Lazaroid-enhanced survival of grafted dopamine neurons does not increase target innervation

The lazaroid U-74006F enhances survival of grafted ventral mesencephalic neurons. In this study the intraocular grafting model was used and survival and outgrowth from fetal ventral mesencephalic grafts treated with U-74006F was evaluated in nigrostriatal co-grafts. Fetal lateral ganglionic eminence was implanted into the anterior eye chamber and left to mature. Fetal ventral mesencephalon was then implanted and the eyes were treated with U-74006F. The lazaroid treatment enhanced survival of tyrosine hydroxylase (TH)-positive neurons, but did not enhance TH-positive nerve fiber growth into the striatal portions of the co-grafts. However, a marked increase in nerve fiber formation was found within the ventral mesencephalic grafts. In conclusion, increased cell survival enhanced nerve fiber formation within the ventral mesencephalic portion of the co-graft and not, as expected, in the striatal part.     

Co-grafted embryonic striatum increases the survival of grafted embryonic dopamine neurons

To enhance the current therapeutic benefit of dopamine (DA) neuron grafts in Parkinson's disease, strategies must be developed that increase both DA neuron survival and fiber outgrowth into the denervated striatum. Previous work in our laboratory has demonstrated that dopaminergic neurons grow to greater size when co-grafted with striatal cell suspensions and display extensive tyrosine hydroxylase-positive (TH+) projections, but no conclusion could be reached concerning enhancement of survival of grafted DA neurons. The aim of the present study was to characterize further the potential trophic effects of striatal co-grafts on grafted mesencephalic DA neuron survival. Unilaterally lesioned male Fischer 344 rats were grafted with either a suspension of mesencephalic cells or with both mesencephalic and striatal cell suspensions. Co-grafts were either mixed together or placed separately into the striatum. Lesioned rats receiving no graft served as controls. Rotational behavior was assessed following amphetamine challenge at 2 weeks prior to grafting and at 4 and 8 weeks following grafting. Only rats receiving co-grafts of nigral and striatal suspensions separated by a distance of 1 mm showed significant behavioral recovery from baseline rotational asymmetry. Both mixed and separate striatal co-grafts were associated with a doubling of DA neuron survival compared with solo mesencephalic grafts. In the mixed co-graft experiment, DA neurite branching appeared enhanced and TH-rich patches were observed, whereas with co-grafts that were separated, TH+ innervation of the intervening host striatum was increased significantly. These results provide the first evidence suggesting that nigral-striatal co-grafts, particularly those placed separately and in proximity to each other, increase both DA neuron survival and neurite extension from the mesencephalic component of the grafts.     

Long-term treatment with haloperidol or clozapine does not affect dopamine D4 receptors in rat frontal cortex

We examined the effects of long-term treatment with haloperidol and clozapine on dopamine D4 receptors in rat frontal cortex. Dopamine D4 receptor binding sites were indirectly determined from the displacement experiments of [3H]clozapine binding using nemonapride. Three-weeks administration of haloperidol (0.5 mg/kg) or clozapine (10 mg/kg) did not significantly affect the D4 receptors in the frontal cortex. The density of D2 receptors, determined by [3H]spiperone binding to striatum, was increased by long-term treatment with haloperidol, but it was not significantly changed by that with clozapine.     

Granulocyte colony-stimulating factor does not enhance phagocytosis or microbicidal activity of human mature polymorphonuclear neutrophils in vitro

The direct effects of human granulocyte colony-stimulating factor (hG-CSF) on mature polymorphonuclear neutrophils (PMNs) in vitro were studied with regard to chemotaxis, superoxide production, and phagocytosis and microbicidal activity against the following viable microorganisms: Staphylococcus aureus, serum-resistant Pseudomonas aeruginosa, and Candida albicans. Recombinant hG-CSF (rhG-CSF) acted as a chemoattractant for human PMNs in a dose-dependent manner. The chemotactic response of PMNs to N-formyl-methionyl-leucyl-phenylalanine (FMLP) was not enhanced by rhG-CSF at any of the concentrations used. rhG-CSF did not induce the generation of superoxide by itself. However, rhG-CSF was able to prime human PMNs and to enhance O2- release stimulated by FMLP in a dose-dependent manner. rhg-CSF did not enhance phagocytosis or killing of the three species of microorganisms by normal PMNs. With PMNs obtained from patients who had hematological disorders or solid tumors, no enhancement of the microbicidal activity was observed in most cases. Microbial killing mediated by PMNs depended on the ratio of PMNs to target organisms. We concluded from these facts that the most important effect of rhG-CSF was to increase the number of the peripheral PMNs and not to enhance the functions of mature PMNs.     

Grapefruit juice does not enhance the effects of midazolam and triazolam in man

OBJECTIVES: Since grapefruit juice (Gra) inhibits hepatic P450 (CYP3A4), we studied its potential to enhance the effects of midazolam (Mid) and triazolam (Trz), which are metabolized by the CYP3A4 isoenzyme. METHODS: In Study I parallel groups of healthy students were given orally Mid 10 mg with water or grapefruit juice (GraMid), two placebo groups receiving water or Gra. The effects of Mid were measured by psychomotor tests and by self-rating on visual analogue scales before and 30 and 90 min after intake. Study II was similar, but the post-treatment tests were at 45 and 90 min, and the active drugs used were 0.250 mg Trz, GraTrz, and Mid 10 mg. In the crossover Study III, 6 subjects took Mid 10 mg alone and with Gra (GraMid) and 750 mg erythromycin (EryMid). Performance tests were made and blood was sampled before and 30, 60 and 90 min after intake. Midazolam and its active metabolite alpha-OH-midazolam were assayed by gas chromatography (GC) and radioreceptor assay (RRA). RESULTS: In Study I, both Mid and GraMid impaired digit symbol substitution (DSS), letter cancellation (LC) and flicker fusion (CFF) at 90 min. GraMid had more effect (P < 0.05) than Mid on the DSS performance. Mid caused drowsiness at 30 and 90 min. Both Mid and GraMid caused clumsiness and a feeling of impaired performance at 90 min. In Study II, the active drugs impaired objective test performances (DSS, LC, CFF) at 90 min, without having a clear subjective effect. In Study III, Mid, EryMid and GraMid impaired performance in the DSS, LC and CFF tests. EryMid proved stronger than Mid and GraMid on DSS and LC tests at 30 min. Mean values of plasma midazolam (and alpha-OH-midazolam) at 30, 60, 90 and 120 min after Mid 10 mg were 68(19), 61(19), 43(14) and 42(12) micrograms.l-1. The corresponding values after EryMid were 164(14), 137(13), 104(10) and 89(10) micrograms.l-1, and after GraMid 60(12), 69(16), 61(15) and 57 (14) micrograms.l-1. CONCLUSIONS: The grapefruit juice used did have any particular interaction with oral doses of 10 mg midazolam and 0.25 mg triazolam in healthy young subjects.     

Tenoxicam does not enhance the spread of sensory block produced by intrathecal lidocaine

A chemically synthesized human pro-urokinase (pro-UK) CDNA was cloned into the expression vector PET-11d and expressed in E. coli BL21(DE3) pLysS under the control of the T7 promoter. Using 0.1 mmol/L IPTG induction, the expression level of the recombinant pro-UK attained up to 15% of the total bacterial proteins and existed as inclusion bodies. After denaturation and renaturation in vitro, the expressed pro-UK was purified to be identified by Zn2+ selective precipitation, immuno-affinity chromatography, and benzamidine affinity adsorption. The specific activity of the purified human pro-UK was about 110,000 IU/mg.     

NM23 gene product expression does not predict lymph node metastases or survival in young patients with colorectal cancer

PURPOSE: To develop a hepatic artery embolization protocol and investigate its efficacy in a prospective study treating patients with hereditary hemorrhagic telangiectasia and predominant hepatic involvement. MATERIALS AND METHODS: One man and four women with hereditary hemorrhagic telangiectasia presented with symptoms of high-output heart failure, abdominal angina, or severe portal hypertension. The hepatic arteries were embolized in stages in three to five sessions at 1- to 15-week intervals. After peripheral embolization with polyvinyl alcohol particles, proximal arteries were embolized with coils. Computed tomography and assessment of cardiac output were performed before and after therapy and at the end of follow-up (median, 25 months; range, 12-55 months). RESULTS: After embolization, analgesics and antiemetics were necessary for a median of 5 and 2 days, respectively. Other than ischemic cholangitis (one patient), no complications were observed. The mean cardiac output decreased significantly (P < .05) from 14.2 L/min to 8.0 L/min. Symptoms of high-output heart failure, abdominal angina, and portal hypertension resolved in all patients. Seven months after embolization, one patient died of postoperative sepsis after an unsuccessful surgical attempt to create a portacaval shunt. Delayed recurrence of symptoms was not noted in the other patients. CONCLUSION: In symptomatic patients with hereditary hemorrhagic telangiectasia and predominant hepatic involvement, embolization of the hepatic arteries in stages is well tolerated by the patients and results in good clinical improvement at midterm follow-up.     

Disruption of p53 function in immortalized human cells does not affect survival or apoptosis after taxol or vincristine treatment

OBJECTIVE: We assessed the feasibility of contrast-enhanced color Doppler, power Doppler, and spectral duplex sonography for visualization and quantification of flow through transjugular intrahepatic portosystemic shunts (TIPS) in patients in whom the baseline sonographic evaluation was unsatisfactory. SUBJECTS AND METHODS: Thirty-three patients underwent color Doppler, power Doppler, and spectral duplex sonography after TIPS insertion or before TIPS revision (mean time interval +/- SD, 1 +/- 1 day). All sonograms were obtained before and after patients received echo-enhancing contrast material. Sonography was evaluated with regard to presence or absence of flow in the mid portion, portal segment, and hepatic segment of the shunt. The maximal peak velocity was measured in the mid portion of the shunt. For identifying and quantifying stenoses, the percentage of luminal diameter reduction was calculated at the tightest part of the shunt. Shunt angiography and measurements of portosystemic pressure gradients were independently evaluated and compared with the sonographic findings. RESULTS: Flow visualization on unenhanced color Doppler sonography was significantly improved through the use of power Doppler sonography and contrast-enhanced color Doppler and power Doppler sonography (p < .01). Between contrast-enhanced power Doppler and contrast-enhanced color Doppler sonography, a significant difference was found in the portal and hepatic segments (p < .05). All shunt stenoses (n = 8) and occlusions (n = 3) were revealed by power Doppler sonography, whereas color Doppler sonography failed to reveal six of eight stenoses. Compared with unenhanced sonography, the quality of spectral duplex sonography was improved in eight patients after contrast enhancement (p < .05). Maximal peak velocity ranged from 54 to 252 cm/sec (mean +/- SD, 132.7 +/- 52.1 cm/sec) in normal shunts and from 24.5 to 70.0 cm/sec (mean +/- SD, 45.0 +/- 18.9 cm/sec) in stenosed shunts. No correlation was found between maximal peak velocity and portosystemic pressure gradients (r = .28). CONCLUSION: Unenhanced power Doppler and contrast-enhanced color and power Doppler sonography can be helpful in the assessment of TIPS status in patients who previously underwent unsatisfactory sonography. These techniques may allow anatomic evaluation and quantification of shunt stenosis in most patients. Contrast enhancement may also considerably improve the quality of spectral duplex sonography.     

Chondroitin/dermatan sulphate promotes the survival of neurons from rat embryonic neocortex

Recently we have shown that biglycan, a small chondroitin sulphate proteoglycan of the extracellular matrix, supports the survival of cultured neurons from the developing neocortex of embryonic day 15 rats. Here we investigate the structure-function relationship of this neurotrophic proteoglycan and show that chondroitin/dermatan sulphate chains are the active moieties supporting survival. Heparin, a highly sulphated glucosaminoglycan, is less active than the galactosaminoglycans (chondroitin-4-sulphate, chondroitin-6-sulphate and dermatan sulphate), whereas hyaluronic acid, an unsulphated glucosaminoglycan, does not support neuron survival. Galactosaminoglycans must be in direct contact with neurons to cause survival. Experiments with elevated potassium concentrations and antagonists of voltage-gated calcium channels exclude the involvement of membrane depolarization. However, genistein and an erbstatin analogue, which are inhibitors of tyrosine kinases with low specificity, abolished neuron survival in the presence of chondroitin/dermatan sulphate, whereas a selective inhibitor of neurotrophin receptor kinases (K252a) had no suppressive effect. Thus, yet unidentified tyrosine kinases are involved in the chondroitin/dermatan sulphate-dependent survival of neocortical neurons. In the embryonic stages of rat neocortical development chondroitin sulphate is mainly located in layers I, V and VI and the subplate. Chondroitin sulphate expression is maintained after birth, extends up to cortical layer IV on postnatal day 7, and is down-regulated until postnatal day 21 concomitant with the period of naturally occurring cell death. The latter observation is consistent with a putative role of chondroitin sulphate in the control of neuron survival during cortical histogenesis.     

Nitric oxide-dependent production of cGMP supports the survival of rat embryonic motor neurons cultured with brain-derived neurotrophic factor

Trophic factor deprivation induces neuronal nitric oxide synthase (NOS) and apoptosis of rat embryonic motor neurons in culture. We report here that motor neurons constitutively express endothelial NOS that helps support the survival of motor neurons cultured with brain-derived neurotrophic factor (BDNF) by activating the nitric oxide-dependent soluble guanylate cyclase. Exposure of BDNF-treated motor neurons to nitro-L-arginine methyl ester (L-NAME) decreased cell survival 40-50% 24 hr after plating. Both low steady-state concentrations of exogenous nitric oxide (<0.1 microM) and cGMP analogs protected BDNF-treated motor neurons from death induced by L-NAME. Equivalent concentrations of cAMP analogs did not affect cell survival. Inhibition of nitric oxide-sensitive guanylate cyclase with 2 microM 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) reduced the survival of BDNF-treated motor neurons by 35%. cGMP analogs also protected from ODQ-induced motor neuron death, whereas exogenous nitric oxide did not. In all cases, cell death was prevented with caspase inhibitors. Our results suggest that nitric oxide-stimulated cGMP synthesis helps to prevent apoptosis in BDNF-treated motor neurons.     

Overexpression of Bcl-2 does not rescue impaired B lymphopoiesis in IL-7 receptor-deficient mice but can enhance survival of mature B cells

IL-7 receptor-deficient (IL-7R(-/-)) mice are lymphopenic as a result of defective cell production at early steps in both B and T lymphopoiesis. In the bone marrow, there is an incomplete block in B cell development at the transition from the pro-B to the pre-B cell stage. As a consequence, peripheral lymphoid organs of IL-7R(-/-) mice contain abnormally low numbers of mature surface (s) Ig-expressing B cells and this is accompanied by a relative increase in immature sIg- B cells. Transgenic expression of the anti-apoptotic protein Bcl-2 in IL-7R(-/-) mice rescues the defect in T cell development and in mature T cell function. The present report shows that constitutive expression of Bcl-2 is incapable of rescuing B lymphopoiesis in IL-7R(-/-) mice but can enhance survival of those mature B cells which escape the developmental arrest. Thus the essential role of IL-7R signaling in B lymphoid cells cannot be replaced by Bcl-2, indicating that in B lymphopoiesis IL-7R signaling is necessary for promoting cell division and/or for inhibiting a Bcl-2-insensitive pathway to apoptosis.     

Adrenalectomy does not affect the nocturnal peak of Fos expression within hypothalamic pro-opiomelanocortin neurons

Clinical and evoked-potential studies in internal capsule and corona radiata infarction are lacking. We report the results of a clinical and central motor conduction time (CMCT) study in 16 patients with internal capsule and 17 with computed tomography (CT)-proven corona radiata infarction. Patients's outcome was defined at the end of 3 months on the basis of the Barthel Index score. Four patients with type A capsular infarction (middle third of posterior limb of internal capsule) all had severe weakness, while 2 also had persistently unrecordable CMCT and poor outcome. Twelve patients with type B internal capsular infarction (genu, anterior limb, anterior or posterior third of posterior limb) had a milder degree of weakness, and CMCT was recordable in 9. At 3 months' follow-up, however, CMCT was recordable in all 12 patients. All of these patients had a partial (n = 4) or complete (n = 5) recovery. Thirteen patients with type A corona radiata infarction (middle third of corona radiata) had more pronounced weakness, and CMCT was unrecordable in all of these patients except 1 on initial examination. Follow-up after 3 months was possible in 8 patients, and CMCT became recordable in 3. One of these patients had complete, 3 partial, and 4 poor recovery. In type B corona radiata infarction (anterior or posterior third of corona radiata), the clinical signs and CMCT did not follow a regular pattern. Clinical and CMCT abnormalities in internal capsular infarction followed a more predictable pattern compared with those in corona radiata infarction. A less predictable pattern of weakness and CMCT change in corona radiata infarction may be attributed to a less definite organisation of motor pathways compared with the internal capsule.     

Renal dysfunction does not alter the pharmacokinetics or LDL-cholesterol reduction of atorvastatin

The objective of this study was to determine the effects of renal dysfunction on the steady-state pharmacokinetics and pharmacodynamics of atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Nineteen subjects with calculated creatinine clearances ranging from 13 mL/min to 143 mL/min were administered 10 mg atorvastatin daily for 2 weeks. Pharmacokinetic parameters and lipid responses were analyzed by regression on calculated creatinine clearance. Correlations between steady-state atorvastatin pharmacokinetic or pharmacodynamic parameters and creatinine clearance were weak and, in general, did not achieve statistical significance. Although the elimination rate constant, lambda z (0.579), was significantly correlated with creatinine clearance, neither maximum plasma concentration (Cmax, -0.361) nor oral clearance (Cl/F, 0.306) were; thus, steady-state exposure is not altered. Renal impairment has no significant effect on pharmacodynamics and pharmacokinetics of atorvastatin.     

Monohydroxyethylrutoside, a dose-dependent cardioprotective agent, does not affect the antitumor activity of doxorubicin

The cumulative dose-related cardiotoxicity of doxorubicin is believed to be caused by the production of oxygen- free radicals. 7-Monohydroxyethylrutoside (monoHER), a semisynthetic flavonoid and powerful antioxidant, was investigated with respect to the prevention of doxorubicin-induced cardiotoxicity in mice and to its influence on the antitumor activity of doxorubicin in vitro and in vivo. Non-tumor-bearing mice were equipped with a telemeter in the peritoneal cavity. They were given six weekly doses of 4 mg/kg doxorubicin i.v., alone or in combination with either 100 or 250 mg/kg monoHER i.p., 1 h prior to doxorubicin administration and for the following 4 days. Cardiotoxic effects were measured from electrocardiogram changes up to 2 weeks after treatment. Protection against cardiotoxicity was found to be dose dependent, with 53 and 75% protection, respectively, as calculated from the reduction in the increase in the ST interval. MonoHER and several other flavonoids with good antioxidant properties were tested for their antiproliferative effects in the absence or the presence of doxorubicin in A2780 and OVCAR-3 human ovarian cancer cells and MCF-7 human breast cancer cells in vitro. Some flavonoids were directly toxic at 50 and 100 microM, whereas others, including monoHER, did not influence the antiproliferative effects of doxorubicin at these concentrations. The influence of monoHER was further tested on the growth-inhibitory effect of 8 mg/kg doxorubicin i.v., given twice with an interval of 1 week in A2780 and OVCAR-3 cells that were grown as s.c. xenografts in nude mice. MonoHER, administered 1 h before doxorubicin in a dose schedule of 500 mg/kg i.p. 2 or 5 days per week, was not toxic and did not decrease the antitumor activity of doxorubicin. It can be concluded that monoHER showed a dose-dependent protection against chronic cardiotoxicity and did not influence the antitumor activity of doxorubicin in vitro or in vivo.     

Resuscitation of the injured patient with polymerized stroma-free hemoglobin does not produce systemic or pulmonary hypertension

BACKGROUND: Hemoglobin-based blood substitutes appear poised to deliver the promise of a universally compatible, disease-free alternative to banked blood. However, vasoconstriction following administration of tetrameric hemoglobins has been problematic, likely because of nitric oxide binding. Polymerized hemoglobin is effectively excluded from the abluminal space because of its size, and is thus less likely to perturb vasorelaxation. We therefore hypothesized that hemodynamic responses would be no different in injured patients receiving polymerized hemoglobin versus banked blood. METHODS: Injured patients requiring urgent transfusion were randomized to receive either polymerized hemoglobin or banked blood. Systemic arterial pressure, pulmonary arterial pressure, cardiac index, pulmonary capillary wedge pressure, systemic vascular resistance, and pulmonary vascular resistance were measured serially. RESULTS: There was no difference in any of the measured hemodynamic parameters between patients resuscitated with polymerized hemoglobin versus blood. CONCLUSIONS: Polymerized hemoglobin given in large doses to injured patients lacks the vasoconstrictive effects reported in the use of other hemoglobin-based blood substitutes. This supports the continued investigation of polymerized hemoglobin in injured patients requiring urgent transfusion.     

Treatment of E2E2 homozygous familial dysbetalipoproteinemic subjects with gemfibrozil does not enhance the binding of their d < 1.019 lipoprotein fraction to the low-density lipoprotein receptor

DNA content analysis of formalin fixed paraffin embedded (FFPE) tissue permits determination of the influence of DNA content on the prognosis in cohorts of patients for whom the clinical outcome is known. Of key importance in such an analysis is the accuracy of DNA content determination. Variations in the quality of DNA histograms from FFPE tissues of different types prompted a comparative evaluation of the preparative methodology of FFPE soft tissue sarcomas for DNA flow cytometry. Following deparaffination and rehydration of fixed tissue, and prior to fluorochrome staining, tissue blocks of 15 DNA aneuploid soft tissue sarcomas were subjected to repeated experimental (time x concentration) enzyme exposures. The goal of these studies was to define the optimal tissue specific retrieval technique with the coefficient of variation, maintenance of DNA aneuploidy, and DNA index as endpoints. After optimizing the technique, the DNA content of 50 soft tissue neoplasms derived from FFPE specimens was compared to the corresponding fresh surgical tissue. The observed 14 percent error rate in the determination of DNA ploidy status suggest limited utility for FFPE tissue in prospective therapeutic trials of soft tissue sarcoma.     

Blocking nerve growth factor binding to the p75 neurotrophin receptor on sympathetic neurons transiently reduces trkA activation but does not affect neuronal survival

Nerve growth factor interacts with the trkA tyrosine kinase receptor and with the p75 neurotrophin receptor. It is clear that trkA mediates most, if not all, of the stereotypical responses of sympathetic neurons to nerve growth factor but the role of the p75 neurotrophin receptor is unclear. In this study, we have asked whether a functional interaction between p75 neurotrophin receptor and trkA exists in primary sympathetic neurons by disrupting nerve growth factor binding to p75 neurotrophin receptor. Acute assays reveal that blocking antibodies directed against p75 neurotrophin receptor reduce nerve growth factor-mediated trkA tyrosine phosphorylation and reduce the amount of nerve growth factor which binds the trkA receptor. This reduction in trkA activity is relatively short-lived in vitro and blocking antibodies to p75 neurotrophin receptor do not inhibit long-term survival of nerve growth factor-dependent primary neurons. Together, these data indicate that p75 neurotrophin receptor and trkA interact within primary neurons to enhance nerve growth factor binding to the trkA receptor under conditions of acute but not chronic nerve growth factor exposure.     

Neutropenia does not prevent etodolac- or indomethacin-induced gastrointestinal damage in the rat

Neutrophils have been implicated in the acute formation of gastric mucosal erosions induced by nonsteroidal antiinflammatory drugs. The aims of the present study were to determine, in rats, the role of neutrophils in the pathogenesis of etodolac- and indomethacin-induced gastrointestinal ulceration and blood loss. Both drugs caused gastrointestinal ulceration, which was associated with increased blood loss, a rise in plasma haptoglobin concentration, and a rise in the number of circulating neutrophils. A marked infiltration of neutrophils occurred only in ileal tissue. Pretreatment with a selective antineutrophil serum induced a significant neutropenia, which failed to inhibit either etodolac- or indomethacin-induced gastrointestinal ulceration and blood loss. A further study demonstrated that the antineutrophil serum did not prevent gastric erosions induced by indomethacin, but it inhibited carrageenan paw edema, which is dependent, in part, on neutrophil infiltration and activation. It is concluded that neutrophils do not contribute to gastrointestinal ulceration and blood loss induced by nonsteroidal antiinflammatory drugs. Furthermore, in contrast with previous studies, our results provide no evidence that neutrophils contribute to indomethacin-induced acute gastric erosion formation.     

The incremental validity of the MMPI-2: When does therapist access not enhance treatment outcome?

The present study examined whether therapist access to the Minnesota Multiphasic Personality Inventory (MMPI-2) predicted favorable treatment outcome, above and beyond other assessment measures. A manipulated assessment design was used, in which patients were randomly assigned either to a group in which therapists had access to their MMPI-2 data or to a group without therapist access to such information. Illness severity, improvement ratings, number of sessions attended, and premature termination were indicators of therapy outcome. Results indicated that therapist access to the MMPI-2 data did not add to the prediction of positive treatment outcome beyond that predicted by other measures in this setting. Findings from this initial study suggest that, compared with other resources, perhaps in clinical settings with an emphasis on diagnosis-based and evidence-based treatment, the MMPI-2 may not provide incrementally valid information. However, these effects warrant replication across different settings and samples. Guidelines for future studies are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)