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PubMedDate not supplied

Extended Range Proteomic Analysis (ERPA): a new and sensitive LC-MS platform for high sequence coverage of complex proteins with extensive post-translational modifications-comprehensive analysis of beta-casein and epidermal growth factor receptor (EGFR).

We have developed a new and sensitive LC-MS platform, Extended Range Proteomic Analysis (ERPA), which is able to achieve very high sequence coverage and comprehensive characterization of post-translational modifications in complex proteins. This new platform provides advantages of both the top-down and bottom-up proteomic approaches by combining (i) digestion of the protein with an enzyme, such as Lys-C, which cuts less frequently than trypsin, leading to on average a higher molecular weight peptide size, (ii) high-performance LC separation of the resulting fragments, (iii) a new data acquisition strategy using the LTQ-FTMS, a hybrid mass spectrometer that couples a linear ion trap with a Fourier transform ion cyclotron resonance (FTICR) cell, for analysis of peptides in the range of 0.5 to 10 kDa, and (iv) new data analysis methods for assigning large peptide structures and determining the site of attachment of post-translational modifications as well as structural features from the accurate precursor mass together with MS(2) and MS(3) fragmentations. The LC retention of the Lys-C fragments is increased, relative to a tryptic digest, due to the generally greater hydrophobicity of the larger peptides, a result that is particularly important for peptides containing hydrophilic modifications such as glycosylation and phosphorylation. Furthermore, additional positively charged arginine and lysine residues in the Lys-C fragments enhance the sensitivity of the post-translationally modified phospho- and glycopeptides by at least 10-fold relative to tryptic fragments. In typical operation, the FTICR cell provides a survey scan with the high mass resolution (> 100 000) and accurate mass (<2 ppm) to characterize the higher charge-state precursor ions of the larger peptides. In parallel, the linear ion trap provides MS(2) and MS(3) fragmentation spectra, with a scan speed sufficiently fast for on-line LC-MS. Together, these data provide multiple means to determine or enhance the confidence of assignment of large or complicated peptide. Using ERPA, we demonstrate >95% sequence coverage in the analysis of two heavily phosphorylated and glycosylated proteins, beta-casein at the 50 fmole level and the epidermal growth factor receptor (EGFR) at the 1 pmole level. In summary, the combination of digestion strategy, high-performance separation, and the hybrid LTQ-FTMS instrument enables comprehensive characterization of large proteins, including posttranslational modifications.

Amino Acid Sequence↗
PubMed1997

The impact of sociodemographic variables on immunization coverage of children.

The dependence of immunization coverage of children in the municipalities of Vienna and Klagenfurt on the sociodemographic variables of their parents is investigated. According to the Austrian vaccination program, the following vaccinations are recommended: diphtheria/tetanus (DT), measles/mumps (MM), poliomyelitis (oPV), tickborne encephalitis (TBE), tuberculosis (BCG) and whooping cough (P). The aim of the study is to identify risk groups, as are children that are not well covered. A cross-sectional study using vaccination certificates of second grade schoolchildren in Vienna and Klagenfurt was performed. A multivariate logistic regression model is used. In Vienna a representative sample of second grade schoolchildren (n = 585) was investigated, in Klagenfurt all second grade schoolchildren (n = 824). The investigation took place during the 1993/1994 schoolyear. In Vienna 34.8% of the children have all the vaccinations recommended, in Klagenfurt 59.6%. Children of Austrian mothers have the best immunization coverage, followed by children whose mothers are from 'other countries', 'not stated', and 'former Yugoslavia'. The immunization rate increases with the mother's increasing age. It is lower if the father is unemployed. The effects of the variables age and unemployment are not dependent on nationality. Children from Klagenfurt are more often completely immunized than children from Vienna. The mother's education does not have a significant influence. The Austrian immunization program is not sufficient to provide a high level of herd immunity. The immunization program recommends vaccinations but does not include a system for finding and recording riskgroups (non-immunized). To improve the situation eight steps needed for a setup of surveillance and containment system are recommended.

Austria↗
PubMed2000

Dynamics of mucosal dimensions after root coverage with a bioresorbable membrane.

BACKGROUND: So far, the clinical effects of the placement of a resorbable membrane for guided tissue regeneration have not been studied in humans in great detail. The dynamics of the resorptive processes, in particular, appear to be rather speculative. In the present longitudinal study, specific alterations of the dimensions of the dentogingival mucosa were explored after surgical root coverage by using a bioresorbable membrane and a coronally-repositioned flap. METHODS: The study population consisted of 14 patients with a total of 31 predominantly shallow, Miller class I, II or III recessions. The thickness of the masticatory and lining mucosa before and after surgical intervention was measured with an ultrasonic device. RESULTS: Mean (+/-sd) recession depth and width were 2.85+/-1.29 and 4.46+/-1.14 mm, respectively. After 12 months, 51+/-29% of the recession depth (p<0.001) and 13+/-35% of its width (n.s.) were covered. Root coverage seems to be rather defect-type sensitive with best results obtained at canines with relatively shallow recessions. Mucosal thickness was considerably increased after surgery with a gradual decrease during the following 9 months. Thus, thickness of the marginal tissue rose from 0.82+/-0.27 mm to 1.49+/-0.54 mm 3 months after placement of the membrane (p<0.001). After 12 months, a mean thickness of 1.03+/-0.40 mm was observed (p<0.001). Even more pronounced alterations were noted for the alveolar lining mucosa with a threefold increase of thickness 3 months after surgery and a gradual decrease to about 1 mm after 12 months. CONCLUSIONS: The present results point to the considerable space making capacity of the bioresorbable membrane which probably allows for the ingrowth of a granulation tissue derived from the underlying structures. The gradual decline in mucosal thickness between months 6 and 9 after surgery may be paralleled by the maturation of the granulation tissue while complete resorption of the membrane had been accomplished.

Absorbable Implants↗
PubMed2006

Evaluating coverage of genome-wide association studies.

Genome-wide association studies involving hundreds of thousands of SNPs in thousands of cases and controls are now underway. The first of many analytical challenges in these studies involves the choice of SNPs to genotype. It is not practical to construct a different panel of tag SNPs for each study, so the first generation of genome-wide scans will use predefined, commercially available marker panels, which will in part dictate their success or failure. We compare different approaches in use today, and show that although many of them provide substantial coverage of common variation in non-African populations, the precise extent is strongly dependent on the frequencies of alleles of interest and on specific considerations of study design. Overall, despite substantial differences in genotyping technologies, marker selection strategies and number of markers assayed, the first-generation high-throughput platforms all offer similar levels of genome coverage.

Case-Control Studies↗
PubMed2005

Population coverage and nonresponse bias in a large-scale human exposure study.

We used estimates derived from screener variables of the National Human Exposure Assessment Survey (NHEXAS) Phase I field study in EPA Region V (one of three NHEXAS Phase I field studies) to examine biases resulting from survey nonresponse and/or incomplete population coverage inherent in the study design. For variables with population values obtainable from Census projections, the combined effect of nonresponse and coverage bias was tested for after each stage of nonresponse using design-based weights. For variables where population values were not available as Census projections, nonresponse bias was tested for after the screener stage of nonresponse using weights adjusted for screener nonresponse. Additional tests for bias were performed using final survey weights to evaluate the performance of survey weight adjustments in reducing observed bias. Comparison of biases estimated using both design-based and adjusted weights was used to identify potentially important weight adjustment variables for future exposure studies, identify possible weaknesses in survey design strategies, and support the use of nonresponse and poststratification weight adjustments to reduce bias in future survey studies.

Bias↗
PubMed2002

Did the London Initiative Zone investment programme affect general practice structure and performance in East London? A time series analysis of cervical screening coverage and asthma prescribing.

A programme of incentives was set up in the London Initiative Zones to improve primary care in inner London based on the findings of the Tomlinson Enquiry in 1992. This descriptive study is a 4-y time series analysis of changes in general practice structure in East London as the result of London Initiative Zone investment, and an exploration of the possible effect of investment on practice performance. We used routinely available administrative data for the whole analysis. General practice characteristics and two selected performance indicators: the asthma prophylaxis to bronchodilator ratio and cervical cytology screening rate, for all practices in the East London and the City Health Authority for 4 y, 1993-1996, were used. Both reflect practice efficiency, but relate to different aspects of practice performance. The prescribing indicator is more indicative of the quality of clinical practise, whereas cervical screening coverage relates more to the characteristics of the practice population and to practice organisation. Repeated measures analyses were used to identify trends and to explore the relationship between changes in practice characteristics and performance. Graphical methods were used to compare East London trends with the rest of England. There were significant improvements in practice structure as the consequence of London Initiative Zone investment. There was a positive association with improvements in practice performance, but East London still lagged some way behind national patterns. The findings suggest that while improvements in asthma prescribing follow the national trend, practices have difficulty in achieving and sustaining the 80% target for cervical cytology screening, and that an overall population coverage of 80% may be in doubt.Increased investment in practice staffing may be influential in improving some aspects of performance. However, in common with other inner cities, a greater effort and more innovative strategies may be needed to achieve a standard of performance equal to the best.

Anti-Asthmatic Agents↗
PubMed2003

The effect of surface coverage on conformation changes of bovine serum albumin molecules at the air-solution interface detected by sum frequency generation vibrational spectroscopy.

The air-BSA solution interface has been investigated by various techniques for years. From these studies we know that BSA molecules segregate at the BSA solution-air interface, and the surface coverage increases with the increase of the bulk solution concentration. However, questions still remain as to whether the protein changes conformation, orientation, or a combination of the two upon adsorption. In this paper, by using sum frequency generation (SFG) vibrational spectroscopy we found that the conformation of interfacial BSA molecules changes dramatically at the solution-air interface, compared to that of the native BSA in solution. The hydrophobic methyl groups of BSA molecules at this interface tend to align along the surface normal. The degree of such conformational changes of surface BSA molecules depend on the surface coverage, indicating that the protein-protein interaction plays a very important role in determining the conformation of interfacial protein molecules. At very low surface concentration, the adsorbed BSA molecules unfold substantially. Our results can provide a molecular interpretation of results obtained from other studies such as protein layer thickness and surface tension measurements of protein solution.

Journal Article↗
PubMed2006

Microkinetic modeling of CO TPD spectra using coverage dependent microcalorimetric heats of adsorption.

CO adsorption on the ternary methanol synthesis Cu/ZnO/Al2O3 catalyst was studied in detail by means of adsorption microcalorimetry and flow temperature-programmed desorption (TPD). Based on these experimental data, we established a microkinetic analysis method, which provides information about the adsorption kinetics of CO on the catalyst surface. Experimentally derived microcalorimetric heats of adsorption were applied in a microkinetic model to simulate TPD curves with varying initial coverage. Two approaches were used: an integral approach based on evaluation of the integral heats of adsorption which predicts the experimental TPD curves roughly and provides first approximations for the preexponential factors. The second, more detailed approach was based on the simulation of the adsorption isotherm taking the experimentally determined coverage-dependence of the heat of adsorption into account. This approach led to a significantly improved agreement between experimental and simulated TPD curves. Moreover, it was possible to derive the standard entropy of adsorption. The general applicability of our approaches is demonstrated by analyzing the CO TPD and microcalorimetry data obtained with a binary ZnO-free Cu/Al2O3 catalyst.

Journal Article↗
PubMed2001

Changes in Expanded Program for Immunization coverage for mother and child in Krakor, Cambodia 1996--1998.

We evaluated a training intervention aimed at enhancing the roles of health centre staff, Village Health Volunteers (VHVs) and Traditional Birth Attendants (TBAs) within the Expanded Program for Immunization (EPI) in the district of Krakor, Cambodia. We conducted population-based surveys to determine the coverage of the EPI at baseline (1996) and after the intervention (1998), using data from health cards for mothers and their children and history data. Statistically significant changes over the 2-year period were apparent for tetanus, BCG, polio and DTP, supporting the positive impact the training intervention had on immunization coverage in the district.

Adult↗
PubMedDate not supplied

The distally based sural artery flap for ankle and foot coverage.

The sural artery flap is a distally based fasciocutaneous flap that has many advantages to offer for coverage in the foot and ankle area. It has the largest arc of rotation of all the regional flaps and does not require sacrifice of any major artery, and moderate-to-large-sized defects can be covered adequately. The dissection technique is simple, and donor site morbidity is minimal. We report our experience with 17 cases. Age range was from 13 to 56 years. Ten (59%) defects were posttraumatic, 3 (17%) were related to reconstructive surgery of the foot or tendon Achilles', 2 (11%) resulted from tumor resection, and 1 each were from infection and gunshot wound. The smallest flap was 6 x 4 cm and the largest was 15 x 12 cm, with the average size being 11 x 7.5 cm. In 5 cases, the donor site was closed primarily, and in other cases, split-thickness skin graft was needed. The short saphenous vein was included in the pedicle in all cases. There was no incidence of complete flap necrosis. Follow-up ranged from 3 to 30 months. Two cases (12%) developed partial superficial necrosis. In 1 case, there was partial wound dehiscence that needed debridement and repair. Another case had postoperative discharge, which subsided after removal of the calcaneal plate. None of the patients complained of any functional problem related to loss of sensation along the lateral border of the foot. The sural island flap is a reliable, safe, and easy method of providing soft tissue coverage in the area of the foot and ankle.

Adolescent↗
PubMed2001

Modified dorsalis pedis flap for coverage of a pretibial pressure sore after hip rotationplasty.

Rotationplasty is a well-established procedure after total femur resection, especially in children. Rehabilitation is superior to disarticulation of the hip or hemipelvectomy because patients regain hip and knee function.(1) A tight fit of the prosthetic shaft is essential. The pretibial area has a low physiological resistance to pressure and shear forces, and is thus at increased risk of developing pressure-related complications. Skin defects with exposure of skeletal elements require flap coverage. The dorsalis pedis flap is one of the surgical options available for skin coverage of the proximal anterior leg. It can be rotated to cover almost any site on the anterior aspect of the leg if the pedicle is mobilised up to the anterior tibial artery.(2)Since donor site complications are common, this flap has few indications.(3)

Antineoplastic Agents↗
PubMed2000

[Strategy for defect coverage in extensive degloving and crush injuries of 4 fingers].

Severe crush injuries with avulsion require specific treatment strategies. Usually we find complete loss of soft tissue, nerves and vessels, where only tendons and parts of the phalanges are preserved. Primary reconstructive procedures are usually not possible due to the complexity of the injury with severely destroyed structures. Bone shortening should be avoided in order to maintain finger length and motion. Therefore, emergency soft-tissue coverage represents the first step. Later, sensibility and mechanical stability of the skin should be restored. In our clinic, seven patients with this injury pattern were treated. Three cases involved four finger crush-avulsion injuries. In all cases, we performed a primary soft-tissue coverage with a pedicled flap. In a second session, the skin areas of the first web space of both feet were transplanted as neurovascular flaps. With this strategy, a useful hand function could be restored. The functional results are described and advantages and disadvantages of various techniques discussed.

Adult↗
PubMed2001

[Revascularization and defect coverage of the hand: special applications of the radialis forearm flap].

During the last years, a large number of newly designed flaps have been presented, suitable to cover defects of the hand. Some of them, namely the retrograde interossea-posterior and the lateral arm flaps, found their way into daily clinical routine. They even seem to have replaced the standard flaps for defect coverage to the hand, the pedicled groin flap and the radial forearm flap. Especially the radial forearm flap seems to become an obsolete procedure, as it requires sacrificing a main forearm artery. Three patients are presented who suffered from complex injuries to their hands and were treated with radial forearm flaps in a single-stage primary procedure. In two hands, the arterial palmar arches and the soft-tissues of the palm were reconstructed by use of a distally pedicled radial forearm flap. Collateral arteries of ischemic fingers were implanted into the flap artery to achieve revascularization and a vein graft was interposed between the stumps of the radial artery to reestablish an orthograde blood flow. A free radial forearm flap harvested from the contralateral uninjured forearm was used to replant a torn-out forearm. In all cases, primary healing was achieved without complications. Primary treatment of complex injuries to the hand and forearm often requires revascularization of ischemic parts of the limb and coverage of large soft-tissue defects at the same time. The radial forearm flap, either as a distally pedicled flap or as a free flap, meets all the needs or in particular is appropriate to perform such demanding primary procedures. The destruction of the arterial palmar arches does not present a contraindication against the use of a distally pedicled radial forearm flap, but actually is a strong indication to reconstruct the radial artery by a vein graft.

Adolescent↗
PubMed2001

[Distal pedicled sural island flap-plasty for defect coverage of the distal lower extremity].

Soft tissue defects on the distal lower extremity often need extended reconstructive procedures, especially if tendinous, articular, or bony structures are exposed. The use of local flaps in the perimalleolar, pretibial and calcaneal area is limited, often free tissue transfer is required. The distally based sural island flap is a pedicled soft-tissue flap on the vascular axis of the sural nerve. It can be raised as a fasciocutaneous or a lipofascial flap. We report our experience of 16 cases, nine of these cases in the lipofascial technique. The aim of soft tissue coverage was reached in 15 cases. In one patient a partial necrosis of the flap occurred requiring a reoperation with free flap coverage. The main advantages of the technique are the extended arc of rotation in the problematic area of the ankle and the lower extremity, the easy and fast preparation and the stable flap perfusion. The lipofascial as well as the fasciocutaneous flap have some risk of loss or donor-site morbidity that can be avoided by adhering strictly to certain operative principles.

Adolescent↗
PubMed2004

[Consequences of the press coverage for the doctor/patient-relationship].

The influence of press coverage is very important for the doctor-patient relationship. On the one hand nowadays the media provides the possibility to get informed by the media in advance. On the other hand it sometimes leads to grotesque over reactions on certain medical innovations. Often a simple solution is offered too fast. For example the side-effects of drugs are demonstrated in an absolutely exaggerated way. In this article examples for both, the positive and the negative effects of press coverage on medical issues, are presented.

Drug-Related Side Effects and Adverse Reactions↗
PubMed2005

[The vaccination coverage among children aged 24 - 30 months in pediatric offices November 1999 - May 2001. The influence of socio-demographic characteristics].

BACKGROUND: The goal of this study was to investigate the influence of socio-demographic factors on vaccination coverage of 24-30 month old children in paediatric practices. METHODS: Vaccination coverage (VC) was documented for 15,682 children in 196 paediatric practices mainly in the region of Nordrhein. Data on socio-demographic factors were collected for 8,457 children and their influence on the vaccination status (VS) was investigated by means of logistic regression analysis. RESULTS: Complete age-appropriate VC for all vaccines recommended by the Standing Committee for Vaccination (STIKO) was 49.9 %. Complete VC for Diphtheria/Tetanus (DT) was 74.6 % and for first dose measles/mumps/rubella (MMR), 82.1 %. The following factors were associated with complete VS for DT and MMR: completion of last recommended well-child visit, parents living together, low number of siblings, short time to reach practice, parents stating they felt adequately informed about vaccinations. Complete vaccination for DT was inversely associated with being health insured through social security and for MMR with the mother having graduated from high school. CONCLUSIONS: A high proportion of 24-30 month old children did not have an age appropriate VS. Targeted parental education and timely vaccination strategies that take into account socio-demographic risk factors for low vaccination uptake are required.

Child, Preschool↗
PubMed2006

[Vacuum-assisted closure as temporary coverage in the "problem zone hand"].

INTRODUCTION: Vacuum therapy of hand defect problematic due to the interdigital folds and in particular due to the small surface. As a temporary cover in staged procedures, e. g. following excision of tumor-suspicious skin alterations at the hand, and/or at the fingers, the application of vacuum therapy results not only in a sterile, temporary cover of the wound, furthermore it promotes wound conditioning and reduction of the wound area as well as lymph and edema reduction. PATIENTS AND METHODS: A 75 year old female patient presented herself with a skin alteration at the right dorsal ring finger and the tentative diagnosis of a Morbus Bowen like lesion was raised. Due to the unclear histological status, a staged procedure with excision of the tumour and temporary defect coverage by means of vacuum therapy until final histological evaluation was indicated. We accomplished the radical excision of the unclear skin tumour at the proximal phalanx under preservation of the synovial sheath of the tendon. Subsequently, the wound was temporarily closed with vacuum therapy. Histological examination revealed the complete removal of a solar keratosis. Finally, after 7 days of vacuum therapy as a sterile dressing, with obvious reduction of wound area and simultaneous decrease of edema, the defect was finally covered with a reversed cross finger flap from the adjacent middle finger. The donor site was covered with a full thickness skin graft harvested from the right forearm. The further course was without complication after flap dissection and complete healing. DISCUSSION: Vacuum therapy represents a usefull procedure for temporary wound coverage. Especially at hand defects, when nerves, tendons or bones following trauma or staged procedures are exposed, vacuum therapy can be successfully applied utilizing the special surgical "hand glove" technique.

Aged↗
PubMed1993

Management of chronic achilles tendon infection with musculotendinous gracilis interposition free-flap coverage.

Management of infected Achilles tendon repair poses a significant reconstructive problem. Thorough debridement is most important and resection of non-viable tendon substance is required. Reconstruction of such tendon defects requires vascularized soft-tissue coverage that is stable and that offers the possibility of functional restoration. Gracilis free-tissue transfer is an effective means of providing stable, durable, well-vascularized, soft-tissue coverage in an infected Achilles tendon repair. The microsurgical anastomoses are technically straightforward. Cybex II dynomometer measurements, performed 6 months following free-tissue transplantation, revealed strength (torque) and power, at an angular velocity of 45 degrees per second, of: 59 percent and 52 percent, respectively, compared to the uninjured side. Endurance was assessed at an angular velocity of 120 degrees per second over a 15-second test interval, and was noted to be 81 percent, compared to the normal ankle. Excellent functional results and acceptable soft-tissue contour can be expected with this technique.

Achilles Tendon↗