Is on-demand treatment effective in patients with severe haemophilia?

On-demand therapy enables stopping haemorrhages rapidly, reducing joint pain and restoring joint mobility, but does not prevent the beginning and subsequent development of haemophilic arthropathy. The main objective of this study was to identify the clinical and orthopaedic status of severe haemophilic patients with bleeding phenotype receiving on-demand treatment in Spain. We conducted an epidemiological, observational, retrospective study, recruiting 167 patients from 36 centres (92% of them with haemophilia A), median age at enrolment of 35 years. Forty per cent of the patients received a combination of on-demand and short-term prophylaxis regimen; the rest was under on-demand treatment. One hundred and forty-five patients (87%) reported at least one bleeding episode and 22 (13%) of the biologically severe patients had no bleeding phenotype. Seventy-one per cent of the studied population presented established haemophilic arthropathy, reaching 80% if we exclude patients without bleeding phenotype. Forty-three per cent of these patients had one or two joints affected, 28% of them had three or four affected joints, 20% reported five or six affected joints and 9% more than six injured joints. An increase in established haemophilic arthropathy with age was observed. Forty-six patients underwent orthopaedic surgery at least once. These data show that on-demand therapy is not effective in preventing the development of haemophilic arthropathy in severe haemophilic population with bleeding phenotype. Therefore, we suggest that the optimal treatment in these patients should be based on prophylaxis. We recommend analysing the reasons for ending prophylaxis, in case its reinstatement should be necessary.

Simple and rapid analytical method for the simultaneous determination of cetrimonium chloride and alkyl alcohols in hair conditioners.

A simple method for the simultaneous determination of a cationic surfactant (cetrimonium chloride) and four non-ionic surfactants (1-tetradecanol, 1-hexadecanol, 1-octadecanol and 1-eicosanol) has been developed. Direct extraction of the analytes from the sample with methanol and a subsequent separation using reversed-phase high-performance liquid chromatography with refractive index detection are the steps followed in the procedure. The column used was a Luna C18 and the mobile phase consisted of a 0.1 M KClO(4) solution prepared on a 95:5 mixture of methanol and water. This solution was adjusted to pH 2.8 with phosphoric acid. Recoveries close to 100% were obtained in spiked commercial hair conditioner samples for the surfactants assayed using this method. Limits of detection were 10.4, 16.7 and 22.9 mg kg(-1) of cetrimonium chloride, 1-hexadecanol, 1-hexadecanol and 1-1-octadecanol respectively. The methodology was successfully applied to nine commercial hair conditioners of several types and different brands. All hair conditioners but one contained at least two of the surfactants included in this study.

Chromosomal constraints in Gram-positive bacteria revealed by artificial inversions.

We used artificial chromosome inversions to investigate the chromosomal constraints that preserve genome organization in the Gram-positive bacterium Lactococcus lactis. Large inversions, 80-1260 kb in length, disturbing the symmetry of the origin and terminus of the replication axis to various extents, were constructed using the site-specific Cre-loxP recombination system. These inversions were all mechanistically feasible and fell into various classes according to stability and effect on cell fitness. The L. lactis chromosome supports only to some extent unbalance in length of its replication arms. The location of detrimental inversions allowed identification of two constrained chromosomal regions: a large domain covering one fifth of the genome that encompasses the origin of replication (Ori domain), and a smaller domain located at the opposite of the chromosome (Ter domain).

Diagnóstico diferencial de síndromes de glicoproteínas deficientes en carbohidratos (CDG) / Differential diagnosis of carbohydrate deficient glycoprotein syndrome

Antecedentes: los síndromes de glicoproteínas deficientes en carbohidratos (CDG) son un grupo de errores congénitos multisistémicos caracterizados por una anormal glicosilación de un gran número de glicoproteínas séricas. Se han descrito varios defectos enzimáticos que dan lugar a diferentes fenotipos clínicos y a distintas anomalías bioquímicas en la glicosilación de la transferrina sérica. Hasta el momento, se han identificado seis deficiencias enzimáticas: tipos Ia (deficiencia en fosfomanosa mutasa), Ib (deficiencia en fosfomanosa isomerasa), Ic (deficiencia en glucosiltransferasa), Id (deficiencia en manosiltransferasa), Ie (deficiencia en dolicol-fosfato-manosa sintasa 1) y II (deficiencia en N-acetilglucosaminiltransferasa II). Métodos: en este estudio, proponemos un procedimiento para el diagnóstico diferencial de síndromes CDG apoyándonos en las manifestaciones clínicas y en el estudio de isoformas de sialotransferrinas séricas (CDT); confirmando el diagnóstico con la determinación de las actividades enzimáticas involucradas en la ruta metabólica en leucocitos o en fibroblastos y el análisis de mutaciones. Resultados: este procedimiento nos ha permitido diagnosticar 6 casos de CDG tipo Ia. Conclusiones: creemos que se debería proceder a la búsqueda de esta enfermedad en todos aquellos pacientes a los que se hayan descartado otras causas de afectación multisistémica (AU)

Genome plasticity among related ++Lactococcus strains: identification of genetic events associated with macrorestriction polymorphisms.

The genomic diversity of nine strains of the Lactococcus lactis subsp. cremoris (NCDO712, NCDO505, NCDO2031, NCDO763, MMS36, C2, LM0230, LM2301, and MG1363) was studied by macrorestriction enzyme analysis using pulsed-field gel electrophoresis. These strains were considered adequate for the investigation of genomic plasticity because they have been described as belonging to the same genetic lineage. Comparison of ApaI and SmaI genome fingerprints of each strain revealed the presence of several macrorestriction fragment length polymorphisms (RFLPs), despite a high degree of similarity of the generated restriction patterns. The physical map of the MG1363 chromosome was used to establish a genome map of the other strains and allocate the RFLPs to five regions. Southern hybridization analysis correlated the polymorphic regions with genetic events such as chromosomal inversion, integration of prophage DNA, and location of the transposon-like structures carrying conjugative factor or oligopeptide transport system.

A natural large chromosomal inversion in Lactococcus lactis is mediated by homologous recombination between two insertion sequences.

Comparative analysis of chromosomal macrorestriction polymorphism of the two closely related Lactococcus lactis subsp. cremoris strains MG1363 and NCDO763 revealed the presence of a large inversion covering half of the genome. To determine what kind of genetic element could be implicated in this rearrangement, the two inversion junctions of MG1363 and NCDO763 chromosomes were cloned and characterized. Nucleotide sequence analysis showed the presence of one copy of the lactococcal IS905 element in each junction. Each copy of this element contained the same nucleotide mutation that inactivates the putative transposase. Comparison of the sequences surrounding the insertion sequence demonstrated that the large inversion arose from a single-step homologous recombination event between the two defective copies of the IS905 element. The large inversion presumably conferred no selective disadvantage on strain NCDO763 because this rearrangement did not alter the oriC-terC symmetry of the chromosome and the local genetic environment.

[Spontaneous bacterial peritonitis due to Listeria monocytogenes]. / Peritonitis bacteriana espontánea por Listeria monocytogenes.

We present a case of spontaneous bacterial peritonitis (SBP) caused by Listeria monocytogenes in a patient previously diagnosed as alcoholic liver cirrhosis. The clinical presentation, biochemical data and outcome of the patient are compared with those of cases of SBP caused by Listeria monocytogenes in patients with cirrhosis published in the Spanish and English literature. Twelve out of 20 cases described in the literature were published by Spanish authors. This greater proportion could be related to dietary habits (greater consumption of fruits and vegetables), climatic or demographic factors. We underline the importance of pursuing a microbiological diagnosis since Listeria monocytogenes is intrinsically resistant to cefotaxime, the antimicrobial often selected to empirically treat SBP episodes.

[Trends of child mortality form tumors in Catalonia (1975-1992)]. / Tendencias de la mortalidad infantil por tumores en Cataluña (1975-1992).

BACKGROUND: Childhood mortality from tumors has decreased in industrialized countries. The aim of this paper is to study the trend of mortality from tumors in children (under 15 years old) during the period 1975-1992. METHODS: Using data from the Department of Health and Social Security's Register of Mortality, age-group standardized (to world population) mortality rates for each sex were analyzed. Analysis was carried out on total mortality caused by childhood tumors and on main causes of death (leukemia, brain cancer, non-Hodgkin lymphoma, bone cancer and non-specified tumors). A Poisson's regression model was used to analyze mortality trends. RESULTS: Childhood tumors caused 8.7% of all deaths in boys and 8.5% of all deaths in girls between 1990-1992. Thus, standardized mortality rates have decreased significantly, in 1975-1977 standardized mortality rates for boys and girls were 71.20 and 68.05 respectively, in 1990-1992 these rates had fallen to 55.45 and 41.30. The annual percentage decrease in cancer mortality rates for boys was 2% and for girls was 3.1%. Main causes of deaths were leukemia and brain cancer. CONCLUSIONS: Between 1975-1992 a significant downward trend in childhood tumors mortality has been observed, more prominent in main causes of death and in girls. The principal explanation for this trend is an increased survival, consequence of changes in childhood tumors therapy.

[An improvement in the AIDS mortality statistics in Catalonia]. / Mejora de las estadísticas de mortalidad por SIDA en Cataluña.

Differences between the number of AIDS death reported to the mortality register and to the AIDS register in Catalonia, Spain are relatively small, due to bot registers cooperation. Official mortality statistics are able to identify 78% of AIDS deaths. This proportion can be increased if the deaths caused by AIDS indicative diseases are included. The overall proportion of false positives when comparing both registers is 8.2%. Analysis of the available information from death certificates is useful to suggest simple recommendation to improve the quality of AIDS mortality data.

[Cancer mortality trends in Catalonia: 1975-1990]. / Evolución de la mortalidad por cáncer en Cataluña: 1975-1990.

BACKGROUND: Cancer is one of the most important health problems in developed countries. The aim of this paper is to analyze mortality trends due to cancer in Catalonia from 1975 to 1990. METHODS: Cancer mortality trends have been studied for each sex separately. Rates were standardized by direct method, using world population as standard; also, truncated (35-65 years old) and cumulative rates (0-74) were calculated. Annual percentage of change was estimated from a Poisson's regression model. RESULTS: An increase of cancer mortality was observed between 1975 and 1990 among men but not in women. Lung cancer is the main cause of death from cancer in men and breast cancer in women. Both these cancers showed a significative increase in their mortality during the period of study. Among men, there is a significative increase in the following cancers: oral cavity, colon, pancreas, melanoma, non-Hodgkin's lymphoma and myeloma; and there is a decrease in the following cancers: stomach, testicle and brain. Among women, there is a significative increase in cancer mortality due to the following: ovarian, colon, pancreas, melanoma and non-Hodgkin's lymphoma; while decrease in the following: stomach, liver and uterus. Also, lung cancer mortality among women is decreasing. CONCLUSION: The increasing trend observed in lung cancer mortality rates among men and in breast cancer among women are the main causes of concern. Therefore, priorities in cancer control underlined by this analysis should include emphasis on smoking control and developing breast cancer screening.

[Differential mortality by sex in Catalonia]. / Mortalidad diferencial según el sexo en Cataluña.

The purpose of the study is to analyse the evolution of sex differentials in mortality rates in Catalonia (Spain), to assess which causes of death have the higher differentials and to compare the results with other countries. Standardized mortality rates (direct method), sex mortality ratios and differences were obtained. Mortality data refers to 1985 to allow for comparison. Men had higher mortality than women, for cancer, accidents and diseases of the digestive tract. Women had higher mortality rates for endocrine diseases, mental disorders, cardiovascular, skin and muscle-skeleton diseases and ill-defined causes. The evolution in recent years shows a relative stabilization after an increasing trend observed from 1960 to 1979. In general, men had a 60% higher than women age-adjusted mortality rates in the four countries to which Catalonia is compared. Suicide and accidents showed the highest sex mortality ratios. Diabetes showed a different ratio in Catalonia and Spain (higher female mortality rate) compared to other countries. The causes of death with higher male mortality were accidents, as well as causes associated with smoking (lung cancer and ischemic heart disease).

[Years of potential life lost: comparison of 3 calculation methods]. / Anys potencials de vida perduts: comparació de tres mètodes de càlcul.

Two methods of assessing Years of Potential Life Lost (YPLL): 0 to 65 years and 1 to 70 years are compared to a third, 0 to life expectancy which is considered a priori the most appropriate. In addition we would like to corroborate that YPLL is a complementary indicator of the crude rate of mortality. The results show that the first cause of YPLL remains tumors in all the methods. However, differences appear in the second and following causes. Disparities are also found in crude rates as YPLL reflect causes of death of the youngest age groups of the community. The method 0 to life expectancy is considered the least arbitrary and consequently it is recommended to calculate YPLL.

fixK, a gene homologous with fnr and crp from Escherichia coli, regulates nitrogen fixation genes both positively and negatively in Rhizobium meliloti.

Nitrogen fixation genes are shown to undergo a complex positive and negative regulation in Rhizobium meliloti. Activation of fixN by fixLJ is shown to require a third regulatory gene, fixK. As fixK is activated by fixLJ, we propose a cascade model for fixN regulation such that fixLJ activates fixN via fixK. In addition fixK negatively regulates expression of the nif-specific activator nifA as well as its own expression by autoregulation. Thus nifA and fixK are subject to a mixed regulation, positive (by fixLJ) and negative (by fixK). The sequence of fixK shows homology with the Escherichia coli regulators fnr and crp, which makes fixK the third characterized member of this family of prokaryotic regulators.