Determination of vertebral endplate deformation under load using micro-computed tomography.

Endplate strength plays an important role in preventing vertebral failure of normal vertebrae and in cases where surgical intervention has replaced the disc with an implant or has altered the vertebral loading. We have developed a non-contact method based on the principles of image guided failure analysis, mechanical testing, and micro-computed tomography analysis, which allows for in vitro quantification of endplate deformation under axial load. The method allows for the implementation of a repeated measures experimental design, each specimen acting as its own control. Our methodology was validated using cadaveric functional spine units, loaded stepwise from 200 N to a maximum of 2000 N. The loading protocol was repeated over two days, allowing time for recovery of the disc mechanical properties. We found no meaningful difference in measured force, stiffness, and endplate deformation between day 1 and day 2. The mean fiducial registration error was less than 0.015 mm for all three axes. Endplate deformation could be reproducibly estimated. The root mean squared error was 0.03 mm, which is the effective precision of the method. Using this micro-CT based method, the effect of interbody implants, grafts, disc replacement strategies, and surgical procedures such as nucleotomy and vertebral cement augmentation on endplate mechanical behaviour can be ascertained.

Regional variation in vertebral bone morphology and its contribution to vertebral fracture strength.

Vertebral fractures may result in pain, loss of height, spinal instability, kyphotic deformity and ultimately increased morbidity. Fracture risk can be estimated by vertebral bone mineral density (BMD). However, vertebral fractures may be better defined by more selective methods that account for micro-architecture. Our aim was to quantify regional variations in bone architecture parameters (BAPs) and to assess the degree with which regional variations in BAPs affect vertebral fracture strength. The influence of disc health and endplate thickness on fracture strength was also determined. The soft tissue and posterior elements of 20 human functional spine units (FSU) were removed (T9 to L5, mean 74.45+/-4.25 years). After micro-CT scanning of the entire FSU, the strength of the specimens was determined using a materials testing system. Specimens were loaded in compression to failure. BAPs were assessed for 10 regions of the vertebral cancellous bone. Disc health (glycosaminoglycan content of the nucleus pulposus) was determined using the degree of binding with Alcian Blue. Vertebrae were not morphologically homogeneous. Posterior regions of the vertebrae had greater bone volume, more connections, reduced trabecular separation and more plate-like isotropic structures than their corresponding anterior regions. Significant heterogeneity also exists between posterior superior and inferior regions (BV/TV: posterior superior 12.6+/-2.8%, inferior 14.6+/-3%; anterior superior 10.5+/-2.2%, inferior 10.7+/-2.4%). Of the two endplates that abutted a common disc, the cranial inferior endplate was thicker (0.44+/-0.15 mm) than the caudal superior endplate (0.37+/-0.13 mm). Our study found good correlations between BV/TV, connective density and yield strength. Fracture risk prediction, using BV/TV multiplied by the cross sectional area of the endplate, can be improved through regional analysis of the underlying cancellous bone of the endplate of interest (R(2) 0.78) rather than analysis of the entire vertebra (R(2) 0.65) or BMD (R(2) 0.47). Degenerated discs lack a defined nucleus. A negative linear relationship between disc health and vertebral strength (R(2) 0.70) was observed, likely due to a shift in loading from the weaker anterior vertebral region to the stronger posterior region and cortical shell. Our results show the importance of considering regional variations in cancellous BAPs and disc health when assessing fracture risk.

Population genetics of an invasive species, Heracleum mantegazzianum: implications for the role of life history, demographics and independent introductions.

The population genetic structure of an invasive, nonindigenous riparian weed (Heracleum mantegazzianum) in the northeast of England was investigated using microsatellite DNA markers. Data were used to assess the size and frequency of introductions into three catchments and the subsequent spread. We sampled 13 populations, including a remote population (Perivale, London) for comparison. Five loci were screened and considerable variation was found. Results revealed greater overall variation between populations from different catchments than those in the same catchment, and suggested the generation of population structure in the relatively short time since the initial introduction. Between-catchment variation may reflect population structure generated by local founders as the species spread and may indicate a large initial founder population at the time of the introduction into Britain, or multiple introductions. Within-catchment variation was consistent with expectations based on the water-borne dispersal of seeds in this species, and the relatively small dispersal range of likely pollinators. Independent introductions stand out in some cases as exceptions to the general pattern. Taken together the results are consistent with a relatively large initial founder population, and the subsequent spread of the species in local founder populations, followed by some level of inbreeding within local populations and novel introductions in some localities.

Treatment with parathyroid peptides and estrogen replacement for severe postmenopausal vertebral osteoporosis: prediction of long-term responses in spine and femur.

Fifteen women with severe vertebral osteoporosis were treated with daily parathyroid peptide (hPTH) plus hormone-replacement co-therapy (HRT) for 1 year. Eight other patients were randomized to HRT alone. Co-therapy with hPTH and HRT resulted in an impressive mean treatment response at the spine (dual-energy X-ray absorptiometry DXA) 15% above baseline; P < 0.015 compared with the HRT group) at 2 years, while at the proximal femur and radius there were smaller increases. hPTH co-therapy led to a significantly positive metabolic calcium balance at 1 year (by 2.13 mmol Ca/day, equivalent to a 5% annual increment in total body calcium; P = 0.015). The magnitude of the lumbar spine DXA response at 2 years depended statistically on the increase in bone formation rate, measured with 85Sr (r2 adjusted 0.48; P < 0.005) and patients with a large spine DXA response had larger calcium balance improvements (P < 0.03). Plasma osteocalcin changes tracked closely with increases in bone formation rate (r2 = 0.87). In seven patients treated throughout with HRT alone, and in eight hPTH-treated patients (three of whom switched to bisphosphonate therapy at year 4). DXA spine changes seen in years 3-5 were minimal, with no evidence of a statistically significant difference between groups. It is concluded that hPTH or comparable PTH receptor activators remain the most promising anabolic treatment for osteoporosis currently under clinical evaluation and a 6- or 12-month measurement of bone formation or a marker predicts the 2-5 year bone density outcome. Post-hPTH treatment, loss of bone appeared preventable with anti-resorptive therapy.

Symptomatology and health care utilization of women primary care patients who experienced childhood sexual abuse.

OBJECTIVE: The purpose of this study was to (1) determine the symptomatology of women primary care patients who experienced childhood sexual abuse (CSA), using both a self-report survey and a chart review, and (2) determine their health care utilization patterns, using chart and information system reviews. METHOD: An ex post facto research design was used. Women primary care patients who experienced CSA were compared with those who reported no CSA. Participants were recruited from a random sample of women patients from a large primary care clinic. They were mailed the survey; chart and information system reviews were conducted on those who returned surveys. RESULTS: Of the 395 participants, 23% reported past CSA on the survey. Women who experienced CSA reported 44 out of 51 physical and psychosocial symptoms more frequently than their counterparts who reported no past CSA. Further, they experienced these symptoms more intensely and in greater number. In their charts, however, far fewer differences in symptoms between groups were found. Nonetheless, women who experienced CSA visited the primary care clinic an average of 1.33 more times than women with no CSA, and they incurred an average of $150 more in primary care charges over a 2-year period. CONCLUSIONS: The findings indicate that many women primary care patients who experienced CSA suffer multiple symptoms that are not reflected in their charts. In addition, the findings demonstrate that not only is CSA associated with increased primary care visits, but also increased primary care costs, as measured by charges.

Residential status and birth outcomes: is the rural/urban distinction adequate?

In studies comparing the birth outcomes of rural and urban women, residency status is frequently defined dichotomously as either rural or urban. Since residency status appears to be a continuum, however, the usefulness of other categorization systems needs to be explored. The purpose of this study was to compare birth outcomes using a three-level variable for residency status (rural, rural adjacent to urban, and urban). The study population was comprised of women who delivered by cesarean section over an 18-month period (N = 263) at a tertiary care hospital. Data were collected from patient charts, interviews, and the hospital information system. Residency status was determined by county of residence. Birth outcomes examined included gestational age, birthweight, Apgar scores, maternal complications, length of hospital stay, and costs of hospital care. Rural women had worse birth outcomes overall and traveled the greatest distance for delivery. Rural-adjacent women had the best birth outcomes of the three groups, yet were the youngest, least educated, least likely to be married, and the least likely to be privately insured. By using a nondichotomous three-level variable for residency status, two distinct groups of rural women were identified whose maternal health care needs may differ from each other.

EPR evidence for the involvement of free radicals in the iron-catalysed decomposition of qinghaosu (artemisinin) and some derivatives; antimalarial action of some polycyclic endoperoxides.

EPR experiments confirm that reaction of qinghaosu and some related endoperoxides with Fe2+ in aqueous acetonitrile leads to the production of carbon-centred radicals derived by rapid rearrangement of first-formed cyclic alkoxyl radicals. Signals obtained from qinghaosu itself with spin-traps DMPO and DBNBS are assigned to the adducts (15) and (16), a finding which accounts for the formation of the major products (11) and (14).

Healthcare reform in Puerto Rico. Managed care in a unique environment.

To reduce healthcare costs, Puerto Rico has adopted an innovative managed-care program to replace its old public healthcare system. Under the new program, healthcare funding for the medically indigent is being transferred from government-run hospitals and clinics to contracted private insurers who provide a wide range of services on a capitated payment plan. This well-planned initiative addresses the need to cut healthcare costs in Puerto Rico, but whether it will successfully meet the healthcare needs of beneficiaries in the long run is up for debate.

Geriatric hemodialysis patients: a comparative study of vascular access.

OBJECTIVES: To compare vascular access in hemodialysis patients > or = 65 years of age with those < 65 years on the following: 1) comorbid disease status, 2) types of vascular access used, and 3) outcome. SAMPLE/SETTING: Hemodialysis patients in a four-state region (Iowa, Kansas, Nebraska, and Missouri) from both free-standing and hospital-affiliated providers were sampled (n = 267). A stratified sampling strategy was used in order to obtain approximately equal-sized age groups (< 65 years and > or = 65 years). DESIGN: A descriptive, longitudinal study with a 1-year follow-up period. METHODS: Following the placement of a permanent vascular access, information was collected by the dialysis nursing staff about the configuration of the access, needle gauge used for cannulation, dialysis prescriptions, diabetic status, and other comorbid disease conditions. Odds ratios (OR) for vascular access thrombosis (VAT) risk were calculated between the two age groups. RESULTS: Comparisons between the two age groups suggest a higher frequency of polytetrafluorethylene (PTFE) grafts in the > or = 65-year-old age group. Peripheral vascular disease (PVD) prevalence was also higher in elders. Oral anticoagulants reduced the risk of VAT in those < 65-year-old group. Patients age > or = 65 years with a PTFE graft experienced a higher risk of VAT (OR 3.38, 95% confidence interval 1.43, 8.11) than those in the same age group with an arteriovenous fistula (AVF). CONCLUSIONS: PTFE grafts are used more frequently among geriatric hemodialysis patients, possibly due to the increased prevalence of peripheral vascular disease (PVD). While use of oral anticoagulants is effective in reducing the risk of VAT among those < 65 years, it did not significantly reduce VAT risk in geriatric hemodialysis patients. This observation may be due to the higher frequencies of PTFE grafts in elderly patients.

Diagnostic yield of bronchoalveolar lavage and bronchoscopic lung biopsy for detection of Pneumocystis carinii.

OBJECTIVE: To assess the need to perform a bronchoscopic lung biopsy (BLB) in addition to bronchoalveolar lavage (BAL) to obtain a definitive diagnosis of Pneumocystis carinii pneumonia. DESIGN: We retrospectively reviewed the results of concurrently collected paired BAL and BLB specimens to determine the diagnostic yield of both methods for the detection of P. carinii organisms. MATERIAL AND METHODS: During a 3-year period, the BAL fluid specimens stained with a commercially available direct immunofluorescence monoclonal antibody (DFA) reagent and the BLB specimens stained with Grocott methenamine-silver nitrate (GMS) were assessed for the presence of P. carinii. BAL fluid was routinely collected from multiple sites and combined into a single specimen for testing. RESULTS: During the 3-year period of study, 119 patients were identified who had paired BAL fluid and BLB specimens tested for the presence of P. carinii. Of the 119 patients, 16 had either BAL fluid that could not be interpreted or BLB tissue that was inadequate. Of the other 103 patients, 21 had P. carinii pneumonia. The sensitivity of the DFA method on BAL fluid and of the GMS method on BLB was 95% and 43%, respectively. CONCLUSION: For detection of P. carinii, the diagnostic yield is significantly higher for DFA-stained BAL specimens than for GMS-stained BLB specimens.

Somatization in Hispanics.

1. Major psychological disorders are found universally, but their form and content are modified by culture. In addition, the expression of psychosocial distress is largely shaped by cultural values and beliefs. 2. Preliminary research indicates Hispanics are more likely to somatize than Anglos when experiencing psychosocial disorders or psychosocial distress. 3. Additional research is required into the sources of stress for hispanic women, especially those born in the United States, and its effect on their health.

Gastrointestinal calcium absorption and dietary calcium load: relationships with bone remodelling in vertebral osteoporosis.

Patients with vertebral osteoporosis have a wide range of bone loss rates, bone remodelling rates and capacities for gastrointestinal (GI) calcium absorption. To test the hypothesis that variations in GI absorptive capacity determine rates of bone loss or remodelling, we have sought relationships between calcium absorption or vitamin D metabolite levels on the one hand and rates of cancellous and cortical bone loss (measured by serial quantitative computed tomography in the radius; n = 25) or indices of bone remodelling in tetracycline-prelabelled transiliac biopsies (n = 41) on the other, in a sequential untreated group. Calcium absorption (net and true) was measured in 18-day balances and by a two-isotope deconvolution method (fractional absorption and maximum absorption rate, MAR). There was no significant seasonal effect on any of these four measures of calcium absorption (variance ratio, F = 0.52-1.61, p > 0.1) or on 1,25-dihydroxyvitamin D levels (F = 0.13, p > 0.1; range 11-69 pg/ml), notwithstanding the expected seasonal effect on 25-hydroxyvitamin D levels (mean 18.7 ng/ml, zenith mid July, semi-amplitude 7.5 ng/ml; F = 6.82, p < 0.01). Neither this metabolite nor 1,25-dihydroxyvitamin D correlated with any index of calcium absorption (p > 0.1). No measure of calcium absorption (or intake) had a significant relationship with radial cortical or cancellous bone loss (p all > 0.1) but cancellous bone loss was associated with the rate of endogenous calcium excretion (r = 0.50, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Symptoms of female survivors of child sexual abuse.

Women who suffered sexual abuse as children often experience a variety of physical and psychosocial symptoms as adults. Identifying this pattern of symptoms might assist health professionals in recognizing and treating nonreporting survivors of child sexual abuse. In this study, the Adult Survivors of Incest (ASI) Questionnaire (Brown & Garrison, 1990) was used to determine the symptoms and contributing factors for 22 adult survivors of child sexual abuse. Six physical symptoms were experienced by 50% of the subjects, and over 75% of the subjects experienced 11 psychosocial symptoms. The number of physical symptoms correlated significantly with other victimizations (r = .59) and number of psychosocial symptoms (r = .56). The findings suggest that the ASI Questionnaire was effective in identifying patterns of symptoms and contributing factors of adult survivors of child abuse. Additional study is needed to determine the usefulness of this questionnaire in identifying nonreporting survivors in clinical situations.

hPTH 1-34 treatment of osteoporosis with added hormone replacement therapy: biochemical, kinetic and histological responses.

Twelve patients with vertebral fracture osteoporosis were recruited into a trial of treatment with hPTH 1-34 by daily injection for 1 year combined (from the 5th month) with an anti-resorptive agent (oestrogen, n = 9; nandrolone, n = 3). Treatment outcomes were monitored by biochemical and radiotracer measurements together with histomorphometry of transiliac biopsies before and at the end of treatment following double in vivo pre-labelling with demethylchlortetracycline. Indices of whole body bone formation, obtained from the analysis of 85Sr data, showed substantial increases (P less than 0.005) for all three indices measured) while biochemical (hydroxyproline) and kinetic measurements of bone resorption showed modest and equivocal changes only. As a result calcium balance improved. Gastrointestinal calcium absorption showed a tendency to improve, while urine calcium decreased; but these changes were statistically not significant except for radiocalcium absorption in the oestrogen treated subgroup. Histomorphometry revealed substantial increases in cancellous bone volume as reported previously with hPTH 1-34 given alone. However, iliac (as distinct from whole body) indices related to bone formation and resorption appeared to have returned towards pre-treatment values by the time of the second biopsy under the influence of the anti-resorptive agent given with the hPTH 1-34. It is confirmed that hPTH 1-34 therapy can increase iliac cancellous bone mass (as well as spinal cancellous bone mass as reported earlier) without a long-term increment in whole body bone resorption, providing the hPTH is combined with an anti-resorptive agent.

Treatment of type 1 Gaucher's disease affecting bone with aminohydroxypropylidene bisphosphonate (pamidronate).

Two patients with Type 1 (adult) Gaucher's disease and major skeletal involvement with multiple fractures have been treated with the second generation bisphosphonate pamidronate for extensive periods. There was evidence of an immediate reduction in bone resorption, with increased calcium absorption (delayed in Patient 1), improved calcium balance and maintained or improved bone density indices in the axial and peripheral skeleton. There was no evidence of immediate relapse on treatment cessation. No toxic effects of pamidronate treatment were identified and subjective skeletal pain diminished in both patients. Histomorphometry of transiliac bone biopsies obtained before the start of treatment, after double in vivo tetracycline labelling, represents one of the earliest reports of the quantitative findings in iliac bone invaded by Gaucher cells.

Periodic courses of human 1-34 parathyroid peptide alternating with calcitriol paradoxically reduce bone remodelling in spinal osteoporosis.

In an attempt to achieve an anabolic response in both axial and peripheral bone, we treated twelve patients with osteoporosis using human 1-34 parathyroid peptide given discontinuously. The peptide was given as seven daily subcutaneous injections followed by 21 days' treatment with 0.25 mg calcitriol orally. This regime was repeated cyclically for at least sixteen cycles, of which the first four were at a lower dose of hPTH 1-34 than used subsequently. The results of treatment were monitored by kinetic, densitometric, histomorphometric and biochemical studies performed before and during treatment. Two patients developed hPTH 1-34 binding in their plasma during treatment: this was presumed to be due to the development of antibodies. The remainder, instead of increasing their indices of bone turnover as judged by iliac bone histomorphometry, were found to have consistent reductions in trabecular resorption surfaces. The other indices of bone formation and resorption measured showed no change or comparable reductions. The small increases seen in total body calcium were consistent with 'in-filling' of deleted basic multicellular units (BMUs). Because there is no evidence that calcitriol alone causes comparable reductions in activation of bone remodelling in osteoporosis, interruption of treatment with hPTH 1-34 after 7 days may have led to a failure of the activation mechanism to proceed to the resorption stage, with a consequent overall reduction in remodelling activity. This type of treatment regime, with its calcitonin-like effect, might be effective in reducing net bone loss due to imbalance between bone formation and resorption at the BMU level, particularly in patients with increased numbers of BMUs ('high turnover' osteoporosis).(ABSTRACT TRUNCATED AT 250 WORDS)