Association of heart rate response with scan and left ventricular function on adenosine stress myocardial perfusion imaging.

To evaluate the association of heart rate (HR) response with abnormal scan and/or left ventricular (LV) function in patients undergoing adenosine myocardial perfusion imaging, we prospectively studied 164 consecutive patients who underwent a standard adenosine stress test (without exercise) and myocardial perfusion imaging (MPI) using technetium-99m sestamibi radioisotope. Change in HR was calculated by subtracting HR at rest from peak HR. The percentage change in HR was calculated. All patients underwent stress and resting single photon emission computed tomography (SPECT) imaging. Left ventricular ejection fraction (EF) was calculated using gated SPECT. Mean age was 54 ± 11.7 years and 126 of the patients (72%) were men. We divided the patients into 2 groups: group 1(42 patients, 25%) had normal scans and group 2(122 patients, 74.3%) had abnormal scans; abnormal scans were defined as presence of either fixed defects, reversible defects, or both. Average HR increased by 35 beats/min in the normal scan group compared with 23 beats/min in the abnormal scan group (p=0.002). Sixty four (64) patients (39%) had reduced EF (<45%). This group had an average HR and percentage HR increase of 23 beats/min (27%) compared with an increase of 35 beats/min (38%) in patients with normal EF (p=0.002 and p=0.02, respectively). Thus, a diminished HR response had a significant association with both an abnormal scan and reduced EF on adenosine MPI.

Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over.

Mice that are deficient in either the Pms2 or Msh2 DNA mismatch repair genes have microsatellite instability and a predisposition to tumours. Interestingly, Pms2-deficient males display sterility associated with abnormal chromosome pairing in meiosis. Here mice deficient in another mismatch repair gene, Mlh1, possess not only microsatellite instability but are also infertile (both males and females). Mlh1-deficient spermatocytes exhibit high levels of prematurely separated chromosomes and arrest in first division meiosis. We also show that Mlh1 appears to localize to sites of crossing over on meiotic chromosomes. Together these findings suggest that Mlh1 is involved in DNA mismatch repair and meiotic crossing over.

Tumour susceptibility and spontaneous mutation in mice deficient in Mlh1, Pms1 and Pms2 DNA mismatch repair.

Germline mutations in the human MSH2, MLH1, PMS2 and PMS1 DNA mismatch repair (MMR) gene homologues appear to be responsible for most cases of hereditary non-polyposis colorectal cancer (HNPCC; refs 1-5). An important role for DNA replication errors in colorectal tumorigenesis has been suggested by the finding of frequent alterations in the length of specific mononucleotide tracts within genes controlling cell growth, including TGF-beta receptor type II (ref. 6), BAX (ref. 7) and APC (ref. 8). A broader role for MMR deficiency in human tumorigenesis is implicated by microsatellite instability in a fraction of sporadic tumours, including gastric, endometrial and colorectal malignancies. To better define the role of individual MMR genes in cancer susceptibility and MMR functions, we have generated mice deficient for the murine homologues of the human genes MLH1, PMS1 and PMS2. Surprisingly, we find that these mice show different tumour susceptibilities, most notably, to intestinal adenomas and adenocarcinomas, and different mutational spectra. Our results suggest that a general increase in replication errors may not be sufficient for intestinal tumour formation and that these genes share overlapping, but not identical functions.

Morphological features of coronary arteries and lesions in hearts from five species of sharks collected from the northwestern Atlantic Ocean.

Morphological features of coronary arteries and incidental lesions are reported from hearts in five species of sharks, the shortfin mako shark, Isurus oxyrhinchus Rafinesque, thresher shark Alopias vulpinus (Bonaterre), blue shark, Prionace glauca L., the smooth dogfish, Mustelus canis (Mitchill), and spiny dogfish, Squalus acanthias L. Sharks were collected from the northwestern Atlantic between June and August from 1996 to 2010. They were necropsied dockside and the hearts were preserved in buffered formalin. Routine sections including ventricle/conus arteriosus and the atrio-ventricular junctions were embedded in paraffin, stained with common histological and immunohistochemical methods and examined by brightfield microscopy. Myointimal hyperplasia, medial myo-myxomatous hyperplasia and bifurcation pads were observed commonly, and medial muscle reorientation and epicardial myeloid tissues were rare. All the above features differed in severity, prevalence and distribution depending on anatomical site and shark species/size. Morphometric analysis indicated that myomyxomatous hyperplasia is associated with luminal narrowing of blood vessels. As suggested previously, the described morphological features are most likely physiological responses to blood flow characteristics. Vascular and cardiac lesions were uncommon and included, granulomatous proliferative epicarditis with fibroepitheliomas, myxomatous epicardial expansions, medial arterial vacuolation, myocardial fibrosis, acute ventricular emboli and parasitic granulomas. The lesions of embolism, proliferative and granulomatous epicarditis and myocardial fibrosis were in all sharks associated with capture events including retained fishing hooks. The significance and aetiopathogenesis of medial vacuolation and epicardial myxomatous expansions remains unclear.

TGF-beta/extracellular matrix interactions in dentin matrix: a role in regulating sequestration and protection of bioactivity.

TGF-beta isoforms sequestrated in dentin matrix potentially provide a reservoir of bioactive molecules that may influence cell behavior in the dentin-pulp complex following tissue injury. The association of these growth factors with dentin matrix and the influence of such associations on the bioactivity of growth factors are still unclear. We used surface plasmon resonance technology in the BIAcore 3000 system to investigate the binding of TGF-beta isoforms 1 and 3 to purified decorin, biglycan, and EDTA soluble dentin matrix components. TGF-beta isoforms 1 and 3 were immobilized on sensorchips CM4 through amine coupling. For kinetic studies of protein binding, purified decorin and biglycan, isolated EDTA soluble dentin matrix, and dentin matrix immunodepleted of decorin and/or biglycan were injected over TGF-beta isoforms and allowed to interact. Programmed kinetic analysis software provided sensorgrams for each concentration of proteoglycan or dentin matrix extract injected. Purified decorin and biglycan and dentin matrix extract bound to the TGF-beta isoforms. However, the association with TGF-beta3 was much weaker than that with TGF-beta1. After immunoaffinity depletion of the dentin matrix extract, the level of interaction between the dentin matrix extract and TGF-beta was significantly reduced. These results suggest isoform-specific interactions between decorin/biglycan and TGF-beta isoforms 1 and 3, which may explain why TGF-beta3 is not detected in the dentin matrix despite being expressed at higher levels than TGF-beta1 in odontoblasts. These proteoglycans appear to play a significant role in TGF-beta/extracellular matrix interactions and may be important in the sequestration of these growth factors in the dentin matrix.

Chromosomal influence on meiotic spindle assembly: abnormal meiosis I in female Mlh1 mutant mice.

In mouse oocytes, the first meiotic spindle is formed through the action of multiple microtubule organizing centers rather than a pair of centrosomes. Although the chromosomes are thought to play a major role in organizing the meiotic spindle, it remains unclear how a stable bipolar spindle is established. We have studied the formation of the first meiotic spindle in murine oocytes from mice homozygous for a targeted disruption of the DNA mismatch repair gene, Mlh1. In the absence of the MLH1 protein meiotic recombination is dramatically reduced and, as a result, the vast majority of chromosomes are present as unpaired univalents at the first meiotic division. The orientation of these univalent chromosomes at prometaphase suggests that they are unable to establish stable bipolar spindle attachments, presumably due to the inability to differentiate functional kinetochore domains on individual sister chromatids. In the presence of this aberrant chromosome behavior a stable first meiotic spindle is not formed, the spindle poles continue to elongate, and the vast majority of cells never initiate anaphase. These results suggest that, in female meiotic systems in which spindle formation is based on the action of multiple microtubule organizing centers, the chromosomes not only promote microtubule polymerization and organization but their attachment to opposite spindle poles acts to stabilize the forming spindle poles.

X-linked lymphoproliferative syndrome. Natural history of the immunodeficiency.

The X-linked lymphoproliferative syndrome is characterized by immunodeficiency to Epstein-Barr virus (EBV) manifested by severe or fatal infectious mononucleosis and acquired immunodeficiency. We studied immune responses in six males of a well-characterized kindred with the X-linked lymphoproliferative syndrome. Two males were studied before and during acute fatal EBV infection. Both individuals demonstrated normal cellular and humoral immunity before EBV infection. During acute EBV infection, both individuals developed vigorous cytotoxic cellular responses against EBV-infected and -uninfected target cells. Anomalous killer and natural killer T cell activity was demonstrated against a variety of lymphoid cell lines, autologous fibroblasts and autologous hepatocytes. Effector cells responsible for anomalous killing reacted with a pan-T cell monoclonal antibody, and belonged to the OKT.8 T cell subset. Death in each case was caused by liver failure, but one patient developed extensive liver necrosis, whereas the other developed a massive infiltration of the liver with EBV-infected immunoblasts after aggressive immunosuppressive therapy. Immunological studies were performed on four males who had survived EBV infection years previously. They demonstrated global cellular immune defects with deficiencies of lymphocyte proliferative responses to mitogens and antigens, humoral immune deficiencies, abnormalities of regulatory T cell subsets and deficient natural killer cell activity. We propose that an aberrant immune response triggered by acute EBV infection results in unregulated anomalous killer and natural killer cell activity against EBV infected and uninfected cells. These studies suggest that global immune defects appearing in males with X-linked lymphoproliferative syndrome who survive EBV infection are epiphenomenon.

Expression of the Saccharomyces cerevisiae GAL7 gene on autonomous plasmids.

We used a combination of cloned DNA fragments encoding the GAL7 gene, yeast plasmid vectors, and chromosomal gal7 deletions to characterize the in vivo transcription of the GAL7 gene on autonomously replicating plasmids. Our results demonstrated that a plasmid-borne 3.1-kilobase DNA fragment containing the GAL7 gene provides sufficient information to mimic the regulated expression of the chromosomal location. Normal expression of GAL7 could occur in the absence of DNA encoding the functional genes of the GAL cluster region and was not altered when the gene was adjacent to other plasmid elements such as autonomously replicating sequences or centromeres. The chromosomal and single-copy centromeric plasmid locations of GAL7 were indistinguishable in their response to growth conditions (induction by galactose, repression by glucose) and positive and negative regulatory factors (GAL4 and GAL80). Increasing the gene dosage to more than 200 copies per cell resulted in constitutive expression of the GAL7 mRNA; fully induced mRNA levels were increased more than 10-fold at these high gene dosages. When cells were shifted from noninducing to inducing conditions, the initial time of appearance and the rate of accumulation of GAL7 mRNA were altered in cell populations containing multiple GAL7 genes. The induction kinetics and final accumulation of the chromosomal GAL10 mRNA were also affected by the presence of multiple copies of the GAL7 gene; these results are consistent with a model involving limiting amounts of regulatory factors.

The human MLH1 cDNA complements DNA mismatch repair defects in Mlh1-deficient mouse embryonic fibroblasts.

The DNA mismatch repair gene hMLH1 is reported to function in mutation avoidance, cell cycle checkpoint control, the cytotoxicity of various DNA-damaging agents, and transcription-coupled nucleotide excision repair. Formal proof of the involvement of hMLH1 in these processes requires single gene complementation. We have stably expressed hMLH1 from a transfected cDNA in Mlh1-deficient mouse embryonic fibroblasts. Expression of hMLH1 restored normal levels of mPMS2 protein, reduced spontaneous base substitution and microsatellite mutations, increased sensitivity to the toxic effects of 6-thioguanine (6-TG), and restored 6-TG-induced cell cycle arrest. Our studies confirm that hMLH1 has an essential role in the maintenance of genomic stability and the potentiation of 6-TG cytotoxicity and provide a system for detailed structure/function analysis of the hMLH1 protein.

Enhanced intestinal adenomatous polyp formation in Pms2-/-;Min mice.

Analysis of two human familial cancer syndromes, hereditary nonpolyposis colorectal cancer and familial adenomatous polyposis, indicates that mutations in either one of four DNA mismatch repair gene homologues or the adenomatous polyposis coli (APC) gene, respectively, are important for the development of colorectal cancer. To further investigate the role of DNA mismatch repair in intestinal tumorigenesis, we generated mice with mutations in both Apc and the DNA mismatch repair gene, Pms2. Whereas Pms2-deficient mice do not develop intestinal tumors, mice deficient in Pms2 and heterozygous for Min, an allele of Apc, develop approximately three times the number of small intestinal adenomas and four times the number of colon adenomas relative to Min and Pms2+/-;Min mice. Although Pms2 deficiency clearly increases adenoma formation in the Min background, histological analysis indicated no clear evidence for progression to carcinoma.

Role of DNA mismatch repair in the cytotoxicity of ionizing radiation.

The DNA mismatch repair (MMR) system in mammalian cells not only serves to correct base mispairs and other replication errors, but it also influences the cellular response to certain forms of DNA damage. Cells that are deficient in MMR are relatively resistant to alkylation damage because, in wild-type cells, the MMR system is thought to promote toxicity via futile repair of alkylated mispairs. Conversely, MMR-deficient cells are sensitive to UV light, possibly due to the requirement for MMR factors in transcription-coupled repair of active genes. MMR deficiency has been associated with familial and sporadic carcinomas of the colon and other sites, and so, we sought to determine the influence of MMR status on cellular response to ionizing radiation, an agent commonly used for cancer therapy. Fibroblast cell lines were established from transgenic mice carrying targeted disruptions of one of three MMR genes in mammalian cells: Pms2, Mlh1, or Msh2. In comparison to wild-type cell lines from related mice, the Pms2-, Mlh1-, or Msh2-nullizygous cell lines were found to exhibit higher levels of clonogenic survival following exposure to ionizing radiation. Because ionizing radiation generates a variety of lesions in DNA, the differences in survival may reflect a role for MMR in processing a subset of these lesions, such as damaged bases. These results both identify a new class of DNA-damaging agents whose effects are modulated by the MMR system and may help to elucidate pathways of radiation response in cancer cells.

Altered expression of hMSH2 and hMLH1 in tumors with microsatellite instability and genetic alterations in mismatch repair genes.

To date, at least four genes involved in DNA mismatch repair (MMR) have been demonstrated to be altered in the germline of patients with hereditary nonpolyposis colon cancer: hMSH2, hMLH1, hPMS1, and hPMS2. Additionally, loss of MMR function has been demonstrated to lead to the phenomenon of microsatellite instability (MIN) in tumors from these patients. In this study, we have examined the protein expression pattern of hMSH2 and hMLH1 by immunohistochemistry in paraffin-embedded tumors from 7 patients with MIN+ sporadic cancer, 13 patients with familial colorectal cancer, and 12 patients meeting the strict Amsterdam criteria for hereditary nonpolyposis colon cancer. The relationship between the expression of these two gene products, the presence of germline or somatic mutations, and the presence of tumor MIN was examined. Nineteen of the 28 tumors studied demonstrated MIN, whereas mutations in hMLH1 and hMSH2 were detected in 6 and 2 patients, respectively. Of the eight MIN+/mutation+ cases, the absence of protein expression was observed for the corresponding gene product in all but one case (missense mutation in hMLH1). However, seven MIN+/mutation- cases also showed no expression of either hMLH1 (n = 5), hMSH2 (n = 1), or both (n = 1), whereas four MIN+/mutation- cases demonstrated normal expression for both. None of the MIN-/mutation- cases (n = 9) demonstrated an altered expression pattern for either protein. These data suggest that examination of protein expression by immunohistochemistry may be a rapid method for prescreening tumors for mutations in the MMR genes.

Mlh1 deficiency enhances several phenotypes of Apc(Min)/+ mice.

Defects in APC and DNA mismatch repair genes are associated with a strong predisposition to colon cancer in humans, and numerous mouse strains with mutations in these genes have been generated. In this report we describe the phenotype of Min/+ Mlh1-/- mice. We find that these doubly mutant mice develop more than three times the number of intestinal adenomas compared to Min/+ Mlh1+/+ or +/- mice but that these tumors do not show advanced progression in terms of tumor size or histological appearance. Full length Apc protein was not detected in the tumor cells from Min/+ Mlh1-/- mice. Molecular analyses indicated that in many tumors from Min/+ Mlh1-/- mice, Apc was inactivated by intragenic mutation. Mlh1 deficiency in Min/+ mice also led to an increase in cystic intestinal crypt multiplicity as well as enhancing desmoid tumorigenesis and epidermoid cyst development. Thus, Mlh1 deficiency influences the somatic events involved in the development of most of the phenotypes associated with the Min mutation. Oncogene (2000).

Characterisation of non-transferrin-bound iron (ferric citrate) uptake by rat hepatocytes in culture.

Under conditions of iron overload plasma transferrin can be fully saturated and the plasma can transport non-transferrin-bound Fe which is rapidly cleared by the liver. Much of this Fe is complexed by citrate. The aim of the present work was to characterise the mechanisms by which Fe-citrate is taken up by hepatocytes using a rat hepatocyte cell culture model. The cells, after one day in culture, were incubated with 59Fe-labelled Fe-citrate for varying time periods, then washed and Fe uptake to the membrane and intracellular compartments of the cell was determined by radioactivity measurements. Maximal rates of internalisation of Fe occurred at a Fe:citrate molar ratio of 1:100 or greater, a pH of approximately 7.4 and an extracellular Ca2+ concentration of 1.0 mM. Fe uptake showed Michaelis-Menten kinetics and was a temperature-dependent process. The K(m) and Vmax for Fe internalisation by the cells at 37 degrees C were approximately 7 microM and 2 nmol/mg DNA/min (25 x 10(6) atoms/cell/min), respectively; and the Arrhenius activation energy was 35 kJ/mol. The transition metals, Zn2+, Co2+ and Ni2+, inhibited Fe uptake when used at 10 and 100 times the concentration of Fe. The rate of Fe internalisation from Fe-citrate was found to be approximately 20 times as great as that from Fe-transferrin with Fe concentrations of 1 and 2.5 microM for both forms of Fe. The rate of Fe uptake by iron-loaded hepatocytes obtained from rats which had been fed carbonyl Fe was not significantly different from that by normal hepatocytes. These experiments show that rat hepatocytes in primary culture have a high capacity to take up non-transferrin-bound Fe in the form of Fe-citrate and that uptake occurs by facilitated diffusion. The iron transport process does not appear to be regulated by cellular Fe levels.

Characterization of protease-activated receptor-2 immunoreactivity in normal human tissues.

PAR-2 is a second member of a novel family of G-protein-coupled receptors characterized by a proteolytic cleavage of the amino terminus, thus exposing a tethered peptide ligand that autoactivates the receptor. The physiological and/or pathological role(s) of PAR-2 are still unknown. This study provides tissue-specific cellular localization of PAR-2 in normal human tissues by immunohistochemical techniques. A polyclonal antibody, PAR-2C, was raised against a peptide corresponding to the amino terminal sequence SLIGKVDGTSHVTGKGV of human PAR-2. Significant PAR-2 immunoreactivity was detected in smooth muscle of vascular and nonvascular origin and stromal cells from a variety of tissues. PAR-2 was also present in endothelial and epithelial cells independent of tissue type. Strong immunolabeling was observed throughout the gastrointestinal tract, indicating a possible function for PAR-2 in this system. In the CNS, PAR-2 was localized to many astrocytes and neurons, suggesting involvement of PAR-2 in neuronal function. A role for PAR-2 in the skin was further supported by its immunolocalization in the epidermis. PAR-2C antibody exemplifies an important tool to address the physiological role(s) of PAR-2.

Clinical significance of monitoring early symptom change to predict outcome.

Even with efforts to develop medication algorithms for the treatment of psychiatric illnesses, there is no single authoritative method that can be used to incorporate multiple factors in the treatment decision process. For this reason, physicians are faced with the often daunting task of sifting through the numerous treatment options for psychiatric illness to develop an approach that will prove the most successful for their patients. Investigating patient patterns of response, particularly during the acute phase of treatment, and bearing them in mind when developing treatment protocols may assist clinicians in optimally managing the degree and course of symptom response. We present here a consideration of the timing and nature of response as well as individual patient predictors, which may impact therapy decisions. Furthermore, we explore the clinical significance of integrating response patterns into the treatment approach. We believe that an analysis of response patterns, in conjunction with the use of other practice guidelines, is a viable method to more effectively navigate critical decision points in the treatment process and ultimately have a dramatic effect on patient outcome.

Correlation of the octanol/water partition coefficient with clearance half-times of intratracheally instilled aromatic hydrocarbons in rats.

Studies on the lung retention of polycyclic aromatic hydrocarbons (PAH) after inhalation have indicated that, in general, the PAH are rapidly cleared from the respiratory tract. Clearance of the PAH from the lungs is best described as bi-phasic, with the long-term component of the clearance curve having a half-time of greater than 24 h. The purpose of this study was to determine whether a relationship exists between the lipophilicity (as measured by the octanol/water partition coefficient, P) of various PAH and the short-term and long-term clearance half-times of PAH in rat lungs. Female F344/Crl rats were administered intratracheally 1 nmol of 14C-labelled anthracene (AN), benz[a]anthracene (BA), 1-nitropyrene (NP), 6-nitrobenzo[a]pyrene (6-NBP), or dibenzo[c,g]carbazole (DBC). At various times after instillation rats were sacrificed and the amount of 14C remaining in the lungs was determined. Octanol/water partition coefficients were experimentally determined for each of the PAH used. Clearance of 14C from rat lungs following instillation of the different PAH was biphasic. In all cases, greater than 85% of the initial dose instilled was cleared with a half-time of less than 1 h. The half-times for clearance of the residual 14C (1-15% of the dose) were 26, 30, 36, 53 and 63 h for AN, NP, 6-NBP, BA and DBC, respectively. The log of the octanol/water partition coefficients for the different PAH examined ranged from 4.1 (AN) to 6.05 (DBC). Plots of the octanol/water coefficients vs. the long-term clearance half-time for the PAH indicated a linear correlation (p less than 0.001; r2 = 0.96). The results from this study indicate that the greater the lipophilicity of the PAH, the slower the long-term clearance of a small fraction (1-15%) of PAH from rat lungs. These data suggest that predictions of long-term lung clearance can be made for PAH with log octanol/water partition coefficients between 4 and 6.

Dysphoria as a moderator of the relationship between perceived effort and perceived ability.

Although Heiderian logic (F. Heider, 1958) proposes an inverse relationship between ability and effort, research has uncovered dramatic individual differences in the judged relationship between the two. Some view ability and effort as positively related; others view them as negatively related. Study 1 explored dysphoria as a moderator of this relationship by gathering dysphoric and nondysphoric individuals' perceptions of their effort and ability on daily activities. Although ability and effort generally were positively related, dysphorics reported lower ability on high effort tasks. In Study 2, Ss rated their effort as high or low. Dysphorics discounted ability when effort was high; nondysphorics reported the greatest ability when they expended the greatest effort. Collectively, there was no support for an inverse relationship between ability and effort. However, dysphorics infer less ability than nondysphorics following high effort.

Results of the 1993 survey of the American Association of Academic Chief Residents in Radiology.

RATIONALE AND OBJECTIVES: A survey of chief residents of academic radiology programs is conducted annually on behalf of the American Association of Academic Chief Residents in Radiology (A3CR2). Data are obtained to improve the training of diagnostic radiology residents and to increase the understanding of radiologists and their associates about issues of interest to radiologists in training. METHODS: Questionnaires were mailed to 133 accredited programs in the United States and Canada. A wide variety of demographic and common interest questions were asked. The analysis took into account geographic location of the responders and the size of the residency program. Comparisons were made to the data from prior years. RESULTS: Completed surveys from 93 programs (70%) were returned. The percentage of women residents is increasing. Important regional and size variations exist in several areas including salary, workload, prior clinical training, resident/fellow ratios, post residency plans, and call schedules. Although many chief residents feel knowledgeable about the health care system, opinions about the future of radiology and medical care are tentative. CONCLUSIONS: This survey provides important demographic information about academic radiology residency programs. The summary information regarding plans for fellowship training, resident call schedules, and opinions about socioeconomic issues may be useful for chief residents, program directors, and departmental chairmen.

Patient participation in physical therapy goal setting.

BACKGROUND AND PURPOSE: An important part of treatment planning in physical therapy is effective goal setting. The Guide to Physical Therapist Practice recommends that therapists should identify the patient's goals and objectives during the initial examination in order to maximize outcomes. The purpose of this study was to examine whether therapists seek to involve patients in goal setting and, if so, what methods they use. Therapists' attitudes toward participation and patient satisfaction with the examination were also examined. SUBJECTS AND METHODS: Twenty-two physical therapists audiotaped the initial examination of 73 elderly patients (mean of 76.4 years of age, SD = 7.1, range = 65-94). The audiotaped examinations were then scored using the Participation Method Assessment Instrument (PMAI) to determine the frequency of attempts made by therapists to involve patients in goal setting. Therapists and patients completed surveys following the examinations. RESULTS: Therapists' use of participation methods during examinations ranged from a minimum of 1 to a maximum of 19 out of 21 possible items on the PMAI. The therapists stated that they believed that it is important to include patients in goal-setting activities and that outcomes will be improved if patients participate. Patients also indicated that participation is important to them. DISCUSSION AND CONCLUSION: In most cases, the therapists did not fully take advantage of the potential for patient participation in goal setting. Patient and therapist education is needed regarding methods for patient participation during initial goal-setting activities.