MBL2 polymorphism and risk of severe infections in multiple myeloma patients receiving high-dose melphalan and autologous stem cell transplantation.

Severe infections related to treatment are common in patients with multiple myeloma (MM). Genetic polymorphisms of the immune system may influence the risk of infections. Mannan-binding lectin (MBL) is part of the innate immune system, and individuals homozygous for wild-type MBL encoding gene (MBL2) have a well-functioning MBL pathway of complement activation, in contrast to individuals carrying one or two variant alleles. We evaluated 113 courses of high-dose melphalan and autologous stem cell transplantation (ASCT) in patients with MM. Patients homozygous for wild-type MBL2 had a significantly reduced risk of septicaemia during the ASCT procedure compared with patients carrying variant MBL2: Odds Ratio (OR) 0.19 (95% CI: 0.04-0.77), (P=0.02) in multivariate analysis. The risk of Common Toxicity Criteria grade 3-4 infections in general was not affected by wild-type MBL2: OR 1.20 (95% CI: 0.52-2.78), (P=0.67). The findings indicate that MBL to some extent protects against the most severe infections during ASCT.

[An evaluation of a patient education programme for children with asthma at a French teaching hospital ("l'espace du souffle", Nantes) (2002-2003)]. / Programme d'éducation thérapeutique collective pour l'enfant asthmatique à Nantes.

A program of patient education was set up at the CHU of Nantes, for groups of children with asthma in 1997. The aim of this study is to realize a formative evaluation to corelate with some effects. This study was proposed to 99 families with asthmatic children. A written questionnaire, was administered to the parents and children, exploring their satisfaction with the programme, their general knowledge and know-how, biomedical parameters. The observation focused on skills and day-to-day life with the illness. The study was completed by 21 families. The majority of the children, aged 7 to 11 years old, had asthma that needed treatment. All of the parents and children were satisfied with their visit to "l'espace du souffle". They all declared having increased their general knowledge and know-how and biomedical parameters did better. They did, however, feel that they did not know enough about how to recognise precursory symptoms of an attack, about how to practise a sport or how to use "corticoids". They also could not control their personal fear during an attack. During the oral questionnaire a general feeling of stress and worry was clearly noticeable in the parents feeling, that did not appear in the written questionnaire. This patient education program appears to be beneficial. Furthermore, this evaluation highlights some subjects that pass unseen during current individual consultations.

Increased risk and case fatality rate of pyogenic liver abscess in patients with liver cirrhosis: a nationwide study in Denmark.

BACKGROUND: Patients with liver cirrhosis are at increased risk of serious bacterial infections carrying a high case fatality rate. Case reports have suggested an association between liver cirrhosis and pyogenic liver abscess. AIMS: To estimate the risk and case fatality rate of pyogenic liver abscess in Danish patients with liver cirrhosis compared with the background population. METHODS: Identification of all patients with liver cirrhosis and pyogenic liver abscess over a 17 year period in the National Registry of Patients. Information on death was obtained from the Danish Central Person Registry. RESULTS: We identified 22 764 patients with liver cirrhosis and 665 patients with pyogenic liver abscess, of whom 21 were cirrhotics and 644 were non-cirrhotics. The crude incidence rate of liver abscess in cirrhotics was 23.3 (95% CI 14.4-35.6) per 100 000 person years. The age adjusted risk of liver abscess was increased 15-fold in patients with cirrhosis compared with the background population. The 30 day case fatality rates in patients with liver abscess and cirrhosis were 38.5% (13.9-68.4) in alcoholic cirrhosis and 62.5% (24.5-91.5) in non-alcoholic cirrhosis compared with 26.9% (23.5-30.5) in liver abscess patients from the background population. After adjustment for sex, age, and comorbidity, the relative risk of death was increased more than fourfold in alcoholic cirrhosis and non-alcoholic cirrhosis compared with the background population. CONCLUSIONS: Liver cirrhosis is a strong risk factor for pyogenic liver abscess associated with a poor prognosis.

Risk and case fatality rate of meningitis in patients with liver cirrhosis.

Bacterial infections are major causes of morbidity and death in patients with liver cirrhosis. The risk of bacterial meningitis in these patients is unknown, however. In this study on a nation-wide cohort of 22,743 patients with liver cirrhosis in Denmark an incidence rate of bacterial meningitis of 54.4 per 100,000 was found [95% confidence interval (CI) 40.3-71.9]. The highest incidence rate was found in patients with alcoholic cirrhosis, 65.3 per 100,000 person-years (95% CI 46.2-89.6), compared with 34.6 per 100,000 person-years (95% CI 17.3-61.9) in patients with non-alcoholic cirrhosis. The 30-d case fatality rate was 53.1% (95% CI 38.3-67.5), and high age and alcoholic cirrhosis were associated with the highest case fatality rates. The main bacterial pathogens were pneumococci and unspecified bacteria. These findings suggest that patients with liver cirrhosis are at increased risk of bacterial meningitis with a poor prognosis.

Incidence and prognosis of tuberculosis in patients with cirrhosis of the liver. A Danish nationwide population based study.

We examined the incidence rate and prognosis of tuberculosis in a cohort of patients with liver cirrhosis in Denmark. In a study cohort of 22675 patients with liver cirrhosis, we identified 151 cases of tuberculosis from 1977 to 1993. The incidence rate was 168.6 per 100000 person-years of risk, and the highest incidence rate was among men above 65 years of age, with an incidence rate of 246.0 per 100000 person-years of risk. The 30-day case-fatality rate was 27.3% and the 1-year case fatality rate was 47.7%. The results demonstrate that patients with liver cirrhosis are at increased risk of tuberculosis. Additionally, it is suggested that liver cirrhosis is an independent risk factor for tuberculosis, and that patients with liver cirrhosis who acquire tuberculosis have a poor prognosis.

Use of medical chemoprophylaxis and antimosquito precautions in Danish malaria patients and their traveling companions.

BACKGROUND: The number of malaria cases imported to Denmark has been increasing for some years. To analyze the background for this we assessed the use of protective measures in Danish travelers visiting malarious areas. METHOD: Post-travel questionnaires were given during hospitalization to malaria patients, and sent by mail to their traveling companions. RESULTS: In total, 142 persons participated. Only 32% of the travelers used chemoprophylaxis correctly, according to Danish recommendations. Twelve percent of the travelers did not use chemoprophylaxis. Average compliance was 52%. Insufficient drug dosage was reported by 13%, and use of nonrecommended drugs by 7% of the travelers. Thirty-seven percent used insufficient antimosquito precautions, a problem which often coincided with irregular use of chemoprophylaxis. Malaria patients, sole travelers, and travelers with other ethnical background than Danish, were subgroups using insufficient malaria prophylaxis more frequently than healthy traveling companions. CONCLUSION: Insufficient use of the available antimalaria precautions by Danish travelers contributes greatly to maintaining a high incidence of imported malaria. Increased attention from physicians in educating travelers is important for optimizing malaria prophylaxis.

Inhibitory effect of nitric oxide on chemically induced differentiation of human leukemic K562 cells.

The effect of nitric oxide (NO) was investigated in the human K562 cell line during chemically induced erythroid differentiation. Butyric acid (BA) and the anthracycline antitumour drugs aclarubicin (ACLA) and doxorubicin (DOX) were used as differentiating agents. In all cases, cell hemoglobinization was dose dependently inhibited by NO donors such as sodium nitroprusside (SNP). A 50% inhibition of cell differentiation was obtained with 25 microM SNP, which generated less than 2 microM nitrite in 3-day culture media. Increasing SNP concentrations led to higher nitrite accumulation (up to 12 microM with 1 mM SNP) and total inhibition of cell hemoglobinization, but did not have a significant effect on cell proliferation. As shown by Northern blotting, high concentrations of SNP (1 mM) reduced the expression of gamma-globin and porphobilinogen deaminase, but did not change GATA-1 and NF-E2 mRNA levels in ACLA- and BA-treated cells. In contrast, hemin-induced erythroid differentiation was not affected by the presence of NO donors. Altogether, these results show that NO is able to inhibit cell differentiation induced by some (ACLA, DOX, BA), but not all (hemin), agents. The inhibitory effect of NO seems to take place downstream of the regulation of erythroid gene expression.

Retrospective evaluation of exposure to P. falciparum using antibodies to circumsporozoite protein and to cultured P. falciparum antigens.

A Danish school class travelled under primitive circumstances in East Africa for 28 d. Four out of 18 persons had febrile illnesses interpreted as malaria during the journey. Retrospective serological testing for antibodies against the P. falciparum circumsporozoite protein indicated a transmission rate of more than 80% despite extensive protection against mosquito bites. The study demonstrates the use of serological evaluation of malaria transmission risk as well as retrospective immunodiagnosis of clinical malaria. Three of the travellers with febrile illnesses used self-medication with mefloquine, and in 2 of the cases a diagnosis of malaria was supported by a positive immunofluorescence assay for malaria antibodies.

Time-course of butyric acid-induced differentiation in human K562 leukemic cell line: rapid increase in gamma-globin, porphobilinogen deaminase and NF-E2 mRNA levels.

Butyric acid (BA) was shown to induce hemoglobinization of K562 cells in a dose- and time-dependent manner. The maximal differentiation (54% of hemoglobinized cells) was obtained with the 0.5 mM concentration, which induced a 60% inhibition of cell growth at day 3 without cytotoxicity. Parallel to the kinetics of hemoglobinization, a rapid increase in gamma-globin and porphobilinogen deaminase (PBGD) mRNAs was observed in BA-treated cells. This increase was time-dependent and higher for gamma-globin than for PBGD (six- and two-fold at day 3, respectively). In contrast, erythropoietin receptor mRNAs were not affected by BA treatment. Analysis of erythroid transcription factor mRNA levels during the time course of BA treatment showed, for the first time, an early and marked (up to three-fold) increase in p45 NF-E2 mRNA, contrasting with that of GATA-1 mRNA (<1.5-fold). Taken together, these results showed the rapid differentiating effect of BA and suggest the involvement of the NF-E2 transcription factor.