Applications of Interpedicular Distance and Anteroposterior Diameter in the Approximation of the Spinal Canal Area.

INTRODUCTION:  Advancements within the field of medicine revolve around increasing the efficiency of diagnosing and subsequently treating patients. One such advancement is measurements of the central canal using artificial intelligence (AI). The authors propose the possibility of AI measuring two linear distances followed by a subsequent approximation via an area equation. The lumbar spinal canal was approximated by an area calculation using the interpedicular distance (IPD) and anteroposterior diameter (AP diameter). The three shapes evaluated were an ellipse, triangle, and rectangle. METHODS:  IPD, AP diameter, and spinal canal area from L1-L5 were measured in 555 patients using the IMPAX6 (Mortsel, Belgium: Agfa-Gevaert) picture archiving and communication system. Subsequently, an approximated area of the lumbar spinal canal, assuming an ellipse shape, was calculated using ellipse equation/approximation. Triangular and rectangular approximations were done using triangle equation/approximation and rectangle equation/approximation, respectively. The equations used are the geometric equations for the area of each shape described. For example, the triangular approximation used the IPD as the base of the triangle and the AP diameter as the height. Thus, the area approximation was calculated by half of the IPD times the AP diameter. RESULTS:  The percent error of the ellipse approximation was the lowest with a range of error from 8.44% at L1 to 15.51% at L5. The triangle approximation again was the second most accurate with a range of error starting at -26.46% at L5 to -30.96% at L1. Lastly, the percentage errors of the rectangle approximation began at 38.07% at L1 to 47.07% at L5. The ellipse and rectangle approximation consistently overestimated the area of the spinal canal, while the opposite was true for the triangle approximation. A combination of these approximations could be used to construct a second-order approximation. The approximations were all highly correlated with the authors' manual measurements. Approximations at the L2 vertebrae were highest with a correlation of 0.934 closely followed by all approximations at L5 with a value of 0.931. Approximations were least correlated with the L4 vertebrae with a value of 0.905. CONCLUSION: The correlation between the approximation equations and the measured values is significantly related. The ellipse equation best predicted the area of the spinal canal followed by the triangle and then the rectangle approximation. The percent error difference of the ellipse approximation at L1 was similar in error compared to other causes of measurement error. Continued investigation into a second-order approximation may yield a more accurate approximation.

Anatomic Assessment of L1-S1 Neuroforaminal Dimensions Using Computed Tomography in 1,000 Patients: A Follow-Up Study.

OBJECTIVES: While the radiographic criteria for diagnosing central lumbar stenosis are well described, criteria for diagnosing neuroforaminal stenosis (NFS) are unclear. Prior research has utilized magnetic resonance imaging (MRI) to characterize neuroforaminal dimensions (NFDs). However, this approach has inherent limitations that can adversely impact measurement accuracy. Existing literature on the use of computed tomography (CT) to investigate normal NFDs is limited. The purpose of the present study was to describe normal lumbar NFDs that would aid in the establishment of objective quantitative criteria for the diagnosis of NFS. METHODS: This study evaluated CT imaging of 494 female and 506 male subjects between 18 and 35 years of age to determine normal NFDs, specifically the sagittal anteroposterior width, craniocaudal height, and area. Statistical analyses were performed to assess differences in NFDs according to variables including sex, height, weight, body mass index, and ethnicity. RESULTS: Without differentiating between sides or disc levels, mean NFDs were 8.71 mm for sagittal anteroposterior width, 17.73 mm for craniocaudal height, and 133.26 mm2 for area (n = 10,000 measurements each). Male subjects had larger NFDs than females at multiple levels. Asian and Caucasian subjects had larger NFDs than Hispanic and African American subjects at multiple levels. There were no associations between NFDs and anthropometric factors. CONCLUSIONS: The present study describes normal lumbar NFDs in young, healthy patients. NFDs were influenced by sex and ethnicity but not by anthropometric factors.

Premenopausal sexual dimorphism in lipopolysaccharide-stimulated production and secretion of tumor necrosis factor.

OBJECTIVE: To establish whether sexual dimorphism in tumor necrosis factor (TNF) concentration in lipopolysaccharide (LPS)-stimulated whole blood culture is related to menopausal status or hormone concentrations. METHODS: Healthy volunteers (72 premenopausal female, 159 male, and 62 postmenopausal female) completed questionnaires and gave peripheral blood specimens for whole blood LPS-stimulated TNF assay and for selected hormone levels. TNFab microsatellite markers were genotyped. RESULTS: Mean LPS-stimulated TNF level in the premenopausal female group was 18% lower than the postmenopausal female mean (1579 +/- 913 pg/ml compared with 2257 +/- 881 in the men and 1965 +/- 950 in the postmenopausal women; p < 0.0003 and p 0.058, respectively). Analyzing a subset for which blood counts were obtained, mean stimulated TNF per monocyte was lower in the premenopausal female group than in the postmenopausal female group and appeared lower than in the male group (2.67 +/- 1.96 pg/ml per 10(3) monocytes vs 4.44 +/- 2.16 and 3.60 +/- 1.40; p = 0.018 and p = 0.12, respectively). Total plasma cortisol was higher in premenopausal women than men, and, in turn, higher in men than postmenopausal women (mean +/- SD 16.1 +/- 5.7, 12.2 +/- 3.6, and 10.4 +/- 4.3 microg/dl, respectively; p < 0.05 for each comparison). Using multiple linear regression to correct for covariates and TNF allelic effects, premenopausal status predicted TNF level independently from potential confounders or TNF genetic markers (covariate-adjusted decrement of 408 pg/ml; p = 0.0241). In the male group, total cortisol predicted lower TNF level (coefficient -67.5 pg/ml for each microg/dl cortisol; p = 0.0006 after stepwise selection), but total testosterone had no effect. In premenopausal women, LPS-stimulated TNF was not related to total estradiol, testosterone, or cortisol level. CONCLUSION: Premenopausal women had a lower mean whole blood LPS-stimulated TNF level than postmenopausal women, but there was no significant relation to total estradiol, testosterone, or cortisol levels in premenopausal women.

Flavopiridol potently induces small cell lung cancer apoptosis during S phase in a manner that involves early mitochondrial dysfunction.

PURPOSE: Accumulating evidence indicates that small cell lung cancer (SCLC) is defective in many of the regulatory mechanisms that control cell cycle progression. The purpose of this study was to determine the effects of flavopiridol, a pan-cyclin-dependent kinase inhibitor, on growth and apoptosis of SCLC cell lines. EXPERIMENTAL DESIGN: Cell growth was monitored using 3-(4,5dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide (MTT) and clonogenic assays. Induction of apoptosis was assessed using multiple assays, including flow cytometric determination of DNA content and mitochondrial membrane potential, terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL), and Western blot analysis of procaspase 3 and poly(ADP-ribose) polymerase cleavage. RESULTS: Flavopiridol induced growth inhibition and cytotoxicity in multiple SCLC cell lines, with an IC(50) of 50-100 nM and an LD(50) of 150-200 nM in 72-h MTT assays. The cytotoxicity seen in the MTT assay proved to be apoptosis by several criteria. Interestingly, inhibition of caspase activation with the caspase inhibitor Boc-Asp(OMe)-CH(2)F reduced TUNEL labeling by 40% but did not have any effect on the loss of mitochondrial membrane potential (detected as early as 4 h after drug exposure) or cytotoxicity in MTT assays. These results suggest that the primary event in flavopiridol-induced apoptosis involves induction of mitochondrial dysfunction. Cells synchronized with aphidicolin at the G(1)-S border and treated with flavopiridol during S phase showed a marked increase in apoptosis compared with an asynchronous population or a population treated during G(2)-M. Despite the increased apoptosis, a significant proportion of synchronized cells proceeded through S, G(2)-M, and into G(1) phase in the presence of flavopiridol, demonstrating that a high-grade cell cycle arrest is not required for apoptosis. Cells synchronized at the G(1)-S border treated with a short exposure to flavopiridol also showed more than a 10-fold decrease in clonogenicity compared with asynchronous cells treated identically. CONCLUSIONS: Taken together, these data demonstrate that flavopiridol potently and selectively induces SCLC apoptosis preferentially during S phase, in a manner that involves early mitochondrial dysfunction without a requirement for a high-grade block to cell cycle progression. Furthermore, clonogenicity data suggests that prior S phase synchronization could be a highly effective way of enhancing the efficacy of bolus or short infusions of flavopiridol in the clinical setting.

Oral symptoms associated with fibromyalgia syndrome.

OBJECTIVE: Studies have described oral problems associated with fibromyalgia syndrome (FM), including sicca, oral ulcerations, and orofacial pain. We evaluated the prevalence and profile of various oral symptoms in a population of patients diagnosed with FM. METHODS: Subjects diagnosed with FM by American College of Rheumatology criteria (n = 67; all women, mean age +/- SEM 47.6 +/- 2.3 yrs) were enrolled in the study after meeting strict exclusion criteria (i.e., oral mucosal conditions, Sjögren's syndrome, anemia, inflammatory bowel syndrome or other gastrointestinal disturbances, and other disorders that may manifest oral symptoms). Subjective oral evaluations were carried out for each subject, including oral pain (Melzack scale) for glossodynia, throbbing, aching, etc.; temporomandibular joint dysfunction (TMD); xerostomia (including intake of fluids, functional problems, etc.); dysphagia; dysgeusia; and information about frequent oral ulcerations or lesions. Psychological tests included Beck Depression Scale (BDS) and Spielberger Anxiety Scale (SAS) were administered. RESULTS: The results indicated a significant prevalence in some subjects' oral symptoms, compared to age and sex matched control data (mean +/- SEM) for xerostomia 70.9% vs 5.7% (p < 0.001); glossodynia 32.8% vs 1.1% (p < 0.001); TMD 67.6% vs 20% (p < 0.01); dysphagia 37.3% vs 0.4% (p < 0.001); dysgeusia 34.2% vs 1.0% (p < 0.001). Other findings were not significantly different from controls: oral ulcerations/lesions 5.1% vs 4.4% (NS); BDS 34% vs 30% (NS); SAS 21% vs 19% (NS). The average visual analog scale (100 mm) for burning pain was 53.0 +/- 5.6 (p < 0.001). Anxiety and depression scores were no different in the FM subjects compared to controls with chronic pain conditions. CONCLUSION: These data indicate that patients with FM have significantly increased prevalence of xerostomia, glossodynia, dysphagia, dysgeusia, and TMD compared to controls, with no significant difference in clinical oral lesions or psychological status.

Secretion of a unique peptide from interleukin-2-stimulated natural killer cells that induces endomitosis in immature human megakaryocytes.

When interleukin-2 (IL-2) was added to immature, low-ploidy (greater than 80% 2N+4N) megakaryocytes generated in IL-3 and stem cell factor (SCF)-containing liquid cultures of blood mononuclear cells highly enriched in hematopoietic progenitors, a 2- to 6-fold increase in the absolute number of polyploid (more than 8N) megakaryocytes was noted. This effect was found to be indirect and was mediated through natural killer (NK) cells that constitute the major lymphoid cell contaminating day 6 megakaryocyte cell populations. IL-2 had no effect on megakaryocytes generated from CD34(+) cells stimulated with IL-3 and SCF. However, medium conditioned by IL-2-stimulated, but not resting, NK cells (NKCM) contained a trypsin-sensitive factor capable of increasing 2- to 5-fold the number of polyploid megakaryocytes generated in vitro from IL-3 and SCF-stimulated CD34(+) cells. The activity in NKCM was dose dependent and could not be neutralized by an excess of antibodies to IL-6, IL-11, leukemia inhibitory factor (LIF), gp130, stromal cell derived factor-1a (SDF-1a), and thrombopoietin (TPO). Addition of IL-11, but not TPO, to NKCM-containing cultures resulted in further augmentation of polyploidy, with the generation of 50% to 70% polyploid megakaryocytes with a modal ploidy of 16N. This factor is distinct from TPO because it induces endomitosis in IL-3-generated megakaryocytes in vitro, whereas TPO does not, and its activity on megakaryocyte ploidy is not altered by optimal concentrations of TPO. In addition, no message for TPO is detectable in IL-2-stimulated NK cells by reverse transcription-polymerase chain reaction. These findings indicate that IL-2-stimulated NK cells produce a novel peptide, distinct from TPO, IL-6, IL-11, LIF, other gp130-associated interleukins, and SDF1a, that can induce in vitro endomitosis in immature human megakaryocytes in the presence of IL-3 and SCF.

Sexual dimorphism in innate immunity.

OBJECTIVE: To establish whether variation in innate immunity, as measured by the level of tumor necrosis factor (TNF) in lipopolysaccharide (LPS)-stimulated whole-blood culture, is related to sex or HLA. METHODS: Normal volunteers (72 women, 159 men) completed questionnaires and donated peripheral blood specimens. Blood samples were exposed to LPS in a 4-hour in vitro culture, and supernatants were then tested by sandwich-type immunoassay measuring TNF levels. Statistical techniques included multivariate analysis and maximal-likelihood modeling of allelic effects. RESULTS: Both male and female groups showed substantial within-group variation (coefficient of variation 59.1% for women, 40.3% for men). However, the mean +/- SD LPS-stimulated TNF level in the female group was nearly 30% lower than in the male group (1,556+/-919 pg/ml versus 2,203+/-889 pg/ml; P < 0.0001, unadjusted for covariates). Sex was independent of any microsatellite marker allele of TNF (covariate-adjusted increment of 785 pg/ml from female to male sex; P < 0.0001). In multivariate modeling of the female group, the LPS-stimulated TNF level was not independently influenced by menstrual cycle phase, oral contraceptive use, or plasma estradiol level. Allelic modeling showed that significant TNFab microsatellite allelic effects existed (P = 0.002 versus model omitting allelic effects). The female group showed a significantly downward deviation from mean TNF level with TNFa4b5 (-903 pg/ml deviation from the overall mean) and an upward deviation with TNFa10b4 (598 pg/ml). The male group showed significantly higher-than-mean levels with TNFa1b5 (909 pg/ml), TNFa5b7 (1,191 pg/ml), and TNFa6b5 (332 pg/ml). Thus, the two sex groups differed in which of their TNFab marker alleles showed significant deviations from the overall mean. CONCLUSION: Female subjects have a nearly 30% lower innate immune response, stemming largely from influence independent of the HLA-region TNF locus and without further independent variation stemming from plasma estrogen level.