Incidence of Chest Tube Malposition in the Critically Ill: A Prospective Computed Tomography Study

Background: Malposition of percutaneously inserted chest tubes is considered as a rare complication in critically ill patients. Its incidence, however, remains uncertain. The aims of the study were to assess the true incidence of chest tube malposition in critically ill patients and to identify predicting factors.

Methods: The authors prospectively studied 122 chest tubes percutaneously inserted in 75 consecutive critically ill patients. For clinical reasons independent of the study, thoracic computed tomography scanning was performed in 63 patients, allowing direct visualization of 106 chest tubes. Based on these findings, chest tube position was classified as intrapleural, intrafissural, or intraparenchymal. Factors predicting chest tube malposition were analyzed by univariate and multivariate analysis.

Results: The mean delay between chest tube placement and thoracic scan was 3.5 +/- 2.9 days. Twenty-two chest tubes were diagnosed as being intrafissural (21%), and 10 were diagnosed as being intraparenchymal (9%). The only predicting factor associated with the risk of malposition was the use of a trocar for the percutaneous insertion of the chest tube (P = 0.032).     

Steroid glaucoma: corticosteroid-induced ocular hypertension in cats.

This study was undertaken to develop a feline model of corticosteroid-induced ocular hypertension. In the first experiment, eight cats were selected whose intraocular pressure (17 +/- 0.4 mmHg) was consistently below the mean baseline intraocular pressure of our colony (24 +/- 0.5) during the preceding 2 months. Unilateral twice or thrice daily topical application of 10 microliters 1% dexamethasone sodium phosphate caused a gradual intraocular pressure increase that became significant (P less than 0.05) within 2-3 weeks. There was no significant change in body weight, but several eyes developed cataracts. Similar results were obtained with treatment of normotensive cat eyes with dexamethasone, or with 1.0% prednisolone acetate (PredForte) twice a day. Topical application of PGF2 alpha-1-isopropyl ester (0.1 or 0.25 microgram PG equivalent) to such steroid-treated eyes yielded significant intraocular pressure reduction and pupillary miosis, similar in magnitude to those exhibited by normal eyes. When dexamethasone treatment was reduced to once daily, after prolonged twice daily treatment, intraocular pressure decreased only slightly within 10 days. When dexamethasone treatment was stopped, intraocular pressure declined to normal levels within 6-7 days. These findings show that adult cat eyes develop steroid-induced ocular hypertension that is maintained and reversible. As opposed to previous findings on rabbits, steroid-induced feline ocular hypertension appears to be a good model for this clinical condition and may be suitable for the testing of potential glaucoma drugs.     

X-linked dominant chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia

We describe a family with an X-linked dominant chondrodysplasia. Four males and six females were affected through four generations. Identification of skeletal abnormalities and hydrocephaly during the pregnancy of three male fetuses led to termination of the pregnancies. A fourth affected male died at 6 days of life. The four patients had chondrodysplasia, hydrocephaly, and facial features with microphthalmia. Radiographs showed severe platyspondyly and various bone abnormalities including a distinctive metaphyseal cupping of the metacarpals, metatarsals, and phalanges. The affected females were less affected and showed small stature, sometimes associated with body asymmetry and mild mental retardation. This condition appears to be a previously unrecognized X-linked dominant chondrodysplasia.     

Variety and complexity of chromosome 17 translocations in neuroblastoma

In neuroblastoma, the most frequent genetic alteration is gain of chromosome arm 17q, which arises from unbalanced translocations. To document these genetic events more precisely, we performed an extensive study of chromosome 17 breakpoints in 27 neuroblastoma cell lines by using a combination of fluorescence in situ hybridization mapping with BAC/PAC clones and allele analysis with polymorphic markers. All cases exhibited one or more unbalanced chromosome 17 translocations, and 15 distinct breakpoint regions could be mapped. This high variability indicates that gene fusion or disruption events are extremely unlikely to account for the underlying oncogenic role of these translocations. However, breakpoints were not randomly distributed, most of them mapping to the proximal part of 17q. As a result of translocations, all cell lines but one exhibited gain of the 53.5 Mb-->qter fragment, bordered proximally by the clone CTC-462L7. The most telomeric breakpoint, flanked by the clone RP11-443M10, defined the 70.9 Mb-->qter fragment as a region of additional gain. In addition to chromosome gains, loss of heterozygosity for the short arm of chromosome 17 was observed in close to half the cases. It was either related to a chromosome 17 monosomy or to a uniparental isodisomy. Finally, in cases with a single normal chromosome 17, we show that the parental origin of the translocated chromosome 17 can be either distinct or identical to that of the normal chromosome. Similarly, multiple translocations within the same cell line can either involve the same or different chromosome 17 homologues, indicating the likely absence of parental origin bias in the generation of these alterations.     

Impairment of intramacrophagic Brucella suis multiplication by human natural killer cells through a contact-dependent mechanism

Brucella spp. are facultative intracellular bacteria that can establish themselves and cause chronic disease in humans and animals. NK cells play a key role in host defense. They are implicated in an early immune response to a variety of pathogens. However, it was shown that they do not control Brucella infection in mice. On the other hand, NK cell activity is impaired in patients with acute brucellosis, and recently it was demonstrated that human NK cells mediate the killing of intramacrophagic Mycobacterium tuberculosis in in vitro infection. Therefore, we have analyzed the behavior of Brucella suis infecting isolated human macrophages in the presence of syngeneic NK cells. We show that (i) NK cells impair the intramacrophagic development of B. suis, a phenomenon enhanced by NK cell activators, such as interleukin-2; (ii) NK cells cultured in the presence of infected macrophages are highly activated and secrete gamma interferon and tumor necrosis factor alpha; (iii) impairment of bacterial multiplication inside infected cells is marginally associated with the cytokines produced during the early phase of macrophage-NK cell cocultures; (iv) direct cell-to-cell contact is required for NK cells to mediate the inhibition of B. suis development; and (v) inhibition of B. suis development results from an induction of NK cell cytotoxicity against infected macrophages. Altogether, these findings show that NK cells could participate early in controlling the intramacrophagic development of B. suis in humans. It seems thus reasonable to hypothesize a role for NK cells in the control of human brucellosis. However, by impairing the activity of these cells in the acute phase of the illness, the pathogen should avoid this control.     

Thermal acclimation of neonates to prolonged cool exposure as regards sleep stages

The thermal responses of neonates during a cool acclimation period were studied with regard to sleep stages. Sleep stages, body temperatures and metabolic rate (VO2) were studied for seven neonates nursed in incubators and exposed to a cool temperature (thermoneutrality minus 2 degrees C) for 75 h. Each recording session lasted 3 h in the morning: firstly under thermoneutral baseline conditions, then during the first and last 3-h periods of the cool acclimation and finally during the last 3 h of a 24-h recovery period. Sleep structure was modified during the initial hours of cool exposure: the percentage of active sleep increased (AS: +13%, P = 0.028) at the expense of quiet sleep (QS: -11%, P = 0.043). This alteration in sleep structure persisted at the end of the acclimation period. Metabolic heat production only increased in the later period of cool acclimation. Throughout the cool exposure, VO2 increased more (P = 0.040) in QS (+33%) than in AS (+20%) so that by the end of the cool period, VO2 levels were similar in both sleep stages. During cool acclimation, the maintenance of homeothermy is related not only to a change in sleep organization but also to modifications in the thermoregulatory processes in both sleep stages. Considering the importance of AS/QS patterns in the neurobehavioral development of neonates, the present results could have clinical implications for the thermal management of neonates.     

Functional proteomics mapping of a human signaling pathway

Access to the human genome facilitates extensive functional proteomics studies. Here, we present an integrated approach combining large-scale protein interaction mapping, exploration of the interaction network, and cellular functional assays performed on newly identified proteins involved in a human signaling pathway. As a proof of principle, we studied the Smad signaling system, which is regulated by members of the transforming growth factor beta (TGFbeta) superfamily. We used two-hybrid screening to map Smad signaling protein-protein interactions and to establish a network of 755 interactions, involving 591 proteins, 179 of which were poorly or not annotated. The exploration of such complex interaction databases is improved by the use of PIMRider, a dedicated navigation tool accessible through the Web. The biological meaning of this network is illustrated by the presence of 18 known Smad-associated proteins. Functional assays performed in mammalian cells including siRNA knock-down experiments identified eight novel proteins involved in Smad signaling, thus validating this integrated functional proteomics approach.     

Haplotype analysis of the BRCA2 9254delATCAT recurrent mutation in breast/ovarian cancer families from Spain

A frame-shift 9254del5 mutation was independently identified in 12 families, eleven of them with Spanish ancestors, in a BRCA2 screening performed in 841 breast and/or ovarian cancer families and in 339 women with breast cancer diagnosed before the age of 40 at different centers in France and Spain. We sought to analyze in detail the haplotype and founder effects of the 9254del5 and to estimate the time of origin of the mutation. Eight polymorphic microsatellite markers and two BRCA2 polymorphisms were used for the haplotype analyses. The markers were located flanking the BRCA2 gene spanning a region of 6.1 cM. Our results suggest that these families shared a common ancestry with BRCA2 9254del5, which is a founder mutation originating in the Northeast Spanish, with an estimated age of 92 (95% CI 56-141) generations.     

Prolonged hepatitis A infection in an HIV-1 seropositive patient

Hepatitis A virus (HAV) is a worldwide disease; in most cases, it causes an acute self-limited illness that does not lead to a chronic state. The course of HAV viremia in a homosexual male with human immunodeficiency virus type 1 (HIV-1) and the correlation between HIV and HAV viral load, alanine aminotranferase (ALT) level, and CD4(+) lymphocyte count were investigated during the course of the infection. HAV RNA was detected quantitatively up to 256 days after clinical onset. To our knowledge, this specific case is the first report of a prolonged infection with hepatitis A in a male with HIV-1. The ALT levels decreased gradually; however, 286 days after clinical onset of hepatitis, ALT levels were three times higher than normal values. HIV viral load was not affected by the infection with HAV and CD4(+) cell count was stable during the course of the co-infection. The duration and the high-titer viremia of hepatitis A virus in an immunodeficient patient constitute a serious risk of the spread of hepatitis A within this population. As inactivated HAV vaccine is safe in HIV-positive subjects, it would be wise to establish a strategy of preventive vaccination in this high-risk group.