Serological response to pneumococcal vaccination in HAART-treated HIV-infected patients: one year follow-up study

The aim of this study was to evaluate specific IgG responses against pneumococcal serotypes 1, 6B, 14, 19F, 23F at baseline, 1 and 12 months after vaccination with the 23-valent polysaccharide pneumococcal vaccine in 89 HAART-treated HIV-infected patients, 24 antiretroviral "na?ve" HIV-infected and 30 non-HIV-infected healthy subjects. Levels of specific antipneumococcal IgG and the mean fold increase in IgG levels at 1 month as well as the kinetics of antibodies along the 12 months in all groups of HIV-infected patients and healthy subjects were similar. Neither CD4 cell count at baseline nor "nadir" CD4 cells correlated with the response to the vaccine. In conclusion, the immunogenicity conferred by the polysaccharide vaccine in HIV-infected patients under HAART is at least as good as that observed in healthy subjects.     

A case of non-lethal pulmonary air embolism after leukapheresis catheter removal

Mononuclear cell leukapheresis requires good-quality venous access. Catheter placement and removal of the catheter may be associated with life-threatening local or systemic complications. Thus, prompt recognition of these complications and appropriate therapy can be life-saving. We report the case of a young man who presented with an air embolism following removal of a jugular venous catheter after peripheral blood stem cell collection. We have reviewed the signs and symptoms presented by the patient and the methodology used to remove the catheter. Catheter removal requires careful attention in order to avoid potentially serious complications.     

Highly active antiretroviral therapy and outcome of AIDS-related Burkitt's lymphoma or leukemia. Results of the PETHEMA-LAL3/97 study

Short, intensive cycles of chemotherapy have resulted in improved survival in BurkittOs lymphoma/leukemia (BL) in adults. The prognosis of patients with immunodeficiency virus (HIV)-associated BL is considered to be poor, but these patients have seldom been treated with BL-specific protocols. However, a study (PETHEMA-LAL3/97) in which patients with BL were treated regardless of their HIV status failed to find differences between HIV-infected and immunocompetent individuals. Furthermore, patients who received highly active antiretroviral therapy (HAART) seemed to have a slightly better disease-free survival than those who did not (p=0.051). We extended the follow-up analysis to elucidate the role of HAART in the survival of HIV-infected patients included in the PETHEMA-LAL3/97 protocol.     

Prognostic and biological implications of genetic abnormalities in multiple myeloma undergoing autologous stem cell transplantation: t(4;14) is the most relevant adverse prognostic factor, whereas RB deletion as a unique abnormality is not associated with adverse prognosis.

Fluorescence in situ hybridization (FISH) has become a powerful technique for prognostic assessment in multiple myeloma (MM). However, the existence of associations between cytogenetic abnormalities compels us to re-assess the value of each abnormality. A total of 260 patients with MM at the time of diagnosis, enrolled in the GEM-2000 Spanish transplant protocol, have been analyzed by FISH in order to ascertain the independent influence on myeloma prognosis of IGH translocations, as well as RB and P53 deletions. Survival analyses showed that patients with t(4;14), RB or P53 deletions had a significantly shorter survival than patients without these abnormalities. However, patients with RB deletions without other abnormalities in FISH analysis, displayed a similar outcome to those patients without genetic changes by FISH (46 vs 54 months, P=0.3). In the multivariate analysis the presence of t(4;14), RB deletion associated with other abnormalities, age >60 years, high proportion of S-phase cells and advanced stage of the disease according to the International Staging System retained their independent prognostic influence. In summary, RB deletion as a sole abnormality does not lead to a shortening in the survival of MM patients, whereas t(4;14) confers the worst prognosis in MM patients treated with high-dose chemotherapy.     

A randomised, placebo controlled trial of inhaled salbutamol and beclomethasone for recurrent cough

AIMS: To test the hypothesis that inhaled salbutamol or beclomethasone will reduce the frequency of cough in children with recurrent cough. A secondary aim was to determine if the presence of airway hyperresponsiveness (AHR) can predict the response. DESIGN: Randomised, double blind, placebo controlled trial. METHODS: During a coughing phase, 43 children (age 6-17 years) with recurrent cough were randomised to receive inhaled salbutamol or placebo (phase I) for 5-7 days and then beclomethasone or placebo (phase II) for 4-5 weeks, and in a subgroup of children for 8-9 weeks. The children used an ambulatory cough meter, kept cough diaries, and performed the capsaicin cough sensitivity, hypertonic saline bronchoprovocation, and skin prick tests. RESULTS: Salbutamol or beclomethasone had no effect on cough frequency or score, irrespective of the presence of AHR. CONCLUSIONS: Most children with recurrent cough without other evidence of airway obstruction, do not have asthma and neither inhaled salbutamol nor beclomethasone is beneficial.     

Nuclear translocation of beta-catenin in hereditary and carcinogen- induced intestinal adenomas

The physical interaction between beta-catenin and the adenomatous polyposis coli (APC) gene, and the ability of APC to regulate cytoplasmic levels of beta-catenin suggest a role for beta-catenin in colorectal carcinogenesis. In this study, we found that beta-catenin immunoreactivity was detected exclusively in the cell membrane and cytoplasm of morphologically normal intestinal epithelial cells with predominant distribution in the differentiated nonproliferative cell population. In contrast, beta-catenin was localized predominantly in the nucleus of adenomas from Min/+ mice and transgenic mice expressing a mutant truncated form of the APC gene (Apc(delta716) mice). Beta- catenin was expressed predominantly at the cell membrane and cytoplasm of the nontransformed rat intestinal epithelial (RIE-1) cells in culture, whereas predominantly nuclear localization of beta-catenin was observed in the human colon cancer cell line SW480. In the azoxymethane (AOM) treated rats, overexpression and nuclear localization of beta- catenin was observed in all adenomas. Previous studies have indicated the incidence of APC mutations amongst AOM-induced tumors to be 15% or less. These results demonstrate that nuclear localization of beta- catenin is a common event in colorectal tumorigenesis.      

Measurement of benzene oxide in the blood of rats following administration of benzene

Although it is generally assumed that metabolism of benzene proceeds through an initial step involving oxidation to benzene oxide (BO) by CYP450 in the liver, the production of BO has never been unambiguously confirmed in animals dosed with benzene. Furthermore, prevailing hypotheses of the mechanism by which benzene causes cancer have ignored the possibility that BO might play a direct role, despite the fact that BO is electrophilic, binds covalently to cell macromolecules and is presumably genotoxic. A likely reason for this lack of attention to the role of BO in the carcinogenesis of benzene is the presumption that this epoxide is too reactive to escape the hepatocyte after it is formed. We employed gas chromatography-mass spectrometry to measure BO in the blood of F344 rats, both in vitro and up to 24 h following oral administration of benzene. Surprisingly, BO was relatively stable in rat blood at 37 degrees C (estimated half-life = 7.9 min) and, after administering a single dosage of 400 mg benzene/kg body wt, a blood concentration of 90 nM BO (8.5 ng/ml) was measured for approximately 9 h. Using a published PBPK model we estimate that approximately 4.3% of the metabolized dose of benzene was released as BO from the liver into blood. This confirms that BO is, indeed, formed from metabolism of benzene and is sufficiently stable to be distributed throughout the body at levels which are likely to be greater than those of the other electrophilic benzene metabolites.      

Serum C-reactive protein and C3 complement protein levels in severely malnourished Nigerian children with and without bacterial infections

Bacterial infections are the major determinants of fatality in severe protein-energy malnutrition (PEM). Unfortunately, these infections are difficult to diagnose clinically. C-reactive protein (CRP) levels were determined in 17 infected and 10 non-infected Nigerian children with severe PEM and compared with age/ sex-matched apparently healthy controls. The aim was to study the response of this acute phase protein to bacterial infections as well as to assess its value in the diagnosis of infections in severe PEM. C3 complement protein levels were also determined in the same group of subjects. The major organisms isolated in samples from these subjects were S. aureus and the coliforms. Mean CRP level in the non-infected children with severe PEM was 13.8 ± 6.21 mg/1 and rose to 159.83 ± 124.07 mg/1 in the presence of infection. The mean value in healthy non-infected controls was 2.01 ± 0.96 mg/1. The difference in the mean CRP levels between the infected and non-infected PEM children was statistically significant at p < 0.01. The mean difference between the non-infected and the control subjects was not significant. Using a diagnostic level of 20.00 mg/1 of CRP gave a sensitivity of 85.0% and a specificity of 80.0%. This CRP level is a useful index of bacterial infections in severe PEM. C3 complement protein was low in the non-infected malnourished group, but rose significantly in the presence of infection to values similar to that of the healthy controls. C3 protein thus behaves as an acute phase reactant in the presence of infection in severe PEM, and does not appear to be consumed, probably due to a deficiency in the early components of the complement cascade. This suggests a role for C3 measurement in the monitoring of bacterial infections in severe PEM.