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Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations.

Barbiturates and alcohol are frequently found in combination in cases of accidental or intentional fatal self-poisoning. Unfortunately, the lack of any precise knowledge concerning their interaction creates difficult problems when an interpretation of toxicological data is sought. 1 In the following work the joint action of single barbiturates and alcohol is examined and a means of quantifying it is presented. 2 The effects of different amounts of alcohol on fatal amylobarbitone, butobarbitone, pentobarbitone, phenobarbitone and quinalbarbitone blood concentrations are compared. 3 Combined alcohol-barbiturate blood concentration curves connecting those concentration pairs equally effective in causing death are used to quantify the increase in toxicity. The quantitative effects of alcohol appear to be greater with the shorter- and longer-acting barbiturates than with the intermediate-acting derivatives. The different modes of interaction are discussed in terms of the physico-chemical and pharmacokinetic properties of the drugs.

Barbiturates↗

Quantification of functional weakness and abnormal synergy patterns in the lower limb of individuals with chronic stroke.

BACKGROUND: The presence of abnormal muscle activation patterns is a well documented factor limiting the motor rehabilitation of patients following stroke. These abnormal muscle activation patterns, or synergies, have previously been quantified in the upper limbs. Presented here are the lower limb joint torque patterns measured in a standing position of sixteen chronic hemiparetic stroke subjects and sixteen age matched controls used to examine differences in strength and coordination between the two groups. METHODS: With the trunk stabilized, stroke subjects stood on their unaffected leg while their affected foot was attached to a 6-degree of freedom load cell (JR3, Woodland CA) which recorded forces and torques. The subjects were asked to generate a maximum torque about a given joint (hip abduction/adduction; hip, knee, and ankle flexion/extension) and provided feedback of the torque they generated for that primary joint axis. In parallel, EMG data from eight muscle groups were recorded, and secondary torques generated about the adjacent joints were calculated. Differences in mean primary torque, secondary torque, and EMG data were compared using a single factor ANOVA. RESULTS: The stroke group was significantly weaker in six of the eight directions tested. Analysis of the secondary torques showed that the control and stroke subjects used similar strategies to generate maximum torques during seven of the eight joint movements tested. The only time a different strategy was used was during maximal hip abduction exertions where stroke subjects tended to flex instead of extend their hip, which was consistent with the classically defined "flexion synergy." The EMG data of the stroke group was different than the control group in that there was a strong presence of co-contraction of antagonistic muscle groups, especially during ankle flexion and ankle and knee extension. CONCLUSION: The results of this study indicate that in a standing position stroke subjects are significantly weaker in their affected leg when compared to age-matched controls, yet showed little evidence of the classic lower-limb abnormal synergy patterns previously reported. The findings here suggest that the primary contributor to isometric lower limb motor deficits in chronic stroke subjects is weakness.

Journal Article↗

[Separate measurement of radial trabecular and cortical bone mineral density by peripheral quantitative computed tomography (pQCT) in degenerative joint disease].

Degenerative joint disease and osteoporosis, both of which tend to increase with advance in age, were thought to be essentially different mainly because of the artifactually high lumbar spine bone mineral density (BMD) in the former unlike osteoporosis characterized by persistent decrease of BMD. To clarify the relationship between these two diseases, three-dimensional BMD of the trabecular and cortical bone was measured separately in an area of the radius relatively free of degenerative changes by peripheral computed tomography (pQCT). In addition to radiological assessment of spondylosis deformans, quantification of vertebral deformity was attempted by calculation of standard deviation, coefficient of variation, difference between maximum and minimum density divided by the mean of L1-L4. With advance in age and progress of spondylosis deformans, the standard deviation, coefficient of variation difference between the maximum and minimum density and this difference divided by the mean of L1-L4 increased, but radial trabecular bone density, cortcal density and relative cortical volume decreased, suggesting parallel advance of degenerative joint disease and osteoporosis. Sodium etidronate, an antiresorber commonly used in the treatment of osteoporosis, increased mean lumbar spine BMD and markedly decreased the standard deviation, coefficient of variation, difference between the maximum and minimum density and this difference divided by the mean of L1 and L2 but maintained maximum BMD constant, decreasing vertebral deformity due to spondylosis deformans. It is conceivable that calcium release from bone on increased resorption leads to osteoporosis, and calcium entrance into cartilage, causing its hardening, disappearance and degeneration, direct contact between bones, osteoarthritis and subsequent deformity in a single sequence of events.

Absorptiometry, Photon↗

Equity in waiting times for major joint arthroplasty.

OBJECTIVE: To ascertain whether waiting lists are managed in an equitable fashion in a universal health system by examining demographic, socioeconomic and clinical factors, along with 2 health systems variables. DESIGN: A prospective survey by questionnaire. SETTING: The Capital Health Region of Edmonton, Alta. PATIENTS AND METHODS: A cohort of 553 patients, who were waiting for either total hip or total knee replacement surgery, seen between Dec. 18, 1995, and Jan. 24, 1997. INTERVENTIONS: A home visit was made when the patient was first placed on the waiting list and again just before surgery to complete the questionnaires. The Western Ontario and McMaster Universities (WOMAC) instrument and the Medication Quantification Score were administered at the time the patient was placed on the waiting list. MAIN OUTCOME MEASURE: The length of waiting time, defined as the date the patient was put on the waiting list to the date the patient was operated on. RESULTS: There were no biases in waiting time with respect to age, gender, education or work status. Although pain and function were not related to waiting time, multivariate analyses found that marital status, primary language, body mass index, pain medication use and the size of the surgeons' major joint replacement practice determined waiting time for surgery. However, this model explained only 10% of the variance in waiting time. CONCLUSION: Waiting lists were managed unfairly in terms of clinical equity (clinical severity) but managed fairly in terms of social equity.

Aged↗

Correlation between clinical and ultrasound assessment of the knee in children with mono-articular or pauci-articular juvenile rheumatoid arthritis.

BACKGROUND: Ultrasonography of the knee is a non-invasive, readily available and low-cost tool for demonstrating peri-articular tissues. OBJECTIVE: To correlate clinical features with US findings in the detection, quantification and follow-up of inflammatory signs of the knee in children with pauci-articular juvenile rheumatoid arthritis (JRA). MATERIALS AND METHODS: US of both knees was performed in 49 patients on the same day as the clinical examination. All joints were classified into two groups by clinical criteria: group A (active disease) or group B (quiescent disease). Thirteen patients underwent one or more follow-up examinations. US was performed with a small-parts, 7.5-MHz, electronic linear probe by using a technique previously reported. Quantitative assessment of any effusion and synovial thickening was evaluated at the level of the suprapatellar bursa. Wilcoxon and Spearman tests were employed to compare US findings between the two groups and to correlate clinical and US findings within each group, respectively. RESULTS: US demonstrated significant increase of effusion and synovial thickening in group A joints. US enabled visualisation of clinically undetected popliteal cysts in three patients. Correlation between clinical and US findings was significant in group A and positive, though not significant, in group B. CONCLUSIONS: US seems to be a sensitive and reliable method for the assessment and monitoring of knee joint involvement in pauci-articular JRA.

Adolescent↗

Pain in the older adult in the intensive care unit.

Effective pain management of the older adult begins with pain assessment using the proper tools. Understanding the complexities of the older adult in the ICU is the first step; this can be done by integrating the evidence-based practice guidelines provided by the American Geriatrics Society, the Joint Commission on Accreditation of Health Care Organizations (JCAHO pain standards: www.jcaho.org/standard/pm_hap.html), and the Society of Critical Care Medicine into physicians' and nurses' practice. Joint Commission on Accreditation of Health Care Organizations now recommends considering pain as the "fifth vital sign" (JCAHO pain standards: www.jcaho.org/standard/pm_hap.html). In summary, Park et al highlight key concepts that must be considered for all effective treatment plans: "anticipation, recognition, quantification, treatment and reassessment of the needs of the patient." Only then can we anticipate the impacts of chronic and critical illnesses and realize reliable and superior comfort for the elderly.

Aged↗

Definition of distinct compartments in polarized Madin-Darby canine kidney (MDCK) cells for membrane-volume sorting, polarized sorting and apical recycling.

Previous studies of fibroblasts have demonstrated that recycling of endocytic receptors occurs through a default mechanism of membrane-volume sorting. Epithelial cells require an additional level of polar membrane sorting, but there are conflicting models of polar sorting, some suggesting that it occurs in early endosomes, others suggesting it occurs in a specialized apical recycling endosome (ARE). The relationship between endocytic sorting to the lysosomal, recycling and transcytotic pathways in polarized cells was addressed by characterizing the endocytic itineraries of LDL, transferrin (Tf) and IgA, respectively, in polarized Madin-Darby canine kidney (MDCK) cells. Quantitative analyses of 3-dimensional images of living and fixed polarized cells demonstrate that endocytic sorting occurs sequentially. Initially internalized into lateral sorting endosomes, Tf and IgA are jointly sorted from LDL into apical and medical recycling endosomes, in a manner consistent with default sorting of membrane from volume. While Tf is recycled to the basolateral membrane from recycling endosomes, IgA is sorted to the ARE prior to apical delivery. Quantifications of the efficiency of sorting of IgA from Tf between the recycling endosomes and the ARE match biochemical measurements of transepithelial protein transport, indicating that all polar sorting occurs in this step. Unlike fibroblasts, rab11 is not associated with Tf recycling compartments in either polarized or glass-grown MDCK cells, rather it is associated with the compartments to which IgA is directed after sorting from Tf. These results complicate a suggested homology between the ARE and the fibroblast perinuclear recycling compartment and provide a framework that justifies previous conflicting models of polarized sorting.

Animals↗

Quantification of subchondral bone changes in a murine osteoarthritis model using micro-CT.

In the past few years there has been a considerable interest in the role of bone in osteoarthritis. Despite the increasing evidence of the involvement of bone in osteoarthritis, it remains very difficult to attribute the cause or effect of changes in subchondral bone to the process of osteoarthritis. Although osteoarthritis in mice provides a useful model to study changes in the subchondral bone, detailed quantification of these changes is lacking. Therefore, the goal of this study was to quantify subchondral bone changes in a murine osteoarthritis model by use of micro-computed tomography (micro-CT). We induced osteoarthritis-like characteristics in the knee joints of mice using collagenase injections, and after four weeks we calculated various 3D morphometric parameters in the epiphysis of the proximal tibia. The collagenase injections caused cartilage damage, visible in histological sections, particularly on the medial tibial plateau. Micro-CT analysis revealed that the thickness of the subchondral bone plate was decreased both at the lateral and the medial side. The trabecular compartment demonstrated a small but significant reduction in bone volume fraction compared to the contralateral control joints. Trabeculae in the collagenase-injected joints were thinner but their shape remained rod-like. Furthermore, the connectivity between trabeculae was reduced and the trabecular spacing was increased. In conclusion, four weeks after induction of osteoarthritis in the murine knee subtle but significant changes in subchondral bone architecture could be detected and quantified in 3D with micro-CT analysis.

Animals↗

Quantitative magnetic resonance imaging of articular cartilage in knee osteoarthritis.

PURPOSE OF REVIEW: Attempts to evaluate knee cartilage damage and progression seem logical in osteoarthritis research. Magnetic resonance imaging allows for precise visualization of joint structures such as cartilage, bone, synovial tissues, ligaments and menisci, and their pathologic changes. RECENT FINDINGS: Recent advances in magnetic resonance technology have enabled researchers to evaluate cartilage damage and progression over the cross-sectional and longitudinal planes. Although anatomic changes can be seen, for many years the quantification of the cartilage changes has been the real challenge. Quantitative assessment of cartilage morphology using magnetic resonance imaging with fat-suppressed gradient echo sequences and digital postprocessing techniques provides high accuracy and adequate precision for cross-sectional and longitudinal studies in osteoarthritis patients. Recent data on precision, reliability, and sensitivity to change of quantitative parameters of cartilage morphology in osteoarthritis are presented in this review. Longitudinal studies currently available suggest that changes of cartilage volume, potentially as much as 5% per year, occur in osteoarthritis in most knee compartments, exceeding the variability of these measurements. SUMMARY: Magnetic resonance imaging provides reliable and quantitative data on cartilage status throughout all compartments of the knee, and robust acquisition protocols for multicenter trials are now available. Magnetic resonance imaging technology should hopefully reduce the number of patients needed in clinical trials, improve retention of these patients, and reduce the overall costs and the length of clinical trials of treatment response to disease-modifying osteoarthritis drugs.

Cartilage, Articular↗

Fixed atlantoaxial rotary deformity with bilateral facet dislocation.

A 21-year-old patient with Down syndrome who developed rotary atlantoaxial dislocation of C1 and C2 following an upper respiratory infection is presented. Techniques for detection and quantification of this potentially serious dislocation using multidirectional tomography and computerized tomography are described.

Adult↗

Biomechanical analysis of rotational motions after disc arthroplasty: implications for patients with adult deformities.

STUDY DESIGN: An anatomic and biomechanical bench-top basic scientific comparative analysis to determine the appropriateness of total disc replacement (TDR) in a lumbar spine with scoliotic tendencies. OBJECTIVES: Only limited data are currently available studying the application of disc replacement adjacent to scoliosis fusions. Theoretically, motion preservation should help delay the continuum of lumbar degeneration adjacent to scoliosis fusions and rotationally unstable lumbar segments. SUMMARY OF BACKGROUND DATA: As a tertiary referral center for failed TDR, we noticed an alarming number of lumbar spinal rotational iatrogenic instability patterns but none occurring in the cervical spine. It is appropriate to analyze the bench-top rotational stability of disc replacement to predict whether this new technology is feasible for a larger prospective clinical study in the treatment of degenerative scoliosis. METHODS: Measurements were taken from 60 human specimens from the Hamann-Todd Osteological Collection: 1) to determine the rotational arc of influence (AOI) = the angle formed from the center of axial rotation to the outermost extent of the facet joints; and 2) to determine the relative anatomic size discrepancy between the left and right facets proportionately with the cross-sectional area of the intervertebral disc = facet/endplate ratio (FER). Biomechanical testing was performed using fresh frozen human cadaveric spines with the following conditions to determine the rotational stability: 1) intact; 2) resection of ALL, anulus, disc, and PLL simulating the preparation for a TDR; 3) a more radical anular resection; 4) entire 360 degrees anular resection; and 4) insertion of the respective unconstrained-type disc replacement. Using a 6 degrees of freedom spine simulator, unconstrained pure moments of +/-8.0 Nm (lumbar) and +/-3.0 Nm (cervical) were used for axial rotation with quantification of the operative level range of motion and neutral zone, with data normalized to the intact spine condition. RESULTS: There were anatomic limitations in the lumbar spine that make it less desirable to apply uncon-strained disc replacements; indeed, the spine was at risk for iatrogenic lumbar scoliosis. The anulus fibrosis, anterior longitudinal ligament, and the posterior longitudinal ligament are critical structures in preventing iatrogenic scoliosis. The lumbar facet joints are more posteriorly located and are smaller relative to the intervertebral disc, compared with this association in the cervical spine. Because the facet capsular ligaments are mechanically less effective with lower tensile strength in the lumbar spine, multiple-level arthroplasty tends to accentuate scoliotic tendencies; this is independent of prosthetic design and surgical technique. DISCUSSION: Implantation of the lumbar TDR never restored the motion segment back to the rotational stability of the intact segment achieving a range of 120% to 140% rotational range of motion compared with the intact condition. This rotational instability proved to be additive as a two-level lumbar TDR resulted in between 240% and 260% increase in rotational instability compared with the intact condition. CONCLUSION: The neutral zone of the intact cervical spine was restored even using an unconstrained cervical TDR. The greater inherent rotational constraints of the cervical spine make it more amenable to stable multilevel arthroplasty compared with the lumbar spine.

Adult↗

[Survey on the quality of commercial Nigari (crude magnesium chloride [sea water])].

Contents of minerals (Mg, Ca, Na and K), anions (SO4(2-), Br- and Cl) and heavy metals (Pb, Cd, Zn, Hg and As) were determined in 17 commercial samples of Nigari, 15 samples of crude magnesium chloride (sea water) products as a food additive and 2 magnesium-containing foods. Obtained values were compared with the specifications proposed in a draft of the eighth edition of Japan's Specifications and Standards for Food Additives. Out of 15 food additive samples, only 5 samples satisfied the specification. Since the Joint FAO/WHO Expert Committee on Food Additives (JECFA) proposed to lower the limits of heavy metals in food additives, a simple method was developed for the determination of low levels of Pb and Cd by extracting chelates of these metals with organic solvents. The quantification limits for Pb and Cd were 0.5 microg/g and 0.05 microg/g, respectively. It was estimated from the SO4(2-)/Ca ratios that 15 samples were sea water evaporation products, and the remaining 2 were ion-exchange membrane process products. No pollution with heavy metals was found in any of the samples.

Food Additives↗

Derotation osteotomy in the treatment of congenital dislocation of the hip: a review of long-term results.

The authors clinically and radiographically evaluate the long-term results of 257 femoral derotation osteotomies performed between 1959 and 1970 for congenital dysplasia and dislocation of the hip. Tracing the patients was very difficult because of the prolonged follow-up, yet a group of 36 patients was finally gathered. These patients were then uniformly studied and classified through precise quantification, with a numeric reference value, of clinical deficits and radiographic changes. The evaluation of the results confirmed that the effectiveness of femoral derotation osteotomy depends upon its timeliness, correct execution, and potential association with corrective surgery of the acetabular dome. Finally, both preexistent joint damage and the presence of genetic factors in the disease, which often causes relapse in spite of a technically perfect operation, are very important in determining the final result.

Adolescent↗

Radioimmunoassay of IgG and IgM rheumatoid factors reacting with human IgG.

Although IgG rheumatoid factor may play a central role in the pathogenesis of rheumatoid arthritis, previously there have been no precise methods for its specific measurement in serum and synovial fluid. This paper describes a solid phase radioimmunoassay for the independent quantification of IgM and IgG rheumatoid factor reacting with the Fc fragment of human IgG. As measured by this assay, serum IgG rheumatoid factor levels differed significantly between patients with seropositive and seronegative rheumatoid arthritis and normal control subjects. In addition, several sera and joint fluids from patients with seropositive rheumatoid arthritis, even without vasculitis, were shown by gel chromatography to have acid-dissociable complexes of IgG rheumatoid factor suggestive of IgG-IgG dimer or trimer formation.

Alkylation↗

[Age-related changes in systematic inhomogeneities of articular cartilage].

We have considered the question of the quantification of differentiation processes. We investigated articular cartilage of the Caput femoris in 22 cases aged from 0 to 77 years. We measured cell size and volume density. During aging a shifting of the layer with the maximum cell size in relation to the joint surface as well as the formation of two layers with different volume densities take place. We believe that the changes in nutritional and load conditions during life play a role in these processes. We describe these with the term "diversification", characterizing the process of the changing of the degree of structural order.

Adolescent↗

Ultrastructural quantification of cell death after injurious compression of bovine calf articular cartilage.

OBJECTIVE: It has been suggested that chondrocyte death by apoptosis may play a role in the pathogenesis of cartilage destruction in osteoarthritis, but the results of in-vivo and in-vitro investigations have been conflicting. To investigate further the cell death in our in-vitro model for traumatic joint injury, we performed a quantitative analysis by electron microscopy (EM) of cell morphology after injurious compression. For comparison, the TUNEL assay was also performed. DESIGN: Articular cartilage explant disks were harvested from newborn calf femoropatellar groove. The disks were subjected to injurious compression (50% strain at a strain rate of 100%/s), incubated for 3 days, and then fixed for quantitative morphological analysis. RESULTS: By TUNEL, the cell apoptosis rate increased from 7 +/- 2% in unloaded controls to 33 +/- 6% after injury (P=0.01; N=8 animals). By EM, the apoptosis rate increased from 5 +/- 1% in unloaded controls to 62 +/- 10% in injured cartilage (P=0.02, N=5 animals). Analysis by EM also identified that of the dead cells in injured disks, 97% were apoptotic by morphology. CONCLUSIONS: These results confirm a significant increase in cell death after injurious compression and suggest that most cell death observed here was by an apoptotic process.

Animals↗

Quantification of hyperreflexia in amyotrophic lateral sclerosis (ALS) by the soleus stretch reflex.

UNLABELLED: The aim of this study was to quantify upper motor neuron (UMN) involvement in amyotrophic lateral sclerosis (ALS) by the soleus stretch reflex. METHODS: In a group of 24 ALS patients and ten healthy controls the soleus stretch reflex was elicited by a four degree rotation at the ankle joint. Amplitude of the short-latency stretch reflex, threshold, and sensitivity were determined. Peripheral excitation/contraction properties were evaluated by supramaximal stimulation of the tibial nerve. Clinical scores of upper motor neuron involvement were applied. RESULTS: A highly significant correlation between threshold and sensitivity of the stretch reflex and clinical score of upper motor neuron involvement was found; patients with a low threshold and a high sensitivity in general had a high upper motor neuron score. CONCLUSION: It is suggested that upper motor neuron involvement in ALS can be evaluated by using the soleus stretch reflex. This may be useful in monitoring progression of the disease and evaluating new therapies.

Adult↗

Urine cartilage oligomeric matrix protein (COMP) measurement is useful in discriminating the osteoarthritic Thoroughbreds.

OBJECTIVE: To quantify the urinary concentration of cartilage oligomeric matrix protein (COMP), and to evaluate the relationship between urinary COMP concentration and the catabolic activity of synovial fluid (SF) in diseased horses. METHODS: COMP in horse urine was detected by immunoblotting with a monoclonal antibody (mAb; 14G4) raised against equine COMP from articular cartilage. Urine and serum samples were obtained from 83 Thoroughbred horses with aseptic joint diseases (AJD, 79 horses) or septic joint diseases (SJD, four horses) at the time of anesthesia induction, and samples of SF were obtained during surgery. Control samples of urine (n=111) were collected from normal horses free of any orthopedic diseases after they had been racing. COMP concentration was determined in all samples using inhibition enzyme-linked immunosorbent assay (ELISA) with mAb 14G4. SF samples were also used for the quantification of gelatinase activity. RESULTS: Positive bands of COMP fragments were determined on the immunoblots with mAb 14G4. The urinary COMP concentrations in AJD and SJD horses (1.02+/-0.75 and 1.55+/-1.17 microg/100mg creatinine, respectively) were significantly higher than normal (0.57+/-0.29 microg/100mg creatinine). In 55 horses with fractures in the AJD group there was a logarithmic relationship (r=-0.45, P<0.001) between the urinary and SF COMP measurements, while the urinary COMP level was positively correlated with matrix metalloproteinase (MMP)-2 and -9 activities (r=0.30, P<0.05 and r=0.51, P<0.001, respectively) in SF. CONCLUSIONS: The urinary COMP assay with mAb 14G4 is useful for discriminating horses with osteoarthritis. The higher COMP levels in urine from such horses would be indicative of enhanced proteolytic activity, in addition to the increased COMP levels in the diseased joints.

Animals↗