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Background: Primary total hip arthroplasty (THA) is an effective treatment for hip osteoarthritis, assessed by whatever distribution-based measures of responsiveness. Yet, the group level evaluation has provided very little evidence contributes to our understanding of the large variation of treatment outcome. The objective is to develop criteria that classify individual treatment health related quality of life (HRQOL) outcome after primary THA, adjusted by preoperative scores., Methods: We prospectively measured 147 patients' disease specific HRQOL on the date of consultation and 12 months post operation by Western Ontario McMaster Universities Osteoarthritis Index (WOMAC). Regression models were used to determine the "expected" outcome for a certain individual baseline score. The ceiling effect of WOMAC measurement is addressed by implementing a left-censoring method., Results: The classification criteria are chosen to be the lower boundary of the 95% confidence interval (CI) of the estimated median from the regression. The robustness of the classification criteria was demonstrated using the Monte-Carlo simulation., Conclusion: The classification criteria are robust and can be applied in general orthopaedic research when the sample size is reasonable large (over 500).

Purpose: We present extended follow-up findings of the Kingston prospective sizing program for patients with abdominal aortic aneurysm (AAA) smaller than 5.0 cm in diameter, with gender-specific analysis., Methods: From 1976 to 2001, 895 patients (688 men, 207 women) with AAA smaller than 5.0 cm were entered, regardless of fitness, in a prospective sizing program in which computed tomography scans were obtained every 6 months. Operations were performed in fit patients with an increase in AAA size to 5 cm (n = 190), AAA expansion greater than 0.5 cm in 6 months (n = 27), or for other reasons (n = 33). Follow-up continued until AAA rupture, surgery, death, or removal from the program., Results: No AAA smaller than 5.0 cm ruptured during prospective follow-up. There was a statistically significant increase in expansion rate relative to size at entry, with the highest mean expansion rate of 0.52 cm/y for AAA 4.5 to 4.9 cm in diameter. There was no significant difference in AAA expansion rate between men and women. The frequency of surgery was inversely related to age at entry, but was positively related to AAA size at entry, with patients with AAA 4.5 to 4.9 cm at entry 6.8 times more likely (95% confidence interval, 4.3-10.7) to undergo surgery than those with AAA 3.0 to 3.4 cm at entry. Women were older than men at entry, and age at entry in those undergoing surgery was significantly greater in women., Conclusions: The study confirms the results of the United Kingdom Small Aneurysm Trial and the Aneurysm Detection and Management Study, that is, that risk for rupture is extremely unlikely with AAA smaller than 5.0 cm, which enables safe follow-up surveillance programs in both men and women with AAA smaller than 5.0 cm.

A new approach to constructing the profiles of protein families is proposed, which uses only structural similarity of amino acid residues. We derived multiple alignments of protein sequences from 3D superpositions of the protein structures and constructed protein family profiles using structural molecular MNA descriptors. MNA (Multilevel Neighborhoods of Atoms) descriptors were developed earlier and are successfully applied for predicting the biological activity in drug-like compounds. In our approach, each aligned position was described by a set of MNA descriptors calculated for each amino acid residue in the alignment column. In this study, we constructed MNA profiles for trypsin, subtilase, and cytochrome P450 protein families and scanned SWISSPROT with some fragments of these profiles. We also calculated the Independence Accuracy of Prediction for each profile fragment. It was shown that the approach developed could be applied to predict protein function.

With the modern molecular biology techniques, it has been possible to detect, isolate and clone biological macromolecules, which could be used as immunogenes in artificial vaccine constructs. In the post-genomic era, the prospective immunogenic components are searched using bionformatic tools and proteomic technologies. Today it is quite realistic to combine the artificial vaccine constructs from the preselected molecular components. Existing computational methods are able to detect the potential immunogenes in genomic sequences, predict their characteristics and subcellular location. The set of methods is designed to predict the T- and B-epitopes that can be used as components of minimal vaccine constructs. The variety of systems for production and delivery of vaccines are developed and tested. These include transgenic plants, bacterial and viral vectors, DNA molecules etc. Several informational resources provide free access to molecular immunology data and deliver services on prediction of antigenic features. Several artificial vaccines have already been launched, but much more preparations are under preclinical and clinical trials. Computer-aided design of vaccines may significantly decrease time and costs required for their development. Modern bioinformatic technologies are now employed for discovery of more effective and potent vaccine.

Objective: The purpose of this study was to establish the risk of rupture as related to size of abdominal aortic aneurysm (AAA), gender, and expansion of the aneurysm., Methods: Between 1976 and 2001, 476 patients with conditions considered unfit for surgery with AAA 5.0 cm or more were followed with computed tomographic scans every 6 months until rupture, surgery, death, or deletion from follow-up. Surgery was performed for rupture (n = 22), improved medical condition (n = 37), increase in size (n = 95), symptoms (n = 17), and other reasons (n = 24)., Results: Fifty ruptures occurred during the follow-up period. The average risk of rupture (and standard error) in male patients with 5.0-cm to 5.9-cm AAA was 1.0% (0.01%) per year, in female patients with 5.0-cm to 5.9-cm AAA was 3.9% (0.15%) per year, in male patients with 6.0-cm or greater AAA was 14.1% (0.18%) per year, and in female patients with 6.0-cm or greater AAA was 22.3% (0.95%) per year., Conclusion: The risk of rupture in male patients with AAA 5.0 to 5.9 cm is low. The four-time higher risk of rupture in female patients with AAA 5.0 to 5.9 cm suggests a lower threshold for surgery be considered in fit women. The data regarding risk of rupture in patients with AAA 6.0 cm or more may allow more appropriate decision analysis for surgery in patients with unfit conditions with large AAA.

To analyze the interrelationships between the amino acid sequences of the proteins of hepatitis C virus and the functional characteristics of different variants of this virus, a database of protein functional mapping of hepatitis C virus was developed. The database contains amino acid sequences (both full-size and fragmentary) retrieved from accessible databases and experimental data published in literature. The database also contains the results of comparison and treatment of primary data, including alignments and functional regions. On the basis of these data, variable and conservative regions of envelope proteins of hepatitis C virus were revealed. Antigenic and functional maps of structural and nonstructural proteins of the virus were constructed. The most variable region of the envelope protein E2 (HVR1) was analysed. It is assumed that the conservatism of some amino acid positions of HVR1 is related to the functions of this region.

Study Objective: To demonstrate the effect of exclusion of data on delays in scheduling operations in calculating difference in admission rates between two enrolment periods., Design: A prospective cohort study; outcome measure-waiting time for elective admission; study variables-enrolment periods, before 31 March 1997 and after that date; the time of scheduling delay; gender; age; urgency, and type of surgery., Setting: An acute care hospital in Ontario, Canada., Participants: 1173 consecutive cases accepted for elective vascular surgery between 1 July 1994 and 31 March 1999., Main Results: Before adjustment for scheduling delays, a 20% lower admission rate was associated with period 2, rate ratio (RR) = 0.8 (95% confidence intervals (CI)= 0.7, 0.9). The difference between the periods became only marginally significant after the adjustment, RR = 0.9 (95% CI=0.8, 1.0). No difference between the periods was found when admission rates were compared before a delay occurred, RR = 0.9 (95% CI=0.8, 1.1). In delayed patients, those enrolled in period 1 and 2 had, respectively, a 40% and a 60% lower admission rate than the period 1 patients admitted without scheduling delays, RR = 0.6 (95% CI=0.4, 0.8) for period 1 and RR = 0.4 (95%CI=0.3, 0.5) for period 2., Conclusions: The results provide evidence that patients experiencing a delay in scheduling operation have a lower admission rate after the event. Thus, potential for bias exists when between group comparison of waiting time is done without adjustment for an intermediate event that may occur before elective admission.

Background: Referral pattern is a potential confounding factor when waiting-list performance is reported across hospitals or periods. A common concern is the ability to accurately estimate proportions of patients undergoing surgery in the recommended time without considering emergency caseload. In this study, the relation between emergency referrals and the rate of elective admissions to hospital within the recommended time was estimated., Design: A prospective cohort study., Setting: An acute care hospital in Kingston, Ont., Patients: Between 1994 and 1999, 1,173 consecutive patients accepted for elective vascular surgery., Main Outcome Measures: The proportion of patients who underwent surgery within the recommended time, and time to surgery., Study Variables: The weekly number of emergency cases, enrolment periods, urgency and type of surgery., Results: Overall, the proportion of patients who underwent surgery within recommended time was 0.45, (95% confidence interval [CI], 0.42-0.48). Adjusted for enrolment period, urgency and type of surgery, the estimated proportion was 0.57, (95% CI, 0.49-0.64). Compared with surgery for peripheral vascular disease, the odds of the procedure being done within the recommended time were 34% lower for aortic abdominal aneurysm repair and 41% lower for carotid endarterectomy. After adjustment for the case-mix and access attributes, the rate of elective admission within recommended time was on average 30% lower for weeks in which there were 1 to 2 emergency cases (rate ratio [RR] = 0.70, [95% CI, 0.53- 0.93]), and 39% lower for weeks with 3 or more emergency cases (RR = 0.61 [95% CI, 0.53-0.83]), relative to weeks with no emergency cases., Conclusions: When there is an increase in the number of emergency cases, a lower proportion of patients undergo elective surgery within the recommended time. Thus, when performance of surgical servces is evaluated, the probability of patients undergoing elective surgery on time should be adjusted relative to the number of emergency referrals.

Sequences of the E1 and E2 envelope proteins of hepatitis C virus (HCV) (827 non-identical items) were collected from available sources and aligned. Analysis of the alignment identified regions with different sequence variability. It was found that 33% and 50% of positions within E1 and E2, respectively, were highly conservative. Such conservation can be considered as the minimum for maintaining stability of the three-dimensional structure and function of these proteins. Conserved cysteines in E1 and E2 (eight and 18 residues, respectively) were presumed to form intramolecular disulphide bonds. Both envelope proteins were predicted to contain 14 conservative glycosylation sites. Two additional glycosylation sites were predicted in 58% of E1 and 30% of E2 sequences within the corresponding regions. We describe the positions of six conservative regions in E1 and E2, which have several charged and aromatic residues known to participate frequently in protein-protein recognition. Peculiarities in the amino acid content of conservative fragments and putative differences in glycosylation were considered with regard to antigenic specificity and possible binding to surface structures of target cells. We also analysed the hypervariable region 1 (HVR1), located in the E2 protein. Aligned positions of HVR1 were described in relation to the maintenance of conformational stability and recognition of cell receptors.

Objective: To review the variation in time spent on the waiting list for elective vascular surgery provided by a single team of specialists., Design: A prospective cohort study., Setting: An acute care hospital in Ontario., Population: One thousand and eighty-four consecutive patients with vascular problems accepted for elective surgery between 1994 and 1998., Interventions: Abdominal aortic aneurysm (AAA) repair; carotid endarterectomy (CAD); surgery for peripheral vascular disease (PVD); and arteriovenous fistula (AVF) for long-term access in patients with renal failure., Outcome Measures: Time-to-treatment curves, admission rates., Results: The weekly admission rate was 9.8% on average. The proportion of patients who underwent operation was 50% at 7 weeks, 75% at 14 weeks and 90% at 26 weeks. The weekly admission rate varied according to clinical priority, from 42% in priority class 1 to 6% in class 5. In any priority class, the admission rate was not constant over time. Although the proportion of patients operated on within the maximum recommended time in classes 1, 2, 3 and 4 was 52%, 50%, 35% and 20% respectively, the last 10% of patients waited 5 to 16 weeks, 10 to 16 weeks, 16 to 37 weeks, and 25 to 39 weeks respectively. There were statistically significant differences in waiting time by surgical procedure among the least urgent cases, with median times of 7, 10 and 19 weeks for AVF, PVD and CAD procedures, respectively., Conclusions: When queuing procedures are uniform, the waiting times for access to elective vascular surgery provided by the same team of specialists differ considerably for patients with equal surgical needs and urgency. It remains to be examined whether delays in scheduling operations and cancellations affect the waiting time after adjustment for urgency and comorbidity.

In the Zhytomyr region, about 52,000 measurements of the 131I activity in thyroids were performed. On the basis of these measurements, individual doses have been assessed for the people monitored and age-dependent average doses have been estimated for those settlements with more than 11 direct measurements. In order to estimate the pattern of thyroid exposure in the Zhytomyr region, these doses have been interpolated or extrapolated to population groups who were not monitored during May-June 1986. For this purpose, a model has been developed based on a correlation between thyroid dose estimates with the 137Cs deposition and the co-ordinates of the settlements relative to Chernobyl. Collective doses of people who were born in the years 1968 to 1986 were calculated. The radiation-induced thyroid cancer incidence in the period 1991 to 1995 was assessed by subtracting the spontaneous incidence from the observed incidence. The result is considerably lower than that observed in longer periods after external exposures. Possible reasons for this difference are discussed.

The thyroid cancer incidence in the Ukraine among those born in the period 1968-1986 was analyzed with the aim to identify the enhancement due to the Chernobyl accident. Since any Ukrainian data referring to the time period before the accident are scarce and the variation of spontaneous incidences in other countries is immense, the Ukrainian incidences in the period 1986-1989 were used to estimate the baseline risk. Following 1990, the incidence in the southern part of the Ukraine increased by about 30%, independent of age. In the other parts the increase of the incidence depended on age at exposure. In the age group of 9-year-old children, the incidences in three regions defined as the 'high-dose area', the northern, and the middle oblasts, increased by factors of 50, 20, and 6, respectively. These rates (1991-1995) are well above spontaneous rates in other countries. In the age group of 17-year-old juveniles, the incidence increased by a factor of 6 for the 'high dose area' and in the three northern oblasts, whereas in the nine 'middle' oblasts it was similar to the incidence of the 'southern' Ukraine. These rates are within the range found in other countries.

The thyroid doses of 49,360 inhabitants of Pripjat evacuated after the accident at Chernobyl were reconstructed. During their evacuation most of the evacuees passed through highly contaminated territories. The evaluation of a large-scale public survey showed that only about 50% of the evacuees had left the contaminated areas within 5 days and that 30% of them stayed there for more than 30 days. As a first step, the model of dose estimations was improved, and thyroid doses were assessed for the group of evacuees for whom the 131I activity in the thyroids was measured. The 131I incorporation during the first 5 days after the accident was described by a single-intake model (inhalation); later incorporations were assumed to be proportional to the radioiodine activity in milk. As a second step, the correlation between the calculated doses and individual parameters (place of residence in Pripjat, intake of stable iodine, and age at the time of the accident) was described by an empirical equation. This equation was applied to all evacuees who completed the questionnaires of the public survey. Previous dose assessments were found to overestimate the thyroid doses especially for the younger evacuees. On the basis of these estimations, collective doses and the resulting radiation risks for thyroid cancer were assessed for different age groups.

The problem of post-Chernobyl dosimetry is unique in its complexity in the history of radiation medicine and radiation protection. This is because the early experience of mass exposure of people (bombing of Hiroshima and Nagasaki, Windscale and South-Ural accidents, exposure of inhabitants of Nevada in the United States of America, the Semipalatinsk area in the former USSR, the Marshall Islands, and the Goiånia accident in Brazil, and others) differed both in the much simpler structure of the irradiation source and in the number and characteristics of exposed persons. It is obvious that post-Chernobyl dosimetry, both as an independent problem, and as a tool for epidemiological studies, requires significant expertise and economic and technical expenditures. Extensive and deep research has been carried out in Ukraine for the past 10 years. This article reviews the main results of these studies.

The bacteriophage T4 late gene wac (whisker's antigen control) encodes a fibrous protein which forms a collar/whiskers complex. Whiskers function as a helper protein for the long tail fibres assembly and plays a role in regulating retraction of the long tail fibres in response to environmental conditions. In this work we show that expression of the cloned wac gene in Escherichia coli yields a protein oligomer of 53 nm length which we call fibritin, and which is able to complement gpwac T4 particles in vitro. CD spectroscopy of fibritin indicates a 90% alpha-helical content, and scanning calorimetry shows that the protein has several distinct domains. The analysis of the 486 amino acid sequence of fibritin reveals three structural components: a 408 amino acid region that contains 12 putative coiled-coil segments with a canonical heptad (a-b-c-d-e-f-g)n substructure where the "a" and "d" positions are preferentially occupied by apolar residues, and the N and C-terminal domains (47 and 29 amino acid residues, respectively) have no heptad substructure. The distribution of hydrophobic residues within heptads is more similar to a triple than to a double coiled-coil. The alpha-helical segments are separated by short "linker" regions, variable in length, that have a high proportion of glycine and proline residues. Each coiled-coil segment has, on the borders with linker regions, residues that are common to the N and C-terminal caps of the alpha-helices. Full-length and amino-terminally truncated fibritins can be reassembled in vitro after temperature-induced denaturation. Co-assembly of full-length fibritin and the N-terminal deletion mutant, as well as analytical centrifugation, indicates that the protein is a parallel triple-standard alpha-helical coiled-coil. Deletions of various N-terminal portions of fibritin did not block trimerisation but the mutant trimers are unable to bind to T4 particles. The last 18 C-terminal residues of fibritin are required for correct trimerisation of gpwac monomers in vivo. We propose that fibritin might serve as a convenient model for the investigation of folding and assembly mechanisms of alpha-fibrous proteins.

Based on the results of 131I thyroid activity measurements in three districts of the Chernigov region (Ukraine), individual doses were calculated and an approach of the age dependence of the average thyroid exposure was derived. Using the relationships between the thyroid doses and the 137Cs deposition as well as the location relative to the Chernobyl Nuclear Power Plant (NPP), age-dependent average thyroid doses were extrapolated also for those settlements of this region where no monitoring measurements have been carried out. The highest doses were found in the west of the region with the lowest distance to the Chernobyl NPP. In this part, the highest mean of the thyroid dose in a settlement was 3.3 Gy for infants and 0.5 Gy for adults. The collective thyroid dose was 31,000 and 27,000 person-Gy for children and adults, respectively. Based on this assessment, 140 and 21 excess thyroid cancer cases are predicted for children and adults, respectively. In the years 1989 to 1991, in the whole contaminated territory of the Ukraine 0.4-1.2 cases per 100,000 children were observed. Although the absolute numbers are very small, this indicates the possibility of an increase in thyroid cancer morbidity among children. The same trend also seems to be indicated in the Chernigov region. A careful epidemiological study in the future is necessary to enable a final evaluation of radioinduced cancers in this region.

The bacteriophage T4 late gene wac (whisker antigen control) encodes the protein which forms the fibrous structure on the neck of the virion called whiskers. Amino acid sequence analysis of wac gene product, as deduced from the nucleotide sequence, indicate ten alpha-helical domains (19-40 residues long) with coiled-coil structural patterns. These regions comprise about 70% of the entire 486 amino acid sequence. The alpha-helices are separated by short stretches of polypeptide chain which are similar to the loop regions of the globular protein sequences. We propose a structural model for the dimer of wac gene product molecule, that we call fibritin in which two polypeptide chains associate in a parallel fashion and form a segmented alpha-helical coiled-coil rod similar to epidermal keratins.

Gene 22 of bacteriophage T4 encodes a major prohead scaffolding core protein of 269 amino acid residues. From its nucleotide sequence the gene product (gp) 22 has a predicted Mr of 29.9 and a pI of 4.3. The protein is rich in charged residues (glutamic acid and lysine) and contains low amounts of proline and glycine and no cysteine residues. We suggest that gp22 undergoes limited proteolytic processing which eliminates the short C-terminal piece from the molecule during the early steps of prohead assembly. Most amino acid residues of the gp22 polypeptide chain (80%) have an alpha-helical conformation and form seven peculiar alpha-helices. A model suggesting the spatial organization of gp22 is presented. Three long alpha-helices numbered 1 (1A and 1B), 3, and 5 (5A and 5B) are packed in an antiparallel fashion along the major axis of the road-shaped molecule. Two rather short alpha-helices (2 and 4) are located at the distal and proximal ends of the protein molecule, respectively. Helix number 2, which is a proteolytic fragment of gp22 found in mature T4 heads, is packed with helices 1A and 3, similar to a novel element of supersecondary structure, the alpha alpha-corner. Helix number 4 probably interacts with the gp20 connector of the prohead. The implications of the structure of the gp22 molecule for the assembly of the prohead core are discussed.