Second malignancies in the context of lenalidomide treatment: an analysis of 2732 myeloma patients enrolled to the Myeloma XI trial.

We have carried out the largest randomised trial to date of newly diagnosed myeloma patients, in which lenalidomide has been used as an induction and maintenance treatment option and here report its impact on second primary malignancy (SPM) incidence and pathology. After review, 104 SPMs were confirmed in 96 of 2732 trial patients. The cumulative incidence of SPM was 0.7% (95% confidence interval (CI) 0.4-1.0%), 2.3% (95% CI 1.6-2.7%) and 3.8% (95% CI 2.9-4.6%) at 1, 2 and 3 years, respectively. Patients receiving maintenance lenalidomide had a significantly higher SPM incidence overall (P=0.011). Age is a risk factor with the highest SPM incidence observed in transplant non-eligible patients aged >74 years receiving lenalidomide maintenance. The 3-year cumulative incidence in this group was 17.3% (95% CI 8.2-26.4%), compared with 6.5% (95% CI 0.2-12.9%) in observation only patients (P=0.049). There was a low overall incidence of haematological SPM (0.5%). The higher SPM incidence in patients receiving lenalidomide maintenance therapy, especially in advanced age, warrants ongoing monitoring although the benefit on survival is likely to outweigh risk.

Anisotropic phases of superfluid

It has been shown that the relative stabilities of various superfluid states of ^{3}He can be influenced by anisotropy in a silica aerogel framework. We prepared a suite of aerogel samples compressed up to 30% for which we performed pulsed NMR on ^{3}He imbibed within the aerogel. We identified A and B phases and determined their magnetic field-temperature phase diagrams as a function of strain. From these results, we infer that the B phase is distorted by negative strain forming an anisotropic superfluid state more stable than the A phase.

Stability of superfluid 3He-B in compressed aerogel.

In recent work, it was shown that new anisotropic p-wave states of superfluid (3)He can be stabilized within high-porosity silica aerogel under uniform positive strain. In contrast, the equilibrium phase in an unstrained aerogel is the isotropic superfluid B phase. Here we report that this phase stability depends on the sign of the strain. For a negative strain of ∼ 20% achieved by compression, the B phase can be made more stable than the anisotropic A phase, resulting in a tricritical point for A, B, and normal phases with a critical field of ∼ 100 mT. From pulsed NMR measurements, we identify these phases and the orientation of the angular momentum.

Identification of superfluid phases of 3He in uniformly isotropic 98.2% aerogel.

Superfluid ^{3}He confined to high porosity silica aerogel is the paradigm system for understanding impurity effects in unconventional superconductors. However, a crucial first step has been elusive: exact identification of the microscopic states of the superfluid in the presence of quenched disorder. Using a new class of highly uniform aerogel materials, we report pulsed nuclear magnetic resonance experiments that demonstrate definitively that the two observed superfluid states in aerogel are impure versions of the isotropic and axial p-wave states. The theoretically predicted destruction of long-range orbital order (Larkin-Imry-Ma effect) in the impure axial state is not observed.

Hormonal interactions in the control of Arabidopsis hypocotyl elongation.

The Arabidopsis hypocotyl, together with hormone mutants and chemical inhibitors, was used to study the role of auxin in cell elongation and its possible interactions with ethylene and gibberellin. When wild-type Arabidopsis seedlings were grown on media containing a range of auxin concentrations, hypocotyl growth was inhibited. However, when axr1-12 and 35S-iaaL (which have reduced auxin response and levels, respectively) were grown in the same conditions, auxin was able to promote hypocotyl growth. In contrast, auxin does not promote hypocotyl growth of axr3-1, which has phenotypes that suggest an enhanced auxin response. These results are consistent with the hypothesis that auxin levels in the wild-type hypocotyl are optimal for elongation and that additional auxin is inhibitory. When ethylene responses were reduced using either the ethylene-resistant mutant etr1 or aminoethoxyvinylglycine, an inhibitor of ethylene synthesis, auxin responses were unchanged, indicating that auxin does not inhibit hypocotyl elongation through ethylene. To test for interactions between auxin and gibberellin, auxin mutants were grown on media containing gibberellin and gibberellin mutants were grown on media containing auxin. The responses were found to be the same as wild-type Arabidopsis seedlings in all cases. In addition, 1 microM of the auxin transport inhibitor 1-naphthylphthalmic acid does not alter the response of wild-type seedlings to gibberellin. Double mutants were made between gibberellin and auxin mutants and the phenotypes of these appear additive. These results indicate that auxin and gibberellin are acting independently in hypocotyl elongation. Thus auxin, ethylene, and gibberellin each regulate hypocotyl elongation independently.

Parental knowledge about common respiratory infections and antibiotic therapy in children.

BACKGROUND: Widespread antibiotic use has fostered the emergence of antibiotic-resistant bacteria. Parental expectations have been cited as one reason for physicians to overprescribe antibiotics. The objective of this study was to determine parental knowledge about antibiotics and their use for common respiratory tract infections. METHODS: A survey was administered to 100 adults at a rural pediatric office. RESULTS: Many respondents had misconceptions about the etiology of common respiratory tract infections and the effects of antibiotic therapy. Only 54% knew that a virus is the usual cause of the common cold, and 33% thought that a virus causes strep throat. Almost half (46%) believed that antibiotics kill viruses, while 17% were not sure whether antibiotics kill viruses. Most respondents (60%) had never heard about antibiotic resistance. CONCLUSION: Parental knowledge about common respiratory tract infections and about antibiotic therapy is often lacking. Improved parent education may alter parents' expectations concerning antibiotic therapy for their ill children.

Selective induction of endothelial L-selectin ligand in human lung inflammation.

During inflammation, leukocyte emigration from the circulation can be directed by the endothelium, in part by the inducible endothelial adhesion ligand for L-selectin. In this study, endothelial L-selectin ligand expression was localized by immunohistochemistry in human lung in several different types of lung inflammation and in systemic inflammation. Endothelial L-selectin ligand was not seen in normal lung or in acute pneumonia involving neutrophil accumulation. However, the endothelial ligand was seen in most cases of chronic interstitial pneumonia with mononuclear cell accumulation (a mean of 5.9% of microvessels positive). Regarding granulomatous conditions, in sarcoidosis the endothelial ligand was not identified, but in tuberculous infection some expression was seen in a minority of cases (mean 3.3% of microvessels positive). In contrast, consistent, typically extensive ligand induction (mean 33.4% of microvessels positive) was present in bronchiectatic lung showing prominent lymphocytic accumulation and venules with thickened (high) endothelium, the latter being normally characteristic of lymphoid tissue in which L-selectin ligand is known to be constitutively expressed. Lung from subjects with systemic infection was negative for endothelial expression of the ligand. These studies show how in a defined extralymphoid tissue induction of endothelial L-selectin ligand depended not only on the presence or absence of an inflammatory state, but also on the nature of the inflammation.

Functional distribution and further characterization of human endothelial ligand for cellular L-selectin.

In the present study we examine the functional distribution of the human endothelial L-selectin ligand, which determines the sites of extravasation of L-selectin-positive cells. A murine cell line transfected with human L-selectin adhered preferentially to the high endothelial venules (HEV) of human peripheral lymph nodes compared to the HEV of mucosal lymphoid tissues (mean of 0.83 compared to a mean of 0.07 cells per HEV respectively). In addition, an antibody against L-selectin differentially inhibited the adhesion of human lymphocytes to peripheral lymphoid tissue versus mucosal lymphoid tissue HEV (mean 41 and 5% inhibition respectively). Although both sulfoglucuronyl-containing glycolipids and sialyl-Lewis X have been proposed as endothelial ligands for L-selectin, an antibody against the former did not bind to peripheral lymph node endothelium, and an antibody against the latter did not block adhesion of L-selectin-expressing cells. The enzyme O-sialoglycoprotein endopeptidase caused up to an 84% reduction in L-selectin-dependent binding, indicating that sialylated glycoproteins containing O-linked glycans are essential for a large majority of adhesion via L-selectin.

Gene silencing and homology-dependent gene silencing in Arabidopsis: genetic modifiers and DNA methylation.

Transgenes inserted into the plant genome can become inactive (gene silencing) or result in silencing of homologous cellular genes [homology-dependent gene silencing (HDG silencing)]. In an earlier study we reported HDG silencing of chalcone synthase (CHS) in Arabidopsis. This study concerns genetic revertants of one of the CHS HDG-silencing transgenic homozygotes. Two monogenic recessive trans-acting mutations (hog1 and ddm1) that impair gene silencing and HDG silencing were identified. These mutations reduce genomic DNA methylation and affect the quantity and size of CHS mRNA. These results imply that DNA methylation is necessary for both gene silencing and HDG silencing. Two further monogenic, trans-acting, recessive mutations (sil1 and sil2) reduce gene silencing but not HDG silencing. The existence of this mutant class shows that gene silencing involves genes that are not necessary for HDG silencing. A further mutant (Catt) was isolated and has an attenuated HDG-silencing T-DNA.

Introduction of a donor exposure reduction programme for multiple-transfused very-low-birth-weight infants.

OBJECTIVE: To conduct an audit of the frequency of red cell concentrate transfusions (RCCTs) in infants of different weight categories, the donor exposure rate (DER), in these transfused infants and the volume of blood wasted during each transfusion, and to identify from this baseline information specific categories of infants who would benefit from the introduction of a limited donor exposure programme (LDEP). STUDY SETTING: Neonatal wards and neonatal intensive care unit (NICU), Tygerberg Hospital, Western Cape. STUDY DESIGN: A prospective descriptive study and comparison with a historic control group. SUBJECTS: Information on the birth weight, age at the time of each RCCT and number of blood donors to whom an infant was exposed were collected post factum for all infants admitted to the neonatal wards and NICU between May 1993 and May 1994. During this time, the red blood cell concentrate was supplied as single paediatric bags (180 ml) transfused within 14 days of donation. An LDEP was introduced in February 1995. With this system, red blood cells were supplied as triple packs: a main unit of 250 ml with three empty satellite packs allowing up to three separate transfusions. These were assigned to a specific infant and were to be transfused within 21 days of donation. A second system where one adult blood bag was divided into two 180 ml bags and assigned to one infant to be transfused within 35 days of donation was also assessed. RESULTS: Of the 7854 infants admitted during the first 12-month audit period, 387 (4.9%) received 977 RCCTs. Of these, 183 (47.3%) received one transfusion, 72 (18.6%) two transfusions, 51 (13.2%) three transfusions, 27 (7.0%) four transfusions and 54 (13.9%) five or more transfusions. Infants (N = 188) with a birth weight below 1500 g admitted to the NICU were identified as the group with the highest prevalence of RCCTs (68.6%), and it was therefore decided that in the prospective study such infants would qualify for the LDEP. A total of 81 infants was transfused with either the double (N = 47) or the triple bags (N = 34) over a 5-month period. The decrease in the mean DER (+/-SD) was clinically significant when the triple (1.9 +/- 0.8) (P = 0.0001) and the double bags (1.6 +/- 0.8) (P = 0.0001) were compared with the previous single-bag system (4.4 +/- 3.5). Of concern was the large mean volume of concentrated red cells (118.5 +/- 12.5 ml) wasted per transfusion with the single-bag system. CONCLUSIONS: This survey confirmed a high RCCT rate as well as a very high DER in very-low-birth-weight (VLBW) infants treated at a tertiary centre. By assigning a triple or double bag of red cells from one blood donor and extending the storage of blood for small-volume RCCTs in infants from 14 days to 35 days, donor exposure was reduced significantly. We urge the introduction of the multibag blood transfusion system and extended storage period of blood for small-volume RCCT for VLBW infants in South Africa.

Comments on the Health Effects Institute-Asbestos Research (HEI-AR) report: "Asbestos in public and commercial buildings," with emphasis on risk assessment methods used.

A Health Effects Institute--Asbestos Research Report calculates the risk of exposure to environmental asbestos fibers (EAF) by downward extrapolation from the mortality of workers exposed for 20 years. This extrapolation is improper because 1) relative risks of asbestos exposure very likely are not linearly progressive; 2) the composition of EAF may not be equivalent to that in mining or fabricating; 3) the same environmental asbestos concentration probably represents different exposure doses for different populations; and 4) health effects of asbestos exposure on children, seniors, patients, the institutionalized, the handicapped, and the chronically ill may not be the same as those of healthy workers. Evidence of asbestos-related disease among family members of exposed workers demonstrates that the risk observed for EAF is substantially larger than that estimated from downward extrapolation and suggests a basis for an alternative approach to estimating asbestos-related health risks. Such epidemiologic procedures are well established and ought to form the basis for detecting the health effects of EAF. It is also unclear which industry supports HEI-AR.

[Epidemiology of "sick buildings"]. / A epidemiologia dos "edifícios doentes".

The indoor environment of modern buildings, especially those designed for commercial and administrative purposes, constitutes a unique ecological niche with its own biochemical environment, fauna and flora. Sophisticated construction methods and the new materials and machinery required to maintain the indoor environment of these enclosed structures produce a large number of chemical by-products and permit the growth of many different microorganisms. Because modern office buildings are sealed, the regulation of humidification and temperature of ducted air presents a dilemma, since difference species of microorganisms flourish at different combinations of humidity and temperature. If the indoor environment of modern office buildings is not properly maintained, the environment may become harmful to its occupants' health. Such buildings are classified as "Sick Buildings". A review of the epidemiology of building illness is presented. The etiology of occupant illnesses, sources of toxic substances, and possible methods of maintaining a safe indoor environment are described.

Environmental tobacco smoke and indoor air quality in modern office work environments.

Recent attempts to clean the air in modern sealed office buildings appear to have focused on one component of indoor air quality, environmental tobacco smoke (ETS). Prohibiting smoking entirely or designating specific smoking areas has been suggested to improve comfort of office workers and reduce acute symptoms of so-called "building illness." The effectiveness of such methods, as well as the overall relation of ETS to indoor air quality, are here evaluated, based on reviews of a large number of studies of indoor air quality in modern office buildings under normal use and occupancy. Under these conditions, ETS does not appear to contribute significantly to a build-up of contaminants in offices. Also, in two large series of studies of buildings with health and comfort complaints in the US and Canada, ETS does not appear to be associated with cases of building illness.