Sarcopenia and body mass index predict sunitinib-induced early dose-limiting toxicities in renal cancer patients.

BACKGROUND: Little is known on factors predicting sunitinib toxicity. Recently, the condition of low muscle mass, named sarcopenia, was identified as a significant predictor of toxicity in metastatic renal cell cancer (mRCC) patients treated with sorafenib. We investigated whether sarcopenia could predict early dose-limiting toxicities (DLTs) occurrence in mRCC patients treated with sunitinib. METHODS: Consecutive mRCC patients treated with sunitinib were retrospectively reviewed. A DLT was defined as any toxicity leading to dose reduction or treatment discontinuation. Body composition was evaluated using CT scan obtained within 1 month before treatment initiation. RESULTS: Among 61 patients eligible for analysis, 52.5% were sarcopenic and 32.8% had both sarcopenia and a body mass index (BMI)<25 kg m(-2). Eighteen patients (29.5%) experienced a DLT during the first cycle. Sarcopenic patients with a BMI<25 kg m(-2) experienced more DLTs (P=0.01; odds ratio=4.1; 95% CI: (1.3-13.3)), more cumulative grade 2 or 3 toxicities (P=0.008), more grade 3 toxicities (P=0.04) and more acute vascular toxicities (P=0.009). CONCLUSION: Patients with sarcopenia and a BMI<25 kg m(-2) experienced significantly more DLTs during the first cycle of treatment.

Assessment of real-time PCR for quantification of Legionella spp. in spa water.

AIMS: Legionella bacteria ubiquitously colonize natural freshwater and are responsible for legionellosis in humans. Several cases of legionellosis have been associated in particular with the use of whirlpool spas. The objective of this study was to verify whether real-time PCR is applicable for the quantification of Legionella spp. in spa water. METHODS AND RESULTS: The study compared concentrations obtained by real-time PCR vs that obtained by conventional culture for 101 spa water samples. For the culture method, Legionella spp. were detected and quantified in 14 of 101 samples with measured concentrations ranging from 250 to 3.5 × 10(5) CFU l(-1). With the real-time PCR method, Legionella spp. were detected and quantified in 42 of 101 samples with concentrations ranging from 1000 to 6.1 × 10(7) GU l(-1). Results revealed a significant but weak correlation (r(2) = 0.1867) between the two methods. The positive predictive value (35%) of the PCR method compared to conventional culture herein was low. In contrast, the negative predictive value was excellent, reaching 93%. CONCLUSIONS: Real-time PCR could be used as a screening tool to rapidly ascertain the absence of Legionella spp. in spa water. However, a positive result involves the need to resort to conventional culture. SIGNIFICANCE AND IMPACT OF THE STUDY: Data of this study highlighted the pros and cons of quantification of Legionella spp. in spa water with real-time PCR using a commercial quantitative PCR kit in a routine laboratory, when compared to conventional culture.

Relation between plasma trough concentration of abiraterone and prostate-specific antigen response in metastatic castration-resistant prostate cancer patients.

BACKGROUND: Abiraterone (ABI) is a major oral agent for the treatment of metastatic castration-resistant prostate cancer (mCRPC) patients but its systemic exposure is subject to a large inter-individual variability. We aimed to explore the relationship between ABI trough plasma concentration and prostate-specific antigen (PSA) response in mCRPC patients and to identify the critical determinants for its activity. PATIENTS AND METHODS: This is a monocentric prospective observational study in mCRPC patients treated with ABI. The plasmatic concentration of ABI at steady state was measured using liquid chromatography with fluorescence detection. The primary objective was to study the relationship between mean ABI plasma exposure (ABI Cmin) and 3-month PSA response. RESULTS: From 2012 to 2016, 61 mCRPC patients were eligible for pharmacokinetic/pharmacodynamic assessment. Thirty-eight patients experienced PSA response (62%, [confidence interval {CI} 95% 50-78]). In univariate analysis, ABI Cmin was 1.5-fold higher in responders: 12.0 ng/mL (CI 95% 9.4-15.6) versus 8.0 ng/mL (CI 95% 5.8-11.6; P = 0.0015). In multivariate analysis, only ABI Cmin was independently associated with PSA response (odds ratio = 1.12 [CI 95% 1.01-1.25], P = 0.004). By receiver operating characteristic analysis, the optimal threshold for ABI Cmin was 8.4 ng/mL. Progression-free survival (PFS) was significantly higher in patients with ABI Cmin above 8.4 ng/mL (hazard ratio 0.55, [CI 95% 0.31-0.99], 12.2 [CI 95% 9.2-19.5] versus 7.4 [CI 95% 5.5-14.7] months otherwise, P = 0.044). CONCLUSIONS: We showed that ABI trough concentration correlates with PSA response and PFS. Moreover, we could determine a cut-off value of plasmatic concentration for PSA response. Altogether, ABI concentration monitoring appears as a new approach to improve clinical outcome in mCPRC patients.

A history of biological disasters of animal origin in North America.

This paper examines past occurrences in North America relevant to the possibility of biological disasters with animal origins. With respect to naturally occurring animal disease outbreaks, North America, while not as adversely affected by epizootics as other regions, has had its fair share of such outbreaks of both 'traditional' and emerging animal diseases. The traditional category includes such diseases as anthrax, classical swine fever, bluetongue, brucellosis, foot and mouth disease, and the family of equine encephalomyelitis viruses. The emerging diseases include relatively more recent culprits such as postweaning multisystemic wasting syndrome, poultry enteritis mortality syndrome, and newly discovered examples of the transmissible spongiform encephalopathies. Additionally, several serious diseases of human beings that involve animal vectors or reservoirs occur naturally in North America or have emerged in recent decades; these include plague, hantavirus, monkeypox, West Nile virus and avian-derived influenza. At the same time, there have been very few intentional attacks on livestock using biological agents and no recorded cases in North America of animals intentionally being used to transmit disease to humans. According to the historical record, therefore, naturally occurring emerging zoonoses probably constitute the greatest threat in terms of biological disasters with animal origins. However, some of the general trends in terrorist activity, such as the intensification of activities by animal rights extremists against facilities undertaking animal research, mean that the possibility of intentional animal-related biological disasters should not be discounted.

Linkage studies in erythrokeratodermias: fine mapping, genetic heterogeneity and analysis of candidate genes.

Erythrokeratodermias are a clinically heterogeneous group of rare autosomal dominant disorders of cornification with overlapping features including hyperkeratosis and erythema. We ascertained five extended pedigrees with different phenotypes for a linkage study. Three families presented with localized erythrokeratodermia variabilis, and one with erythrokeratodermia and ataxia. Another family had Greither disease associated with variable hyperkeratotic plaques. Despite their phenotypic differences, both erythrokeratodermia variabilis and erythrokeratodermia with ataxia map to a common region in 1p34-p35. Multipoint linkage and haplotype analyses place erythrokeratodermia variabilis between the marker D1S496 and D1S186 with a maximum LOD score of 12.88. Our linkage results provide compelling evidence for genetic homogeneity among families of mixed European and French-Canadian origin. In contrast, results excluded Greither's disease from the established erythrokeratodermia variabilis gene region indicating genetic heterogeneity of erythrokeratodermias. Based on recombinations, two genes assigned to 1p34-p35 were excluded: cartilage matrix protein and avian myelocytosis viral oncogene. Connexin-37 (GJA4), a member of the connexin gene family, maps within the erythrokeratodermia variabilis region and is an attractive candidate gene. Direct sequencing of the coding region of GJA4 in four patients revealed several variations, including a novel polymorphism within the 5' cytoplasmic domain, but no pathogenic mutations were found, thus excluding Connexin-37 as a candidate. There is evidence, however, that other epidermally expressed connexins cluster in this region, and one may yet be determined to play a role in the pathogenesis of erythrokeratodermia variabilis.

Expression of wild-type pinB sequence in transgenic wheat complements a hard phenotype.

Wheat grain hardness is a major factor in the wheat end-product quality. Grain hardness in wheat affects such parameters as milling yield, starch damage and baking properties. A single locus determines whether wheat is hard or soft textured. This locus, termed Hardness ( Ha), resides on the short arm of chromosome 5D. Sequence alterations in the tryptophan-rich proteins puroindoline a and b (PINA and PINB) are inseparably linked to hard textured grain, but their role in endosperm texture has been controversial. Here, we show that the pinB-D1b alteration, common in hard textured wheats, can be complemented by the expression of wild-type pinB-D1a in transformed plants. Transgenic wheat seeds expressing wild-type pinB were soft in phenotype, having greatly increased friabilin levels, and greatly decreased kernel hardness and damaged starch. These results indicate that the pinB-D1b alteration is most likely the causative Ha mutation in the majority of hard wheats.

Malassezia furfur-related colonization and infection of central venous catheters. A prospective study in a pediatric intensive care unit.

OBJECTIVE: To determine the incidence of Malassezia furfur-related colonization and infection of central venous catheters. DESIGN: Prospective clinical study. SETTING: A paediatric intensive care unit at a University Hospital. PATIENTS: 66 newborns with central venous catheters for parenteral nutrition including lipid emulsions (Intralipid). METHODS: When a central venous catheter was removed, it was rinsed with 1 ml of physiological saline, transported at ambient temperature to the clinical laboratory and cultured on Dixon's medium. The tip of the central venous catheter was used for a bacteriological study using Maki's technique. In case of suspected sepsis, blood cultures were obtained using an Isolator tube. RESULTS. 74 central venous catheters were included: mean duration of use of a central venous catheters and infusions of lipid emulsion (Intralipid) were 19.3 +/- 10 days and 8.6 +/- 8 days respectively. Only 2 central venous catheters (2.7%) were colonized by Malassezia furfur: (Mf) one in an asymptomatic newborn, and the other in an infected newborn with signs of sepsis, who most probably died at 4 months of age from refractory hypoxia due to pulmonary hypoplasia, but not from Mf sepsis. CONCLUSIONS: The incidence of Malassezia furfur-related colonization of central venous catheters appears to be low but not negligible, which warrants the use of specific culture techniques.

Anterior approach for removal of a cervical intradural tumor: case report and technical note.

A case of an intradural extramedullary meningioma of the cervical spine excised through an anterior approach is reported. This permitted a complete excision without manipulation of the cord followed by a rapid and complete recovery. The technique of excision and bone grafting is described.

Effects of simulated feeding by snow geese on Scirpus americanus rhizomes.

We simulated the feeding of Greater Snow Geese (Chen caerulescens atlantica) on the rhizomes of three-square bulrush (Scirpus americanus) in a tidal marsh along the St. Lawrence River estuary in Québec. During the spring staging period, aboveground biomass is unavailable and geese feed solely on rhizomes and overwintering buds. An experiment was designed to test the effect of three factors on subsequent growth of Scirpus: the intensity of removal (3 to 77% removal of belowground biomass), the number of "bites" (1, 2 or 3 sections removed) and the number of adventitious buds removed (1, 2 or 3). Rhizomes were dug out in May, treated and transplanted into 85-1 basins sunk in the marsh and filled with marsh soil freed of all plant material. Growth was observed weekly until the end of the growing season in August. Shoots and rhizomes were then collected, dried and weighed to obtain biomass estimates. The net above- and belowground production of Scirpus was inversely related to the initial rhizome biomass removed. At a high level of removal (>35%), the cumulative number of shoots was significantly reduced as early as two weeks after transplantation. The relative reduction in production of the treated rhizomes compared to the control plants was also related to the intensity of removal. An increased number of bites reduced production and the removal of an increased number of adventitious buds further amplified the effect of removal on rhizome production. These experimental results show that even low intensity of feeding by Snow Geese can reduce the production of Scirpus marshes.

Comparison of three in vitro cytotoxicity assays for estimating surfactant ocular irritation.

Three in vitro cytotoxicity assays [neutral red uptake assay (NRU), MTT test and total protein content determination (TPC)] were analysed to assess their value for predicting the ocular irritancy potential of 20 surfactants. For each test, three established cell lines (SIRC rabbit corneal cells, Balb/c 3T3 and L929 mouse fibroblasts) were used. The concentration that induced 50% inhibition relative to controls (IC(50)) was calculated for each test, cell line and chemical. In vivo ocular irritancy data were compared with in vitro results. None of these assays provided a marked correlation of surfactant ocular irritation (Spearman or Pearson correlation coefficient lower than 0.65, P < 0.01 and moderate agreement with Kappa test). An IC(50) threshold of 700 mug/ml was set to discriminate between surfactant irritation and non-irritation. Three compounds were detected as false negatives (CHAPS, CHAPSO and sodium taurocholate), and two as false positives (Triton X155 and Brij 35).

Interlaboratory assessment of the bovine corneal opacity and permeability (BCOP) assay.

A multinational interlaboratory study to investigate the bovine corneal opacity and permeability (BCOP) assay is presented. The aim of this work was to determine the capability and possible limitations of this method to predict ocular irritancy of a large set of chemicals. The assays were carried out in 12 European laboratories with different types of activity. In each of these laboratories 52 substances, with a wide range of structure, physical form and irritant properties, were tested and in vitro scores were compared with those obtained from concurrent rabbit eye (Draize) tests. The technique was easily learned by workers in the participating laboratories, as shown by the fact that there were consistent responses between treated corneas within an individual laboratory. Interlaboratory variability was also very good. It was found that a given laboratory had a 96% chance of classifying irritants or non-irritants similarly to the other laboratories. In addition, it was observed that corneas preserved overnight responded similarly to freshly prepared tissues, thus allowing flexibility for those laboratories where the availability of corneas is limited. Comparisons between in vivo and in vitro data showed that the BCOP data correctly predicted whether a compound would be irritating or non-irritating for 44 of the 52 compounds (84.6%). Specificity and sensitivity were also greater than 84%, and the same number of substances were overestimated as were underestimated (four out of 52). All of the false negatives were solids whereas most of false positives were liquids, indicating that some adjustment in the protocol may be required depending on the physical state of the substance to be tested. All of the substances selected could be evaluated, with no limitation such as colour, insolubility, low or high pH. Given the number of products evaluated and the reproducibility within and among the laboratories involved, the overall results are quite satisfactory and therefore confirm the usefulness of the assay for screening chemicals for ocular irritation.

Lumbar disc excision in the second decade.

Of a series of 1200 consecutive cases of lumbar disc excisions from a general neurosurgical service, 1% of the patients were between the ages of 13 and 18 and 3.7% between 13 and 21. Differences in the clinical picture between adolescents and adults are emphasized. They include a higher ratio of males, a high frequency of radicular pain, a frequent history of trauma, and a lack of neurologic deficit, the latter being particularly striking among the younger patients. There was often a delay between the onset of pain and surgical treatment. This is attributed to a reluctance to consider this diagnosis in young people and to the frequent lack of neurologic deficit. Since the results are often excellent in this age group, early surgical treatment. is advocated.

Phonological skills of children with specific expressive language impairment (SLI-E): outcome at age 3.

Naturalistic speech samples of 29 3-year-olds diagnosed with specific expressive language delay (SU-E) were compared to those produced by 19 age-matched normally developing peers in order to determine their improvement in phonological skills since age 2, when Rescorla and Ratner (1996) studied them. Specifically, the groups were compared with regard to vocalization rate, verbalizations, fully intelligible utterances, phonetic inventories, percentages of consonants correct (PCC), phonological processes, and mean length of utterance (MLU). Results revealed that there was no significant difference between the groups in their numbers of vocalizations (as there had been at age 2), although there continued to be differences in their phonetic inventories, PCC scores, and overall intelligibility. These findings suggest that at age 2 the children with SU-E were not only less phonologically skilled but less talkative, whereas by age 3 they were equally vocal. Analysis of the phonetic inventories of the children demonstrated that for most consonants, the SLI-E group followed the some pattern of development as the comparison children, but more of the normally developing group had productive control of each consonant, consistent with findings of Rescorla and Ratner. There continued to be differences in intelligibility as measured by rates of verbalization (those utterances with at least one intelligible word) and fully intelligible utterances. Using these measures, we found that approximately half the SU-E children had caught up with their normally developing peers in terms of articulation, whereas half of them continued to be significantly delayed. Finally, although some of the late-bloomer group had caught up to the comparison children in language skills, as measured by MLU, many had not, suggesting that there was a tendency for the children to catch up in some articulation skills before catching up in language abilities.

[Neonatal detection of central hypothyroidism]. / Hypothyroïdie centrale de découverte néonatale.

BACKGROUND: Congenital hypothyroidism is very rare compared to primary hypothyroidism. Its early diagnosis may escape neonatal mass screening using TSH assay. CASE REPORT: Anthony was born at 37 weeks, weighing 3,060 g. He presented with hypotony, jaundice, tongue protrusion evoking congenital hypothyroidism. Thyroid function tests favored hypothyroidism central in origin, while the systematic neonatal screening was normal. CONCLUSION: Clinical signs of congenital hypothyroidism must lead to more specific tests when neonatal screening is normal.

[The CHARGE association]. / L'association CHARGE.

The CHARGE association is a polymalformative disease associating coloboma, heart disease, atresia of choanae, retarded growth and development, genital hypoplasia and ear anomalies, CHARGE being an acronym based on these different malformations. The diagnosis requires at least four of these malformations including necessarily coloboma and/or atresia of choanae. The various clinical aspects, the genetics and the therapeutics implications are described.

[Transitory hyperinsulinism with hypoglycemia in asphyxia neonatorum]. / Hyperinsulinisme transitoire avec hypoglycémie par asphyxie néonatale.

BACKGROUND: Hypoglycemia is a well-known complication in neonates small for gestational age and in those with diabetic mothers. Birth asphyxiated infants can develop severe hypoglycemia due to reduced glycogen stores. CASE REPORTS: The first patient was born at 41 weeks, weighing 3,780 g by emergency cesarean section because of fetal distress. He developed a pneumothorax and hypoglycemia. He was given glucose infusion (at day 4: 20 mg/kg/d). Hyperinsulinism was confirmed: blood levels at 18.3 mU/L on day 1 and 11.7 mU/L on day 2. The infusion rate was gradually decreased. The second patient was born at 39 weeks, weighing 2,780 g by emergency cesarean section because of fetal distress. She needed glucose infusion (24 g/kg/d) because of hypoglycemia with hyperinsulinism (12.8 mU/L on day 2 and 11.7 mU/L on day 3). After 5 days, the infusion of glucose was replaced by oral feeding only. CONCLUSION: Transient hypoglycemia in asphyxiated newborn infants with hyperinsulinism must be considered even when hypoglycemia may be difficult to prove.

[Nosocomial infections due to syncytial respiratory virus: which hygienic measures]. / Infections nosocomiales liées au virus respiratoire syncytial: quelles mesures d'hygiène?

Nosocomial respiratory tract infections due to respiratory syncytial virus are common among hospitalized children. The overall prevention is based on 3 points: prevention of person-to-person viral transmission, infection surveillance and staff education. Handwashing is the main protective attitude. Other measures such as gloving, gowning and wearing masks and goggles are discussed. Changes in hospital organisation during epidemic periodes must also be considered.

[Severe head injuries in neonates and infants: physiopathological and therapeutic aspects]. / Traumatismes crâniens graves du nouveau-né et du nourrisson: particularités physiopathologiques et thérapeutiques.

Severe head injuries in infants have specific circumstances such as obstetrical injury, battered infant, shaken infant. Pediatric scales must be used for neurological evaluation, the Bicêtre scale being a sensitive index of clinical course. Transfontanellar ultrasound can be useful as first line tool of evaluation of brain injury, but computerized tomography scan is necessary to correctly assess the brain lesions and the presence of hematoma. Hemorragic lesions can rapidly lead to hypovolemic state which must be prevented, or treated without delay. Treatment requires hemodynamics and hydroelectrolytic support, measures to control intracranial hypertension, sedation, and neurosurgical intervention according to the hemorragic lesions.

[Pathogen role of coronavirus in pediatric intensive care: retrospective analysis of 19 positive samples with indirect immunofluorescence]. / Rôle pathogène des coronavirus en réanimation pédiatrique: analyse rétrospective de 19 prélèvements positifs en immunofluorescence indirecte.

BACKGROUND: Coronaviruses (CV) are ARN-containing agents that are responsible for mild upper respiratory tract infections in adults and children. Their pathogenicity in neonates is not wellknown. POPULATION AND METHODS: Eighty five samples of tracheal or nasopharyngeal secretions were obtained from January to October 1991 from 53 children (29 less than 1 month of age; 19 from 1 month to 1 year; five older than 1 year). They were examined for respiratory syncytial virus, adenovirus, myxovirus influenza and parainfluenza and coronavirus by immunofluorescence (IF). RESULTS: Nineteen samples from nine newborns and three infants were positive for coronavirus. The mean birth weight of the nine neonates was 2100 +/- 840 g; their mean gestational age was 34 +/- 5 weeks and their mean age at diagnosis was 21 +/- 9 days. Apnea and bradycardia were the main symptoms in this group. Blood C-reactive protein was not elevated and blood cultures were sterile. One infant was admitted for near-miss; the two others were admitted at birth because they suffered from chronic lung disease (pulmonary hypoplasia and bronchopulmonary dysplasia). An acute episode of pulmonary deterioration occurred at the time of coronavirus infection. Both died one at 4 months and the other at 10 months. CONCLUSION: Coronaviruses seem to be responsible for respiratory tract infections in hospitalized neonates and chronically ventilated infants.