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脉压变异率（PPV）作为心肺交互的产物，是预测容量反应性的动态指标，但PPV预测急性呼吸窘迫综合征患者容量反应性受到诸多因素影响，如小潮气量通气、自主呼吸、腹内高压，此时可通过改变PPV阈值、潮气量挑战、叹息试验等方法提高其预测准确性；当PPV预测容量反应性准确性受到呼吸系统顺应性降低或右心功能不全影响时，则需要通过被动抬腿试验和呼气末阻断试验才能准确预测容量反应性。.

The mechanisms of crack nucleation and propagation of the lamellar microstructures found in pearlite were studied by in situ transmission electron microscopy. It was found that, in addition to the predominant mechanism of cleavage fracture in the cementite plates, ductile fracture of the cementite plates is another cracknucleation mechanism. The process of failure in the fully lamellar microstructure studied in the present investigation consists of four stages: dislocation pile-ups; single crack nucleation; distribution of crack nucleation; and crack growth, followed by final fracture. Through this study, a description of the lamellar microstructure fracture mechanism has been developed for numerical simulation in future studies.

Epitaxial growth of silicon on Si (001) surface has been studied with interatomic potential based molecular dynamics simulation method. Three silicon interatomic potentials developed separately by Stillinger-Weber, Tersoff, and Bazant-Kaxiras were used. Energetic beam of 8 eV, substrate temperature of 500K and deposition rate of 1.15 ps/atom were used as the deposition conditions. Morphologies of the growth were obtained and densities in the growth direction analyzed. Epitaxial growth under the deposition conditions imposed was found possible only using the Stillinger-Weber potential. Disordered growths of differing degree were obtained using the Bazant-Kaxiras and Tersoff potentials. The disordered growth may be attributed to the existence of an epitaxial transition temperature higher than 500K that these potentials might have.

Grain growth dependence of microstructure in La 2/3 Ba 1/3 MnO 3+δ oxides has been studied in detail. The result shows that the crystals grew along three vertical axes with a concentric terrace pattern in the sample sintered at 1673K while the oxides sintered at 1573K grew with a lateral growth manner. However, the concentric terrace growth pattern resulted in twin microstructure in the cooling processing and the lateral growth manner produced non-twin microstrcuture in the oxides at ambient, respectively. It was found that the oxide with twin microstructure has a much higher saturation magnetization than the non-twin oxide. This may be due to the easier alignment of the domains in the twin-grained oxide through the rearrangement of dislocations in twin-boundaries.

The interfacial characteristics of the TiSi 2/ Si structure were investigated in detail. It was found that the semi-coherent formed with a certain disregistry which was periodically taken up by the misfit dislocations between every three (030)C49 planes. The semi-coherent interface dominated the interfacial structure in the material and was responsible to the wavy surface of TiSi 2/ Si structure. However, the interface accommodated higher energy was a favorable nucleation sites for the C54 phase. Its existence may enhance the C54 phase formation in the further thermal treatments.

Ti thin film is widely used as a diffusion barrier to impede the Al/Cu migrating to the Si substrate in the applications requiring high temperature processes such as high temperature sputtering and reflow developed for via-filling. To improve the bottom coverage without losing the excellent diffusion blockage and other electronic properties, the ionized metal plasma (IMP) deposition technique has been developed. This method has better control of the angular distribution on the substrate, and thus has been used to deposit Ti as diffusion barriers for the subquarter micron device applications. However, the formation mechanism of the epitaxy Ti thin film deposited by ionic metal plasma deposition is not clear. In this work, the epitaxy Ti thin film has been characterized by the transmission electron microscope. The mechanism of the epitaxy Ti thin film formation and also the crystallographic relationship between the Ti and Al thin films in the IMP deposition have been analyzed in detail. The results show that the lattice image of the Ti layer in the sample as deposited has a square-block-like structure with the c axis perpendicular to the interfaces. This structure has anisotropic diffusion properties that can retard the diffusion of Al across the Ti layer in the initial stage of the high temperature Al sputtering or reflow processes.

We have performed a comparative study of Si (001) surface reconstruction employing molecular dynamics simulation using the interatomic potentials of Stillinger–Weber, Tersoff and Bazant–Kaxiras. Simulations were carried out for temperatures at 300 K and 1000 K using each of these three potentials. At 300 K, the three potentials were found to generate surface features comprising mainly the simple (2 × 1) reconstruction. At 1000 K, more complex reconstruction similar to the p (2 × 2) and c (2 × 2) patterns was observed on the surfaces of Stillinger–Weber and Tersoff crystals while the surface generated on Bazant–Kaxiras crystal is characterized by disorderliness with no identifiable pattern of reconstruction.

Effects of temperature and dosage on the evolution of extended defects during annealing of MeV ion-implanted Czochralski (CZ) p-type (001) silicon have been studied using transmission electron microcopy. Excess interstitials generated in a 1 1015 cm−2/1.5 MeV B+ implanted Si have been found to transform into extended interstitial {311} defects upon rapid thermal annealing at 800°C for 15 sec. During prolonged furnace annealing at 960°C for 1 h, some of the {311} defects grow longer at the expense of the smaller ones, and the average width of the defects seems to decrease at the same time. Formation of stable dislocation loops appears to occur only above a certain threshold annealing temperature (∼1000°C). The leakage current in diodes fabricated on 1.5 MeV B+ implanted wafers was found to be higher for a dosage of 1 1014cm−2 and less, as compared to those fabricated with a dosage of 5 1014 cm−2 and more. The difference in the observed leakage current has been attributed to the presence of dislocations in the active device region of the wafers that were implanted with the lower dosage.

To develop a standardized, practical, self-administered questionnaire to monitor pediatric patients with burns and to evaluate the effectiveness of comprehensive pediatric burn management treatments, a group of experts generated a set of items to measure relevant burn outcomes. Children between the ages of 5 and 18 years were assessed in a cross-sectional study. Both parent and adolescent responses were obtained from children 11 to 18 years old. The internal reliability of final scales ranged from 0.82 to 0.93 among parents and from 0.75 to 0.92 among adolescents. Mean differences between parent and adolescent were small; the greatest difference occurred in the appearance subscale. Parental scales showed evidence of validity and potential for sensitivity to change. In an effort to support the construct validity of the new scales, they were compared with the Child Health Questionnaire and related to each other in clinically sensible ways. These burn outcomes scales reliably and validly assess function in patients with burns, and the scales have been developed in such a way that they are likely to be sensitive to change over time.

Ion implantation causes damage to photoresist and brings about the formation of a carbonized layer on the surface of the resist. The relationship between the extent of damage and the etch resistance of the resist was investigated. Four ion species, namely, Si, P, As, and BF2 were used. Heavier ions and higher implant energies generally increase the extent of damage and the density of the carbonized layer. Compared to a fresh resist, the formation of a dense carbonized layer increases the etch resistance whereas the formation of a porous carbonized layer decreases the etch resistance.

Background: Exercise-induced anaphylaxis (EIA) is a unique physical allergy that is triggered by exertion, the clinical spectrum and modifying factors of which have been previously studied. At the time of initial description, it was postulated that other factors contributed to this disorder. Objective: We sought to determine the clinical course and potential modifying factors in EIA. Methods: In 1993, we conducted a cross-sectional analysis of 671 individuals with exercise-associated symptoms for more than a decade using a validated 75-item questionnaire. Subjects met criteria for EIA if they had anaphylactic symptoms, including hypotension or upper airway obstruction, urticaria, or angioedema with physical exertion but without a passive increase in core body temperature. Results: Of 365 (54%) questionnaire respondents, 279 (87%) met criteria for EIA (199 females and 80 males). At the time of study entry, subjects with EIA (mean age, 37.5 years; range, 13 to 77 years) had an average of 10.6 years of symptoms, which were most frequently triggered by aerobic activities such as jogging or brisk walking (78% and 42%, respectively). On average, subjects reported that the frequency of attacks had decreased (47% of subjects) or stabilized (46% of subjects) since onset. One hundred (41%) subjects reported being completely free of attacks in the past year. Subjects reduced their attacks by avoiding exercise during extremely hot or cold weather (44%), avoiding ingestion of certain foods before exercise (37%), and restricting exercise during their allergy season (36%) or humid weather (33%). The most common pharmacologic agents used to manage symptoms were H1 antagonists (56%) and/or epinephrine (31%). However, 28% used no treatment at all. Conclusion: EIA is an episodic condition in which the frequency of attacks tends to stabilize or decrease over time. Improvement appears to result from individual modification of exercise and avoidance of known environmental and ingestible precipitants. (J Allergy Clin Immunol 1999;104:123-7.)

Cu metallization has been widely applied in back-end-of-line (BEOL) of integrated circuit fabrication, as well as in advanced packaging such as 3-D interconnects and through silicon via (TSV). As the device feature size further shrinks copper diffusion barrier layers with high conductivity, good thermal stability and low Cu diffusion coefficient are to be developed. Amorphous metal alloy films of Ta-transition metal (TM = Ni, Cr, Ti) are proposed and examined as a potential copper diffusion barrier. All Ta-TM films deposited on Si showed lower resistivity compared to the conventional Ta nitride films. Ta-Ni films containing up to 86 wt% Ta were found to have as-deposited amorphous phase. Ta-Cr films also contained glassy phase in all studied composition range. However, crystalline phase was observed in the as-deposited Ta-Ti films. The glassy Ta-Ni thin films showed high stability up to 800°C. Beyond this temperature, crystallization of Ta, Ni 3 Si 2 , Ta 2 O 5 and Ta 5 Si 3 were detected. As-deposited glassy Ta-Cr also maintained the amorphous phase up to 800°C, with Ta 2 O 5 and Ta crystalline peak observed. For Ta-Ti films, a solid phase amorphourization was observed when films were annealed at 600°C. The amorphous phase was stable up to 800°C, with Ta x Ti 1−x O 2 crystalline phase has appeared. Therefore it is concluded that Ta-Cr and Ta-Ni has higher glass forming ability and higher thermal stability compared to Ta-Ti films. Copper diffusion barrier performance of Ta-TM films were studied on Cu/Ta-TM/Si stack at different temperatures, ranging from 600 to 800°C. For Cu/Ta-Ti/Si, Solid phase amorphourization of Ta-Ti at 600°C was observed. No Cu 3 Si peaks were observed for all samples until 700°C. XRD study showed that at 700°C, fast reaction between Cu and Si was observed in Ta-Cr and Ta-Ti barriers, while very low Cu 3 Si peak could be observed in Ta-Ni barrier. TEM observation showed that Ta-Ti films lost continuity while Ta-Cr and Ta-Ni still maintained integrity at 700°C. It is therefore concluded that the studied Ta-TM binary metallic thin films can be applied as a good amorphous copper diffusion barrier, with low electrical resistivity, high thermal stability and good copper diffusion retardation performance. In order to reduce the diffusion rate of Cu in barrier, Ta-Ni barrier is preferred, followed by Ta-Cr and Ta-Ti.

The adhesive property of a dual-cure, self-adhesive universal resin luting agent (Rely X Unicem, 3M ESPE) between nickel-chromium (Ni-Cr) and human dentine was compared with three conventional resin luting agents (Calibra, Dentsply; Panavia-F, Kuraray; All-bond 2 CB cement, Bisco). Ten Ni-Cr rods were bonded to human dentine with each of the four luting agents, and were subjected to shear bond test. Results showed that there was no significant difference in shear bond strengths among the luting agents. A dual-cure, self-adhesive universal resin luting agent was shown to have comparable adhesive property between Ni-Cr and human dentine as three other conventional resin luting agents. Given the simplicity of use of the dual-cure, self-adhesive universal resin luting agent, it appears to be promising in clinical applications.

This study was undertaken to investigate the chemical solubility and flexural strengths of 3 zirconia-based dental ceramics: In-Ceram Zirconia (IZ), In-Ceram 2000 YZ CUBES (YZ Zirconia) (Vita Zahnfabrik), and Cercon (Dentsply). A pressable lithium disilicate-reinforced glass ceramic (IPS Empress 2, Ivoclar Vivadent) was used as a control.Ten block specimens (12 x 6 x 4 mm) of each ceramic material were prepared for chemical solubility testing. Each specimen was refluxed in 4% acetic acid solution for 16 hours. The percentage loss of mass and the loss of mass per unit of surface area for each specimen were calculated. Ten bar-shaped (21 x 5 x 2 mm) and 10 disk-shaped (16 mm diameter, 1.2 mm thickness) specimens of each ceramic material were prepared and tested for uniaxial flexural strength (UFS) and biaxial flexural strength (BFS). X-ray diffraction analyses were conducted to determine the relative amount of the monoclinic phase of the as-sintered and fractured surfaces of the zirconia ceramics.There were no significant differences among the ceramics in chemical solubility by percentage mass or mass/surface area. For UFS, YZ Zirconia (899 +/- 109 MPa)Cercon (458 +/- 95 MPa) IZ (409 +/- 60 MPa)Empress 2 (252 +/- 36 MPa). For BFS, YZ Zirconia (1,107 +/- 116 MPa)Cercon (927 +/- 146 MPa)IZ (523 +/- 51 MPa)Empress 2 (359 +/- 43 MPa). The fractured YZ Zirconia surface contained approximately 5 times as much monoclinic phase compared to that of its intact surface. The fractured IZ and Cercon surfaces contained approximately twice as much monoclinic phase compared to those of intact surfaces.The ceramics tested all satisfied the chemical solubility allowance required of core ceramic material (type I, Class 1 or type II, Class 1) according to the International Organization for Standardization 6872:1995(E) specifications on dental ceramic. The zirconia-based ceramics possessed significantly higher flexural strengths than the control lithium disilicate ceramic. Their clinical application appears sufficiently promising for long-term clinical studies to be undertaken.

The objective of this study was to identify reliable and valid instruments to measure cognitive impairment in systemic lupus erythematosus (SLE), and to define minimally important change of cognitive impairment in SLE for clinical trials. Neurocognitive measures used in randomized clinical trials in SLE were reviewed, and response criteria were developed using consensus expert opinion. The definition of cognitive impairment in the ACR nomenclature for neuropsychiatric lupus syndrome was adopted. Cognitive impairment is a deficit of 2.0 or more standard deviations (SD) below the mean, compared to normative data, in the key domains of attention, memory and psychomotor speed. Cognitive decline is defined as a deficit of 1.5—1.9 SD below the mean. Focal decline is defined if impairment exists in one or more measures within one domain, and multifocal decline if impairment exists on measures spanning two or more domains. The combination of ACR neuropsychological battery and the Cognitive Symptoms Inventory (CSI) is recommended to quantitate cognitive function. A clinically important response is defined as an improvement of ≥ 1.0 SD with an effect size of 1.0 in the key domains of the ACR neuropsychological testing, and an improvement of ≥ 1.0 SD with an effect size of 1.0 in functional performance of the CSI. Lupus (2007) 16, 418—425

To establish the minimum dimensions for a non-precious cast metal occlusal rest by using mathematical analysis. An occlusal rest in a removable partial denture (RPD) provides vertical support and allows occlusal forces to be transmitted through the long axis of the abutment tooth.The stress status of an occlusal rest in a posterior tooth-bounded RPD resembles that of a cantilever beam under a uniformly distributed load. A mathematical model based on a short rectangular cantilever beam was derived by using the yield strengths of a cast cobalt-chromium alloy and a cast titanium alloy (Ti-6Al-4V), with an applied static occlusal force of 400 N.For the cobalt-chromium alloy, the minimum rectangular dimensions for a 2.0 mm long occlusal rest are; when the width is 2.0 mm, the depth or thickness should be at least 1.03 mm. For the titanium alloy, the minimum dimensions are; when the width is 2.0 mm, the depth or thickness should be at least 0.85 mm. A decrease in the occlusal width will increase the bending stress, requiring a thicker rest for compensation, which may lead to dentin exposure during the rest seat preparation.The mathematical analysis found that the traditional spoon-shaped occlusal rest seat dimensions comply with the mechanical requirements for non-precious cast metal occlusal rests in RPDs.

Thin-walled roots restored using conventional cast metal post-cores are at risk of fracture. Placing a thick intermediate layer of resin-based composite (RBC), sandwiched between the root dentine and a small-diameter metal post or dowel, may improve the fracture resistance of such roots. In this initial laboratory study, two similar groups each of six decoronated maxillary central incisor teeth were prepared with approximately 1.0 mm thick tapered root canal walls. Cast metal alloy post-cores and metal-ceramic crowns were fabricated and cemented for one group with, and for the other control group without, a thick intermediate layer of RBC. The mean force (N) to fracture the roots was 639.3 (SD 51.6) for the intermediate layer of RBC group and 360.8 (42.9) for the control group, P0.0001. These significantly different findings require clinical confirmation.

Study on the atomic stacking configurations and grain boundary structures of ultrathin nanocrystalline TiN films deposited by the atomic layer deposition technique reveals that the dangling bonds and surface reconstruction may be the intrinsic factors that result in the crystal growth with different configurations. The surface topography of the amorphous SiO2 layer is an extrinsic factor to affect the atomic stacking configurations in ultrathin nanocrystalline TiN films. The analysis indicates that the coherent boundary should be the favored boundary in the connection of the tilt grains. These atomic stacking and grain boundary configurations may be the main factors to produce the pinhole-free, high-density, and homogeneous ultrathin nanocrystalline TiN film prepared by the atomic layer deposition method. This study may provide new insight into the fundamental mechanism and properties of ultrathin TiN films.

We describe a consecutive series of patients with hydroxychloroquine (HCQ) retinopathy. Their clinical features illustrate that with normal renal function there is no threshold for total dosage for HCQ toxicity; that color vision testing is important; that almost all patients complain of altered central vision as their first symptom; and that a normal optic fundus does not exclude the diagnosis. Finally, HCQ retinopathy may progress even when the agent is stopped.

Although widely used and reported in research for the evaluation of groups, measures of health status and health-related quality of life have had little application in clinical practice for the assessment of individual patients. One of the principal barriers is the demonstration that these measures add clinically significant information to measures of function or symptoms alone. Here, we review the methods for evaluation of construct validity in longitudinal studies and make recommendations for nomenclature, reporting of study results, and future research agenda.Analytical review.The terms "sensitivity" and "responsiveness" have been used interchangeably, and there are few studies that evaluate the extent to which health status or health-related quality-of life measures capture clinically important changes ("responsiveness"). Current methods of evaluating responsiveness are not standardized or evaluated. Approaches for the assessment of a clinically significant or meaningful change are described; rather than normative information, however, standardized transition questions are proposed. They would be reported routinely and as separate axes of description to capture individual perceptions.Research in methods to assess the subject's evaluation of the importance and magnitude of a measured change are critical if health status and health-related quality-of-life measures are to have an impact on patient care.

To determine whether longterm lead accumulation is associated with hyperuricemia and gouty arthritis among middle aged and elderly men.In a retrospective cohort study, 777 male participants were evaluated between August 1991 and October 1996 in the Department of Veterans Affairs Normative Aging Study, a 35 year longitudinal study of aging. We examined the development of gout and an increased uric acid level in relation to lead, adjusting for other known risk factors. Lead levels were measured in blood and by K x-ray fluorescence (K-XRF) technique in tibial (cortical) and patellar (trabecular) bone.Blood lead levels in this mostly Caucasian (97%) population were low (mean 5.9 microg/dl, SD 3.5). Bone lead levels were comparable to those described in other general populations. In a multivariate analysis adjusting for the risk factors, age, body mass index, diastolic blood pressure, alcohol intake, and serum creatinine level, there was a positive association between patellar bone lead and uric acid levels (p = 0.02). Of 777 participants, 52 (6.7%) had developed gouty arthritis. In logistic regression of similar covariates, body mass index (p0.0001) and serum creatinine level (p = 0.005) were the strongest determinants of gout; neither bone nor blood lead levels predicted gout in this cohort.The longterm accumulation of lead is associated with an increased uric acid level in middle aged and elderly men. However, this study shows no association between lead and gouty arthritis at the levels arising from community exposure.

New scales for the clinical assessment of patients with systemic lupus erythematosus (SLE) are valid and reliable, and quantitate disease activity. We assessed the responsiveness to change of 2 widely used standardized multi-item lupus activity measures, the revised Systemic Lupus Activity Measure (SLAM-R) and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and their ability to detect clinically relevant changes.Ninety-six (96) patients with definite SLE participated in this study. The group mean age was 45.0 (13.7) years, 91% were female, and the mean disease duration was 14.9 (7.5) years. Sociodemographic information, lupus activity (SLAM-R, SLEDAI), and damage were recorded at baseline. At each of the 5 monthly followup visits, the activity measures were repeated and a transition scale asked the physician if their patient's lupus activity had changed. Five different methods were used to compare the responsiveness of the activity measures studied: 1. the effect size; 2. the standardized response mean; 3. the control standardized response mean; 4. the area under the curve of a receiver operating characteristic (ROC) curve; and 5. a new multiple response modeling approach.Both SLAM-R and SLEDAI are responsive. SLAM-R is consistently, although moderately, more responsive than SLEDAI. All 5 methods of evaluating responsiveness yielded a consistent ranking of disease activity measures.SLAM-R and SLEDAI are responsive measures of lupus activity. SLAM-R appears to be more responsive than SLEDAI.

To determine the prevalence and socioeconomic and clinical predictors of early organ damage in a cohort of patients with systemic lupus erythematosus (SLE) of 2-7 years' duration randomly sampled at 5 centers and balanced by socioeconomic status and race.The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index was measured in 200 patients who met the ACR criteria for SLE with a mean disease duration of 3.8 years. The SLICC/ACR scores for each organ system and the prevalence of damage within organ systems were assessed. Logistic regression analyses evaluated the simultaneous effects of age at diagnosis, disease duration, disease activity, and sociodemographic factors.Sixty-one percent of the patients had damage within 7 years of onset (mean 3.8 yrs). Neuropsychiatric (20.5%) and musculoskeletal (18.5%) systems were the most frequently involved, followed by renal (15.5%) and skin (12.5%) systems, all with median SLICC/ACR organ system scores of 1. In multivariate models, African-American race was associated with skin damage but not with damage in other specific organ systems. Socioeconomic status was not associated with organ system damage. Older age at diagnosis correlated with cardiovascular, musculoskeletal, gastrointestinal, ocular, and pulmonary damage. Clinical factors such as longer disease duration correlated with higher renal and cardiovascular damage, and greater disease activity at diagnosis of SLE correlated with greater renal, musculoskeletal, and pulmonary damage.There is evidence of organ system damage in SLE within a mean of 3.8 years after onset. We found little evidence for differences in early organ damage according to race or socioeconomic status. Damage to most organ systems was related to age at diagnosis of SLE and clinical factors such as disease duration.

This paper describes the characterization of cell lines that stably maintain linear copies of bovine papillomavirus 1 (BPV-1). Cell lines were generated by liposome-mediated transfection of BamH1-linearized virus into C127I cells. Two transfectants with morphologies differing from each other and from that of the parental cell line were characterized. Southern blots indicated that they contain ten to twelve copies of the BPV-1 genome per cell and that the predominant species in both cell lines are linear BPV-1 episomes. One to two copies per genome of a slow migrating species are also present. Both BPV-1 species found in these cells are sensitive to BAL31 digestion. Viral chromosomal ends were amplified by anchored PCR, cloned and sequenced. Our results indicate that no major rearrangements have occurred in the sequence flanking the BamH1 site where the virus used for transfection was linearized. No circular BPV-1 molecules were detected by PCR. The slow migrating species may serve as templates for replication for the linear forms by a yet unidentified mechanism.

To determine whether patients with knee or hip osteoarthritis (OA) who have worse physical function preoperatively achieve a postoperative status that is similar to that of patients with better preoperative function.This study surveyed an observational cohort of 379 consecutive patients with definite OA who were without other inflammatory joint diseases and were undergoing either total hip or knee replacement in a US (Boston) and a Canadian (Montreal) referral center. Questionnaires on health status (the Short Form 36 and Western Ontario and McMaster Universities Osteoarthritis Index) were administered preoperatively and at 3 and 6 months postoperatively. Physical function and pain due to OA were deemed the most significant outcomes to study.Two hundred twenty-two patients returned their questionnaires. Patients in the 2 centers were comparable in age, sex, time to surgery, and proportion of hip/knee surgery. The Boston group had more education, lower comorbidity, and more cemented knee prostheses. Patients undergoing hip or knee replacement in Montreal had lower preoperative physical function and more pain than their Boston counterparts. In patients with lower preoperative physical function, function and pain were not improved postoperatively to the level achieved by those with higher preoperative function. This was most striking in patients undergoing total knee replacement.Surgery performed later in the natural history of functional decline due to OA of the knee, and possibly of the hip, results in worse postoperative functional status.

To study the possible association of silicone-breast-implant exposure and immunologic abnormalities within the Nurses' Health Study, an ongoing prospective cohort study of women.From this cohort, we randomly selected 200 women who had been exposed to silicone breast implants and who had never reported connective tissue diseases during 14 years of follow-up, and 500 age-matched, nonexposed women, including 100 with definite connective tissue diseases validated by medical record review, 100 with at least one symptom of a connective tissue disease, 100 with diabetes, and 200 healthy controls. Assays for antinuclear antibodies (ANA), including anti-dsDNA, anti-ssDNA, anti-Sm/RNP/Ro/La, and anti-Scl-70, rheumatoid factor, immunoglobulins, serum complement, and C-reactive protein level, and anticardiolipin, antithyroglobulin, antithyroid microsomal, and antisilicone antibodies were performed by standard techniques in blood samples collected in 1989 or 1990 before collection of silicone-breast-implant exposure data in 1992.ANA was positive (or = 1:40) in 14% of women with silicone breast implants compared with 20% of healthy women (P = 0.11). Rheumatoid factor was positive (or = 1:40) in 5% of women with silicone breast implants and 2% of healthy women (P = 0.16). Women with silicone breast implants had a significantly higher frequency of anti-ssDNA antibodies than healthy women (41% and 29%, P = 0.012). Duration of implant was associated with a higher frequency of anti-ssDNA antibodies (P = 0.03) but not with ANA or rheumatoid factor. No other significant differences in the frequencies of autoantibodies were observed in silicone breast implant-exposed women. Antisilicone antibodies were not found in any sample.We found no increased frequency of any immunologic abnormalities in women exposed to silicone breast implants, except for anti-ssDNA, which has unknown clinical relevance.

To study the outcome of Lyme disease (LD) in children identified in a total population survey of an endemic island.We conducted a population-based retrospective cohort study off the coast of Massachusetts. Twenty-five children who met the Centers for Disease Control case definition for prior LD were compared with 26 children without LD from the same community. All children with LD received antibiotics during the acute phase of their disease. All 51 children were invited for a clinical evaluation, including 12-lead electrocardiogram (EKG), and measurement of antibodies to Borrelia burgdorferi by antibody-capture ELISA and Western blot.At a mean of 3.2 years from the initial manifestation of LD, children with prior LD did not have a higher prevalence of musculoskeletal or neurological symptoms, examination abnormalities, abnormal EKG, or behavioral difficulties, compared to children with no history of LD.Children who receive appropriate antimicrobial therapy for LD appear to have no demonstrable longterm morbidity.

The goal of orthopaedic interventions is to improve the functional health of patients, particularly physical function. The American Academy of Orthopaedic Surgeons and the Pediatric Orthopaedic Society of North America (POSNA) commissioned a work group to construct functional health outcomes scales for children and adolescents, focusing on musculoskeletal health. The work group developed scales assessing upper extremity function, transfers and mobility, physical function and sports, comfort (pain free), happiness and satisfaction, and expectations for treatment. Parent and adolescent self-report forms were developed and tested on 470 subjects aged 2-18 years. The POSNA scales demonstrated good reliability, construct validity, sensitivity to change over a 9-month period, and ability to outperform a standard instrument, the Child Health Questionnaire physical functioning scale. They were useful for a wide variety of ages and diagnoses. They appear to be ideally suited for orthopaedic surgeons to assess the functional health and efficacy of treatment of their patients at baseline and follow-up.

The multiplex polymerase chain reaction-allele specific oligonucleotides (PCR/ASO) dot blot hybridization method was used to detect 44 mitochondrial DNA point mutations in 2,000 patients suspected as having mitochondrial DNA disorders. These point mutations are classified into four categories. Category I consists of primary disease-causing, heteroplasmic point mutations. Homoplasmic nucleotide substitutions that have been reported to be possibly disease associated are in Category II. Homoplasmic nucleotide substitutions that are thought to be benign polymorphism are included in category III. The novel nucleotide substitutions recently discovered in our laboratory by single strand conformation polymorphism analysis are in category IV. Frequencies of these 44 nucleotide substitutions in 2,000 patients and 262 control individuals were studied. The results indicated that analysis of 12 recurrent disease-causing point mutations in category I identified 5.4% of the patients suspected as having mitochondrial DNA disorders. Since the mitochondrial disorders are a group of complex, heterogeneous, and multisystemic diseases, it is often difficult to confirm clinical diagnosis without molecular studies. Thus, the multiplex PCR/ASO method is an effective approach for initial screening of mtDNA mutations in patients suspected as having mitochondrial DNA disorders.

To provide a single source for the best available estimates of the national prevalence of arthritis in general and of selected musculoskeletal disorders (osteoarthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, the spondylarthropathies, systemic lupus erythematosus, scleroderma, polymyalgia rheumatica/giant cell arteritis, gout, fibromyalgia, and low back pain).The National Arthritis Data Workgroup reviewed data from available surveys, such as the National Health and Nutrition Examination Survey series. For overall national estimates, we used surveys based on representative samples. Because data based on national population samples are unavailable for most specific musculoskeletal conditions, we derived data from various smaller survey samples from defined populations. Prevalence estimates from these surveys were linked to 1990 US Bureau of the Census population data to calculate national estimates. We also estimated the expected frequency of arthritis in the year 2020.Current national estimates are provided, with important caveats regarding their interpretation, for self-reported arthritis and selected conditions. An estimated 15% (40 million) of Americans had some form of arthritis in 1995. By the year 2020, an estimated 18.2% (59.4 million) will be affected.Given the limitations of the data on which they are based, this report provides the best available prevalence estimates for arthritis and other rheumatic conditions overall, and for selected musculoskeletal disorders, in the US population.

To explore the relationship between patients' systemic lupus erythematosus (SLE) activity and physicians' decision to treat with steroids or alternative medication.Baseline information and clinical status was extracted from case histories of 30 patients with lupus and represented in clinical vignettes. These vignettes were then mailed to 60 physicians (rheumatologists and immunologists with experience in the treatment of lupus), asking them in each case whether they would initiate treatment or not. The relationship between the 38 complete responses and the SLE Activity Measure (SLAM-R) and SLE Disease Activity Index (SLEDAI) lupus activity scores was analyzed using a general additive model.SLE disease activity measured by SLAM-R or SLEDAI is a significant predictor (p0.0001) of physicians' decision to initiate treatment for patients with lupus. Variation between physicians was observed but was mostly due to a few outliers. Some other variations remained unexplained by patients' SLE disease activity, damage, or by specific organ involvement.We present reference tables and curves for research that may be used as a basis to derive standardized quantitative criteria for entry in clinical trials. More research is needed on how these tools can be used by clinicians to guide them in their decision to treat or not.

Tick bite control is an important initiative to prevent Lyme disease and other tickborne infections. While several studies have demonstrated that knowledge and awareness of Lyme disease in endemic areas are good, none has evaluated the relative importance of knowledge with other attitudinal and health belief variables to determine motivators of preventive behavior.We conducted a cross-sectional analysis of 304 commuter ferry passengers departing Martha's Vineyard Island, Massachusetts, in August 1992, to ascertain the prevalence of tick-avoidance behaviors among individuals from an endemic area of Lyme disease and to identify the knowledge, behavioral, and demographic variables that best determine precautionary behavior.Overall, survey respondents (n = 304) had very good knowledge of Lyme disease (73% items correct on a knowledge test), but only 59% of respondents reported limiting time in tick areas, 58% usually wore protective clothing, 40% wore tick repellent, and 66% usually performed tick checks. By stepwise linear regression analysis, determinants of tick-avoidance behaviors included perceiving the behavior's benefits as outweighing its inconvenience (P.0001), having confidence in recognizing Lyme disease symptoms (P.0004), believing that Lyme disease is a serious illness (P.0009), and believing that the avoidance behavior is effective in reducing the risk of Lyme disease (P.01). Younger respondents (P.05) performed fewer avoidance behaviors. Visitors (P.0001) performed fewer tick checks than residents. Having confidence that one could find a tick on oneself with a tick check also predicted performance (P.008). Increased general knowledge about Lyme disease did not predict any protective behaviors.Precautionary behaviors were underperformed in an at-risk population despite good knowledge of Lyme disease symptoms and transmission. Instead, performance was related to confidence in finding a tick on oneself and a perception that a precaution's benefit outweighed its inconvenience and would adequately reduce risk for Lyme disease. These data have implications for Lyme disease prevention programs, which typically focus on enhancing general knowledge as a means toward disease reduction.

For over 20 years silicone breast implants have been used for cosmetic and breast reconstruction purposes. They have been recently banned by the American Food and Drug Administration other than for reconstruction or in the setting of a study. Complications of rupture, leaking, bleeding, capsular thickening and contracture are acknowledged but the potential of silicone implants in causing classic rheumatic diseases or a new syndrome has caused much controversy; there are millions of dollars at stake in legal suits. The biological plausibility of silicone breast implants causing disease is not without merit. The epidemiological evidence linking the two are reviewed. There is considerable concern as to whether there will ever be a definitive study of the question.

To investigate the role of hair dye use in the etiology of systemic lupus erythematosus (SLE).Participants included 106,391 women enrolled in the Nurses' Health Study, a prospective cohort study. The subjects were ages 30-55 years in 1976, and were free from SLE and any other connective tissue disease at the time of enrollment. In 1976, 1978, 1980, and 1982, subjects were classified as never-users or ever-users of permanent hair dye, based on self-report. Incidence rates of SLE meeting American College of Rheumatology classification criteria were ascertained and confirmed by chart review.Compared with never-users of permanent hair dye, the age-adjusted relative risks (RR) for the development of SLE among ever-users (n = 85 cases) was 0.96 (95% confidence interval [95% CI] 0.63-1.47). Duration of hair dye use was not related to risk of SLE. Women with 15 or more years of use had no increased risk (RR = 0.92, 95% CI 0.46-1.83). There was no relationship between frequency of use or time since first use and risk of SLE. The results were similar when less stringent criteria for SLE were used.We found no evidence that permanent hair dye use, age at first use, frequency of use, or duration of use is associated with the development of SLE.

Clinical and animal studies suggest a role for female hormones in preventing or ameliorating rheumatoid arthritis and, on the other hand, increasing the risk for systemic lupus erythematosus. However, the body of the epidemiological studies do not support these observations except for one study showing that hormonal replacement therapy increases the risk of developing systemic lupus-erythematosus. Counseling of women on the use of oral contraceptives or postmenopausal hormones should include a discussion of these risks and benefits in addition to the risks of cardiovascular disease, uterine and breast cancer, and osteoporosis.

Strategies to improve responsiveness of quantitative questionnaires and methods for evaluating responsiveness are reviewed. Current methods of evaluating responsiveness are not standardized and are themselves unevaluated. A conceptual model of assessing responsiveness is proposed.

To examine the psychometric properties and construct validity of a self-administered Rheumatoid Arthritis Disease Activity Index (RADAI).Five items of the Rapid Assessment of Disease Activity in Rheumatology (RADAR) questionnaire were aggregated into the RADAI and assessed for their factor loading, internal consistency, and construct validity.In 55 patients with RA, the RADAI had a high internal consistency (Cronbach's alpha = 0.91) and correlated with physician's assessment of disease activity (r = 0.54, P0.01), the swollen joint count (r = 0.54, P0.01), and the C-reactive protein value (r = 0.43, P0.01).The RADAI is a highly reliable and valid self-administered measure of disease activity for clinical, health services, and epidemiologic research. Its sensitivity to change in longitudinal studies needs further study.

Three indices, the SLE Disease Activity Index (SLEDAI), the Systemic Lupus Activity Measure (SLAM) and the British Isles Lupus Assessment Group (BILAG), have been found to be reliable and valid measures of disease activity in patients with systemic lupus erythematosus (SLE). Our aim was to investigate their use and comparative ability to assess change in disease activity over time.Clinical and laboratory features of 8 patients with SLE on each of 3 consecutive visits were abstracted and sent in 3 separate packages to physicians from 8 centers. The order of the patient visit summaries was randomized, and the 3 indices rated in one of 6 specific sequences.The 3 indices were significantly (p0.01) correlated: SLEDAI/SLAM = 0.61, BILAG/SLAM = 0.55, SLEDAI/BILAG = 0.35. The sequence presented, the order of patients and order of index scoring did not contribute significantly (p0.05) to the variation of any of the 3 indices. All 3 indices detected differences among patients (p0.01). Differences between visits were detectable with SLEDAI (p = 0.04) but not with SLAM or BILAG:Our study confirms that the SLEDAI, SLAM and BILAG are comparable disease activity measures. SLEDAI appears to be sensitive to change in disease activity over time.

To evaluate the relationship between neuromuscular impairment and physical functional status in patients with lumbar spinal stenosis.Cross sectional analysis of 217 consecutive patients with lumbar spinal stenosis referred to 3 teaching hospitals. Physical functional status was measured with the physical dimension of the Sickness Impact Profile (P-SIP). Physical and radiological findings were abstracted from clinical records. The neuromuscular findings included pin sensation, strength, deep tendon reflexes and vibration. They were aggregated in a neuromuscular impairment index (NMI). Univariate relationships of the P-SIP and the NMI were analyzed with nonparametric methods. The determinants of physical functional status were evaluated using multiple linear regression models.In 148 patients with complete clinical data, objective weakness of the lower extremity as measured at rest was not related to physical functional status in univariate analyses. Decreased vibration was common and was associated with balance disturbance and reduced physical functional status, reflecting the importance of proprioception loss. In the multivariate regression analysis, neuromuscular deficit explained only 2.5% of the variance in physical functional status. The primary determinants of physical functional status were pain, depression, comorbid conditions and work status.While neuromuscular impairment is an indispensable feature of the diagnostic evaluation, its value in assessing outcome is limited. The decision whether to intervene surgically in patients without cauda equina syndrome or rapidly progressive neurological deficits should therefore be driven by pain and physical disability rather than the degree of neuromuscular impairment.

To determine the prevalence of symptomatic rheumatic disease in rural, urban and suburban areas of Taiwan by a 2-staged population survey.Nine thousand subjects over 20 years old were sampled proportional to age and sex for the area from 3 administrative areas in Taiwan. A pretested questionnaire to screen for potential rheumatic disorders and/or disability was administered in the communities by health workers. Subjects who screened positive were examined by a rheumatologist who assigned a final diagnosis based on established criteria.A total of 8998 persons over age 20 residing in Hen-San (rural area), Sien-Dien (suburban), and Cu-Tien (urban) were studied. Twenty-five percent (2272) of the population indicated rheumatic problems: 1124 of 2271 were evaluated by a rheumatologist with serological and radiological testing. The response rates were 49.7% in Hen-San, 50.7% in Sien-Dien and 48.5% on Cu-Tien. After age and sex adjustment, the prevalence of rheumatic symptoms in Hen-San, Sien-Dien, and Cu-Tien was 24.3, 18.4 and 26.3% respectively. It was significantly higher in rural Hen-San and urban Cu-Tien than in Sien-Dien. The prevalence of rheumatoid arthritis (RA) in Hen-San, Sien-Dien, and Cu-Tien was 0.26, 0.78, and 0.93%, osteoarthritis (OA) was 6.3, 5.8, 5.1%, ankylosing spondylitis (AS) was 0.54, 0.19, 0.4%, gout was 0.16, 0.67, 0.67%, respectively. The prevalence of RA in Sien-Dien and Cu-Tien was significantly higher than in Hen-San (p0.05) but were not statistically different for OA, AS and gout among those 3 sites. Only one case of systemic lupus erythematosus (SLE) was found in urban Cu-Tien for a prevalence of 0.033%.Our results suggest that the prevalence of RA and AS is similar to that reported in Caucasians. We could not confirm anecdotal reports that SLE was common or that it is more common than RA in people of Chinese ancestry. The prevalence of OA of the hip is comparatively uncommon in our population. The difference in prevalence of rheumatism, RA, OA and gout in these areas suggests areas of further study.

In summary, variation is grist for the traditional epidemiologic study of etiologic and prognostic factors. In health service research, it provides an approach to describe what is done in everyday practice, where it's done, and, with more detailed study, what works. Interpretation of such data is complex and fraught with difficulties. Nevertheless, the use of large data sets for research and administrative decisions and the study of practice variation are increasing and make it important for the profession to understand its strengths and limitations.

The contributions of MACs and RRTCs to the generation of arthritis-related biopsychosocial research over the last 15 years have been enormous. However, the assimilation of biopsychosocial concepts into mainstream clinical practice, professional education, and public awareness will require a sustained national effort.

No subject should be exposed to a new drug without fully studying the experience. Methodologic standards implemented in Phase I trials can improve their usefulness. Standardization of outcome measures of impairment and function to permit pooling of data; utilization of techniques to minimise measurement error; collecting information on co-variates known to affect outcome-socioeconomic status, co-morbidity, etc; definition of a meaningful clinical change in absolute and relative forms by consensus techniques. Phase I trials should also incorporate features from single subject crossover designs and sequential trials.