Evaluación de la capacidad de penetración de partículas a cavidades perinasales usando el nebulizador PARI LC SPRINT® SINUS con técnica modificada en individuos sanos y portadores de rinosinusitis crónica por fibrosis quística con cirugía de cavidades perinasales / Evaluation of the penetration ability into perinasal sinuses of particles using the PARI LC SPRINT® SINUS nebulizer with a modified technique in healthy individuals and in cystic fibrosis patients with chronic rhinosinusitis with endoscopic sinus surgery

Introducción: En pacientes con rinosinusitis crónica (RSC) por fibrosis quística (FQ), los microorganismos que colonizan la vía aérea alta son los mismos que dañan el pulmón. Los tratamientos locales con nebulización de las cavidades perinasales (CPN) serían de ayuda. Objetivo: Evaluar la penetración de las partículas nebulizadas a las cavidades perinasales. Material y método: Voluntarios sanos y pacientes con RSC por FQ con cirugía endoscópica funcional (CEF). Se utilizó el nebulizador pulsátil que PARI LC SPRINT® SINUS. La penetración de partículas a las CPN se evaluó con fusión de imágenes cintigráficas SPECT y de tomografía computarizada (CT). Resultados: Se evaluaron 5 voluntarios y 2 pacientes con FQ. El procedimiento indicado por el fabricante del nebulizador fue imposible de realizar. Se modificó la forma de nebulización. Se observó solo el 9% del material nebulizado en las CPN en voluntarios y el 4% en pacientes. Una proporción importante del material nebulizado se depositó en pulmones y tubo digestivo. Conclusión: Los resultados iniciales motivaron la interrupción del estudio original considerando que sería difícil demostrar la diferencia en la efectividad del nebulizado para alcanzar las CPN entre pacientes con y sin CEF. Además, el depósito mayoritario del nebulizado fuera de las CPN, impide aclarar el valor del efecto local respecto a un posible efecto por vía general.

Introduction: In cystic fibrosis patients with chronic rhinosinusitis, the same microorganisms that colonize the upper airway are the ones who damage the lung. Local treatments by nebulization of perinasal sinuses would be helpful in these cases. Aim: To evaluate the penetration ability of nebulized particles into perinasal sinuses. Material and method: Healthy volunteers and cystic fibrosis patients with chronic rhinosinusitis with endoscopic sinus surgery had nasal nebulization using the pulsating nebulizer PARI LC Sprint® SINUS. Fusion of scintigraphic SPECT and CT images was used to evaluate the particles penetration ability into perinasal sinuses. Results: Five volunteers and 2 patients with CF were evaluated. It was not possible to perform the nebulization procedure as indicated by the manufacturer. A continous nebulization was done instead. 9% of the nebulized material was deposited in the perinasal sinuses in volunteers and 4% in patients with CF, while the rest of the particles were distributed in the body, specially in lungs and digestive tract. Conclusions: The main deposition of the nasal nebulized solution was outside the perinasal sinuses. These results led to discontinuation of the study because it would be difficult to prove a difference in the effectiveness of nebulized particles among patients with and without surgery. It also seems impossible to define the real value of local perinasal sinus therapies considering a probable systemic effect.

Haldane's rule revisited: do hybrid females have a shorter lifespan? Survival of hybrids in a recent contact zone between two large gull species.

Haldane's rule predicts that particularly high fitness reduction should affect the heterogametic sex of interspecific hybrids. Despite the fact that hybridization is widespread in birds, survival of hybrid individuals is rarely addressed in studies of avian hybrid zones, possibly because of methodological constraints. Here, having applied capture-mark-recapture models to an extensive, 19-year-long data set on individually marked birds, we estimate annual survival rates of hybrid individuals in the hybrid zone between herring (Larus argentatus) and Caspian (Larus cachinnans) gulls. In both parental species, males have a slightly higher survival rate than females (model-weighted mean ± SE: herring gull males 0.88 ± 0.01, females 0.87 ± 0.01, Caspian gull males 0.88 ± 0.01, females 0.87 ± 0.01). Hybrid males do not survive for a shorter time than nonhybrid ones (0.88 ± 0.01), whereas hybrid females have the lowest survival rate among all groups of individuals (0.83 ± 0.03). This translates to a shorter adult (reproductive) lifespan (on average by 1.7-1.8 years, i.e. ca 25%) compared with nonhybrid females. We conclude that, in line with Haldane's rule, the lower survival rate of female hybrids may contribute to selection against hybrids in this hybrid zone.

Speciation with gene flow in the large white-headed gulls: does selection counterbalance introgression?

We investigated the role of selection in generating and maintaining species distinctness in spite of ongoing gene flow, using two zones of secondary contact between large gull species in Europe (Larus argentatus and Larus cachinnans) and North America (Larus glaucescens and Larus occidentalis). We used the pattern of neutral genetic differentiation at nine microsatellite loci (F(ST)) as an indicator of expected changes under neutral processes and compared it with phenotypic differentiation (P(ST)) for a large number of traits (size, plumage melanism and coloration of bare parts). Even assuming very low heritability, interspecific divergence between L. glaucescens and L. occidentalis in plumage melanism and orbital ring colour clearly exceeded neutral differentiation. Similarly, melanism of the central primaries was highly divergent between L. argentatus and L. cachinnans. Such divergence is unlikely to have arisen randomly and is therefore attributed to spatially varying selection. Variation in plumage melanism in both transects agrees with Gloger's rule, which suggests that latitude (and associated sun and humidity gradients) could be the selective pressure shaping differentiation in plumage melanism. We suggest that strong species differentiation in orbital ring colour results from sexual selection. We conclude that these large gull species, along with other recently diverged species that hybridize after coming into secondary contact, may differ only in restricted regions of the genome that are undergoing strong disruptive selection because of their phenotypic effects.

Molecular and morphological patterns of introgression between two large white-headed gull species in a zone of recent secondary contact.

Incomplete reproductive isolation promotes gene flow between diverging taxa. However, any gene encoding for traits involved in the reproductive barriers will be less prone to introgression than neutral markers. Comparing introgression rates among loci is thus informative of the number and functions of loci involved in the reproductive barriers. This study aimed at identifying possible mechanisms of restriction to gene flow across a zone of recent secondary contact between Larus argentatus and Larus cachinnans by comparing introgression patterns for nine microsatellite loci, a fragment of mitochondrial DNA and a set of phenotypic traits. The low linkage disequilibrium between neutral nuclear markers indicated introgression without any barrier to gene flow. However, asymmetric introgression of mitochondrial DNA suggested that interspecific crosses may be more successful in one direction. The introgression rate for phenotypic traits was variable and low compared to neutral molecular markers. This was particularly evident in colouration of bare parts: individuals with intermediate colouration were scarcer in sympatry than expected if the genomes recombined freely. We hypothesized that one of these variables, the orbital ring colour, may play a role in mate choice, acting as an incomplete premating barrier through assortative mating. This study emphasizes that multilocus approaches are useful to discriminate among possible mechanisms responsible for the maintenance of hybrid zones.

Salmonella Enteritidis phage type 21 outbreak in Austria, 2005.

We report an outbreak of gastroenteritis due to Salmonella Enteritidis PT 21 associated with attending an annual traditional fair in a small Austrian village on 4 May 2005. The outbreak lasted from 4 to 8 May. Descriptive and analytical epidemiological investigations were conducted in order to determine the extent of the outbreak and to identify outbreak risk factors. Of the 115 persons who visited the fair, 85 persons fulfilled the criteria of an outbreak case (attack rate = 73.9%). Stool specimens from 52 patients, including two kitchen staff, were tested for salmonella, and 20 specimens were positive for Salmonella Enteritidis PT 21. The cohort study revealed mixed salad (which included potatoes) as the likely cause of the outbreak (RR: 10.4, 95%CI 2.8 - 39.1; P = < 0.001). The causative agent of the outbreak was cultured from the stock of eggs used at the fair and from all three drag swabs and one barn dust sample collected from the responsible egg laying flock. Molecular subtyping by pulsed-field gel electrophoresis of genomic DNA after XbaI digestion showed that isolates from eggs, from the flock and from humans were indistinguishable. We hypothesise that cross contamination from eggs to boiled potatoes occurred in the kitchen area, where raw eggs were handled by village residents preparing a traditional Viennese egg dressing. Unrefrigerated storage of peeled potatoes may have favoured bacterial growth. Eggs from small rural flocks of laying hens kept in a traditional 'natural' way should not be assumed to be salmonella-free.

Salmonella Enteritidis phage type 21 outbreak in Austria, 2005.

We report an outbreak of gastroenteritis due to Salmonella Enteritidis PT 21 associated with attending an annual traditional fair in a small Austrian village on 4 May 2005. The outbreak lasted from 4 to 8 May. Descriptive and analytical epidemiological investigations were conducted in order to determine the extent of the outbreak and to identify outbreak risk factors. Of the 115 persons who visited the fair, 85 persons fulfilled the criteria of an outbreak case (attack rate=73.9%). Stool specimens from 52 patients, including two kitchen staff, were tested for salmonella, and 20 specimens were positive for Salmonella Enteritidis PT 21. The cohort study revealed mixed salad (which included potatoes) as the likely cause of the outbreak (RR: 10.4, 95%CI 2.8 - 39.1; P=<0.001). The causative agent of the outbreak was cultured from the stock of eggs used at the fair and from all three drag swabs and one barn dust sample collected from the responsible egg laying flock. Molecular subtyping by pulsed-field gel electrophoresis of genomic DNA after XbaI digestion showed that isolates from eggs, from the flock and from humans were indistinguishable. We hypothesise that cross contamination from eggs to boiled potatoes occurred in the kitchen area, where raw eggs were handled by village residents preparing a traditional Viennese egg dressing. Unrefrigerated storage of peeled potatoes may have favoured bacterial growth. Eggs from small rural flocks of laying hens kept in a traditional 'natural' way should not be assumed to be salmonella-free.

[Developing rehabilitation treatment groups for cardiology and orthopaedics -- findings of a research project]. / Entwicklung von Rehabilitationsbehandlungsgruppen (RBG) für die Kardiologie und Orthopädie -- Ergebnisse eines Forschungsprojekts.

The call for a more specific and transparent service and reimbursement system for medical rehabilitation is not new. However, in practice, the idea was not followed up for a long time. This situation changed with the introduction of German Diagnosis Related Groups (DRGs) for acute care settings. It is now strongly being discussed whether such a sophisticated lump sum reimbursement system might also be a viable alternative in the field of rehabilitation. There still exist different opinions over the suitability of a lump sum-system for medical rehabilitation, but the main direction seems to be clear. There is no doubt that medical rehabilitation requires a needs-adapted, differentiated patient classification system. The benefits of such cost-homogeneous groups are evident. They support medical and management services and are suitable for both internal and external use. The main intent of the project presented was to develop such a patient classification system, adapted to the requirements of medical rehabilitation. The project concentrated on orthopaedic and cardiac rehabilitaton. For these two areas, needs-adapted and cost-homogeneous groups (RBG, Rehabilitationsbehandlungsgruppen - Rehabilitation Treatment Groups) were developed in order to adequately represent the underlying service portfolio and to act as a link between acute and post-acute care. In addition, severity level indicators were identified, in order to explain for different needs and resource volumes and in order to create severity-RBGs representing patients with the same severity level. Based on these groups, a needs-adapted lump sum reimbursement system can be developed, allowing for a differentiated service and cost controlling. The project described formed part of the Research Funding Programme Rehabilitation Sciences defrayed by the German Pension Insurance and the Federal Ministry for Education and Research. As part of the Freiburg/Bad Sackingen research network, it was realised at the University BW, Munich.

An exploratory workplace study to investigate the perceived value of continuous low-level heatwrap therapy in manual workers.

BACKGROUND: Between 60 and 80% of the population in industrialized countries experience low back pain at some time in their lives. The physical demands of work, i.e. manual handling, lifting, bending, twisting, awkward postures and whole body vibration are associated with low back symptoms. This study was undertaken to investigate the benefits of a new form of continuous low-level heatwrap therapy available for the symptomatic relief of acute low back pain in the workplace. METHODS: The subjects were recruited to the study upon their visit to the occupational health doctor after being diagnosed with acute low back pain. RESULTS: The study results show that use of the heatwrap therapy significantly reduced pain intensity and impact of pain on everyday activities. The results of the study were further extrapolated to show potential cost reduction benefits of using this heatwrap therapy in the workplace.

[Reuse of "single use" medical devices after quality assured reprocessing: hygienic, legal and economic aspects. Potential for cost savings in interventional cardiology]. / Wiederverwendung von medizinischen Einwegprodukten nach qualitätsgesicherter Wiederaufbereitung: ein Modell zur Kostendämpfung? Diskussion der medizinischen, rechtlichen und wirtschaft- lichen Aspekte mit Berechnung des Einsparpotenzials am Beispiel der interventionellen Kardiologie.

The increasing limitation of resources has stimulated the discussion of the reuse of medical devices labelled for "single use" by the manufacturer. The prerequisites for employment of reprocessing measures are patient safety and cost saving potential. Although reprocessing of single use medical devices has been general practice by many institutions, health care providers and authorities have remained insecure as to hygienic and functional risks, liability and legal aspects. Changes in legislation (German Medical Device Act), guidelines of the Robert Koch Institute (and position of the FDA) and the high quality guaranteed by innovative reprocessing technology have now created the basis for expanded but controlled use of reprocessing techniques for medical devices as a contribution to cost containment. A significant cost saving potential is calculated for the cost-intensive field of interventional cardiology.

[Wishes and possibilities in the face of limited resources]. / Wünsche und Möglichkeiten angesichts begrenzter Ressourcen.

The main intention of health economic studies is to find out how to cope with the prevailing scarcity of resources. But scarcity is comparable to morbidity. As morbidity can not be finally cured by medical intervention, the problem of scarcity can only be solved relatively by economic research. It is evident, that the sensation of scarcity even aggravates with increasing prosperity. That is because human demands do in fact outrun economic potentials. The scarcity of resources therefore demands for setting of priorities. That is what economics in general and health economics in particular has set rules for. Priorities can be set by the state, the market or joint associations. The prevailing system in Germany is based on associations, the so called self-governing body. The scare financial resources are divided into budgets and allocated to service suppliers following predefined negotiation mechanisms within the joint self-administration. In recent years an increasing paternalism of the German government on the joint self-administration can be observed. Although Germany spends more on healthcare than ever before, the scarcity is noticed as threatening. The government currently interferes to cope with this problem. In opposition to that approach critics postulate more individual freedom in decisions for insurance holders, patients, health insurances and suppliers. The principal of subsidiarity intends to strengthen self-responsibility in the health care sector while in return the principle of solidarity within the legal health insurance is reduced.

Automated de novo sequencing of proteins using the differential scanning technique.

Despite the progress in genomic DNA sequencing de novo sequencing of peptides is still required in a biological research environment since many experiments are done in organisms whose genomes are not sequenced. A way to unambiguously retrieve a peptide sequence from a tandem mass spectrum is to assign the correct ion type to the fragments. Here we describe a method which improves the specificity in y-ion assignment throughout the spectrum. The differential scanning technique requires that the peptides are partially 18O labelled at their C-terminus and that two fragment spectra are acquired for each peptide, one selecting the 16O/18O isotopic cluster and a second fragmenting only the 18O labelled ions. When the spectra are acquired with a quadrupole time of flight mass spectrometer y-ions can be very specifically filtered from the spectrum using a computer algorithm. Partial or complete peptide sequences can be assigned automatically simply by finding the most abundant series of fragments spaced by amino acid residue masses. This method was used extensively in a project investigating vesicular transport in bovine brain cells. Human or mouse homologues to the bovine proteins were found in EST databases facilitating rapid cloning of the human homologues.

Multilocation trial of ceftiofur for treatment of postpartum cows with fever.

OBJECTIVE: To evaluate the effect of ceftiofur for treatment of postpartum cows with fever. DESIGN: Multilocation randomized complete block design trial. ANIMALS: 330 cows. PROCEDURE: Cows with rectal temperature > or = 39.5 C (103.1 F) during the first 10 postpartum days were randomly assigned to a treatment (ceftiofur; 1 mg/kg [0.45 mg/lb] of body weight daily for 3 days) or untreated control group. Cure (no additional or alternative antimicrobial treatment used, rectal temperature < 39.5 C, and no other concurrent clinical signs of disease when evaluated at 9 or 10 days after enrollment), milk production, and rectal temperature were evaluated. RESULTS: Ceftiofur-treated cows were significantly more likely to be cured than control cows (56.0 vs 28.9%, respectively), with an odds ratio of 3.14 when vaginal discharge (a factor with moderate interaction with treatment) was present at enrollment. Among cows that had an abnormal calving (a significant interaction factor), treated cows had first milking yield 2.27 kg (5 lb) greater than control cows. Treated cows had a significantly greater reduction in rectal temperature (1.19 C [2.14 Fl), compared with control cows (1.04 C [1.87 F]). CONCLUSIONS AND CLINICAL RELEVANCE: Parenteral administration of ceftiofur significantly improved cure rate, milk yield, and rectal temperature in postpartum cows with fever and vaginal discharge or dystocia. These findings provide information to determine appropriate treatment for postpartum cows, which for years has been debated in the dairy industry.

A novel U2 and U11/U12 snRNP protein that associates with the pre-mRNA branch site.

Previous UV cross-linking studies demonstrated that, upon integration of the U2 snRNP into the spliceosome, a 14 kDa protein (p14) interacts directly with the branch adenosine, the nucleophile for the first transesterification step of splicing. We have identified the cDNA encoding this protein by microsequencing a 14 kDa protein isolated from U2-type spliceosomes. This protein contains an RNA recognition motif and is highly conserved across species. Antibodies raised against this cDNA-encoded protein precipitated the 14 kDa protein cross-linked to the branch adenosine, confirming the identity of the p14 cDNA. A combination of immunoblotting, protein microsequencing and immunoprecipitation revealed that p14 is a component of both 17S U2 and 18S U11/U12 snRNPs, suggesting that it contributes to the interaction of these snRNPs with the branch sites of U2- and U12-type pre-mRNAs, respectively. p14 was also shown to be a subunit of the heteromeric splicing factor SF3b and to interact directly with SF3b155. Immuno precipitations indicated that p14 is present in U12-type spliceosomes, consistent with the idea that branch point selection is similar in the major and minor spliceosomes.

A novel yeast U2 snRNP protein, Snu17p, is required for the first catalytic step of splicing and for progression of spliceosome assembly.

We have isolated and microsequenced Snu17p, a novel yeast protein with a predicted molecular mass of 17 kDa that contains an RNA recognition motif. We demonstrate that Snu17p binds specifically to the U2 small nuclear ribonucleoprotein (snRNP) and that it is part of the spliceosome, since the pre-mRNA and the lariat-exon 2 are specifically coprecipitated with Snu17p. Although the SNU17 gene is not essential, its knockout leads to a slow-growth phenotype and to a pre-mRNA splicing defect in vivo. In addition, the first step of splicing is dramatically decreased in extracts prepared from the snu17 deletion (snu17Delta) mutant. This defect is efficiently reversed by the addition of recombinant Snu17p. To investigate the step of spliceosome assembly at which Snu17p acts, we have used nondenaturing gel electrophoresis. In Snu17p-deficient extracts, the spliceosome runs as a single slowly migrating complex. In wild-type extracts, usually at least two distinct complexes are observed: the prespliceosome, or B complex, containing the U2 but not the U1 snRNP, and the catalytically active spliceosome, or A complex, containing the U2, U6, and U5 snRNPs. Northern blot analysis and affinity purification of the snu17Delta spliceosome showed that it contains the U1, U2, U6, U5, and U4 snRNPs. The unexpected stabilization of the U1 snRNP and the lack of dissociation of the U4 snRNP suggest that loss of Snu17p inhibits the progression of spliceosome assembly prior to U1 snRNP release and after [U4/U6.U5] tri-snRNP addition.

Assessment of growth hormone dynamics in human immunodeficiency virus-related lipodystrophy.

Human immunodeficiency virus (HIV) lipodystrophy (LIPO) is characterized by increased visceral adiposity, peripheral fat atrophy, dyslipidemia, and insulin resistance. GH concentrations are known to vary inversely with excess weight and body fat but have not been investigated in HIV lipodystrophy. Twenty-one subjects with HIV LIPO, 20 HIV-infected nonlipodystrophy subjects (NONLIPO), and 20 control (C) subjects were prospectively recruited for this study and compared. Subjects in the three groups were all male, age-matched [median, 47 yr old (interquartile range, 37-50) LIPO; 41 (37-44) NONLIPO; and 43 (37-49) C], and body mass index-matched [median, 24.3 kg/m(2) (interquartile range, 22.2-26.6) LIPO; 24.4 (23.3-25.9) NONLIPO; and 24.8 (22.7-26.1) C] (P: > 0.05 for all comparisons). Visceral abdominal fat [16,124 mm(2) (11,246-19,790) LIPO; 7,559 (5,134-11,201) NONLIPO; and 8,803 (6,165-11,623) C; P < 0.01 LIPO vs. NONLIPO and LIPO vs. C] and the ratio of visceral abdominal fat to sc abdominal fat [1.37 (0.71-2.44) LIPO vs. 0.57 (0.47-0.78) NONLIPO vs. 0.55 (0.41-0.71) C, P < 0.01 LIPO vs. NONLIPO and LIPO vs. C] were significantly increased in the LIPO subjects but were not significantly different between NONLIPO and C. The mean overnight GH concentration, determined from frequent sampling every 20 min (from 2000 h to 0800 h) was decreased in the LIPO subjects [0.38 microg/L (0.13-0.67) LIPO vs. 0.96 (0.53-1.30) NONLIPO vs. 0.81 (0.49-1.03) C, P < 0.05 LIPO vs. NONLIPO and LIPO vs. C] and not significantly different between NONLIPO and C. Pulse analysis demonstrated decreased baseline GH [0.08 microg/L (0.06-0.21) LIPO vs. 0.19 (0.10-0.32) NONLIPO vs. 0.17 (0.12-0.57) C, P < 0.05 LIPO vs. NONLIPO and LIPO vs. C] and GH peak amplitude [1.06 microg/L (0.46-1.94) LIPO vs. 2.47 (1.22-3.43) NONLIPO and 2.27 (1.36-4.25) C, P < 0.05 LIPO vs. NONLIPO and LIPO vs. C] in the LIPO subjects but no significant difference in pulse frequency. No significant differences were observed between NONLIPO and C for any GH parameter. Insulin-like growth factor-I was not different between the groups. Total body fat (r = -0.40, P = 0.01) and visceral fat (r = -0.58, P = 0.0001) correlated inversely with mean overnight GH concentrations in the HIV-infected patients. In a multivariate regression model, controlling for age, body mass index, body fat, and visceral fat, only visceral fat was a significant predictor of mean GH concentrations (P = 0.0036, r(2) for model = 0.40). These data demonstrate normal GH pulse frequency and insulin-like growth factor-I concentrations but reduced mean GH concentrations, basal GH concentrations, and GH pulse amplitude in patients with HIV lipodystrophy. Increased visceral adiposity is the strongest predictor of reduced GH concentrations in HIV lipodystrophy. Further studies are necessary to determine the clinical significance of reduced GH in patients with HIV lipodystrophy.