Sensitivity to change of the Roland-Morris Back Pain Questionnaire: part 1

BACKGROUND AND PURPOSE: This study estimated the Roland-Morris Back Pain Questionnaire's (RMQ) change score that best classified patients as those who had achieved an important change and those who had not achieved an important change. The study also investigated whether the estimate of change was dependent on patients' initial scores. Subjects and METHODS: The RMQ was administered to 226 patients with low back pain of less than 6 weeks' duration during their initial visit for physical therapy and following 3 to 6 weeks of treatment. A global rating of change was used to classify patients as those who had changed an important amount and those who had not changed. Receiver operating characteristic curves were used to identify the RMQ change score that most accurately classified patients with respect to important change. This analysis was repeated for 5 overlapping subsamples of patients with initial scores 0 to 8, 5 to 12, 9 to 16, 13 to 20, and 17 to 24. RESULTS: The area under the receiver operating characteristic curves increased when patients' initial scores were taken into account. Estimates of important change were 2, 4, 5, 8, and 8 for the initial score intervals mentioned above. CONCLUSION AND DISCUSSION: Important change appears to be dependent on patients' initial RMQ scores. Subsequent inquiry using different hypotheses would add support to the estimates of important change found in this study.     

Pharmacokinetics and metabolism of [14C]dichloroacetate in male Sprague-Dawley rats. Identification of glycine conjugates, including hippurate, as urinary metabolites of dichloroacetate

We have recently isolated a mammary growth factor from the conditioned medium of mouse mammary stromal fibroblasts and identified it as a mouse homologue of human HGF (hepatocyte growth factor). To elucidate the role of HGF in mouse mammary tumorigenesis, we produced recombinant mouse HGF and examined its effects on primary cultures of mouse mammary tumor cells in this study. HGF at concentrations above 20 ng/ml maximally stimulated the growth of mammary tumor cells in primary monolayer culture. HGF also stimulated the three-dimensional growth and branching morphogenesis of mammary tumor cells cultured inside collagen gels. A comparison of the growth-stimulating activity of HGF with that of EGF (epidermal growth factor) and KGF (keratinocyte growth factor) revealed that HGF is the most potent growth factor among the three. Immunological studies using an antibody against mouse HGF demonstrated that 74% of the growth-stimulating activity present in the mammary fibroblast-conditioned medium was abolished by the antibody, indicating that HGF is the major growth factor produced by the fibroblasts. These observations thus suggest a role for HGF as a mammary stromal fibroblast-derived factor which stimulates growth and morphogenesis of adjacent mammary tumor cells in vivo.     

Antibody neutralization-resistant primary isolates of human immunodeficiency virus type 1

Although typical primary isolates of human immunodeficiency virus type 1 (HIV-1) are relatively neutralization resistant, three human monoclonal antibodies and a small number of HIV-1(+) human sera that neutralize the majority of isolates have been described. The monoclonal antibodies (2G12, 2F5, and b12) represent specificities that a putative vaccine should aim to elicit, since in vitro neutralization has been correlated with protection against primary viruses in animal models. Furthermore, a neutralization escape mutant to one of the antibodies (b12) selected in vitro remains sensitive to neutralization by the other two (2G12 and 2F5) (H. Mo, L. Stamatatos, J. E. Ip, C. F. Barbas, P. W. H. I. Parren, D. R. Burton, J. P. Moore, and D. D. Ho, J. Virol. 71:6869-6874, 1997), supporting the notion that eliciting a combination of such specificities would be particularly advantageous. Here, however, we describe a small subset of viruses, mostly pediatric, which show a high level of neutralization resistance to all three human monoclonal antibodies and to two broadly neutralizing sera. Such viruses threaten antibody-based antiviral strategies, and the basis for their resistance should be explored.     

Cloning of the maoA gene that encodes aromatic amine oxidase of Escherichia coli W3350 and characterization of the overexpressed enzyme

The mao operon of Escherichia coli W3350, which comprises the genes maoC and maoA, was cloned and appeared to be similar to that of Klebsiella aerogenes [Sugino, H., Sasaki, M., Azakami, H., Yamashita, M. & Murooka, Y. (1992) J. Bacteriol. 174, 2485-2492]. The gene that encodes aromatic amine oxidase (maoA) was isolated, sequenced, and expressed in E. coli TG2. The purified enzyme exhibited properties characteristic of a copper/topaquinone(TPQ)-containing amine oxidase with respect to the optical absorption and EPR spectra, the size of the subunits, and the optical absorption spectra obtained upon derivatization with hydrazines. However, high-resolution anion-exchange chromatography revealed that the preparation was heterogeneous. The enzyme preparation appeared to consist of at least four enzyme species with different specific activities, A474nm/A340nm ratios and TPQ/subunit ratios. Since the overall properties of the overexpressed enzyme and the authentic enzyme were similar and the separated enzyme species had identical N-terminal amino acid sequences, the heterogeneity does not seem to be caused by improper expression of the gene in the recombinant strain but by factors that interfere with the processing of the specific tyrosine in the precursor enzyme to functional TPQ. Although other causes cannot be excluded, the spectral data and TPQ/subunit ratios reported in the literature for other amine oxidases suggest that suboptimal synthesis of functional TPQ also occurs in other organisms.     

Aluminum kinetics using bicarbonate dialysate with the sorbent system

In the REDY system a sorbent cartridge is used to regenerate the spent hemodialysate so that only six liters of dialysate are required for a treatment. The manufacturer claims that the cartridge can be used to remove aluminum from the dialysate and that it does not add aluminum to the dialysate. This claim for acetate dialysate is supported by the literature, but there are few data available relative to bicarbonate dialysate. The present study evaluates the use of bicarbonate dialysate and the REDY system in regard to aluminum kinetics both in vitro and in vivo. In vitro, the sorbent cartridge removed aluminum from dialysate prepared from water containing as much as 470 micrograms/liter of aluminum, giving a dialysate containing less than 10 micrograms/liter. The first 500 ml of effluent contained 13 micrograms/liter of aluminum but after filtration decreased to below 10 micrograms/liter. Thus, it is unnecessary, as recommended, to discard the first effluent since this unfilterable aluminum will not pass through a dialysis membrane. In vivo, in a crossover study comparing the REDY with single pass, there were no significant differences between the pre- and post-plasma aluminum concentrations, and the dialysate aluminum remained below 4 micrograms/liter during the dialysis. In a second in vivo study the effect of dialysate from tap water on plasma aluminum using the predialysis purification procedure was evaluated. There was no differences between the pre- and post-plasma aluminum concentration. The aluminum levels were comparable to those of the crossover study. The dialysate remained below 4 micrograms/liter during the dialysis.     

Systemic mastocytosis as a cause of osteoporosis

Out of 21 male patients with osteoporosis who visited an outpatient clinic for endocrine diseases in two years (1994-1995), three had systemic mastocytosis as diagnosed histopathologically. Two of these had characteristic features of urticaria pigmentosa, consisting of multiple brown nodules on the skin of trunk and extremities, and a positive Darier sign. In all of them the excretion of the histamine metabolites methylhistamine and methylimidazoleacetic acid in a 24-hour urine specimen was increased. When osteoporosis is diagnosed in men or premenopausal women, underlying pathology could be considered. Cautious investigation of signs and symptoms of systemic mastocytosis in such patients might prove this disease be less rare than is often assumed.     

The Vpu protein of human immunodeficiency virus type 1 forms cation-selective ion channels

Vpu is a small phosphorylated integral membrane protein encoded by the human immunodeficiency virus type 1 genome and found in the endoplasmic reticulum and Golgi membranes of infected cells. It has been linked to roles in virus particle budding and degradation of CD4 in the endoplasmic reticulum. However, the molecular mechanisms employed by Vpu in performance of these functions are unknown. Structural similarities between Vpu and the M2 protein of influenza A virus have raised the question of whether the two proteins are functionally analogous: M2 has been demonstrated to form cation-selective ion channels in phospholipid membranes. In this paper we provide evidence that Vpu, purified after expression in Escherichia coli, also forms ion channels in planar lipid bilayers. The channels are approximately five- to sixfold more permeable to sodium and potassium cations than to chloride or phosphate anions. A bacterial cross-feeding assay was used to demonstrate that Vpu can also form sodium-permeable channels in vivo in the E. coli plasma membrane.     

Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor

Substance P is released in the spinal cord in response to painful stimuli, but its role in nociceptive signaling remains unclear. When a conjugate of substance P and the ribosome-inactivating protein saporin was infused into the spinal cord, it was internalized and cytotoxic to lamina I spinal cord neurons that express the substance P receptor. This treatment left responses to mild noxious stimuli unchanged, but markedly attenuated responses to highly noxious stimuli and mechanical and thermal hyperalgesia. Thus, lamina I spinal cord neurons that express the substance P receptor play a pivotal role in the transmission of highly noxious stimuli and the maintenance of hyperalgesia.