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Closed head injury and the treatment of sequelae after a motor vehicle accident.

Approximately 2 million closed head injuries (CHIs) occur yearly in the United States. Twenty-five percent of these injuries require hospitalization, and 70,000 to 90,000 of those hospitalized suffer long-term disability. This case conference details one such case of CHI in which the patient ultimately died. Close attention is given to the pathophysiology and treatment of this process. Commonly accepted, as well as investigational, modalities of therapy are discussed.

Accidents, Traffic↗

Modeling the active sites in metalloenzymes 5. The heterolytic bond cleavage of H(2) in the [NiFe] hydrogenase of desulfovibrio gigas by a nucleophilic addition mechanism.

The H(2) activation catalyzed by an Fe(II)-Ni(III) model of the [NiFe] hydrogenase of Desulfovibrio gigas has been investigated by density functional theory (DFT/B3LYP) calculations on the neutral and anionic active site complexes, [(CO)(CN)(2)Fe(mu-SH)(2)Ni(SH)(SH(2))](0) and [(CO)(CN)(2)Fe(mu-SH)(2)Ni(SH)(2)](-). The results suggest that the reaction proceeds by a nucleophilic addition mechanism that cleaves the H-H bond heterolytically. The terminal cysteine residue Cys530 in the [NiFe] hydrogenase active site of the D. gigas enzyme plays a crucial role in the catalytic process by accepting the proton. The active site is constructed to provide access by this cysteine residue, and this role explains the change in activity observed when this cysteine is replaced by a selenocysteine. Furthermore, the optimized geometry of the transition state in the model bears a striking resemblance to the geometry of the active site as determined by X-ray crystallography.

Binding Sites↗

Exploring the scope of the 29G12 antibody catalyzed 1,3-dipolar cycloaddition reaction.

[Chemical reaction: See text] 29G12 is a murine monoclonal antibody programmed to catalyze the regio- and enantioselective 1,3-dipolar cycloaddition reaction between 4-acetamidobenzonitrile N-oxide 1a and N,N-dimethylacrylamide 2a (Toker, J. D.; Wentworth, P., Jr.; Hu, Y.; Houk, K. N.; Janda, K. D. J. Am. Chem. Soc. 2000, 122, 3244). Given the unique nature of 29G12 as a protein biocatalyst for this chemical reaction, we have investigated both the substrate specificity and mechanistic parameters of the 29G12-catalyzed process. These studies have shown that while 29G12 is specific for its dipole substrate 1a, the antibody is highly promiscuous with respect to the dipolarophiles it can process. 29G12 accepts a bulky hydrophobic dipolarophile cosubstrate, with rates of product formation up to 70-fold faster than with the original substrate 2a. In all cases, the respective isoxazoline products are produced with exquisite regio- and stereochemical control (78-98% ee). Comparison between the steady-state kinetic parameters from the 29G12-catalyzed reaction of 1a with the most efficient versus the original dipolarophile cosubstrate (2m and 2a, respectively), reveals that while the effective molarities (EM)s are almost identical (EM(2m)) 26 M; EM((2a)) 23 M), the affinity of 29G12 for the larger dipolarophile 2m is more than 1 order of magnitude higher than for 2a [Km(2m) 0.44 +/- 0.04 mM; Km(2a) 5.8 +/- 0.4 mM]. Furthermore, when 2m is the cosubstrate, the affinity of 29G12 for its dipole 1a is also greatly improved [Km(1a) 0.82 +/- 0.1 mM compared to Km(1a) 3.4 +/- 0.4 mM when 2a is the cosubstrate]. An analysis of the temperature dependence of the 29G12-catalyzed reaction between 1a and 2m reveals that catalysis is achieved via a decrease in enthalpy of activation (DeltaDeltaH 4.4 kcal mol(-1)) and involves a large increase in the entropy of activation (DeltaDeltaS 10.4 eu). The improved affinity of 29G12 for the nitrile oxide 1a in the presence of 2m, coupled with the increase in DeltaDeltaS during the 29G12-catalyzed reaction between 1a and 2m supports the notion of a structural reorganization of the active site to facilitate this antibody-catalyzed reaction.

Acrylamides↗

Effects of prebehavioral cognitive work on adolescents' acceptance of condoms.

Two educational strategies designed to promote condom use for sexually transmitted disease protection were tested in a field experiment involving 291 female, adolescent family planning clinic clients. The 1st strategy was designed to enhance attitude-behavior correspondence by increasing direct experience with handling condoms. The 2nd, a contingency-planning exercise, induced clients to generate a mental representation of negotiating condom use with a sexual partner. Both strategies were compared with the standard education. The dependent measures were condom acceptance (operationalized by the number of condoms taken), attitudes, and knowledge. Clients in the contingency-planning condition accepted about 60% more condoms than did other clients. Condom attitudes followed the same pattern, and knowledge did not differ among conditions.

Adolescent↗

Heme packing motifs revealed by the crystal structure of the tetra-heme cytochrome c554 from Nitrosomonas europaea.

Cytochrome c554 (cyt c554), a tetra-heme cytochrome from Nitrosomonas europaea, is an essential component in the biological nitrification pathway. In N. europaea, ammonia is converted to hydroxylamine, which is then oxidized to nitrite by hydroxylamine oxidoreductase (HAO). Cyt c554 functions in the latter process by accepting pairs of electrons from HAO and transferring them to a cytochrome acceptor. The crystal structure of cyt c554 at 2.6 A resolution shows a predominantly alpha-helical protein with four covalently attached hemes. The four hemes are arranged in two pairs such that the planes of the porphyrin rings are almost parallel and overlapping at the edge; corresponding heme arrangements are observed in other multi-heme proteins. Striking structural similarities are evident between the tetra-heme core of cyt c554 and hemes 3-6 of HAO, which suggests an evolutionary relationship between these redox partners.

Amino Acid Sequence↗

[Body image in gynecologic patients before and after radical surgery].

After radical gynecologic surgery women are faced with therapy-induced changes of their body. Since 1995, the body images of women who undergo pelvic exenteration, Wertheim-Meigs-operation or hysterectomy are assessed preoperatively and four and twelve months postoperatively. The aim of this multidimensional prospective study is to get basic information for effective counselling and support. One year after hysterectomy women state to have a normal body image. Cancer patients feel less attractive, less self-confident and more discontented in sexuality depending on therapy-induced changes of their bodies. These women could profit from problem-related preoperative counselling. Postoperative counselling offers will be helpful to support women in the process of acceptance of bodily changes and in the reorganisation of their sexual life.

Body Image↗

Application of genome-wide expression analysis to human health and disease.

The application of genome-wide expression analysis to a large-scale, multicentered program in critically ill patients poses a number of theoretical and technical challenges. We describe here an analytical and organizational approach to a systematic evaluation of the variance associated with genome-wide expression analysis specifically tailored to study human disease. We analyzed sources of variance in genome-wide expression analyses performed with commercial oligonucleotide arrays. In addition, variance in gene expression in human blood leukocytes caused by repeated sampling in the same subject, among different healthy subjects, among different leukocyte subpopulations, and the effect of traumatic injury, were also explored. We report that analytical variance caused by sample processing was acceptably small. Blood leukocyte gene expression in the same individual over a 24-h period was remarkably constant. In contrast, genome-wide expression varied significantly among different subjects and leukocyte subpopulations. Expectedly, traumatic injury induced dramatic changes in apparent gene expression that were greater in magnitude than the analytical noise and interindividual variance. We demonstrate that the development of a nation-wide program for gene expression analysis with careful attention to analytical details can reduce the variance in the clinical setting to a level where patterns of gene expression are informative among different healthy human subjects, and can be studied with confidence in human disease.

Cluster Analysis↗

Expression of two succinyl-CoA synthetases with different nucleotide specificities in mammalian tissues.

For nearly 50 years, succinyl-CoA synthetase in animals was thought to be specific for guanine nucleotides. Recently, we purified and characterized both an ADP-forming succinyl-CoA synthetase from pigeon breast muscle and the GDP-forming enzyme from liver (Johnson, J. D., Muhonen, W. W., and Lambeth, D. O. (1998) J. Biol. Chem. 273, 27573-27579). Using the sequences of the pigeon enzymes as queries in BLAST searches, we obtained genetic evidence that both enzymes are expressed in a wide range of animal species (Johnson, J. D., Mehus, J. G., Tews, K., Milavetz, B. I., and Lambeth, D. O. (1998) J. Biol. Chem. 273, 27580-27586). Here we extend those observations by presenting data from Western and Northern blots and enzymatic assays showing that both proteins are widely expressed in mammals with the relative amounts varying from tissue to tissue. We suggest that both succinyl-CoA synthetases catalyze the reverse reaction in the citric acid cycle in which the ADP-forming enzyme augments ATP production, whereas the GDP-forming enzyme supports GTP-dependent anabolic processes. Widely accepted shuttle mechanisms are invoked to explain how transport of P-enolpyruvate across mitochondrial membranes can transfer high energy phosphate between the cytosol and mitochondrial matrix.

Adenosine Diphosphate↗

Use of ethnographic research for instrument development in a case-control study of immunization use in Haiti.

A rapid ethnographic assessment of barriers to health service utilization was conducted to identify maternal factors predicting use of child immunizations in Haiti. Methods included four focus group interviews, four natural group interviews, individual interviews with 14 health care providers and participant observation at vaccination posts. Analysis of qualitative data identified five categories of maternal factors associated with immunization use: competing priorities, low motivation, socioeconomic constraints, perceived accessibility of services, fears about health or social consequences and knowledge and folk beliefs related to vaccines. Selected variables among these factors were incorporated into a survey instrument designed to compare mothers of completely vaccinated children (cases) with mothers of incompletely vaccinated children (controls). The questionnaire was administered to 299 randomly selected mothers (217 cases, 82 controls). Bivariate and multivariate analyses found that of the factors identified through ethnographic research, only vaccine-related knowledge was significantly associated with immunization status. The utility and constraints of using ethnographic research for instrument development in epidemiological studies are discussed.

Case-Control Studies↗

Epidemiological models and related simulation results for understanding of contraceptive adoption in India.

BACKGROUND: For the first time, models using multilevel analysis of Indian data and related simulation results are reported. They take hierarchical structure into account and incorporate variables from all levels to get correct analysis and proper interpretation of data on current contraceptive use (including sterilization and modern methods). METHODS: The data from an Indian State, Uttar Pradesh (UP), collected by the National Family Health Survey (NFHS) conducted during 10 October 1992 to 22 February 1993 was used. For model I, 7851 currently married women who were neither pregnant nor had continuing post-partum amenorrhoea (PPA) were considered. For model II, these women with at least one child (n = 6748) were used. Two-level logistic regression analysis was carried out for which women's level (level 1) and PSU (Primary Sampling Unit) level (level 2) variables were considered. The results were considered significant at the 5% level of significance. Simulation analysis using each model was also carried out. RESULTS: Model I reveals that those more likely to adopt contraception were women exposed to a TV message (odds ratio [OR] = 1.3; 95% CI: 1.1-1.6); whose houses were pucca (bricks and mortar) (OR = 1.3; 95% CI: 1.1-1.5); who were educated to high school level and above (OR = 2.9; 95% CI: 2.2-3.7); whose husbands were literate with schooling of > or =11 years (OR = 1.7; 95% CI: 1.4-2.1); and who had > or =2 living sons (OR = 2.2; 95% CI: 1.1-4.4). Muslim and other religious women were less likely than Hindu women to adopt contraception (OR = 0.5; 95% CI: 0.4-0.6). Also, the PSU level availability of all weather road was positively associated with contraceptive adoption (OR = 1.4; 95% CI: 1.1-1.7). The PSU level variance, which is the unexplained PSU level variation after controlling for the considered characteristics, was significantly higher. The simulation results revealed that public health education (a TV message) was found to be more effective among less educated women. The PSU level availability of all weather road was as effective as public health education. Similar results were evident from the analysis of second data set (model II) with the noticeable finding that those whose last child is surviving are most likely to adopt contraception (OR = 8.82; 95% CI: 1.01-77.38). CONCLUSIONS: These results reveal that the survival status of the last child has a marked effect on the adoption of contraception in UP. They further support the idea that public health education (a TV message) is more effective among less educated women. Also, the PSU level presence of all weather road is equally effective. Consideration of higher level variables provides not only more accurate results but also important public health clues to help the policy planners.

Adolescent↗

Folate metabolism and requirements.

Folate functions in multiple coenzyme forms in acceptance, redox processing and transfer of one-carbon units, including nucleotides and certain amino acids. Folate-requiring metabolic processes are influenced by folate intake, intake of other essential nutrients, including vitamins B-12 and B-6, and at least one common genetic polymorphism. Estimates of folate requirements have been based on intakes associated with maintenance of normal plasma and erythrocyte folate concentrations and functional tests that reflect abnormalities in folate-dependent reactions. Dietary Reference Intakes for folate that have been developed recently are based primarily on metabolic studies in which erythrocyte folate concentration was considered the major indicator of adequacy. For adults >/=19 y, the Recommended Dietary Allowance (RDA) is 400 microg/d of dietary folate equivalents (DFE); for lactating and pregnant women, the RDAs include an additional 100 and 200 microg of DFE/d, respectively.

Adolescent↗

Feasibility of hospital-based use of peer ratings to evaluate the performances of practicing physicians.

PURPOSE: To address the feasibility of obtaining reliable evaluations of individual physicians from peer ratings undertaken at diverse hospitals. METHOD: Eleven hospitals in diverse locations in the United States were recruited to participate. With the aid of the hospitals' medical directors, up to 40 board-certified internists with admitting privileges were recruited per hospital. Participating physicians provided demographic data about themselves and nominated physician-associates to do peer ratings. Between April 1993 and January 1994, the physicians were rated by their peers, who received a single mailing with no follow-up. The raters used a nine-point Likert scale for 11 cognitive and noncognitive categories. Administrative procedures were coordinated from the American Board of Internal Medicine. Chi-square, Student's t-test, and factor analysis using varimax rotation were used to analyze the results. RESULTS: Of the 4,139 questionnaires that were mailed to peer raters, 3,005 (73%) were returned. Of the 228 physicians who were rated, 187 received ten or more usable ratings, which were used for further analysis. The findings confirmed the results of previous research. The highest mean rating was for the category of integrity, and the lowest was for the category of psychosocial aspects of care. Ten to 11 responses per physician were necessary to achieve a generalizability coefficient of .7. Nearly 90% of the variance in the ratings was accounted for by two factors, one representing cognitive and clinical management skills and the other, humanistic qualities. For 16 physicians (9%), the ratngs of overall clinical skills were less than 7 on a scale from 1 (low) to 9 (high); their ratings for all individual cognitive and noncognitive categories were below the ratings of the other physicians. CONCLUSION: The peer raters' response rate and the analysis of the ratings suggest that the rating process is acceptable to physicians and that it is feasible to obtain reliable, multidimensional peer evaluations of individual physicians practicing in diverse clinical settings.

Employee Performance Appraisal↗

Chernobyl post-accident management: the ETHOS project.

ETHOS is a pilot research project supported by the radiation protection research program of the European Commission (DG XII). The project provides an alternative approach to the rehabilitation of living conditions in the contaminated territories of the CIS in the post-accident context of Chernobyl. Initiated at the beginning of 1996, this 3-y project is currently being implemented in the Republic of Belarus. The ETHOS project involves an interdisciplinary team of European researchers from the following institutions: the Centre d'etude sur l'Evaluation de la Protection dans le domaine Nucleaire CEPN (radiological protection, economics), the Institute National d'Agronomie de Paris-Grignon INAPG (agronomy, nature & life management), the Compiegne University of Technology (technological and industrial safety, social trust), and the Mutadis Research Group (sociology, social risk management), which is in charge of the scientific co-ordination of the project. The Belarussian partners in the ETHOS project include the Ministry of Emergencies of Belarus as well as the various local authorities involved with the implementation site. The ETHOS project relies on a strong involvement of the local population in the rehabilitation process. Its main goal is to create conditions for the inhabitants of the contaminated territories to reconstruct their overall quality of life. This reconstruction deals with all the day-to-day aspects that have been affected or threatened by the contamination. The project aims at creating a dynamic process whereby acceptable living conditions can be rebuilt. Radiological security is developed in the ETHOS project as part of a general improvement in the quality of life. The approach does not dissociate the social and the technical dimensions of post-accident management. This is so as to avoid radiological risk assessment and management being reduced purely to a problem for scientific experts, from which local people are excluded, and to take into consideration the problems of acceptability of decisions and the distrust of the population towards experts. These cannot be solved merely by a better communication strategy. This paper presents the main features of the methodological approach of the ETHOS project. It also explains how it is being implemented in the village of Olmany in the district of Stolyn (Brest region) in Belarus since March 1996, as well as its initial achievements.

Animals↗

Screening process to discover insured persons in need of rehabilitation.

In order to prevent early retirements in Germany, medical rehabilitation measures are implemented among workmen and salaried employees whose fitness for work is jeopardized or diminished. Only around half of those retiring early take advantage of these measures in the last 5 years prior to retirement. To increase the numbers making use of rehabilitation measures, we developed a screening process whereby the pension insurance institutions responsible for the measures are able to identify insured persons in need of rehabilitation and urge them to take part. The screening process comprises two stages: written questioning to determine the probable risk cases by means of predictors of early retirement, and medical clarification of these cases by means of a standardized rehabilitation assessment. The screening process and devices were tested in an experimental trial involving 600 people aged between 45 and 54 insured with a pension insurance institution responsible for workers in the Stuttgart area. Main results were: (1) The screening process was accepted by the insured. Around 70% of the insured took part in the screening. (2) The questionnaire is suitable for pre-selection of the probable risk cases that require medical clarification. Given complete answers, 83% of the cases were correctly classified in comparison with the judgement of the pension insurer's physicians. (3) The screening was effective, i.e. it increased the participation of insured persons in need of rehabilitation in rehabilitation measures. Compared with a control random sample, in the experimental trial, 70% more rehabilitation measures were applied for and approved.

Aged↗

Postoperative quality of life in vestibular schwannoma patients measured by the SF36 Health Questionnaire.

OBJECTIVE: To quantify the postoperative quality of life in patients following surgical treatment for vestibular schwannoma. STUDY DESIGN: Patient self-assessment using the short form 36 (SF36) multidimensional quality of life health questionnaire. Sex- and age-matched normalized scores were calculated using a standardized process and accepted normative data. SETTING: Tertiary referral skull base unit. RESULTS: An 80% response rate (90 patients) was achieved. The postoperative quality of life in vestibular schwannoma patients, as quantified by seven of the eight SF36 health scales was less than the appropriate matched healthy standard. Comparison of a variety of preoperative patients and tumor factors-different operative approaches (translabyrinthine and retrosigmoid), tumor size (group cut of points of tumor diameter 1.5 mm and 2.5 mm), patient sex, and ranking of patient age-showed no statistically significant difference in measured quality of life outcomes for each of these traditional predictors. CONCLUSION: Reduced quality of life in patients after surgical treatment for vestibular schwannoma, coupled with the low tumor growth rates and minimal preoperative symptoms, supports a conservative approach to patient management. The advantages and disadvantages of a variety of approaches used to measure the quality of life after surgical treatment of vestibular schwannoma and their impact on clinical decision making for patients, are discussed.

Adult↗

Logistics and transplant coordination activity in the GRAGIL Swiss-French multicenter network of islet transplantation.

BACKGROUND: Since the Edmonton trial in 2000, increasing numbers of transplant centers have been implementing islet transplantation programs. Some institutions have elected to associate in multicenter networks, such as the Swiss-French GRAGIL (Groupe Rhin-Rhône-Alpes-Genève pour la Transplantation d'Ilots de Langerhans) consortium. METHODS: All pancreata offers to the University of Geneva Cell Isolation and Transplantation Center from within the network in 2002 and 2003 were reviewed. Islet preparations were attributed to the most suitable recipient on a centrally managed waiting list. All shipments were performed by ambulance in less than 5 hr. RESULTS: Over the period of study, 260 pancreata were offered, from a total of 1,304 cadaveric donors in the four allocation regions (20%). Fifty-two patients were on the waiting list at any time during this 2-year period. The percentage of organs offered varied in the range of 0.5% to 42%, depending on region of origin, with a correlation with number of patients on the waiting list in each region. Of these, 104 (40%) were accepted for processing. Ninety-two pancreata were actually processed, resulting in 42 islet preparations being transplanted. The number of international equivalents of transplanted preparations was 378,500+/-16,000 versus 165,400+/-15,400 (P<0.0001) for nontransplanted preparations. Total cold ischemia time was 6+/-0.3 hr for transplanted preparations versus 6.7+/-0.4 hr for nontransplanted preparations (not significant). CONCLUSIONS.: A high rate of pancreas offers, successful isolation, and islet transplantation can be achieved in multicenter networks such as GRAGIL. Such an approach can expand both the donor pool and the recipient population.

Adult↗

Statistical models for carbon-nitrogen film growth

We studied models of deposition and erosion, with two species of particles, that represent quantitatively many features of amorphous carbon-nitrogen film grown under plasma enhanced chemical vapor deposition. In the original model, the columns of the deposit are independent, and particles C and N are released with probabilities p and 1-p, respectively. An incident C particle always aggregates upon contact with the surface. An N particle annihilates with a top C particle with probability q and aggregates with probability 1-q. An N particle always annihilates with a top N. A critical line separates the regimes of growth (p>q/2) and erosion (p<q/2). For fixed q, when p decreases towards the critical value p(c)=q/2, the bulk concentration of N (x(N)) increases, and the growth rate r decreases. The rxx(N) curve for q=0.25 agrees with data from films grown in acetylene-nitrogen atmospheres. In order to represent the blocking of surface bonds by hydrogen atoms, we considered a second model in which any aggregation process is accepted with probability alpha, otherwise it is rejected. For q=0.25 and alpha=0.3, the rxx(N) curve agrees with data from films grown in methane-nitrogen and methane-ammonia atmospheres. The fitting values of q and alpha were inferred from related experiments. In order to test the influence of lattice structure and spatial correlations, we also studied those models in simple cubic lattices, considering that the aggregation must satisfy the restricted solid-on-solid model conditions for the difference of heights in neighboring columns, while the erosion is random. We obtained similar results for rxx(N) curves, confirming the validity of those models to represent the kinetics of amorphous films growth. It was also observed that the surface roughness increases with x(N), which agrees qualitatively with several experiments on carbon-nitrogen films growth with ion bombardment.

Journal Article↗