Psychological interventions improve quality of life despite persistent pain in endometriosis: results of a 3-armed randomized controlled trial.

PURPOSE: Despite standard medical treatment endometriosis is often associated with disabling pain and poor quality of life (QoL). Studies indicate that psychological interventions (PIs) may improve pain and QoL, yet studies on the effects of PIs for women with endometriosis are sparse and limited by low-quality study designs. Therefore, this study aimed, in a rigorous three-armed design, to evaluate the effect of PIs on chronic pelvic pain (CPP) and QoL in women with endometriosis. METHODS: This three-armed parallel, multi-center randomized controlled trial included fifty-eight endometriosis patients reporting severe CPP [≥ 5 for pain intensity measured on a 0-10-point numeric rating scale (NRS)]. Patients were randomly assigned to (1) Specific mindfulness- and acceptance-based psychological intervention (MY-ENDO), (2) Carefully matched non-specific psychological intervention (Non-specific), or (3) A wait-list control group (WL). The primary outcome was pelvic pain intensity/unpleasantness measured on NRS. Secondary outcomes included endometriosis-related quality of life, workability, pain acceptance, and endometriosis-related symptoms. Differences in outcomes between groups at post-treatment follow-up were analyzed using mixed linear models. Analyses were performed on an intention-to-treat basis. RESULTS: Compared to WL, psychological intervention (MY-ENDO + Non-specific) did not significantly reduce pain. However, psychological intervention did significantly improve the QoL-subscales 'control and powerlessness', 'emotional well-being', and 'social support' as well as the endometriosis-related symptoms 'dyschezia' and 'constipation'. MY-ENDO was not superior to Non-specific. CONCLUSIONS: Women with endometriosis may have significant and large effects of psychological intervention on QoL despite an ongoing experience of severe CPP. TRIAL REGISTRATION: 12 April 2016, clinicaltrials.gov (NCT02761382), retrospectively registered.

Parathyroid hormone independently predicts fracture, vascular events, and death in patients with stage 3 and 4 chronic kidney disease.

Doctors do not know whether treatment of high parathyroid hormone levels is linked to better outcomes in their patients with kidney disease. In this study, lower parathyroid hormone levels at baseline were linked to lower risk of fracture, vascular events, and death in people with kidney disease. PURPOSE: Chronic kidney disease (CKD) affects ~ 20% of older adults, and secondary hyperparathyroidism (HPT) is a common condition in these patients. To what degree HPT predicts fractures, vascular events, and mortality in pre-dialysis CKD patients is debated. In stage 3 and 4 CKD patients, we assessed relationships between baseline serum PTH levels and subsequent 10-year probabilities of clinical fractures, vascular events, and death. METHODS: We used Marshfield Clinic Health System electronic health records to analyze data from adult CKD patients receiving care between 1985 and 2013, and whose PTH was measured using a second-generation assay. Covariates included PTH, age, gender, tobacco use, vascular disease, diabetes, hypertension, hyperlipidemia, obesity, GFR, and use of osteoporosis medications. RESULTS: Five thousand one hundred eight subjects had a mean age of 68 ± 17 years, 48% were men, and mean follow-up was 23 ± 10 years. Fractures, vascular events, and death occurred in 18%, 71%, and 56% of the cohort, respectively. In univariate and multivariate models, PTH was an independent predictor of fracture, vascular events, and death. The hazards of fracture, vascular events and death were minimized at a baseline PTH of 0, 69, and 58 pg/mL, respectively. CONCLUSIONS: We found that among individuals with stage 3 and 4 CKD, PTH was an independent predictor of fractures, vascular events, and death. Additional epidemiologic studies are needed to confirm these findings. If a target PTH range can be confirmed, then randomized placebo-controlled trials will be needed to confirm that treating HPT reduces the risk of fracture, vascular events, and death.

DXA Errors Are Common and Reduced by Use of a Reporting Template.

OBJECTIVE: High quality dual energy X-ray absorptiometry (DXA) acquisition, analysis, and reporting demands technical and interpretive excellence. We hypothesized that DXA errors are common and of such magnitude that incorrect clinical decisions might result. In this 2-phase study, we evaluated DXA technical and interpretation error rates in a clinical population and subsequently assessed if implementing an interpretation template reduced errors. METHODS: In phase 1, DXA scans of 345 osteoporosis clinic referrals were reviewed by International Society for Clinical Densitometry-certified technologists (n = 3) and physicians (n = 3). Technologists applied International Society for Clinical Densitometry performance standards to assess technical quality. Physicians assessed reporting compliance with published guidance, relevance of technical errors and determined overall and major error prevalence. Major errors were defined as "provision of inaccurate information that could potentially lead to incorrect patient care decisions." In phase 2, a DXA reporting template was implemented at 2 clinical DXA sites after which the 3 physicians reviewed 200 images and reports as above. The error prevalence was compared with the 298 patients in phase 1 from these sites. RESULTS: In phase 1, technical errors were identified in 90% of patients and affected interpretation in 13%. Interpretation errors were present in 80% of patients; 42% were major. The most common major errors were reporting incorrect information on bone mineral density change (70%) and incorrect diagnosis (22%). In phase 2, at these 2 clinical sites, major errors were present in 37% before and 17% after template implementation. Template usage reduced the odds of major error by 66% (odds ratio 0.34, 95% confidence interval 0.21, 0.53, and p < 0.0001). CONCLUSION: DXA technical and interpretation errors are extremely common and likely adversely affect patient care. Implementing a DXA reporting template reduces major errors and should become common practice. Additional interventions, such as requiring initial and ongoing training and/or certification for technologists and interpreters, are suggested.

What analytic method should clinicians use to derive spine T-scores and predict incident fractures in men? Results from the MrOS study.

UNLABELLED: In this study, the area under the curve was highest when using the lowest vertebral body T-score to diagnose osteoporosis. In men for whom hip imaging is not possible, the lowest vertebral body T-score improves the ability to diagnose osteoporosis in men who are likely to have an incident fragility fracture. INTRODUCTION: Spine T-scores have limited ability to predict fragility fracture. We hypothesized that using lowest vertebral body T-score to diagnose osteoporosis would better predict fracture. METHODS: Among men enrolled in the Osteoporotic Fractures in Men Study, we identified cases with incident clinical fracture (n = 484) and controls without fracture (n = 1,516). We analyzed the lumbar spine bone mineral density (BMD) in cases and controls (n = 2,000) to record the L1-L4 (referent), the lowest vertebral body, and International Society for Clinical Densitometry (ISCD)-determined T-scores using a male normative database and the L1-L4 T-score using a female normative database. We compared the ability of method to diagnose osteoporosis and, therefore, to predict incident clinical fragility fracture, using area under the receiver operator curves (AUCs) and the net reclassification index (NCI) as measures of diagnostic accuracy. ISCD-determined T-scores were determined in only 60 % of participants (n = 1,205). RESULTS: Among 1,205 men, the AUC to predict incident clinical fracture was 0.546 for L1-L4 male, 0.542 for the L1-L4 female, 0.585 for lowest vertebral body, and 0.559 for ISCD-determined T-score. The lowest vertebral body AUC was the only method significantly different from the referent method (p = 0.002). Likewise, a diagnosis of osteoporosis based on the lowest vertebral body T-score demonstrated a significantly better net reclassification index (NRI) than the referent method (net NRI +0.077, p = 0.005). By contrast, the net NRI for other methods of analysis did not differ from the referent method. CONCLUSION: Our study suggests that in men, the lowest vertebral body T-score is an acceptable method by which to estimate fracture risk.

Fasting and postprandial spot urine calcium-to-creatinine ratios do not detect hypercalciuria.

SUMMARY: Clinicians can diagnose high urine calcium by asking patients to collect urine for 24 h or to provide a random urine specimen. In this study, random urine calcium levels were not as accurate as those from the 24-h collection. Clinicians should only use 24-h collections to diagnose high urine calcium. INTRODUCTION: Clinicians diagnose hypercalciuria using a 24-h urine calcium (24HUC) or a spot urine-calcium-to-creatinine ratio (SUCCR) specimen. The SUCCR is reportedly interchangeable with the 24HUC. However, studies to date show mixed results when comparing SUCCR and 24HUC values. We systematically compared fasting and postprandial SUCCR measurements to 24HUC measurements using Bland-Altman analysis. METHODS: Twenty-one postmenopausal women aged 58 ± 7 years came to the research ward for three 24-h inpatient stays. At each study visit, research nurses collected fasting morning (n = 62) and postprandial (n = 62) spot urine specimens along with carefully timed and complete 24-h urine specimens (n = 63) from each woman. RESULTS: Hypercalciuria was present in 13 24HUC samples (21%) using an upper limit of 250 mg/24-h. The fasting SUCCR underestimated the 24HUC (Bland-Altman bias -71 mg/24-h), with a sensitivity and specificity for diagnosing hypercalciuria of 0% and 98%, respectively. The postprandial SUCCR overestimated the 24HUC (Bland-Altman bias +61 mg/24-h), with a sensitivity and specificity of 77% and 61%, respectively. The average of fasting and postprandial SUCCR measurements had a lower Bland-Altman bias of -3 mg/24-h but demonstrated a sensitivity and specificity of only 42% and 78%, respectively. CONCLUSIONS: The SUCCR is not interchangeable with the 24HUC. The fasting SUCCR systematically underestimates, and the postprandial SUCCR systematically overestimates, 24HUC. The average SUCCR demonstrates low sensitivity and specificity for hypercalciuria. Clinicians must use the 24HUC to diagnose hypercalciuria in postmenopausal women.

Health-related quality of life in women with endometriosis: psychometric validation of the Endometriosis Health Profile 30 questionnaire using confirmatory factor analysis.

STUDY QUESTION: Which of the competing models of the Endometriosis Health Profile 30 Questionnaire (EHP-30) factor structure is best supported by confirmatory factor analysis (CFA)? SUMMARY ANSWER: Findings support a five-factor first-order model of the EHP-30, thereby lending support to the model originally suggested by the questionnaire developers. WHAT IS KNOWN ALREADY: Endometriosis has a negative impact on quality of life, and measures specifically developed to address this impact, such as the EHP-30, are vital in research and disease management. Previous studies have found different models of the EHP-30 factor structure, and generated uncertainty regarding how to use the questionnaire. CFA can be applied to compare competing factor models and determine the underlying structure of a questionnaire. STUDY DESIGN SIZE DURATION: This cross-sectional multicenter study included 304 women with endometriosis recruited from three different public health service endometriosis clinics (referral centers for treatment of severe endometriosis) and the Danish Endometriosis Patients Association from 2014 to 2015. PARTICIPANTS/MATERIALS SETTING METHODS: Diagnosis of endometriosis was confirmed in medical records for 84.2% and by histology for 66.8% of participants. Questionnaires (the licensed Danish version of the EHP-30) were sent by post two times with a 6- to 12-week interval. CFA was used to examine construct validity and Bland-Altman plots to examine test-retest reliability and the convergent validity with the Short Form 36 version 2. MAIN RESULTS AND THE ROLE OF CHANCE: Response rate was high (87.6%). CFA supported the original first-order five-factor structure of the EHP-30, and thereby, the use of five separate scale-scores in clinical and research practice. Visual inspection of Bland-Altman plots suggested excellent test-retest reliability of the EHP-30 and supported the use of a disease specific quality of life instrument for women with endometriosis. LIMITATIONS REASONS FOR CAUTION: Diagnosis could not be confirmed through histology data in 33.2% of participants. However, subgroup analyses based on women with confirmed histology only, yielded similar results. Data related to menstrual cycle stage and the use of hormonal and pain medication during questionnaire completion were not collected. A larger study, including data from different countries on different continents, would be better designed to exclude potential population bias. WIDER IMPLICATIONS OF THE FINDINGS: EHP-30, with its original five-factor structure, appears to be a valid, stable, and specific quality of life measure for women with endometriosis. It seems easy to understand, quick to administer, and importantly, scoring might be unaffected by cyclical/menstrual pain symptoms related to endometriosis. The finding of a five-factor model from different studies across several countries supports the crosscultural validity of the EHP-30. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Danish Endometriosis Association, which is a nongovernmental organization run by women with endometriosis and by a scholarship from the Health Research Fund of Central Denmark Region. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: The Danish Data Protection Agency (J.nr: 2013-41-2264).

Adjustment for body mass index and calcitrophic hormone levels improves the diagnostic accuracy of the spot urine calcium-to-creatinine ratio.

SUMMARY: Providers diagnose hypercalciuria using a 24-hour or random urine samples. We compared calcium measurements from paired 24-hour and morning urine samples; measurements correlated poorly. We developed a formula to correct random urine calcium levels. Corrected levels showed excellent agreement with 24-hour measurements. Until validation, providers should diagnose hypercalciuria using 24-hour tests. INTRODUCTION: Hypercalciuria is a risk factor for osteoporosis and nephrolithiasis. The 24-hour urine calcium (24HUC) measurement is the gold standard to diagnose hypercalciuria, but the spot urine calcium-to-creatinine ratio (SUCCR) is more convenient. Although authors claim they are interchangeable, we observed inconsistencies during the conduct of a clinical trial. Therefore, we systematically evaluated agreement between the tests. METHODS: During a 28-inpatient calcium absorption studies in 16 postmenopausal women, we simultaneously collected paired fasting morning and 24-hour urine specimens. RESULTS: We found moderate correlation between paired SUCCR and 24HUC specimens (r = 0.57, p = 0.002), but the SUCCR underestimated 24HUC by a mean of 83 mg (Bland-Altman). We diagnosed hypercalciuria (24HUC >250 mg) in eight specimens using the 24HUC, but only in two specimens using the SUCCR (25% sensitivity). We developed a regression model to predict 24HUC using SUCCR, parathyroid hormone, body mass index, and 1,25(OH)(2)D. The model improved diagnostic sensitivity to 100% and decreased Bland-Altman bias of the SUCCR to +0.06 mg/kg/24-hour. CONCLUSIONS: We conclude that the SUCCR underestimates urine calcium loss and does not reliably diagnose hypercalciuria. A formula derived from multivariate regression incorporating other readily measurable variables greatly improved the SUCCR's accuracy. Future studies must verify this correction before clinical implementation.

A mixture of Persistent Organic Pollutants (POPs) and Azoxymethane (AOM) show potential synergistic effects on intestinal tumorigenesis in the A/J Min/+ mouse model.

A multitude of cancer types, including breast, testicular, liver and colorectal cancer, have associations with exposure to Persistent Organic Pollutants (POPs). The present study aimed to investigate whether a mixture of POPs could affect intestinal tumorigenesis in the A/J Min/+ mouse, a model for human colorectal cancer (CRC). Pollutants were selected for their presence in Scandinavian food products and the mixture was designed based on defined human estimated daily intake levels. Mice were exposed through the diet, at control, low and high mixture concentrations, for 10 weeks. In a separate experiment, mice also received one subcutaneous injection of Azoxymethane (AOM) to explore whether this carcinogenic compound influenced the effect of the POPs. Intestinal tumorigenesis was examined by surface microscopy and histopathology. Moderate and dose-dependent increases in tumorigenesis were observed after dietary POP exposure. The AOM treatment alone stimulated the growth of colonic lesions, but did not increase the formation of new lesions. Combined AOM treatment and POP exposure demonstrated a synergistic effect on lesion formation in the colon, and to a lesser extent in the small intestine. This synergy was also evident by an increased number of malignant colonic tumors (carcinomas). In conclusion, the study shows that a mixture of POPs interacted synergistically with a known carcinogen (AOM), causing increased intestinal tumorigenesis in the A/J Min/+ mouse model.

Assay variation confounds the diagnosis of hypovitaminosis D: a call for standardization.

Endemic hypovitaminosis D contributes to osteoporosis development. However, variation in 25-hydroxyvitamin D (25OHD) measurement is reported and confounds the diagnosis of vitamin D insufficiency/deficiency. This report emphasizes the marked variability observed in serum 25OHD measurements between laboratories.Initially, postmenopausal women had serum 25OHD determinations: 42 in laboratory A, 20 in laboratory B. Their mean (sem) serum 25OHD concentrations were 46 (2.1) and 21 (2.3) ng/ml in laboratories A and B, respectively. Furthermore, there was little overlap in serum 25OHD among these clinically similar individuals. Specifically, 17% of those measured in laboratory A but 90% in laboratory B were below an arbitrary threshold value of 32 ng/ml.Subsequently, serum was obtained from 10 healthy adults. Two aliquots from each individual, one of which was spiked with 20 ng/ml 25OHD, were sent to six laboratories. Substantial variability was noted between these six laboratories. The mean serum 25OHD concentration ranged from 17.1-35.6 ng/ml. Similarly, the mean increase produced by spiking with 20 ng/ml ranged from 7.7-18.0 ng/ml.In conclusion, 25OHD assays yield markedly differing results; whether an individual is found to have low or normal vitamin D status is a function of the laboratory used. If the medical community is to make progress in correcting widespread hypovitaminosis D, 25OHD measurement must be standardized.

Dubowitz syndrome: long-term follow-up of an original patient.

Dubowitz syndrome is an autosomal recessive disorder of growth retardation, characteristic face, mild mental retardation, and eczema originally described by Dubowitz [1965]. Little information is available on natural history and adulthood in this disorder. We report on a 30-year-old woman who was one of the first patients to be diagnosed with the condition [Grosse et al., 1971, Z Kinderheilkd 110:175-187]. Microcephaly, short stature, leg length discrepancy, hyperextensible joints, spina bifida occulta, and absence of anterior cruciate ligaments were present. Her facial appearance had been modified by several plastic surgery procedures. Eczema resolved with age, with occasional flareups. Asthma, headaches, and seizures were additional medical findings. Speech delays, an unusually soft, high-pitched voice, submucous cleft palate, and velopharyngeal insufficiency were noted in childhood. Mild mental retardation was present. At age 30 years she is living independently in her own apartment and working full-time in a nearby sheltered workshop.

Disseminated histoplasmosis in systemic lupus erythematosus: case report and review of the literature.

OBJECTIVES: To report a patient who developed both central nervous system systemic lupus erythematosus (SLE) and disseminated histoplasmosis and to review the literature regarding histoplasma infection in patients with SLE. METHODS: MEDLINE review of the medical literature published in English. RESULTS: Disseminated histoplasmosis occurs rarely in patients with SLE. The main risk factor is treatment with corticosteroids at doses of 20 mg/d or greater. Fever, dyspnea, pleurisy, and weight loss are typical presenting symptoms. The most commonly involved tissues are lung, liver, and bone marrow. In our patient, both SLE flare and disseminated histoplasmosis were present simultaneously. CONCLUSIONS: Opportunistic infection is an important complication of SLE and may be difficult to diagnose. Symptoms of infection may mimic those of a lupus flare, or conversely, symptoms may be masked by the use of corticosteroids. Fever, unexplained tissue involvement, atypical clinical patterns, and poor response to immunosuppressive therapy should alert the clinician to aggressively pursue evaluation of possible infection in patients with SLE.

Autoantibodies and common viral illnesses.

OBJECTIVES: To review the literature about common autoantibodies produced in association with viral infection. METHODS: Medline review of the medical literature published in English. RESULTS: Common viral infections are often associated with low-titer, polyspecific autoantibodies. However, high-titer antinuclear antibodies, double-stranded DNA antibodies, anticardiolipin antibodies, and other subtype antibodies may be found. Hepatitis C and B virus, human immunodeficiency virus, and parvovirus B19 appear to be associated with autoantibodies more commonly than other viruses. CONCLUSIONS: Transient autoantibodies resulting from viral infections are not uncommon. Clinical and laboratory follow-up over time will help distinguish between connective tissue disease and self-limited illness.

Freeze substitution as a means of preserving meningeal vessel morphology.

This study compares freeze substitution with formaldehyde fixation as a means of preserving meningeal vessel morphometry. The diameters of vessels fixed by freeze substitution correlated very well with the in vivo diameters of the same vessels (correlation coefficient 0.9766). On the other hand, diameters of vessels perfusion fixed with 10% buffered formalin displayed poor correlation with in vivo diameters of the same vessels (correlation coefficient 0.1594).

Experiences from the Danish programme for eradication of bovine virus diarrhoea (BVD) 1994-1998 with special reference to legislation and causes of infection.

The main experiences from the Danish bovine virus diarrhoea (BVD) eradication programme over 5 years from 1994 to 1999 are presented. The last 3 years of the programme has been strongly supported by legislation. The most important regulations have been blood testing of live animals before movement to other herds, common pastures or exhibitions, and monitoring of all herds at regular intervals for the presence of the infection. Nevertheless, free herds have experienced infection, e.g., 204 dairy herds in 1998. Of herds found to be infected in the period from July 1997 through June 1998 after previously having been registered to be BVD-free, 67 herds were thoroughly investigated. Nineteen herds (28%) were found infected because of purchase of pregnant cows or heifers which delivered persistently infected (PI) calves, and 24 (36%) and two (3%) because of PI animals on neighbouring pastures or in neighbouring farm houses, respectively. In five herds (7%) pregnant heifers had become infected on one and the same common pasture, while in 17 herds (25%) no immediate cause of infection could be demonstrated. Yet, airborne spread from PI herds as a source of infection was suspected in some of these cases. It was furthermore concluded from investigations presented, that antibody-positive AI bulls were a remote but unlikely possibility. Free-living deer in Denmark had to be considered uninfected. Presence of PI-animals in sheep on infected farms has been seen and is paid attention to in individual cases. The results underline the need for legislation to be used in eradication programmes in areas with a high prevalence of infection and to be introduced right from the beginning in order to minimise the risk of infection for free herds.

Vitamin D and calcium levels in Ugandan adults with human immunodeficiency virus and tuberculosis.

BACKGROUND: Vitamin D increases cathelicidin production, and might alter mortality due to tuberculosis (TB) in human immunodeficiency virus (HIV) coinfection. However, due to abundant sun exposure, vita min D levels might be excellent among Ugandans with HIV and TB. METHODS: We measured 25(OH)D and calcium levels in 50 HIV-negative, 50 HIV-infected and 50 TB-HIV coinfected Ugandan adults. RESULTS: Mean ± standard deviation 25(OH)D levels were 26 ± 7 ng/ml in HIV-negative, 28 ± 11 ng/ml in HIV-infected and 24 ± 11 ng/ml in TB-HIV co-infected adults (P > 0.05 all comparisons). Vitamin D deficiency (< 12 ng/ml) was present in 10% of the HIV-infected subjects, 12% of the TB-HIV co-infected and none of the healthy controls (P = 0.03 for healthy vs. TB, P > 0.05 for other comparisons); 20% of the healthy controls, 22% of the HIV-positive and 38% of the TB-HIV co-infected subjects (P = 0.047 for healthy vs. TB, P > 0.05 for other comparisons) had suboptimal vitamin D levels (< 20 ng/ml). No participant had hypercalcemia. Serum 25(OH)D levels correlated positively with body mass index (r = 0.22, P = 0.03) and serum calcium levels (r = 0.18, P = 0.03). CONCLUSIONS: Ugandan HIV-infected adults with and without TB commonly had suboptimal vitamin D levels. Clinical trials are needed to evaluate the effect of vitamin D on health outcomes in HIV-infected patients with low vitamin D levels.

Adherence to alendronate in male veterans.

UNLABELLED: In one Veterans Affairs' medical center, alendronate non-adherence was more likely in male veterans who smoke or report side effects, and less likely in men undergoing bone densitometry during therapy. Providers urgently need programs to increase adherence to osteoporosis medications. Initial programs should target patients with risk factors for non-adherence. INTRODUCTION: Adherence to osteoporosis therapy in men is unknown. We hypothesized that ca. 50% of men at one center would be adherent to alendronate and one or more patient-specific factors would associate with adherence. METHODS: We conducted a retrospective chart review study of male veterans to determine the rates and predictors of alendronate adherence over two years. We excluded women, men who received primary care elsewhere and those who took alendronate for indications other than low bone mass. We defined adherence as a medication possession ratio > or =80% in the first 24 months of therapy. RESULTS: Adherence in the first 12 and 24 months of therapy was 59% and 54%, respectively. In multivariate analyses, non-adherence was more likely in men using tobacco (OR 2.08, 95% CI 1.13, 3.84, p = 0.02) and reporting side effects (OR 2.06, 95% CI 1.14, 3.73, p = 0.02) and less likely in men undergoing bone density during therapy (OR 0.49, 95% CI 0.26, 0.90, p = 0.02). CONCLUSIONS: Alendronate non-adherence is more likely in male veterans who smoke or report side effects, and less likely in men having bone densitometry during therapy. Providers urgently need programs to increase adherence to osteoporosis medications. Initial programs should target patients with risk factors for non-adherence.

Patient variables impact lumbar spine dual energy X-ray absorptiometry precision.

INTRODUCTION: Changes in bone mineral density are used to monitor osteoporosis therapy. To determine whether a change in bone mass is clinically significant, the precision of bone mineral density measurements must be known. METHODS: We therefore measured the impact of vertebral body exclusion on dual energy X-ray absorptiometry (DXA) precision. At one university and one Veterans Affairs DXA center, three radiology technologists each scanned 30 participants twice, with repositioning between scans, to estimate DXA precision. Three International Society for Clinical Densitometry-certified physicians reviewed all lumbar spinal scans to note the presence of focal structural defects. We calculated precision for subsets of vertebrae, and for virtual samples of patients with and without physician-identified vertebral focal structural defects. We graphed the reciprocal of least significant change versus bone area to determine the dependence of precision on interpreted scan area. RESULTS: Within each sample, greater interpretable bone area improved precision. The contribution of interpreted bone area to precision differed among the samples, ranging from 57 to 94%. Greater population bone mineral density heterogeneity and presence of focal structural defects each decreased precision. CONCLUSION: All bone densitometry centers must determine precision using a sample representative of their served populations. Failure to do so may lead to incorrect determination of least significant change. Population heterogeneity, vertebral body exclusion and presence of focal structural defects each decreases precision.

Rapid freezing and frozen sectioning as a means of preserving brain vessel morphometric characteristics.

A study was performed for the purpose of determining whether ordinary frozen sections of brain could preserve in vivo parenchymal arteriole morphometric characteristics. The results showed that flash-freezing followed by frozen sectioning is just as reliable a means of preserving brain arteriole morphometric characteristics as the time consuming process of flash-freezing followed by freeze substitution.

Distribution of HLA class II alleles among Scandinavian patients with systemic lupus erythematosus (SLE): an increased risk of SLE among non[DRB1*03,DQA1*0501,DQB1*0201] class II homozygotes?

HLA-DRB1, -DRB3, -DQA1 and -DQB1 alleles were determined by DNA typing in 51 Scandinavian patients with systemic lupus erythematosus (SLE) and 129 controls. DRB1*03,DRB3*0101,DQA1*0501,DQB1*0201 were significantly increased in the patient group, with relative risks (RR) of 2.80, 3.07, 3.55 and 2.12, respectively. These alleles are in strong linkage disequilibrium, and their possible relative contributions in predisposition to SLE are difficult to distinguish. The strongest association was found for DQA1*0501, which is in linkage disequilibrium with DRB1*03 as well as DRB1*11,12 (DR5). An increased frequency of DRB1*11,12 was observed (RR = 1.89, ns). No association with DRB1*15,16 (DR2) was found. The patients had a higher frequency of HLA class II homozygosity than the controls (RR = 5.05, p = 0.0005). When compared to the low-risk group (nonDRB1*03 class II heterozygotes), the cases homozygous for DRB1*03,DQA1*0501,DQB1*0201, known to be in linkage disequilibrium with the complement allele C4A*Q0, had the highest relative risk of developing SLE (RR = 16.39, p = 0.0002). However non[DRB1*03,DQA1*0501,DQB1*0201] class II homozygotes had a higher relative risk (RR = 4.68, p = 0.0147) than DRB1*03,DQA1*0501,DQB1*0201 heterozygotes, known to carry the C4A*Q0 allele (RR = 2.72, p = 0.0088). This may suggest that HLA class II molecules are directly involved in susceptibility to SLE.

Effect of intracarotid hyperosmolar mannitol on cerebral cortical arterioles--a morphometric study.

The morphometric response of cerebral cortical arterioles to intracarotid hyperosmolar mannitol was assessed utilizing a technique of rapid freezing of rat brain tissue in vivo. A significant decrease in the wall to lumen (W/L) ratio was noted in the small parenchymal arterioles (20-49 mu) (p less than .0001) ipsilateral to the mannitol infusion. Larger arterioles showed a decreased W/L ratio but this change was not significant. Control infusion of 0.9% NaCl resulted in no change in arteriolar caliber. These results indicate that intracarotid hyperosmolar mannitol causes a direct vasodilatory response in small cerebral cortical arterioles.