A critical evaluation of discography in patients with lumbar intervertebral disc disease

STUDY DESIGN: The study is a prospective observational study of 48 continuous patients with symptomatic lumbar degenerative disk disease. Each patient underwent discography, MRI, and a biochemical analysis of disk lavage fluid. OBJECTIVES: The purpose of this study was to correlate concordant pain on discography with MRI grade and biochemical markers of inflammation in a clinical setting. SUMMARY OF BACKGROUND DATA: The pathophysiology of degenerative disk disease is complex. Discography is used to differentiate symptomatic from asymptomatic levels. MRI is used to image changes in disk water content. Biochemical assays have identified molecular markers of inflammation. To date, no study has correlated concordant pain on discography with MRI findings and biochemical markers. METHODS: Forty-eight (48) continuous patients with symptomatic lumbar degenerative disk disease gave informed consent for study entry. Patient sex, age, insurance, work status and visual analog score (VAS) were recorded. MRI was obtained and Pfirrmann grading was performed by a single spine surgeon. Discography with disc lavage was performed by a single anesthesiologist. Lavage samples were tested for inflammatory markers with high resolution multi-plex bead immunoassays and ELISA with >5 pg/ml resolution. RESULTS: None of demographic variables was significantly related to concordant pain on discogram by chi-squared tests and Mann-Whitney U-test. The Pfirrmann score was significantly different for patients with and without concordant pain at L3-L4 (p<0.001), but was insignificant at other levels after multitest correction. Pfirrmann scores were significantly different at any level in patients with and without concordant pain. VAS scores were not significantly correlated with opening pressures at any level. Despite the presence of serum proteins in the disk lavage fluid, none of the tested inflammatory mediators was identified by multi-plex bead immunoassays and ELISA. CONCLUSIONS: There are only weak correlations between demographic, discogram, and radiographic variables. Response to discogram cannot be predicted by non-invasive means. The disk lavage method was unable to identify the presence of specific inflammatory peptides with multi-plex immunoassays and ELISA.     

The sooty moulds

Sooty moulds are a remarkable, but poorly understood group of fungi. They coat fruits and leaves superficially with black mycelia, which reduces photosynthesis rates of host plants. Few researchers have, however, tried to quantify their economic importance. Sooty moulds have been well-studied at the morphological level, but they are poorly represented in a natural classification based on phylogeny. Representatives are presently known in Antennulariellaceae, Capnodiaceae, Chaetothyriaceae, Coccodiniaceae, Euantennariaceae, Metacapnodiaceae and Trichomeriaceae and several miscellaneous genera. However, molecular data is available for only five families. Most sooty mould colonies comprise numerous species and thus it is hard to confirm relationships between genera or sexual and asexual states. Future studies need to obtain single spore isolates of species to test their phylogenetic affinities and linkages between morphs. Next generation sequencing has shown sooty mould colonies to contain many more fungal species than expected, but it is not clear which species are dominant or active in the communities. They are more common in tropical, subtropical and warm temperate regions and thus their prevalence in temperate regions is likely to increase with global warming. Sooty moulds are rarely parasitized by fungicolous taxa and these may have biocontrol potential. They apparently grow in extreme environments and may be xerophilic. This needs testing as xerophilic taxa may be of interest for industrial applications. Sooty moulds grow on sugars and appear to out-compete typical “weed” fungi and bacteria. They may produce antibiotics for this purpose and their biochemical potential for obtaining novel bioactive compounds for medical application is underexplored.     

Cortical brain mapping of peripheral nerves using functional magnetic resonance imaging in a rodent model

The regions of the body have cortical and subcortical representation in proportion to their degree of innervation. The rat forepaw has been studied extensively in recent years using functional magnetic resonance imaging (fMRI), typically by stimulation using electrodes directly inserted into the skin of the forepaw. Here we stimulate the nerve directly using surgically implanted electrodes. A major distinction is that stimulation of the skin of the forepaw is mostly sensory, whereas direct nerve stimulation reveals not only the sensory system but also deep brain structures associated with motor activity. In this article, we seek to define both the motor and sensory cortical and subcortical representations associated with the four major nerves of the rodent upper extremity. We electrically stimulated each nerve (median, ulnar, radial, and musculocutaneous) during fMRI acquisition using a 9.4-T Bruker scanner (Bruker BioSpin, Billerica, MA). A current level of 0.5 to 1.0 mA and a frequency of 5 Hz were used while keeping the duration constant. A distinct pattern of cortical activation was found for each nerve that can be correlated with known sensorimotor afferent and efferent pathways to the rat forepaw. This direct nerve stimulation rat model can provide insight into peripheral nerve injury.     

Synergistic effect of low dose Cyclosporine A and human interleukin 10 overexpression on acute rejection in rat lung allotransplantation

Objective: Electroporation mediated transfer of plasmid DNA into peripheral muscle results in high transfection efficiency. The aim of this study was to investigate the effect of gene transfer of human IL-10 (hIL-10) into the tibialis anterior muscle (MTA) in combination with low dose Cyclosporine A (CsA) on acute rejection of lung allografts in the rat. Methods: Lung allotransplantation was performed from male BN donor to male Fisher F344 rats. Gene transfer was achieved by intramuscular injection into the MTA of the recipient followed by electroporation (4×20 ms impulses at 200 V/cm) 24 h prior to the transplantation. Group A (n=5) received CsA (2.5 mg/kg bw ip) for 5 days post-transplant and group B (n=5) 2.5 μg of PCIK hIL-10 (plasmid expression vector containing human CMV immediate early gene promoter and enhancer) and a low dose CsA (2.5 mg/kg bw i.p.). Graft function was assessed by blood gas at day 5 after exclusion of the native lung. Animals were sacrificed and blood was drawn to measure serum hIL-10 levels (ELISA) and tissue was sampled for histological grading of rejection. Results: Local expression of hIL-10 was confirmed at the mRNA level by in situ hybridization. All group A control animals showed severe signs of rejection. At day 5 all grafts in group B showed good gas exchange mean PaO2 233±123 mmHg, vs 44±8 mmHg in group A. Histological examination revealed moderate to severe rejection in all animals in group A (IIIB, ISHLT) in contrast to low moderate rejection in group B (II–IIIA). hIL-10 serum levels on day 5 were 14±7 pg/ml in group B vs. 0 in group A. Conclusions: Electroporation mediated hIL-10 overexpression in a peripheral muscle of the recipient in combination with low dose CsA reduces acute rejection in this model of rat lung allotransplantation.     

Impact of a conjugate vaccine on community-wide carriage of nonsusceptible Streptococcus pneumoniae in Alaska

BACKGROUND: Streptococcus pneumoniae is a leading cause of invasive bacterial disease and pneumonia among children. Antimicrobial resistance among pneumococci has increased in recent years and complicates treatment. The introduction of heptavalent pneumococcal conjugate vaccine (PCV7) could reduce acquisition of antimicrobial-resistant pneumococci. METHODS: We obtained 1350 nasopharyngeal swabs for culture from 1275 children aged 3-59 months presenting at 3 clinics in Anchorage, Alaska, during the winters of 2000, 2001, and 2002, as PCV7 was being introduced into the routine immunization schedule. We recorded the frequency of use of antibiotics as well as the dates of doses of PCV7 for enrolled children. We used multivariate logistic regression modeling to identify independent risk factors for overall carriage of pneumococci and carriage of PCV7-type pneumococci, cotrimoxazole-nonsusceptible (COT-NS) pneumococci, or penicillin-nonsusceptible (PCN-NS) pneumococci. RESULTS: The proportion of children who were up-to-date for age, with respect to PCV7 vaccination, increased from 0% in 2000 to 55% in 2002. Carriage of PCV7-type pneumococci decreased by 43% (P<.0001). Risk of carriage of PCV7-type pneumococci was lower in 2002 than in 2000, independent of vaccination status, suggesting an indirect effect of vaccination. Carriage of COT-NS, but not PCN-NS, pneumococci also decreased (38%; P=.02), not only among vaccinated children but also among unvaccinated children without recent use of antibiotics. CONCLUSIONS: Introduction of PCV7 into the routine infant immunization schedule in a community with a high prevalence of antimicrobial-resistant pneumococci appears to reduce transmission of PCV7 vaccine serotypes and COT-NS pneumococci but has no impact on overall carriage of pneumococci or carriage of PCN-NS pneumococci.     

Inpatient Management of Pulmonary Embolism: Clinical Characteristics and Mortality in a High-Volume Tertiary Care Center

Journal of Thrombosis and Thrombolysis - The optimal management strategy for submassive or intermediate risk pulmonary embolism (IRPE)—anticoagulation alone versus anticoagulation plus...     

Angiotensin II receptors and prolactin release in pituitary lactotrophs

Logical properties of angiotensin II receptors in the rat adenohypophysis were analyzed in cultured rat pituitary cells incubated with angiotensin II and known stimuli of pituitary hormone secretion. PRL release during incubation for 3 h with 3 nM angiotensin II was consistently increased by 68 +/- 5%, comparable with that elicited by TRH (63.1 +/- 4%). The ED50 of 0.5 nM for PRL release by angiotensin II was significantly lower than that of TRH (2.9 nM) in the same cell cultures. The antagonist analog [Sar1,Ala8]angiotensin II prevented the angiotensin-induced rise in PRL production but not that evoked by TRH, whereas dopamine and SRIF inhibited basal, angiotensin, and TRH-stimulated PRL release. Angiotensin II also caused a small increase in ACTH release but had no effect on the release of LH, TSH, and GH. Angiotensin II binding and PRL release were measured in partially purified lactotrophs prepared by elutriation, by which the initial cell suspension was separated into seven fractions. Most of the lactotrophs were present in the two fractions eluted at flow rates of 15.7 and 19.8 ml/min, as indicated by their immunoreactive PRL content. The 2.5- to 3.2-fold enrichment of lactotrophs was accompanied by a 2- to 3.5-fold increase in angiotensin II receptor concentration, with no change in binding affinity (Ka = 3.5 x 10(9) M-1). In the same fractions, angiotensin II-induced PRL release was similarly increased by 1.6- to 3.5-fold above basal, compared with values of less than 1 in the initial cell suspension and other fractions. The preferential location of angiotensin II receptors in the lactotroph-containing fractions and the close correlation between angiotensin II binding sites and stimulation of PRL release indicate the functional importance of the pituitary angiotensin II receptor sites. These findings also suggest that angiotensin II could contribute to the physiological regulation of PRL secretion.     

X-linked chronic granulomatous disease: correction of NADPH oxidase defect by retrovirus-mediated expression of gp91-phox

Chronic granulomatous disease (CGD) is an inherited immunodeficiency resulting from the inability of an individual's phagocytes to produce superoxide anions because of defective NADPH oxidase. The disease may be treated by bone marrow transplantation and as such is a candidate for somatic gene therapy. Two thirds of patients have defects in an X- linked gene (X-CGD) encoding gp91-phox, the large subunit of the membrane cytochrome b-245 component of NADPH oxidase. Epstein-Barr virus-transformed B-cell lines from patients with CGD provide a model system for the disease. We have used retrovirus-mediated expression of gp91-phox to reconstitute functionally NADPH oxidase activity in B-cell lines from three unrelated patients with X-CGD. The protein is glycosylated and membrane associated, and the reconstituted oxidase is appropriately activated via protein kinase C. The kinetics of superoxide production by such reconstituted cells is similar to that of normal B-cell lines. These data show the potential of gene therapy for this disease.