Carbon dioxide recruitment threshold as a predictor of successful weaning in chronic obstructive pulmonary disease patients: A pilot study

Abstract Several methods have been used to predict successful weaning and extubation among chronic obstructive pulmonary disease (COPD) patients. The objective of this study is to determine whether carbon dioxide recruitment threshold (PCO₂RT) can be used as adjunct to conventional weaning parameters to predict early weaning and successful extubation. Twelve COPD patients who were ready to be extubated based on conventional weaning parameters were divided into group A ( n = 7) and group B ( n = 5). Group A were those patients with better weaning parameters and hence a higher probability of successful extubation as compared to group B. Carbon dioxide apnoeic threshold (PCO₂AT) was obtained by hyperventilating the patient using an increment of two breaths per min until apnoea occurs. At this point, the PCO₂AT or the PaCO₂ during said apnoeic period was recorded. A dead space of 150 cc is then added to the circuit until the patient starts to breathe as evidenced by the sensitivity trigger indicator. The PCO₂ obtained at this period is termed PCO₂RT. After weaning for 30 min on a T-tube, another arterial blood gas is determined and this is called the PCO₂SB or the CO₂ level after 30 min on spontaneous breathing. If the PCO₂SB-PCO₂RT difference is high with a sensitivity of 85.71% and specificity of 100% vs sensitivity of 57.14% and specificity of 60% using the conventional weaning parameters. Thus an increase in PCO₂SB at 30 min T-tube is indicative of impending respiratory pump failure and that other causes of failure to wean must be investigated.     

Mapping of α- and β-globin genes on Antarctic fish chromosomes by fluorescence in-situ hybridization

The pathways and mechanisms of genomic change that have led to the peculiar haemoglobinless phenotype of the white-blooded Antarctic icefishes (16 species in the family Channichthyidae) constitute an important model for understanding the rapid diversification of the Antarctic notothenioid fish flock. To provide complementary structural information on genomic change at globin-gene loci in Antarctic fish species, cytogenetic studies and in-situ chromosomal mapping have been undertaken. Using a DNA probe containing one α- and one β-globin gene from the embryonic/juvenile globin gene cluster of the red-blooded species Notothenia coriiceps, we mapped the cluster on the chromosomes of Antarctic teleosts by fluorescence in-situ hybridization. As anticipated on the basis of its molecular organization, the cluster was located on a single chromosome pair in all of the red-blooded fish species probed (N. coriiceps, N. angustata, Trematomus hansoni, T. pennellii). In contrast, the α/β-globin probe did not recognize complementary sequences on the chromosomes of the white-blooded species Chionodraco hamatus and Channichthys rhinoceratus. These results represent the first example of chromosomal mapping of embryonic/juvenile globin genes in teleostean fishes. Beyond its relevance to the evolutionary history of Antarctic notothenioids, this work contributes to our understanding of the evolution of the chromosomal loci of globin genes in fishes and other vertebrates. This revised version was published online in July 2006 with corrections to the Cover Date.     

Systemic absorption of 3H-fenticonazole after vaginal administration of 1 gram in patients

Fourteen women, five with normal cervicovaginal mucosa (Group 1), five with cervical carcinoma (Group 2) and four with relapsing vulvovaginal candidiasis (Group 3) were enrolled and completed this open clinical trial. Each subject received a single dose of 1.82 +/- 0.3 g on average of vaginal paste (for ovules) containing about 1000 mg of 3H-fenticonazole nitrate (266 microCi). Twelve hours after vaginal administration, the paste was removed by vaginal washing. Blood, urine and stool samples were collected at specified time intervals for five days. Plasma, urine, stools and all used material in contact with the paste were assayed for radioactivity. No measurable levels of radioactivity were detected in plasma of subjects of Groups 1 and 3 while in 4 of the 5 subjects with cervical carcinoma (Group 2) fenticonazole was detected during the 24 h after administration with a peak level at about 8 hours. For a period of 5 days, 0.4-1.5% of the dose on average was recovered from urine, and 0.18-0.32% from feces. Based on the excretion data, the extent of vaginal absorption of fenticonazole nitrate in women with vulvovaginal candidiasis was 1.81 +/- 0.57% of the dose, while in women with normal cervicovaginal mucosa it accounted for 0.58 +/- 0.28% of the administered dose. In patients with cervical carcinoma, absorption was 1.12 +/- 0.53%. The maximum amount absorbed corresponds to an exposure of about 0.4 mg/kg of fenticonazole nitrate (for a subject weighing 50 kg). Consequently, the vaginal administration of one ovule containing 1000 mg of fenticonazole nitrate seems to be devoid of risk for patients.     

Similar CD40 ligand expression on EL-4 thymoma cell lines with widely different helper activity for B lymphocytes.

A mutagenized subclone of the murine EL-4 thymoma (clone B5) is approximately 30 times more potent than parental EL-4 cells in stimulating proliferation and Ig secretion of murine or human B cells by direct cell contact in the presence of appropriate cytokines. In this study we found that CD40 ligand (CD40L) expression was constitutive and very similar on EL-4 B5 and parental EL-4 cells according to Northern blot and flow cytometry. Activation with phorbol 12-myristate 13-acetate (PMA) alone, PMA and ionomycin, interleukin-1 (IL-1) or human T-cell supernatant did not lead to significant CD40L up-regulation. A receptor-binding assay with soluble CD40 did not reveal different ligand affinities. However, murine and human soluble CD40-IgFc fusion proteins inhibited human B-cell stimulation by EL-4 B5 cells in the presence of human T-cell supernatant. Inhibition was 96% when soluble CD40 was added on day 0 of culture and progressively decreased when the CD40 was added subsequently. Ig secretion by cytoplasmic Ig-positive cells was no longer inhibited. These findings imply that, although CD40 ligand is necessary for B-cell activation by EL-4B5 cells, additional molecule(s) must be responsible for the increased helper activity of the EL-4 B5 clone.     

Could mitochondrial haplogroups play a role in sporadic amyotrophic lateral sclerosis?

Mitochondrial impairment has been implicated in the pathogenesis of the amyotrophic lateral sclerosis (ALS). Furthermore, mitochondrial-specific polymorphisms were previously related to other neurodegenerative diseases, such as Parkinson, Friedreich and Alzheimer disease. To investigate if specific genetic polymorphisms within the mitochondrial genome (mtDNA) could act as susceptibility factors and contribute to the clinical expression of sporadic ALS (sALS), we have genotyped predefined European mtDNA haplogroups in 222 Italian patients with sALS and 151 matched controls. Individuals classified as haplogroup I demonstrated a significant decrease in risk of ALS versus individuals carrying the most common haplogroup, H (odds ratio 0.08, 95% confidence interval 0.04-0.4, p < 0.01). Further stratification of the dataset by sex, age and site of onset of disease and survival failed to reach significance for association. Our study provides evidence of the contribution of mitochondrial variation to the risk of ALS development in Caucasians. Further it may help elucidate the mechanism of the mitochondrial dysfunction detectable in ALS, and may be of relevance in development of strategies for the treatment of this disease.     

N,N-dialkylaminosubstituted chromones and isoxazoles as potential anti-inflammatory agents.

The ability of some N,N-dialkylaminosubstituted chromones and isoxazoles to inhibit the protein kinase C (PKC) dependent signal transduction pathway was tested. As a cellular model, human neutrophils stimulated with either phorbol myristate acetate (PMA) or formylmethionine-leucine-phenylalanine (f-MLF) were used. The efficiency of the compounds was established by their capacity to reduce the O2- production by activated human neutrophils. Compounds carrying a 3-bis(2-methoxyethyl)amino group, a substituent found active in previously tested tricyclic compounds, do not show significant anti-PKC activity in this study. On the other hand, substitution with a 1-piperidinyl group leads all tested compounds to a high biological activity against stimulated neutrophils.     

Posterior knee pain: primary symptom of a small non-occlusive venous clot.

A healthy 9 year old girl presented with severe posterior knee pain and a small segmental non-occlusive popliteal venous thrombosis. The case is relevant for its unique presentation and symptoms. Lack of recanalisation persisted at one year follow up.     

Loss of RhoB expression in human lung cancer progression.

PURPOSE: RhoB is a low molecular weight GTPase belonging to the Ras protein superfamily. Whereas most Rho proteins have been shown to have a positive role in proliferation and malignant transformation, the specific role of RhoB appears more divergent. We reported previously that RhoB inhibits cell proliferation in various human cancer cells. Here, we studied the specific role played by RhoB in human lung cancer. EXPERIMENTAL DESIGN: We analyzed the expression of RhoB protein by immunostaining in human lung tissues ranging from normal to invasive carcinoma from different histological types in two large independent studies of, respectively, 94 and 45 samples. We then studied the cellular effect of RhoB overexpression in a model of lung cancer (A549, adenocarcinoma) and tumorigenicity in nude mice. RESULTS: We showed in both studies that RhoB protein was expressed in normal lung and decreased dramatically through lung cancer progression (P < 0.01). Interestingly, RhoB expression was lost in 96% of invasive tumors and reduced by 86% in poorly differentiated tumors compared with the nonneoplastic epithelium. Moreover, the loss of expression of RhoB correlated significantly with tumor stage and proliferative index, whereas no correlation was found between RhoB and p53 or Bcl-2 expression. We then showed that ectopic expression of RhoB in lung cancer cell line A549 suppressed cell proliferation, anchorage-independent growth, and xenograft tumor growth in nude mice. CONCLUSIONS: RhoB loss of expression occurs very frequently in lung carcinogenesis, reinforcing its putative tumor suppressive activity, and raising the value of its potential use in cancer therapy.