Malnutrition in childhood lymphoblastic leukemia: a predictor of early mortality during the induction-to-remission phase of the treatment.

BACKGROUND: Previous reports have shown that undernourished children with acute lymphoblastic leukemia (ALL) have a poorer long-term survival as compared with children with normal nourishment status. It has been shown that both the relapse and mortality rates of undernourished children with ALL are higher during the continuation phase of the chemotherapy and are apparently related to a poor tolerance of ablative chemotherapy. No previous articles have analyzed the early mortality rate of these patients. METHODS: We carried out a case-control study, and have studied the effect of severe malnutrition on the mortality of 17 children with ALL during the initial induction-to-remission phase of the treatment. These 17 cases were compared with 76 controls who had survived at least the phases of induction and consolidation. RESULTS: It was found that the chance of dying during the initial phase of the treatment was 2.6 times higher (confidence interval 95%: 0.55-11.89) in undernourished children with ALL than in those children with normal nourishment status. The risk of death increased with the severity of undernourishment (p = 0.04). CONCLUSIONS: These data confirm the prognostic value of malnutrition in children with ALL and suggest that undernourishment may also influence early mortality during the induction-to-remission phase of the treatment.     

Catechol-O-methyltransferase (COMT) gene variants predict response to bupropion therapy for tobacco dependence.

BACKGROUND: Although bupropion is efficacious for smoking cessation, only a minority of smokers are able to quit. Pharmacogenetic research may improve treatment outcomes through discovery of DNA sequences predictive of successful pharmacotherapy for subgroups of smokers. We investigated variants in the catechol-O-methyltransferase (COMT) gene in a smoking cessation trial of bupropion. METHODS: A double-blind, placebo-controlled, 10-week trial of bupropion and counseling (with a 6-month follow-up period) was conducted at two university-based smoking cessation research programs. Abstinence was biochemically verified at the end of treatment and at 6 months after the target quit date. RESULTS: At the end of the treatment phase, statistically significant interaction effects indicated that COMT haplotypes of two SNPs (rs737865 and rs165599) predicted the efficacy of bupropion compared with placebo. This interaction effect was attenuated at 6-month follow-up. CONCLUSIONS: COMT haplotypes at rs737865 and rs165599 may predict a favorable outcome for bupropion treatment for smoking cessation. European-American smokers with a G allele at both SNPs may not benefit from bupropion treatment. Small numbers of some COMT haplotypes limit interpretation of response. If study findings are confirmed in additional large studies, COMT genotyping could be applied to identify likely responders to bupropion treatment for smoking cessation.     

Improvement of IVF outcome in poor responders by discontinuation of GnRH analogue during the gonadotropin stimulation phase--a function of improved embryo quality.

PURPOSE: To assess the efficacy of a protocol involving the discontinuation of the GnRH analogue at the mid-phase of ovarian stimulation for IVF in patients with a previous poor response. METHODS: Prospective case-control evaluation compared with same patient's previous performance. Thirty-six patients enrolled in an IVF program were treated in two consecutive cycles. The first with a standardized protocol utilizing midluteal administration of Nafarelin (N) 600 mcg/d continued throughout the stimulation phase with human menopausal gonadotropin (hMG) until follicles of 20 mm were identified by transvaginal ultrasound (Standard group). Patients with a poor response in the Standard cycle were treated in the subsequent cycle with N and hMG initially in a similar manner, then N was stopped after 5 days of hMG stimulation (N-stop group). All clinical and laboratory aspects of treatment were done in a similar fashion in both cycles, each patient acting as her own control. RESULTS: Results were analyzed by paired t test. The change in each parameter in the N-stop cycle was expressed as the percent change as compared with the standard protocol cycle for each patient. Peak estradiol (E2) and number of aspirated oocytes were increased in the N-stop cycle (+16.9% and +28%, respectively), but insignificantly so. The percent of cleaving embryos was significantly increased by 27.9% (p = 0.03) in the N-stop cycle, as embryo morphology was improved by 22% (p = 0.02). The efficacy of gonadotropin treatment was enhanced in the N-stop cycle, as expressed by a 32.5% increase in oocytes retrieved per hMG ampoule administered (p = 0.04). Three cycles of 36 were cancelled during the N-stop cycle, whereas only one was cancelled in the standard protocol cycle. Of the 36 patients, 7 conceived in the N-stop protocol and 5 are ongoing pregnancies. CONCLUSION: Discontinuation of GnRH-a during ovarian stimulation for IVF has a beneficial, but not statistically significant, effect on both E2 and oocyte production. Embryo cleavage rates and morphology were significantly improved, this may be due to improved oocyte quality, which may have been responsible for achieving pregnancies. The efficacy of gonadotropin treatment was enhanced when GnRH-a was discontinued. These results hint that GnRH-a may have a direct negative effect on folliculogenesis and oocytes, which is apparent especially in poor responder patients.     

Clonal population of flucytosine-resistant Candida tropicalis from blood cultures, Paris, France

Candida tropicalis is a diploid ascomycetes yeast responsible for 4%-24% of candidemia. Resistance to flucytosine is rarely described for this species but was observed for 45 (35%) of 130 C. tropicalis isolates recovered from blood cultures in the Paris area in a 4-year survey. The aims of this study were to test the hypothesis that the flucytosine-resistant isolates could represent a subgroup and to determine the relationship between epidemiologic and genomic data. Epidemiologic data and gene sequences were analyzed, and molecular typing was performed. Our results suggest that a clone of flucytosine-resistant isolates, associated with malignancies and a lower mortality than that for other C. tropicalis isolates, is widespread in the Paris area. We propose the analysis of 2 polymorphic microsatellite markers coupled with URA3 sequencing to track the clone.     

Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease): clinico-pathological study of three cases

Introduction We report three cases of sinus histiocytosis, a rare disease of unknown aetiology with massive lymphadenopathy (SHML), also known as Rosai-Dorfman (RD) disease, in a paediatric population. This proliferative histiocytic disorder is defined by histological and immunohistochemical (IHC) characteristics and can manifest as nodal involvement with variable enlargement of the lymph nodes (two cases) and extranodal manifestations involving skin and larynx involvement (one case). One patient had hypergammaglobulinemia. The morphological investigation revealed that all lymph nodes showed hyperplasia of sinuses with abundant histiocytic cell with intracytoplasmic lymphocytes. Skin and larynx biopsies showed a histiocyte and lymphocyte infiltrate with similar characteristics. An ultrastructural study was carried out on material from one patient. In the IHC study, SHML cells expressed phagocytic markers such as CD68 and S100, but markers for Langerhan’s (CD1a) or dendritic cells (DRC, CD23 and CNA42) were absent. Two patients had a complete remission after surgical excision and no other treatment, but the third patient was treated with radiotherapy after a relapse with obstruction of the upper airway.Conclusion This disorder must be considered in the differential diagnosis of young patients who exhibit massive or multiple lymphadenopathies, especially when involvement of the cervical area occurs. Due to the good outcome of the disease, a conservative approach is justified.     

Comparison of the effects of sterilisation techniques on subsequent DNA profiling

It is important that contamination from extraneous DNA should be minimised on items used at crime scenes and when dealing with exhibits within the laboratory. Four sterilisation techniques (UV, gamma and beta radiation and ethylene oxide treatment) were examined for their potential to degrade contaminating DNA to such an extent that subsequent DNA profiling was impossible. This work indicated that the most successful technique to reduce DNA contamination was ethylene oxide treatment. Of the radiation techniques tested in this study, gamma was the most successful at eradicating DNA and UV radiation was the least. None of the contaminated samples treated with ethylene oxide and subsequently subjected to DNA analysis met the DNA profile criteria necessary for acceptance on the UK National DNA Database. Contaminated cotton swabs and micro-centrifuge tubes treated with ethylene oxide showed a marked decrease in amplifiable DNA post-treatment. Ethylene oxide treatment to sterile swabs and tubes did not significantly affect subsequent DNA analysis.