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PubMed1997

Amyloid beta 2-microglobulin is modified with imidazolone, a novel advanced glycation end product, in dialysis-related amyloidosis.

We have recently demonstrated by immunohistochemistry that amyloid beta 2-microglobulin (beta 2m) is modified with advanced glycation end products (AGEs) in dialysis-related amyloidosis (DRA). To further investigate the role of the Maillard reaction in the pathogenesis of DRA, we produced a monoclonal antibody to imidazolone, a novel AGE, and a reaction product of arginine and 3-deoxyglucosone (3-DG) which was accumulated in uremic serum. Then we determined the localization of imidazolone in the amyloid tissues by immunohistochemistry using the antibody. The connective tissues in carpal tunnel and ligamentum flavum were obtained from six patients with carpal tunnel syndrome and two patients with destructive spondyloarthropathy. Imidazolone was localized to all the beta 2m-positive amyloid deposits in these patients. Western blotting using the antibody demonstrated that beta 2m extracted from the synovium amyloid of hemodialysis patients was modified with imidazolone. Further, beta 2m isolated from the blood ultrafiltrate of hemodialyzed patients was also modified with imidazolone. In vitro incubation of beta 2m with 3-DG produced imidazolone-modified beta 2m. In conclusion, amyloid tissue beta2m is modified with imidazolone in patients with DRA. 3-DG accumulating in uremic serum may be involved in the modification of beta 2m with imidazolone.

Aged↗
PubMed1998

Modifier genes in humans: strategies for identification.

A number of genetic disorders exhibit inter- and intra-familial variability. Understanding the factors that control the expression of disease genes should provide insight into the fundamental disease processes and will have implications for counselling patients. Different mechanisms can account for this variability, including environmental factors, genotype-phenotype correlations and imprinting. There is also evidence that, in a number of genetic diseases, gene expression is under the control of modifier loci. In cases where the biological basis of the genetic disease is understood, any genes involved in the pathogenic process represent candidate modifier genes which can easily be evaluated. Alternatively, modifiers can be identified through approaches such as mouse models. Since modifier genes will generally be common and because of confounding environmental influences, linkage analyses in humans will generally be based upon affected or discordant sib pairs. Discordant sib pairs represent an attractive option for linkage studies, because recurrence rates are high and the reduced survival characteristics associated with severe phenotypes will make the likelihood of obtaining clinical material from two living cases difficult. Furthermore, the use of discordant siblings will select for those siblings which possess sufficient dissimilarity at the modifier locus to overcome any shared environmental influence.

Animals↗
PubMed2004

Exclusion of an extracolonic disease modifier locus on chromosome 1p33-36 in a large Swiss familial adenomatous polyposis kindred.

Familial adenomatous polyposis (FAP), an autosomal dominantly inherited colorectal cancer predisposition syndrome, displays considerable inter- and intrafamilial phenotypic heterogeneity, which represents a major problem in genetic counselling of APC mutation carriers. The Min mouse model indicated a putative disease modifier locus on chromosome 4, which is syntenic to human chromosome 1p35-36. This finding was subsequently supported by parametric and nonparametric linkage analyses in FAP families, however, without identifying functional variants in candidate genes. Recently, germline mutations in the base-excision repair gene MYH (1p33-34) have been described in patients with multiple adenomas, pointing to a possible role as disease modifier in FAP. Here, we present critical reassessment of one of the largest FAP kindreds published, which was previously used in linkage mapping of 1p35-36. In this family, all affected members harbour the same APC germline mutation (5945delA), but display marked phenotypic variability, in particular regarding the occurrence of extracolonic disease that segregates in several branches of the family tree. Using updated clinical information, additional mutation carriers and polymorphic markers, fine mapping of the critical region as well as mutation analysis of the MYH gene were performed. These investigations allowed us to significantly exclude (i) the 1p33-36 region as a modifier locus and (ii) MYH as a modifier gene for extracolonic disease in this FAP kindred. Our results do not eliminate 1p33-36 from suspicion in other families, but clearly indicate that in our family linkage analysis of further putative candidate regions is necessary to identify a disease modifier locus in FAP.

Adenomatous Polyposis Coli↗
PubMed2000

Persistent, antigen-specific, therapeutic antitumor immunity by dendritic cells genetically modified with an adenoviral vector to express a model tumor antigen.

Dendritic cells (DC) are potent antigen-presenting cells that play a critical role in the initiation of cellular immune responses. Using a BALB/c syngeneic colon carcinoma cell line expressing a model tumor antigen beta-galactosidase (betagal), we previously reported (Song et al, J Exp Med 1997; 186: 1247-1256) that immunization of mice with a single injection of DCs genetically modified with an adenovirus vector expressing betagal confers potent protection against a lethal intravenous tumor challenge, as well as suppression of pre-established lung tumors, resulting in a significant survival advantage. In the present study, we have addressed the question: how long does the memory of tumor antigen- specific immunity persists after DC priming in vivo using this genetically modified DC-based cancer vaccination strategy? To accomplish this, two groups of mice were evaluated: (1) mice surviving >400 days following protection from an initial intravenous tumor challenge after immunization with DC genetically modified to express betagal; and (2) mice surviving >300 days that had previously demonstrated regression of pre-established lung tumors after treatment with DC immunization. By analyzing the antigen-specific cytotoxic T lymphocyte response and challenging these long-term survival mice with a second subcutaneous tumor administration, the data demonstrate that a single administration of DC genetically modified to express a model antigen induces long-lasting, antigen-specific antitumor immunity in both naive and tumor-bearing hosts, observations that have important implications in the development of genetically modified DC-based antitumor vaccination strategies. Gene Therapy (2000) 7, 2080-2086.

Adenoviridae↗
PubMed2000

Enhancement of antitumor immunity against B16 melanoma tumor using genetically modified dendritic cells to produce cytokines.

Dendritic cells (DC) that have been genetically modified to express cytokine genes may be novel tools for inducing antitumor immune responses. In the present study, the pMX retroviral vector was modified to express the mouse IL-2 (mIL-2pMX) and mouse IL-12 (mIL-12pMX) genes. Supernatants from 293 cells transfected with pMX retroviral vectors were harvested and used to transduce mouse lin- bone marrow (BM) progenitor cells. After 48 h co-culture with pseudotype retrovirus, BM cells were cultured for 12 days in the presence of mGM-CSF, mSCF and mTNF-alpha to obtain a DC-enriched fraction. Flow cytometric analysis showed that GFP protein expression in these cultures was 20-40% and that 40-50% of the cultured BM cells were positive for the DC marker, DEC205. About 60% of cells sorted for DEC205 also expressed GFP. The supernatants of DC-mIL-2 and DC-mIL-12 cultured for 48 h contained 5.2 +/- 0.15 and 33.9 +/- 2.6 ng cytokine protein per milliliter, respectively. Intratumoral injection of DC-mIL-2 or DC-mIL-12 on days 8 and 15 after the intradermal injection of 1 x 105 B16F10 cells, resulted in a significant reduction in tumor size by day 21, as compared with mice treated with unmodified DC or DC-GFP. Longer term analysis as assessed at day 42 revealed that B16 tumor-bearing mice treated with cytokine gene-modified DC survived significantly longer than mice from other groups. Spleen cells obtained from DC-treated mice were specifically sensitized for the generation of CTL by subsequent restimulation with gene-modified DC. These results suggested that DC genetically modified to express IL-2 or IL-12 can induce potent antitumor responses against well-established, poorly immunogenic B16F10 tumors. Gene Therapy (2000) 7, 2113-2121.

Animals↗
PubMed2002

Erythrocyte-mediated delivery of drugs, peptides and modified oligonucleotides.

An important determinant for the success of every new therapy is the ability to deliver the molecules of interest to the target cells or organ. This selective delivery is even more complex when the therapeutic agents are peptides, modified oligonucleotides or genes. In this paper we summarize the possibility of using autologous erythrocytes for the delivery and targeting of new and conventional therapeutics. In fact, a number of macromolecules can be encapsulated by different procedures into human erythrocytes. These modified cells can then be re-infused into the same or a compatible recipient where they can circulate for several weeks. However, drug-loaded erythrocytes can also be modified to be selectively recognized by tissue macrophages. These phagocyte cells recognize the modified drug-loaded erythrocytes which are able to release their content into the macrophage. The feasibility and safety of the use of erythrocytes as drug delivery systems was evaluated in 10 cystic fibrosis patients, where a sustained release of corticosteroids from dexamethasone 21-phosphate-loaded erythrocytes was obtained. In vitro human erythrocytes were found to be able to deliver ubiquitin analogues and modified oligonucleotides to macrophages. Thus, drug-loaded erythrocytes are safe and useful carriers of new and conventional therapeutics and can be advantageous delivery systems for new clinical applications where proteins and oligonucleotides are therapeutic agents.

Cystic Fibrosis↗
PubMed1995

Determination of cadmium in whole blood and urine electrothermal atomic absorption spectrometry using palladium-based modifiers and in situ decontamination.

The determination of Cd in whole blood and urine by electrothermal atomic absorption spectrometry using Pd-based modifiers and in situ decontamination was studied. The performance of Pd, Pd + NH4NO3, and Pd + Mg(NO3)2 as modifiers were compared with respect to maximum pyrolysis and atomization temperatures, background attenuation, linear calibration range and matrix interference. Samples were diluted (1 + 4) with 0.1% Triton X-100 (blood) or 0.2% HNO3 (urine), and introduced onto the graphite tube platform already containing the in situ dried and decontaminated modifier. The influence of modifier volume and concentration, as well as that of the dilution ratio was investigated. The proposed procedure involves the use of Pd(NO3)2 + (Mg(NO3)2 as modifier, a pyrolysis temperature of 700 degree C and an in situ decontamination step of 1200 degrees C. The atomization temperature was 1700 degrees C. The detection limit (n = 10, k = 3) was 0.22 micrograms l-1 for both samples. Typical relative standard deviation values (n = 3) were below 3%. Using matrix-matched standards, good agreement was observed between experimental and reference values in the analysis of certified reference materials. Interlaboratory comparison data have confirmed the validity of the proposed analytical procedure.

Cadmium↗
PubMed1991

Some reactions of carbon monoxide and oxygen with carbodi-imide-modified cytochrome c.

The reactivity of carbodi-imide-modified tuna and horse heart cytochromes c with the ferrous ion ligands CO and O2 has been studied. Both modified cytochromes bind one molecule of CO. Stopped-flow and flash-photolysis experiments indicate the presence of three kinetic processes in the reaction of the cytochromes with CO. The second-order rate constants associated with all three kinetic process are pH-independent being 2.8 x 10(5) M-1.s-1, 3.8 x 10(4) M-1.s-1 and 4 x 10(3) M-1.s-1 under all conditions studied. The concentration-dependence of the contributions made by each of the processes to the overall absorbance change indicates that the fast and slow kinetic phases are associated with two forms of the cytochromes which are in equilibrium, whereas the intermediate phase arises from a separate cytochrome species. The quantum yield for the photodissociation of CO from the ferrous cytochromes is unusually low. Both modified cytochromes are capable of binding and reducing O2. In the presence of excess reductant, the modified cytochromes can catalytically reduce large molar excesses of O2. In the absence of excess reducing agent, the oxy complex initially formed undergoes a pH-dependent intramolecular electron-transfer process with half-life approx. 10 min. EDC [1-ethyl-3-(3-dimethylaminopropyl)carbodi-imide]-promoted internal cross-linking is proposed to account for differences between the EDC-modified proteins and carboxymethylated cytochrome c.

Animals↗
PubMed1991

Identification of the CoA-modified forms of mitochondrial acetyl-CoA acetyltransferase and of glutamate dehydrogenase as nearest-neighbour proteins.

A 52 kDa protein could only be co-purified with the CoA-modified forms of acetyl-CoA acetyltransferase (acetoacetyl-CoA thiolase) (EC 2.3.1.9) from rat liver mitochondria. Immunoprecipitations of these modified forms with anti-(acetyl-CoA acetyltransferase) IgG or anti-(52 kDa protein) IgG yielded, in addition to the appropriate proteins, the 52 kDa protein or the CoA-modified form of acetyl-CoA acetyltransferase (41 kDa) respectively. This was demonstrated by SDS/PAGE and immunoblots. The modified forms containing the 52 kDa protein could be cross-linked by 1,5-difluoro-2,4-dinitrobenzene to a high-molecular-mass complex containing both the 41 kDa and 52 kDa proteins. The 52 kDa protein was identified as mitochondrial glutamate dehydrogenase (EC 1.4.1.3) by amino acid sequence analysis. The results of co-immunoprecipitation and cross-linking characterize the CoA-modified forms of acetyl-CoA acetyltransferase and the glutamate dehydrogenase as nearest-neighbour proteins.

Acetyl-CoA C-Acetyltransferase↗
PubMed1992

Studies on epitopes on low-density lipoprotein modified by 4-hydroxynonenal. Biochemical characterization and determination.

Oxidation of human low-density lipoprotein (LDL) was found to be accompanied by the generation of various reactive aldehydes. One of them, 4-hydroxynonenal (HNE), was shown to modify LDL to a form which represents a good model of oxidized LDL (ox-LDL). In order to investigate the epitopes newly formed on HNE-modified LDL, a polyvalent antiserum to HNE-LDL [anti-(HNE-LDL)] was raised in rabbits and the non-specific components were removed with native LDL coupled to CNBr-Sepharose 4B. Competitive fluorescence immunoassay analysis showed that anti-(HNE-LDL) recognized HNE-LDL, copper-oxidized LDL, HNE-albumin and to a lower extent HNE-modified high-density lipoprotein 3 (HNE-HDL3) and ox-HDL3 but not native LDL. A certain degree of cross-reactivity of the antibody with LDLs modified by either hexanal or 2,4-heptadienal was found. No reaction was obtained with LDL labelled with malondialdehyde. From the abilities of HNE-modified poly(L-amino acids) to compete with HNE-LDL for binding to anti-(HNE-LDL), it is postulated that lysine, tyrosine, arginine and histidine are involved in the formation of HNE-derived epitopes on apolipoprotein B (apo B). Using a double-sandwich fluorescence immunoassay [capture antibody: anti-(apo B); detection antibody: anti-(HNE-LDL)] we found that the HNE-derived epitopes were expressed at a far higher degree in ox-LDL and HNE-LDL than in native LDL.

Aldehydes↗
PubMed1996

Immunochemical detection of CoA-modified mitochondrial matrix proteins.

An in vitro assay mixture consisting of mitochondrial matrix proteins from rat liver and CoA resulted in the formation of CoA-modified proteins. CoA-modified proteins were demonstrated by detection of CoA. CoA was released from the proteins by dithioerythritol treatment under denaturing conditions and was identified by (a) its retention time on HPLC, (b) its absorption spectrum and (c) its activity in a CoA-specific assay. This CoA represents protein-bound CoA and, in addition, protein-bound palmitoyl-CoA when MgATP was also present in the in vitro assay. The detection of immunoreactive proteins using mono-specific anti-CoA antibodies exclusively identifies CoA-modified proteins. The specificity of these antibodies can be used to identify both endogenously occurring CoA-modified proteins and proteins that have been modified in the in vitro assay. An intact thiol group of CoA is an essential precondition for the modification to occur.

Acetyl-CoA C-Acetyltransferase↗
PubMed1999

Laboratory evaluation of a compomer and a resin-modified glass ionomer cement for orthodontic bonding.

The mean shear debonding force of stainless steel orthodontic brackets with microetched bases bonded with either a compomer or a resin-modified glass ionomer cement was assessed. In addition, the amount of cement remaining on the enamel surface following bracket removal was evaluated. Finally, survival time of orthodontic brackets bonded with these materials was assessed following simulated mechanical stress in a ball mill. Debonding force and survival time data were compared with those obtained for brackets bonded with a chemically cured resin adhesive, a light-cured resin adhesive, and a conventional glass ionomer cement. There were no significant differences in mean shear debonding force of brackets bonded with the compomer, resin-modified glass ionomer, chemically cured resin adhesive, or the light-cured resin adhesive. Brackets bonded with a conventional glass ionomer cement had a significantly lower mean shear debonding force than that recorded for the other materials. The Adhesive Remnant Index (ARI) mode score indicated that significantly less cement remained on the enamel following debonding of brackets cemented with resin-modified or conventional glass ionomers compared with other adhesives. The median survival time for brackets cemented with the compomer, resin-modified glass ionomer, chemically cured resin, or light-cured resin were significantly longer than for brackets cemented with conventional glass ionomer. The compomer and the resin-modified glass ionomer adhesive appear to offer viable alternatives to the more commonly used resin adhesives for bracket bonding.

Acid Etching, Dental↗
PubMed2003

Effects of thermocycling on the bond strength of a resin-modified glass ionomer cement: an in vitro comparative study.

This study investigated the effects of thermally induced stresses (thermocycling) on the shear bond strength of resin-modified, chemically cured, glass ionomer cement for use as an orthodontic bonding agent. A conventional no-mix composite resin was also used as a control. Mesh-based metal orthodontic brackets were bonded to extracted human premolars using either the resin-modified glass ionomer cement or the no-mix composite resin. Specimens were stored either in water at 37 degrees C for 24 hours for baseline data or thermocycled between 5 degrees C and 55 degrees C for 200 and 20,000 cycles before testing the in vitro shear bond strengths. Thermocycling reduced shear bond strengths for all specimens. The resin-modified glass ionomer cement showed a 11.1% decrease after 200 thermocycles and 26.5% decrease after 20,000 thermocycles, whereas the no-mix adhesive resin showed only 5.7% and 17.9% reductions, respectively. Analysis of variance showed statistically significant differences between the mean shear bond strengths of the groups at the P < .001 level of significance. For the resin-modified glass ionomer cement groups, the predominant bond failure site was at the bracket-adhesive interface. The results of this study suggest strongly that resin-modified glass ionomer cements offer a viable alternative to conventional no-mix composite resins, with satisfactory in vitro shear bond strength even after 20,000 thermocycles.

Analysis of Variance↗
PubMed2001

Evaluation of various electrocardiographic criteria for left ventricular hypertrophy in patients with stable angina pectoris: influence of using modified limb electrodes.

BACKGROUND: Left ventricular hypertrophy (LVH) in coronary heart disease is associated with poor prognosis. Electrocardiography (ECG) criteria for LVH, when using ECG with modified limb electrode positions, has not been validated in patients with angina pectoris. METHODS: Echocardiography and resting ECGs with modified limb electrode positions, i.e. with the limb leads placed on the abdomen instead of the extremities, were registered from 468 patients (295 men) with stable angina pectoris. To evaluate the influence of using modified limb electrode positions, ECGs with standard and modified limb electrode positions were compared in a control group consisting of 50 other patients. RESULTS: The ECG criteria for LVH according to the Perugia score, the Minnesota code and Romhilt & Estes reached the highest sensitivity values, 27-31% in men and 24-38% in women, while the sensitivities of different Cornell criteria were as low as 6-10% in men and 19-29% in women. In the control group, the R- and S-wave amplitudes of the precordial leads were only slightly changed, as expected, whereas those of the limb leads changed considerably. Based on these results, we corrected aVL in the main study, which increased the sensitivity of the Cornell voltage criteria from 15 to 30%, while the specificity was maintained at 95%. CONCLUSIONS: ECGs registered with modified limb electrode positions can be used to detect LVH with traditional ECG criteria, but changes in the limb leads are considerable and influence the sensitivities.

Abdomen↗
PubMed2003

Effect of modified eros centre on some reproductive parameters of the sow.

The effect of a modified eros centre on weaning to oestrus interval, follicle size, ovulation and farrowing rate and total born litter size was investigated. In modified eros centre 94.4% and in group housing 79.1% of the sows (p < 0.01) expressed oestrus within 10 days post-weaning. Weaning to oestrus interval was shorter (p < 0.001) for sows kept in modified eros centre. The interval from onset of oestrus to the time of ovulation was longer for sows in group housing (p=0.05). The time of ovulation was negatively correlated (r=-0.50) with the interval from weaning to oestrus (p=0.005). The time of ovulation after onset of oestrus was significantly (p < 0.05) shorter for sows expressing oestrus within 2-4 days of weaning, compared with the animals that expressed oestrus between days 5 and 6 post-weaning and was shortest for sows expressing oestrus after day 6 post-weaning. Farrowing rate was not affected by a modified eros centre. Litter size tended to be smaller in group-housed weaned sows (p=0.10). The timing of last artificial insemination relative to time of ovulation did not affect litter size (p > 0.10). The implication of these results is that a modified eros centre may improve some of the post-weaning oestrous parameters of the sow.

Animals↗
PubMed2001

Modified plication of the tunica albuginea in treating congenital penile curvature.

OBJECTIVE: To describe a modified plication technique and compare the results with the Nesbit procedure for treating congenital penile curvature. PATIENTS AND METHODS: Eleven men with congenital penile curvature were treated by a modified tunica albuginea plication technique. An artificial erection was induced by normal saline injection; in the areas where plication was planned, Buck's fascia was opened longitudinally and dissected a short distance toward the midline to free the neurovascular bundles. Allis clamps were used to grasp the tunica albuginea and "bumps" created. Two interrupted U-shaped sutures using 2/0 polyglactin were placed underneath each Allis clamp to secure the bump. The results were analysed retrospectively and compared with the results of 11 other men treated using the Nesbit procedure. RESULTS: The mean (range) follow-up was 25 (12-47) months for the Nesbit procedure and 15 (8-26) months for the modified plication procedure. In the Nesbit group, eight patients had satisfactory cosmetic and functional results; three complained of penile shortening and one had erectile dysfunction. In the modified plication group, 10 patients reported satisfactory cosmetic and functional results; one complained of penile shortening, two were concerned about the indurations of the penis but none had erectile dysfunction. CONCLUSIONS: The modified plication technique is easier to perform, is more often successful and causes fewer surgical complications than the Nesbit procedure for treating congenital penile curvature.

Adolescent↗
PubMed1996

Removal of soluble biologic response modifiers (complement and chemokines) by a bedside white cell-reduction filter.

BACKGROUND: Biologic response modifiers infused with stored platelet concentrates (PCs) are believed to contribute to symptoms seen during transfusion reactions. Although prestorage white cell reduction is known to decrease the production of some biologic response modifiers during storage, the possibility that poststorage (bedside) white cell reduction could reduce the amount of biologic response modifiers already present in stored PCs during bedside filtration has not been well studied. STUDY DESIGN AND METHODS: Individual PCs were pooled on storage Days 2 and 5 and passed through a third-generation white cell-reduction filter. The results from a series of in vitro PC assays were studied, before and immediately after filtration, as were levels of C3a and interleukin 8 (n = 5). Levels of other biologic response modifiers-C5a, interleukin 1 beta, interleukin 6, tumor necrosis factor alpha, and RANTES-were also studied. Removal of interleukin 8 and RANTES was studied further by using serial filtration of units of PC. RESULTS: For the in vitro platelet assays studied, pH was unchanged after filtration from prefiltration values in units of PCs pooled on storage Day 2 or 5. A 4 log10 reduction in white cells was reliably seen after filtration in Day 2 and 5 pooled PCs. Postfiltration platelet loss was 14.8 percent for Day 2 pooled PCs and 9.6 percent for Day 5 pooled PCs. For pools of both Day 2 and Day 5 platelets, postfiltration levels of CD62 (P-selectin, CD62P) were unchanged from prefiltration levels, as were results for morphology scores. Levels of C3a decreased after filtration in both the Day 2 pooled PCs (448 ng/mL before filtration vs. 20 ng/mL after filtration) and the Day 5 pooled PCs (1976 ng/mL before filtration vs. 124 ng/mL after filtration). Levels of interleukin 8 were similarly reduced after filtration in the Day 2 pooled platelets (188 pg/mL before filtration vs. 27 pg/mL after filtration) and the Day 5 pooled platelets (2234 pg/mL before filtration vs. 799 pg/mL after filtration). Levels of interleukin 8 in other components evaluated after filtration declined similarly. However, levels of the proinflammatory cytokines interleukin 1 beta and interleukin 6 did not decline after filtration. Serial filtration studies showed that, although levels of interleukin 8 and RANTES were initially lowered by filtration, they returned to prefiltration values with increases in the volume of filtration. CONCLUSION: The third-generation bedside filter used in this study reliably reduced the level of white cell contamination to 4 log10 white cells per PC. It also lowered the levels of interleukin 8, RANTES, and C3a. The filter did not, however, remove (scavenge) the proinflammatory cytokines interleukin 1 beta and 6. The mechanism of chemokine and C3a removal by the filter is unknown, but it may be related to ionic interactions between these biologic response modifiers and the filter medium.

Blood Transfusion↗
PubMed2003

The effect of modifying patient-preferred spinal movement and alignment during symptom testing in patients with low back pain: a preliminary report.

OBJECTIVE: To examine the effect on symptoms of modifying patient-preferred movements and alignments of the lumbar spine during patient examination. DESIGN: Repeated-measures study in which patients with low back pain (LBP) participated in a standardized examination that included tests of symptoms with various movements and positions. SETTING: Six university-affiliated outpatient physical therapy clinics and the local community. PARTICIPANTS: Five trained physical therapists examined a total of 185 patients (102 women, 83 men; mean age, 41.89+/-13.29 y) with LBP. The majority of patients had multiepisode, chronic LBP. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The examination included tests of symptoms with various alignments and movements in several different positions. Seven tests were designated as primary tests. Tests that increased symptoms were followed immediately by a secondary test in which (1) patient-preferred lumbar spine movement was modified or (2) the lumbar spine was positioned in a neutral alignment. Patients reported the effect of the secondary test on symptoms relative to their symptoms with the primary test. Three responses were possible: symptoms increased, remained the same, or decreased. RESULTS: Eighty-three percent of the patients reported an increase in symptoms with 1 or more of the 7 primary tests. Ninety-five percent who reported an increase in symptoms with at least 1 of the primary tests reported a decrease in symptoms with 1 or more of the 7 secondary tests. The majority of patients reported a decrease in symptoms when the spinal movement or alignment was modified for 6 of the 7 secondary tests. CONCLUSIONS: Modifying the symptom-provoking movements and alignments of the spine during symptom testing resulted in a decrease in symptoms for the majority of patients. Information about specific modifications that provide relief of LBP symptoms is important because it can be used to design a treatment program that focuses on training a patient to modify the same movements and alignments in their everyday activities.

Adult↗