The relative value of lumbar roentgenograms, metrizamide myelography, and discography in the assessment of patients with chronic low-back syndrome

This prospective study evaluated the relative value of lumbar roentgenograms, metrizamide myelography, and discography in identifying structural sources for chronic low-back syndrome. One hundred and eight patients with chronic low-back syndrome were evaluated. Patients had not previously had pathology identified which could explain their pain. On discography, 83 patients (78%) had their pain reproduced at least one abnormal level, identifying a structural component to their pain. Only 22 patients (21%) had all levels of pathology identified by roentgenograms and an additional 17 (16%) had pathology appropriately identified by a combination of myelograms and roentgenograms. Using roentgenograms, myelography, and discography, organic pathology was identified which could explain the patient's symptoms in 100 of 108 patients (93%). Based on this study, we think discography is an important diagnostic tool for use in evaluating patients with chronic low-back syndrome. Discography is essential to adequately identify abnormal levels in patients being considered for fusions. Roentgenograms and myelograms are inadequate evaluation in this chronic pain group in that lack of organic pathology cannot be assumed in the presence of normal roentgenograms and myelograms.     

On the origin of antibodies to immunoglobulin genetic markers in rheumatoid arthritis. An outline of a novel concept of the nature of rheumatoid arthritis--transduction in man

Anti-Gm's in rheumatoid arthritis patients detect products of the Mendelian genes G1ma, G1mx, G3mb, G3mc, G3mg, G3mst. Commonly, these anti-Gm's are specific for other individuals immunoglobulin allotypes. Reasons are given for the contention that such anti-Gm's in patients with rheumatoid arthritis are indicative of the expression of nonnominal allotypes, the genes for which have been transferred from one individual to another by means of a B cell virus. This process - akin to transduction and occurring after the tolerance induction period - may lead to a chimaeric state of the B cell compartment in rheumatoid arthritis patients. Special features of Ig gene regulation in normal B cell progression are allelic exclusion and the excision-expulsion-rejoining of DNA segments. Perturbation of B cell regulation by external genomes may be favoured by allelic exclusion. The DNA excision-rejoining processes may have consequences for concomitant (viral) nucleic acid assembly, particularly for viruses sharing nucleotide sequences with the Ig switch regions.     

Age-related reference limits for urine levels of albumin, orosomucoid, immunoglobulin G and protein HC in children

Urine levels of albumin, orosomucoid (alias alpha1-acid glycoprotein), immunoglobulin G (IgG) and protein HC (alias alpha1-microglobulin) were determined in 247 healthy Swedish infants and children aged 1 day to 15 years. Urine samples were collected and stored in conditions known to guarantee stable protein levels. The protein levels were measured both as mass concentrations (mg l(-1)) and as protein-creatinine ratios (mg mmol(-1)). In an effort to arrive at practically useful upper reference limits, the variability with age for both units was analysed. The variability with age for the levels of three of the four proteins was considerably lower when the levels were expressed as creatinine ratios rather than as mass concentrations. The results allowed suggestion of the following upper reference limits, expressed as mg mmol(-1) creatinine, for use in clinical practise: IgG, 1 month to 15 years: 1.0; protein HC, 1 month to 15 years: 0.8; orosomucoid, 1 month to 15 years: 0.5; albumin, 1 month to 1 year: 3.8; 1-5 years: 3.3; 6-10 years: 2.7; 11-15 years: 2.1. In the immediate neonatal period the urine levels of all proteins were high and very variable.     

Genetic characterization of the fusidic acid and cadmium resistance determinants of Staphylococcus aureus plasmid pUB101

We report the cloning of the fusidic acid and cadmium resistance determinants from Staphylococcus aureus plasmid pUB101. The pUB101 fusidic acid resistance determinant was located on a 2.9 kb HindIII fragment. Sequencing of this fragment revealed three putative open reading frames (ORFs) of 213 (far1), 152 (orf152) and 170 amino acids (orf170), which are flanked by the right-hand end of insertion sequence IS431/257 (IS431/257RH) and a partial ORF. Far1 and Orf152 demonstrated homology with a chromosomally encoded fibronectin-binding protein of Listeria monocytogenes and the putative protein YosT, found on the SP beta c2 prophage of Bacillus subtilis, respectively. Transformation of S. aureus with a construct containing a 949 bp far1-specific amplicon led to the isolation of a fusidic acid-resistant transformant, thereby identifying the pUB101 fusidic acid resistance structural gene. Between orf152 and far1 we identified a unique 113 bp symmetrical element and other repeat elements that may be involved with the control of orf152 and/or far1 expression. Hybridization of Southern blots revealed that far1 was not located on the chromosome or plasmid content of a limited number of Australian, UK and Hong Kong fusidic acid-resistant isolates. The pUB101 cadmium resistance determinant was located on a 3.6 kb HindIII fragment that carried a cadDX operon, remnants of two putative plasmid replication protein genes and IS431/257RH. Sequence analysis also demonstrated the presence of a single-stranded origin of replication, normally found on rolling circle replicating plasmids, within the putative promoter region of the cadDX operon.     

Production, characterization and use of monoclonal antibodies against the major extracellular human cysteine proteinase inhibitors cystatin C and kininogen

Murine monoclonal antibodies against the major cysteine proteinase inhibitors of human biological fluids, cystatin C and kininogen, were produced. The cystatin C antibody, HCC3, with a Ka of 2 x 10(7) l/mol, increased the inhibition of papain by cystatin C and was suitable for use in immunoblotting, immunohistochemistry and in the construction of a sensitive sandwich enzyme immunoassay for quantification of cystatin C. It recognized not only free cystatin C but also cystatin C in complexes with cysteine proteinases. The kininogen antibody, HK4, was directed against the third, cysteine proteinase inhibitory domain of the heavy chain of kininogen (Ka = 1 X 10(7) l/mol), but did not influence the papain inhibitory activity of kininogen. It reacted with free kininogen as well as kininogen in complex with cysteine proteinases. Both antibodies could be used for the production of specific immunosorbents.     

Cystatin C reduces the in vitro formation of soluble Abeta1-42 oligomers and protofibrils

There are an increasing number of genetic and neuropathological observations to suggest that cystatin C, an extracellular protein produced by all nucleated cells, might play a role in the pathophysiology of sporadic Alzheimer's disease (AD). Recent observations indicate that small and large soluble oligomers of the beta-amyloid protein (Abeta) impair synaptic plasticity and induce neurotoxicity in AD. The objective of the present study was to investigate the influence of cystatin C on the production of such oligomers in vitro. Co-incubation of cystatin C with monomeric Abeta1-42 significantly attenuated the in vitro formation of Abeta oligomers and protofibrils, as determined using electron microscopy (EM), dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting, thioflavin T (ThT) spectrofluorimetry and gel chromatography. However, cystatin C did not dissolve preformed Abeta oligomers. Direct binding of cystatin C to Abeta was demonstrated with the formation of an initial 1:1 molar high-affinity complex. These observations suggest that cystatin C might be a regulating element in the transformation of monomeric Abeta to larger and perhaps more toxic molecular species in vivo.     

A review of spinal injuries in the invasive cardiologist: part 1. Biomechanics and pain generation

This review provides a perspective of spinal injuries related to invasive cardiology, an understanding of the anatomy and physiology of the spine, the etiology and pathophysiology of spinal injuries, and options for prevention and treatment. Because of the breadth of this review, it has been divided into two parts with the first describing the biomechanics and generation of back pain and the second discussing treatment options and prevention of back injury. A comprehensive overview of the biomechanics of the spine from the individual vertebral unit to the complex motions involved in everyday life is reviewed. The significant intrinsic and extrinsic factors playing a role in the mechanism of disc damage, including occupational hazards encountered by the invasive cardiologist, are discussed. We also address the mechanisms of pain generation in the spine and the role that inflammation plays, which explains the presence of symptoms with little or no detectable pathology on imaging studies.     

Microcalorimetric studies on uraemic plasma.

The heat production by human plasma in healthy and uraemic subjects has been measured by direct isothermal microcalorimetry. The plasma from uraemic subjects displayed an increased heat production compared to that of normal plasma. The heat production by plasma from healthy subjects, but not by that from uraemic patients, was both proportional to the amount of thiol groups in the plasma and also to the oxidation of the thiol groups. The oxygen consumption of uraemic plasma was proportional to the heat production. The heat production by samples from uraemic patients was significantly correlated to the plasma concentration of creatinine, whereas no such correlation was found between the concentration of urea and heat production of such samples.