with long GnRH-agonist protocols have been reported. The differences might be due to an impact on oocyte number and quality or on the endometrium. If any stimulation protocol had a negative impact on oocyte quality, then further evidence of this effect would be observed following frozen-thawed embryo transfer originating from that stimulation cycle. The outcome of frozen-thawed embryo transfer was retrospectively analysed using the long protocol with triptorelin depot 3.75 mg (n = 215) or 0.1 mg/day (n = 83), or GnRH-antagonist protocol with either HCG (n = 69) or GnRH-agonist (n = 25) for final oocyte maturation. The outcomes measured were implantation rate, clinical pregnancy rate, ongoing pregnancy rate and embryo survival rate. All outcomes were similar in the four groups. It is concluded that the potential for frozen-thawed embryos to implant and develop following transfer is independent of the GnRH-analogue and the final oocyte maturation protocol used in the collection cycle. Lower IVF embryo transfer success using GnRH-antagonist/GnRH-agonist protocol does not appear to be related to an adverse effect on oocyte quality.     

Chromosome localizations of genes for five cAMP-specific phosphodiesterases in man and mouse

Cyclic nucleotides are important second messengers that mediate a number of cellular responses to external signals. Cyclic nucleotide phosphodiesterases play a role in signal transduction by regulating the cellular concentrations of these messengers. Here, we have applied Southern analyses of somatic cell hybrid lines and of recombinant inbred (RI) mouse strains as well as fluorescence chromosomal in situ hybridization (FISH) to chromosomally localize five cAMP-specific nucleotide phosphodiesterase genes in human and mouse. GenesDPDE1, DPDE2, DPDE3, andDPDE4 that share sequence homology with theDrosophila dunce gene were assigned to human chromosomes 19 (DPDE1 andDPDE2), 5q12 (DPDE3), and 1p31 (DPDE4) and to mouse chromosomes 8, 9, 13, and 4, respectively. The high-affinity cAMP-specific phosphodiesterase gene (HCP1) was mapped to human chromosome 8q13-q22. Since these genes are potential candidates for involvement in psychiatric or behavioral disorders, knowledge of their chromosomal localizations will facilitate the discovery of their association with disease genes as they are being mapped by linkage studies.     

Raising awareness and providing free screening improves cervical cancer screening among economically disadvantaged Lebanese/Armenian women.

Women need to practice cervical screening regularly to reduce morbidity and mortality. The purpose of this study was to examine the impact of an intervention program on knowledge, attitude, and practice of cervical screening in the population of Lebanese/Armenian women. The design was a cross-sectional, quasi-experimental posttest survey following a year long intervention program. The sample included 176 women, who were members of the Armenian Relief Cross in Lebanon. Interventions consisted of educational classes, media messages, and free screening. The instrument was a self-administered questionnaire. Knowledge of women with intervention was higher (p > .05) and practice rate increased between intervention and comparison groups. No difference in attitude was noted. The study was successful in raising awareness and increasing screening in the sample. It is recommended to continue helping women to overcome barriers for cervical screening.     

Phyllodes tumor metastatic to thyroid Hürthle cell adenoma

We present a case of a malignant phyllodes tumor metastasizing to a Hürthle cell adenoma of the thyroid. A 55-year-old woman underwent mastectomy for a malignant phyllodes tumor. Two years later, she presented with a left thyroid mass, which was a single, circumscribed, soft, deep red-brown nodular lesion with an eccentric area of firmer consistency. Histologically, the thyroid tumor was composed of 2 distinct types of cellular proliferation. Atypical spindle cells were infiltrating between the Hürthle cell cords and follicles in a fibrosarcomatous pattern. A battery of immunohistochemical stains was applied to both the thyroid and breast tumors for comparison. Based on the histologic and immunophenotypic features of the fibrosarcomatous components of both the breast and thyroid tumors, we rendered a diagnosis of cystosarcoma phyllodes metastatic to Hürthle cell adenoma. To the best of our knowledge, this unusual case is a first report of tumor-to-tumor metastasis of a sarcoma to a primary thyroid neoplasm.     

Familial Mediterranean fever gene and protection against asthma.

BACKGROUND: Asthma is an inflammatory airway disease caused by interaction between susceptibility genes and diverse environmental factors. In Israel, asthma seems to be familial and more severe in patients of Iraqi Jewish descent. On the other hand, asthma is less frequent in individuals with familial Mediterranean fever, an autoinflammatory disease prevalent in the Iraqi Jewish community and linked to mutations in the familial Mediterranean fever gene, designated MEFV. OBJECTIVES: To explore a possible role for mutated MEFV in the reduced susceptibility to asthma and to determine its expression in Israeli subjects of Iraqi origins. METHODS: Using a case-control approach, we studied the presence of the 3 most common MEFV mutations (M694V, V726A, and E148Q) in DNA samples from 75 patients with asthma and 45 asymptomatic first-degree relatives, all of Iraqi Jewish origin. The severity of asthma was evaluated using a published severity score. RESULTS: Eleven patients with asthma and 14 of their relatives carried 1 or 2 mutations in the MEFV gene, a carrier rate significantly lower in patients with asthma than in their first-degree relatives and in ethnically matched healthy individuals (P < .03 and P < .003, respectively). Carriers of MEFV mutations had less severe disease, compared with noncarriers (P < .002). CONCLUSION: These findings suggest that MEFV mutations may have a protective effect in the pathogenesis of asthma.     

Oral administration of muscle derived small molecules inhibits tumor spread while promoting normal cell growth in mice

Tumor metastases are extremely rare in striated muscles. This is surprising given the fact that this tissue constitutes 60% of body weight. The present study focuses on small molecules produced and secreted by muscle cells which possess anti-cancer activity in vivo. Recently we have shown that a low molecular weight fraction (<1000 Dalton) of skeletal muscle cell conditioned medium (muscle factor-MF), markedly inhibits the proliferation of carcinoma, sarcoma or melanoma cell lines in vitro. The MF exerts a cytostatic effect on tumor cell growth and arrests the cells in the G0/G1 of the cell cycle. However, normal cell proliferation, such as bone marrow and fibroblasts, was stimulated following incubation with MF. In this study, the effect of orally administered MF on melanoma and sarcoma growth was examined in mice. The administration of MF to mice inoculated intravenously with melanoma (B16–F10) or sarcoma (MCA-105) cells, resulted in a statistically significant inhibition of metastatic lung foci. In a different model, melanoma was induced in the foot pad and after development of a local lesion, the leg was amputated. A prolonged survival time was observed in the MF treated groups. Since the MF stimulated bone marrow cell proliferation in vitro, we decided to test its efficacy as an inhibitor of the myelotoxic effect exerted by chemotherapy, in vivo. MF, administered after chemotherapy, restored the number of white blood cells and yielded an increased percentage of neutrophils compared with the decline in these parameters after administration of chemotherapy alone. Thus, it is indicated that MF exerted a systemic anti tumor and chemoprotective effect when given orally. It can be concluded that it is bioavailable and is not biodegradable in the digestive system. MF may be considered as a potential therapy for the prevention of tumor spread. This revised version was published online in July 2006 with corrections to the Cover Date.