Respiration resolved imaging with continuous stable state 2D acquisition using linear frequency SWEEP.

PURPOSE: To investigate the potential of continuous radiofrequency (RF) shifting (SWEEP) as a technique for creating densely sampled data while maintaining a stable signal state for dynamic imaging. METHODS: We present a method where a continuous stable state of magnetization is swept smoothly across the anatomy of interest, creating an efficient approach to dense multiple 2D slice imaging. This is achieved by introducing a linear frequency offset to successive RF pulses shifting the excited slice by a fraction of the slice thickness with each successive repeat times (TR). Simulations and in vivo imaging were performed to assess how this affects the measured signal. Free breathing, respiration resolved 4D volumes in fetal/placental imaging is explored as potential application of this method. RESULTS: The SWEEP method maintained a stable signal state over a full acquisition reducing artifacts from unstable magnetization. Simulations demonstrated that the effects of SWEEP on slice profiles was of the same order as that produced by physiological motion observed with conventional methods. Respiration resolved 4D data acquired with this method shows reduced respiration artifacts and resilience to non-rigid and non-cyclic motion. CONCLUSIONS: The SWEEP method is presented as a technique for improved acquisition efficiency of densely sampled short-TR 2D sequences. Using conventional slice excitation the number of RF pulses required to enter a true steady state is excessively high when using short-TR 2D acquisitions, SWEEP circumvents this limitation by creating a stable signal state that is preserved between slices.

Orthopaedic Web Links (OWL): a way to find professional orthopaedic information on the internet.

BACKGROUND: Finding useful high-grade professional orthopaedic information on the Internet is often difficult. Orthopaedic Web Links (OWL) is a searchable database of vetted online orthopaedic resources. OWL uses a subject directory (OWL Directory) and a custom search engine (OWL Web) to provide a list of resources. The most effective way to find readily accessible, full text on-subject material suitable for education of an orthopaedic surgeon or trainee has not been defined. QUESTIONS/PURPOSES: We therefore (1) proposed a method for selecting topics and evaluating searches and (2) compared the search results from an orthopaedic-specific directory (OWL Directory), a custom search engine (OWL Web), and standard Google searches. METHODS: A scoring system for evaluation of the search results was developed for standardized comparison. Single words and sets of three words from randomly selected examination questions provided the search strings to compare the three strategies. RESULTS: For single keyword searches, the OWL Directory scored highest (16.4/50) of the three methods. For the three keywords searches, OWL Web had the highest mean score (26.0/50), followed by Google (22.8/50), and the OWL Directory (1.0/50). OWL Web searches had higher scores than Google searches, while returning 800 times fewer search results. CONCLUSION: The OWL Directory of orthopaedic subjects on the Internet provides a simple browsable category structure to find information. The OWL Web search engine scored higher than Google and resulted in a greater proportion of valid, on-subject, and accessible resources in the search results.

Using PubMed effectively to access the orthopaedic literature.

PubMed is the free public Internet interface to the US National Library of Medicine's MEDLINE database of citations to medical scientific articles. Many orthopaedic surgeons use PubMed on a regular basis, but most orthopaedic surgeons have received little or no training in how to use PubMed effectively and express frustration with the experience. Typical problems encountered are data overload with very large numbers of returns to look through, failure to find a specific article, and a concern that a search has missed important papers. It is helpful to understand the system used to enter journal articles into the database and the classification of the common types of searches and to review suggestions for the best ways to use the PubMed interface and find sources for search teaching and assistance.

The ross ice shelf project.

A hole was drilled through the Ross Ice Shelf 450 kilometers from the barrier. Scientific sampling through this hole revealed a sparse population of crustaceans, fish, and microbial biomass. The seabed consists of mid-Miocene glaciomarine mud. Geothermal heat flow is average. Oceanographic data indicate an active circulation and melting at the base of the ice.

Orthopaedic information: how to find it fast on the Internet.

The Internet is a rapidly expanding source of information that has gained a valued place in the knowledge armamentarium of the orthopaedic surgeon. Access to current knowledge, published literature, and a vast array of academic, federal, and commercial information has changed the information landscape for both orthopaedic surgeons and their patients. It is valuable to highlight readily available information for orthopaedic surgeons to use for continuing medical education, literature updates, patient education materials, and presentations. There are multiple techniques for accessing and organizing orthopaedic information as well as for identifying and using specific, high-quality, frequently updated Internet sources of information.

A study of the structure-activity relationship for diazaborine inhibition of Escherichia coli enoyl-ACP reductase.

Enoyl acyl carrier protein (ACP) reductase catalyses the last reductive step of fatty acid biosynthesis, reducing the enoyl group of a growing fatty acid chain attached to ACP to its acyl product using NAD(P)H as the cofactor. This enzyme is the target for the diazaborine class of antibacterial agents, the biocide triclosan, and one of the targets for the front-line anti-tuberculosis drug isoniazid. The structures of complexes of Escherichia coli enoyl-ACP reductase (ENR) from crystals grown in the presence of NAD+ and a family of diazaborine compounds have been determined. Analysis of the structures has revealed that a mobile loop in the structure of the binary complex with NAD+ becomes ordered on binding diazaborine/NAD+ but displays a different conformation in the two subunits of the asymmetric unit. The work presented here reveals how, for one of the ordered conformations adopted by the mobile loop, the mode of diazaborine binding correlates well with the activity profiles of the diazaborine family. Additionally, diazaborine binding provides insights into the pocket on the enzyme surface occupied by the growing fatty acid chain.

Rat eosinophils: isolation and characterization of superoxide production.

Studies with isolated cells are important to the understanding of mechanisms by which eosinophils participate in allergic inflammation. Due to species variability, isolation techniques and cell biology need to be defined for each source. We developed methods to obtain rat eosinophils with purity and viability exceeding 90%, characterized the superoxide anion production of these cells in response to standard activators, and compared these results with those previously obtained in our laboratories with the use of human eosinophils. Rat eosinophils responded vigorously to phorbol myristate acetate and poorly to platelet-activating factor and to N-formyl-methionyl-leucyl-phenylalanine, parallel to the responses of human eosinophils. In contrast, rat eosinophils responded unlike human eosinophils to other activators, having a larger response to calcium ionophore A23187, a smaller response to serum-treated or serum-opsonized zymosan, and a negative rather than positive modulatory effect of cytochalasin B. We conclude that rat eosinophils can be obtained in high purity and with intact responsiveness to a number of different activators.

Weighted criteria for the diagnosis of systemic lupus erythematosus.

The preliminary American Rheumatism Association (ARA) criteria for classification of systemic lupus erythematosus (SLE) were evaluated for sensitivity and specificity in 87 patients with SLE and 73 without SLE from a rheumatology population. Using these data, Bayes' theorem was employed to weight the criteria so that a scoring system could be developed, allowing more accurate use of the criteria in diagnosis. Combinations of serologic test results were evaluated in a similar manner. Comparison of weighted scores with criteria counts showed greater sensitivity and specificity of the former whether the 1971 or modified 1982 ARA criteria were used. Weighted criteria may be more useful in clearly defining patient populations for studies of SLE.

Development of systemic lupus erythematosus after thymectomy for myasthenia gravis. Studies of suppressor cell function.

Systemic lupus erythematosus developed in an 18-year-old man three years after thymectomy for myasthenia gravis. The patient had considerable defects in suppressor cell function that seemed to be partially reversed in vitro by the addition of thymic hormone.

Familial late complement component (C6, C7) deficiency with chronic meningococcemia.

Two patients with chronic meningococcemia were found to lack hemolytic complement, one because of C6 deficiency, the other because of C7 deficiency. In both cases family studies were consistent with inheritance of the deficiencies as non-HLA-linked, autosomal co-dominant traits. Functional studies showed the deficient sera to support monocyte chemotaxis but not phagocytosis or lysis of meningococci. Both patients have remained well following antibiotic treatment.

Development of antinuclear antibodies during acebutolol therapy.

Eleven patients were studied while taking the beta blocker acebutolol for a period ranging from 12 to more than 24 wk. Control titers for fluorescent antinuclear antibody (ANA) were obtained in all. Serial testing was performed over the duration of the therapy and following its discontinuation. Additional immunologic testing was performed in most patients. The patients were observed closely for the development of clinical autoimmune disease. Using a sensitive assay, fluorescent ANA developed in 8 of 9 patients with negative values in the control period. In no patient has evidence of clinical autoimmune disease developed. In general, the titers of ANA tended to rise with increasing duration of therapy and decline after its discontinuation. Positive lupus erythematosus cell preparations were also observed in several patients. These data suggest that autoantibodies are frequently induced by acebutolol and, although no evidence of clinical autoimmune disease has been reported, immunologic surveillance is warranted.

Calcium bioavailability from a calcium- and sulfate-rich mineral water, compared with milk, in young adult women.

Some mineral waters have a high calcium content and may contribute a significant part of the human daily requirements. Calcium bioavailability from a calcium- and sulfate-rich mineral water (CS-W) containing 11.2 mmol Ca/L (467 mg/L) was compared with that from milk in nine healthy young women. Calcium absorption was measured in the fasting state with a dual-label stable-isotope technique. Fractional absorption rates from milk and CS-W were 25.0 +/- 6.7% and 23.8 +/- 4.8% (means +/- SD), respectively, and did not differ significantly (P = 0.05). Urine was collected for 36 h after the administration of the oral stable isotope while the subjects consumed a controlled diet and a quantity of milk or CS-W providing 25 mmol (1000 mg) Ca. No significant difference was found in the excretion of calcium, nor in the excretion of the two stable isotopes. Mean urinary sulfate excretion was significantly increased by 35% when the CS-W was consumed. No significant correlation was found between 36-h urinary excretion of the intravenous calcium tracer and sulfate, sodium, or urine volume. Therefore, calcium from the CS-W was as well absorbed and retained as that from milk, and no calciuric effect of sulfate was found, showing that such mineral waters can be valuable dietary sources of calcium.

Quality of life in multiple sclerosis. Comparison with inflammatory bowel disease and rheumatoid arthritis.

Multiple sclerosis (MS) and other chronic illnesses can drastically decrease quality of life (QOL), but there has been little systematic study of QOL in patients with chronic medical diseases. We analyzed QOL in 68 patients with MS, 164 patients with inflammatory bowel disease, and 75 patients with rheumatoid arthritis. The previously validated test instrument was a standardized interview consisting of 41 questions clustered in four subscales: functional and economic scale, social and recreational scale, affect and life in general scale, and medical problems scale. Patients were included in the study if they had a definite medical diagnosis and disease duration of 10 years or longer. In the patients with MS, Kurtzke's Expanded Disability Status Scale correlated strongly only with the medical problems score. Of Kurtzke's Functional System Scales, only the visual Functional System Scores was correlated with total QOL and subscale scores, suggesting that vision is strongly related to QOL. Duration of MS was unrelated to QOL scores. There were significant differences between patients with MS, inflammatory bowel disease, and rheumatoid arthritis on the subscale and total QOL scores. Results suggested that QOL was best in the inflammatory bowel disease group and worst in the MS group. Numerous statistically significant differences on individual questions were evident, suggesting that unique clinical profiles differentially characterize these diseases. Assessments of QOL are a meaningful addition to impairment scales, such as Kurtzke's Expanded Disability Status Scale. Furthermore, QOL scores may meaningfully measure the impact of a chronic medical disease, such as MS, compare the impacts of different diseases, and assess the effects of therapeutic intervention.

Measurement of DNA-binding immunoglobulins in systemic lupus erythematosus.

A radioimmunoadsorbant assay for quantitating DNA antibody in the IgM, IgG, and IgA classes is described. The method was standardized allowing expression of results in absolute terms. Effects of rheumatoid factor on the results were investigated. The new assay was found to correlate well with the Farr assay for DNA antibody. Serum levels of DNA antibody in all three immunoglobulin classes reflected the degree of clinical activity of SLE.

Use of C6- and C7-deficient human sera in quantitative hemolytic assays for C6 and C7.

Quantitative hemolytic assays for C6 and C7 using as R reagents sera from patients deficient in these components are described. The assays gave linear results. Normal range for serum C6 was found to be 21,400--41,700 C6 hemolytic units/ml; for serum C7 the normal range was 5540--9860 C7 hemolytic units/ml.

Platelet-bound IgG in systemic lupus erythematosus with and without thrombocytopenia.

A new assay for IgG bound to autologous platelets is described, in which IgG is dissociated from platelets washed at low pH, then measured by radioimmunoassay. Platelet-bound IgG was found to be elevated in thrombocytopenic patients with SLE and reduced in non-thrombocytopenic patients with this disease. There was a close inverse correlation of platelet-bound IgG and platelet count. Immune complexes did not interfere with the assay.

Relationship of renal histopathology in SLE nephritis to immunoglobulin class of anti-DNA.

Using a newly-developed solid-phase radioimmunoassay for DNA-binding immunoglobulins, immunoglobulin M (IgM), immunoglobulin G (IgG) and immunoglobulin A (IgA) anti-DNA were measured in serums from 11 patients with active untreated systemic lupus erythematosus (SLE) with nephritis. All patients underwent renal biopsy and were classified according to standard criteria as having diffuse or focal proliferative glomerulonephritis. Although both groups had almost identical total anti-DNA (13.1 versus 13.9 micrograms/ml, respectively), the IgM to IgG ratio was significantly higher (p less than 0.01) in the group with DPGN (7.51) than in the group with FPGN (1.10). We suggest that the switchover mechanism from IgM to IgG antibody production is more profoundly impaired in SLE with severe renal disease than in SLE with mild renal disease.

Outcome of first-trimester exposure to low-dose methotrexate in eight patients with rheumatic disease.

PURPOSE: Methotrexate (MTX), when used to treat malignancy or psoriasis, has been implicated in anecdotal reports as a teratogen or abortifacient in the first trimester of pregnancy. We are unaware of any previous reports that describe the course of gestation and the effect on subsequent offspring in patients treated with low-dose oral MTX for rheumatoid arthritis, and therefore present our experience. PATIENTS AND METHODS: We report on eight women experiencing 10 pregnancies. Mean number of weeks of gestation while taking MTX was 7.5 (range 2 to 20 weeks). Outcome of pregnancies included five full-term babies (FTB), three spontaneous abortions (SAB), and two elective abortions. RESULTS: There were no significant differences in either the FTB or SAB group when considering risk factors including smoking, alcohol, concomitant medications, and age. One of three in the SAB group had recurrent abortions prior to MTX therapy. All five of the FTB group had uncomplicated pregnancies and deliveries. All offspring were of normal height and weight at birth with no physical abnormalities. All children reached growth, development, and intellectual stages normally, and their present mean age is 11.5 years. No observed learning disabilities or medical abnormalities have occurred in any of these children. CONCLUSION: In this uncontrolled study we failed to demonstrate tertogenicity of MTX. However, the possibility of abortion due to MTX use remains.

Wegener's granulomatosis in the pediatric age group.

Six cases of Wegener's granulomatosis (WG) occurring in patients younger than 21 years are described. Only 11 other cases in the pediatric age group have been reported, and all 17 of these patients had the onset of the disease during the second decade of life. Wegener's granulomatosis is a systemic disease characterized by a clinical triad of paranasal sinus and nasal mucosa involvement, pulmonary infiltration and cavitation, and renal disease with hematuria. The most common presenting symptoms are malaise and fever, sinusitis, epistaxis, and hematuria. Most patients have roentgenographic evidence of pulmonary and sinus disease and laboratory evidence of renal involvement on initial evaluation. The prognosis of WG was formerly dismal; more than 90% of patients died in less than two years, but with recent therapeutic regimens, more than 50% of these patients are surviving. The treatment we recommend consists of nitrogen mustard with adrenocorticotropic hormone or prednisone for the induction of remission, followed by cyclophosphamide and prednisone as maintenance drugs. This regimen has proved effective in inducing a remission in four of four patients.

Therapy for rheumatoid arthritis: combinations of disease-modifying drugs and new paradigms of treatment.

The last 10 years have witnessed a change in the way rheumatologists view rheumatoid arthritis (RA). It is no longer considered a slowly progressive disease limited to the joints, but rather an aggressive systemic disease that results in clinically significant morbidity early in its course and can contribute to excess mortality. Heightened awareness of the health impact of RA has spurred a search for effective therapy to be applied early in the course of disease for patients with moderate to severe RA. Combinations of disease-modifying antirheumatic drugs (DMARD) have become an increasingly popular alternative to sequential monotherapy. In this report, we review published series of patients with RA who have been treated with combinations of DMARDs, sometimes including chemotherapeutic agents, with some critical comment. Published paradigms of treatment are also reviewed and a new strategy is presented. The "step-down bridge" strategy allows early treatment with at least four DMARDs, but may place some patients with mild disease at an inappropriately high risk of adverse effects. The "sawtooth" strategy gives little guidance as to which DMARD(s) should be chosen for initial treatment. We describe a "graduated-step" strategy that provides numerical grading to match disease severity and disease activity with appropriate initial therapy and that facilitates therapeutic decisions throughout the course of treatment.