Influence of CA 15-3 blood level and doubling time on diagnostic performances of 18F-FDG PET in breast cancer patients with occult recurrence

AIM: To evaluate the influence of CA 15-3 blood level and doubling time on diagnostic performances of 18F-FDG PET in breast cancer patients with occult recurrence. MATERIALS AND METHODS: Thirty-five 18F-FDG PET examinations in 32 patients with CA 15-3 blood level above the normal range, and negative conventional imaging within 3 months before PET examination were included in this retrospective study. PET examinations were reviewed blindly by two experienced nuclear medicine physicians who were unaware of any clinical, biological or radiological information. CA 15-3 assays performed prior to the PET examinations and all using the same technique were collected and used for doubling time calculation if (1) no therapeutic modification occurred in the meantime, and (2) the delay between assays was less than 6 months. RESULTS: Median CA 15-3 blood levels were higher in the positive PET group (100 U x ml(-1)) than in the negative group (65 U x ml(-1)) (P=0.04). The likelihood of depicting recurrence was higher in patients with a short doubling time (<180 days) (P=0.05), a CA 15-3 blood level >60 U x ml(-1) (P=0.05), and when a short doubling time was associated with a CA 15-3 blood level >60 U x ml(-1) (P=0.03). CONCLUSIONS: The likelihood of depicting recurrence was influenced by CA 15-3 blood level and doubling time. Further studies are required to confirm that selections of patients based on those criteria could improve the sensitivity of positron emission tomography in the detection of breast cancer recurrence, particularly in the case of low CA 15-3 blood level.     

Multiple sclerosis patients show sexual dimorphism in cytokine responses to myelin antigens

Multiple sclerosis affects more women than men. The reasons for this are unknown. Previously, we have shown significant differences in women versus men in inflammatory cytokine responses to the major protein component of myelin, proteolipid protein (PLP), which is thought to be a target in MS patients. Here, using the ELISPOT assay, we examined sex differences in single-cell secretion of Th1 and Th2 cytokines from freshly isolated PBMC between relapsing remitting (RR) MS patients and healthy individuals. Cells were stimulated with MS-associated antigens including proteolipid protein (PLP), myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), and non-disease related antigens. Our data show a sex bias in the cytokine responses to multiple MS-relevant myelin antigens: Women with MS show IFNgamma-skewed responses and men with MS show IL-5-skewed responses. These data extend our previous findings [Pelfrey, C.M., Cotleur, A.C., Lee, J.C., Rudick, R.A. 2002. Sex differences in cytokine responses to myelin peptides in multiple sclerosis. J. Neuroimmunol. 130, 211-223.]: (1) by demonstrating gender skewing in cytokine responses to an expanded myelin antigen repertoire, which includes MBP, MOG and PLP; (2) by showing TNFalpha and IL-10 do not display comparable gender skewing compared to IFNgamma and IL5; (3) by defining the patient population as early, untreated RRMS patients to avoid confounding factors, such as different disease stages/disability and immunomodulatory therapy; and (4) by showing HLA type does not appear to underlie the gender differences. These findings may explain increased susceptibility to MS in women and could contribute to the differences in disease severity between men and women.     

Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases

Several case reports suggest that rituximab (RTX) could be effective in steroid-dependent nephrotic syndrome, but RTX efficacy has not yet been studied in a series of patients. Safety and efficacy of RTX were assessed in a multicenter series of 22 patients aged 6.3-22 years with severe steroid-dependent nephrotic syndrome or steroid-resistant but cyclosporin-sensitive idiopathic nephrotic syndrome. Patients were treated with two to four infusions of RTX. Seven patients were nephrotic at the time of RTX treatment. Peripheral B cells were depleted in all subjects. Remission was induced in three of the seven proteinuric patients. One or more immunosuppressive (IS) treatments could be withdrawn in 19 patients (85%), with no relapse of proteinuria and without increasing other IS drugs. RTX was effective in all patients when administered during a proteinuria-free period in association with other IS agents. When relapses occurred, they were always associated with an increase in CD19 cell count. Adverse effects were observed in 45% of cases, but most of them were mild and transient. This study suggests that RTX could be an effective treatment for severe steroid-dependent nephrotic syndrome.     

Multilevel modelling of somatotype components: the Portuguese sibling study on growth,fitness, lifestyle and health

Background: Somatotype is a complex trait influenced by different genetic and environmental factors as well as by other covariates whose effects are still unclear.

Aims: To (1) estimate siblings’ resemblance in their general somatotype; (2) identify sib-pair (brother–brother (BB), sister–sister (SS), brother–sister (BS)) similarities in individual somatotype components; (3) examine the degree to which between and within variances differ among sib-ships; and (4) investigate the effects of physical activity (PA) and family socioeconomic status (SES) on these relationships.

Subjects and methods: The sample comprises 1058 Portuguese siblings (538 females) aged 9–20 years. Somatotype was calculated using the Health-Carter method, while PA and SES information was obtained by questionnaire. Multi-level modelling was done in SuperMix software.

Results: Older subjects showed the lowest values for endomorphy and mesomorphy, but the highest values for ectomorphy; and more physically active subjects showed the highest values for mesomorphy. In general, the familiality of somatotype was moderate (ρ?=?0.35). Same-sex siblings had the strongest resemblance (endomorphy: ρ_SS > ρ_BB > ρ_BS; mesomorphy: ρ_BB = ρ_SS > ρ_BS; ectomorphy: ρ_BB > ρ_SS > ρ_BS). For the ectomorphy and mesomorphy components, BS pairs showed the highest between sib-ship variance, but the lowest within sib-ship variance; while for endomorphy BS showed the lowest between and within sib-ship variances.

Conclusions: These results highlight the significant familial effects on somatotype and the complexity of the role of familial resemblance in explaining variance in somatotypes.     

A significant increase in kdr in Anopheles gambiae is associated with an intensive vector control intervention in Burundi highlands

Objectives and Methods In Burundi, the occurrence of the knock down resistance (kdr) mutation in Anopheles gambiae sensu lato (s.l.) was determined for six consecutive years within the framework of a vector control programme. Findings were also linked with the insecticide resistance status observed with bioassay in An. gambiae s.l. and An. funestus. Results The proportion of An. gambiae s.l. carrying the East Leu‐Ser kdr mutation was 1% before the spraying intervention in 2002; by 2007 it was 86% in sprayed valleys and 67% in untreated valleys. Multivariate analysis showed that increased risk of carrying the kdr mutation is associated with spraying interventions, location and time. In bioassays conducted between 2005 and 2007 at five sites, An. funestus was susceptible to permethrin, deltamethrin and DDT. Anopheles gambiae s.l. remained susceptible or tolerant to deltamethrin and resistant to DDT and permethrin, but only when kdr allele carriers reached 90% of the population. Conclusions The cross‐resistance against DDT and permethrin in Karuzi suggests a possible kdr resistance mechanism. Nevertheless, the homozygous resistant genotype alone does not entirely explain the bioassay results, and other mechanisms conferring resistance cannot be ruled out. After exposure to all three insecticides, homozygote individuals for the kdr allele dominate among the surviving An. gambiae s.l. This confirms the potential selection pressure of pyrethroids on kdr mutation. However, the high occurrence of the kdr mutation, even at sites far from the sprayed areas, suggests a selection pressure other than that exerted by the vector control programme.