Similarity to the self influences memory for social targets.

The construct of the self is important in the domain of memory research. Recent work has shown that person memory is influenced by similarity of social targets to the self. The current experiments investigate self-similarity as defined by traits and political ideology to better understand how memory for social targets is organised. Across three experiments, participants formed positive or negative impressions based on each target's picture, a trait-implying behavior (Experiments 1 & 2), and/or political ideology (conservative/liberal label in Experiment 2; political-ideological belief statements in Experiment 3) followed by a memory test. Results showed a self-similarity effect dependent on valence in Experiment 1, but not in Experiments 2 or 3 when participants processed ideological information associated with targets. These results suggest that self-similarity has an effect on memory for social targets, but that ideological information disrupts self-focused processing of others, suggesting that ideological information also has a powerful influence on what people remember about others (i.e. social targets).

A Case of Successful Thromboelastographic Guided Resuscitation after Postpartum Hemorrhage and Cardiac Arrest.

Amniotic fluid embolism (AFE) is an unusual cause of life threatening peri partum hemorrhage (PPH). AFE resuscitation is often associated with renal and respiratory insufficiency, and a coagulopathy similar to disseminated intravascular coagulation (DIC). Resuscitation requires immediate recognition and limited use of crystalloid. We present a case of PPH caused by AFE with resultant cardiac arrest, renal and respiratory failure, and DIC-like coagulopathy, whose successful resuscitation was guided by perfusionist-directed serial thromboelastography (TEG). Viscoelastic tests (VET)s, including the TEG and rotational thromboelastometry (ROTEM), may provide more individualized blood component therapy (BCT) in the treatment of severe PPH associated with AFE as has been previously noted with trauma resuscitation in the literature. However, VET's efficacy is often limited by a lack of standardization, quality assurance norms, and consistent operator proficiency. We suggest that there may be a role for perfusionsts adept at utilizing TEG in the optimization of BCT and adjunctive hemostatic agents in severely hemorrhagic patients. This patient's successful resuscitation demonstrates the importance of resuscitation guided by the perfusionist or other medical professionals with expertise in TEG guided resuscitation and how the administration of specific blood products and hemostatic agents guided by the TEG can help optimize patient outcomes in comparison to traditional 1:1:1 packed red blood cells (PRBC) /fresh frozen plasma (FFP) /platelets ratios given to severely hemorrhaging patients.

Test-retest reliability of the Capute scales for neurodevelopmental screening of a high risk sample: Impact of test-retest interval and degree of neonatal risk.

AIM: Reliable and valid screening and assessment tools are necessary to identify children at risk for neurodevelopmental disabilities who may require additional services. This study evaluated the test-retest reliability of the Capute Scales in a high-risk sample, hypothesizing adequate reliability across 6- and 12-month intervals. METHODS: Capute Scales scores (N = 66) were collected via retrospective chart review from a NICU follow-up clinic within a large urban medical center spanning three age-ranges: 12-18, 19-24, and 25-36 months. On average, participants were classified as very low birth weight and premature. Reliability of the Capute Scales was evaluated with intraclass correlation coefficients across length of test-retest interval, age at testing, and degree of neonatal complications. RESULTS: The Capute Scales demonstrated high reliability, regardless of length of test-retest interval (ranging from 6 to 14 months) or age of participant, for all index scores, including overall Developmental Quotient (DQ), language-based skill index (CLAMS) and nonverbal reasoning index (CAT). Linear regressions revealed that greater neonatal risk was related to poorer test-retest reliability; however, reliability coefficients remained strong. CONCLUSIONS: The Capute Scales afford clinicians a reliable and valid means of screening and assessing for neurodevelopmental delay within high-risk infant populations.

Executive functions among youth with Down Syndrome and co-existing neurobehavioural disorders.

BACKGROUND: Executive function (EF) deficits are a recognised component of the cognitive phenotype of youth with Down Syndrome (DS). Recent research in this area emphasises the use of behaviour ratings, such as the Behavior Rating Inventory of Executive Functions-Preschool Version (BRIEF-P), to capture the real-world applications of executive functions. To account for the intellectual functioning of youth with DS, this measure is used out of age range; however, its psychometric properties when used in this fashion are unknown. The goals of this study are to evaluate psychometric characteristics of the BRIEF-P among youth with DS and to examine the pattern of EF strengths/weaknesses in children with DS and co-occurring psychiatric conditions. METHOD: A total of 188 clinically referred youth with DS, ages 3-13 were rated by their caregivers using the BRIEF-P. These youth were evaluated by a clinician with expertise in DS and were characterised as having no co-occurring behavioural disorder (Typical DS group), co-occurring Autism Spectrum Disorder (DS + ASD) or co-occurring Disruptive Behaviour Disorder (DS + DBD). RESULTS: An exploratory factor analysis of item-level BRIEF-P data from clinically referred youth with DS supported the theoretically derived three-factor structure originally proposed for the BRIEF-P (Emergent Metacognition, Flexibility and Inhibitory Self-Control); however, the item composition of each factor varied somewhat in comparison to the original structure of the measure. Group comparisons indicate that, while youth with typical DS evidence fewer executive function difficulties across all domains, youth with DS + ASD show the greatest weaknesses in Emergent Metacognition, and youth with DS + DBD show significant difficulties in both Emergent Metacognition and Inhibition. CONCLUSIONS: These findings offer preliminary support for use of the BRIEF-P with clinically referred youth with Down Syndrome. Some scoring modifications may be necessary if the theoretically derived index scores are to be used with this population. BRIEF-P scores may offer an empirical basis for differentiating DS youth with varying behavioural profiles.

Effects of winter growing program on visceral organ mass, composition, and oxygen consumption of beef steers during growing and finishing.

The purpose of this experiment was to investigate the effects of winter growing program on organ mass, composition, and oxygen consumption in beef steers. A total of 46 steers were used for the experiment. Four steers were randomly selected as an initial slaughter group. Remaining steers were randomly allotted to 1 of 4 treatment groups: 1) fed a high-concentrate diet for ad libitum intake (CF); 2) grazed on wheat pasture (WP); 3) fed a sorghum silage-based growing diet (SF); or 4) program fed a high-concentrate diet (PF). Steers in the WP, SF, and PF groups were managed to achieve approximately equal rates of BW gain during the growing phase. After the growing phase (112 d), steers in the WP, SF, and PF treatments were adapted to a high-concentrate diet for finishing. Steers from all treatments were slaughtered at a fat thickness of 1.27 cm as estimated by ultrasound. In addition, 6 steers from each treatment were randomly selected for slaughter at the end of the growing phase. Weights of all individual organs were measured and tissue samples of duodenum and liver collected. At the end of the growing phase, WP steers had greater (P < 0.05) small intestine, liver, and kidney mass than SF and PF steers. In contrast, mesenteric fat mass and total visceral fat content were greatest (P < 0.01) for PF, intermediate for SF, and least for WP steers. Mass of total viscera and total splanchnic tissues (TST) did not differ (P > 0.10) among treatments. At final slaughter, mass of mesenteric fat, total viscera, and TST were similar among treatments, but liver weights remained greatest (g/kg of empty BW; P < 0.01) for WP steers. There were no differences in oxygen consumption of duodenum or liver tissue on an equal weight basis (microL.min(-1.)g(-1)) at the end of either period. Growing program affected mass of components of the TST at the end of the growing phase, which contributed to differences in rate of splanchnic organ growth during finishing. We conclude that program feeding a high-concentrate diet during the growing phase may result in greater ADG and G:F during the subsequent finishing period compared with forage-based diets due to less accretion of visceral organ mass resulting in reduced maintenance energy requirements during finishing.

Effects of winter growing programs on subsequent feedlot performance, carcass characteristics, body composition, and energy requirements of beef steers.

The purpose of this study was to investigate the effects of winter growing program on subsequent finishing performance, carcass merit, and body composition of beef steers. Four steers were slaughtered to determine initial body composition. Remaining steers (n = 256) were blocked by BW and randomly allotted to 1 of 4 treatment groups: 1) ad libitum fed a high-concentrate diet (CF), 2) grazed on wheat pasture (WP), 3) fed a sorghum silage-based diet (SF), or 4) program fed a high-concentrate diet (PF). Steers in the WP, SF, and PF groups were managed to achieve approximately equal rates of BW gain. After the growing phase (112 d), 6 steers were randomly selected from the WP, SF, and PF treatments for determination of body composition. Remaining steers were adapted to a high-concentrate diet for finishing and slaughtered at 1.27 cm of 12th-rib fat. Six steers from each treatment were used to determine carcass, offal, and empty body composition. During the growing phase, WP, SF, and PF steers gained 1.15, 1.10, and 1.18 kg/d, respectively, and ME intake did not differ (P = 0.50) among treatments. Program-fed and SF steers had greater (P < 0.05) offal and empty body fat content than WP steers. Gain in offal and empty body fat was greatest (P < 0.05) for PF steers, intermediate for SF steers, and least for WP steers. During the finishing phase (123, 104, 104, 196 d for WP, SF, PF, and CF, respectively) DMI was greater (P < 0.01) for SF steers (10.9 kg/d) than for PF steers (10.1 kg/d); WP steers were intermediate (10.4 kg/d). Daily BW gain was greatest (P < 0.05) for SF steers (2.02 kg/d), intermediate for PF steers (1.85 kg/d), and least for WP and CF steers (1.64 and 1.63 kg/d, respectively). Accretion (kg/d) of carcass and empty body mass was less (P < 0.05) for WP and CF steers compared with PF and SF steers. Calf-fed steers had greater (P < 0.05) fat content of offal than SF and PF steers; WP steers were intermediate. Gain in empty body and carcass energy (Mcal/d) was greater (P < 0.05) for PF steers than CF steers with SF and WP steers being intermediate. At slaughter, SF steers had reduced (P < 0.01) yield grades and greater marbling scores compared with CF and WP steers; PF steers were intermediate. In conclusion, growing programs that increase fat composition of feeder calves did not negatively affect subsequent finishing performance. Finishing steers as calves may reduce retained energy of carcass tissues and increase internal fat during high-grain feeding compared with steers that previously underwent a growing program.

Successful Treatment of Primary Vaginal Papillary Serous Adenocarcinoma Using Chemoradiation Followed by Brachytherapy.

Advances in treatment have not recently been reported in rare primary vaginal adenocarcinomas. A 56-year-old woman with a chronic vaginal cyst and possible in utero diethylstilbestrol exposure presented with postmenopausal bleeding. Biopsy of the vagina revealed high-grade papillary serous adenocarcinoma. MRI showed a 6-cm vaginal tumor and 3-cm left inguinal lymph node with metastasis. The patient initially received concurrent cisplatin and radiation. She then received high-dose-rate brachytherapy for further local control. Brachytherapy following external beam radiation with concurrent cisplatin led to clinically undetectable cancer at 24 months with minimal side effects.

An upper limit for caloric density of finishing diets.

This review assessed the relationships between dietary energy density and animal performance in an effort to evaluate a possible upper limit for energy density in finishing diets for cattle. Data were combined from 49 experiments (69 trials; 243 treatment observations) in which the dietary ME concentration (Mcal/kg of DM) was varied by level of concentrate, grain source, grain processing, and level of supplemental fat. Dietary concentrations of ME were determined using 1) NRC values of ME from diet ingredients; or 2) values derived from the literature, in which ingredient ME had been calculated from animal performance. Procedures for pooling data from multiple studies were used. The dependent variable was fit to a model that included a random slope and intercept clustered by trial. Trial-adjusted dependent variables (animal performance and carcass characteristics) were regressed on the independent variable (dietary ME concentration). Models were fit to cubic equations, and then reduced from cubic to quadratic to linear equations when the cubic and quadratic terms were not significant at P > 0.10. When NRC values were used, the relationship of DMI (% of BW) to dietary ME was linear (DMI decreased as ME increased; R2 = 0.631). However, the slope of ME intake (Mcal/kg of BW(0.75)) vs. dietary ME content did not differ (P > 0.25) from zero, supporting the concept that ruminants on high-grain diets (2.7 to 3.3 Mcal of ME/kg of DM) eat to maintain constant energy intake. Quadratic relationships were observed (P < 0.05) when ADG and G:F vs. dietary ME concentration were analyzed. Gain:feed was maximized with 3.46 (NRC) to 3.65 (calculated) Mcal/kg of ME from the total diet, 2.99 (NRC) to 3.40 (calculated) Mcal/kg of ME from grain, and 0.43 (NRC) to 0.53 (calculated) Mcal/kg of ME from supplemental fat. Most relationships of carcass traits to dietary ME were not significant (P > 0.10). Increased 12th-rib fat at greater ME and increasing KPH suggests greater fat deposition with increasing caloric density. Assuming that NRC ME values for ingredients commonly used in finishing diets are correct, the upper caloric limit for maximizing ADG and G:F was 3.16 and 3.45 Mcal/kg of DM, respectively. Reaching the upper caloric limit for G:F would require most grains to be processed or fed in high-moisture form. Whether maximizing G:F results in the most desirable carcass composition and yield of retail cuts should be determined.

Role of primate magnocellular red nucleus neurons in controlling hand preshaping during reaching to grasp.

Reaching to grasp is of fundamental importance to primate motor behavior and requires coordinating hand preshaping with limb transport and grasping. We aimed to clarify the role of cerebellar output via the magnocellular red nucleus (RNm) to the control of reaching to grasp. Rubrospinal fibers originating from RNm constitute one pathway by which cerebellar output influences spinal circuitry directly. We recorded discharge from individual forelimb RNm neurons while monkeys performed a reach-to-grasp task and two tasks that were similar to the reach-to-grasp task in trajectory, amplitude, and direction but did not include a grasp. One of these, the device task, elicited reaches while holding a handle, and the other, the free-reach task, elicited reaches that did not require any specific hand use for task performance. The results demonstrate that coordinated whole-limb reaching movements are associated with large discharge modulations of RNm neurons predominantly when hand use is included. Therefore RNm neurons can at best only make a minor contribution to the control of reaching movements that lack hand use. We evaluated relations between the discharge of individual RNm neurons and electromyographic (EMG) activity of forelimb muscles during the reach-to-grasp task by comparing times of peak RNm discharge to times of peak EMG activity. The results are consistent with the view that RNm discharge may contribute to EMG activity of both distal and proximal muscles during reaching to grasp especially digit extensor and limb elevation muscles. Relations between the discharge of individual RNm neurons and movements of the metacarpi-phalangeal (MCP), wrist, elbow, and shoulder joints during individual trials of task performance were quantified by parametric correlation analyses on a subset of neurons studied during the reach-to-grasp and free-reach tasks. The results indicate that MCP extensions were consistently preceded by bursts of RNm discharge, and strong correlations were observed between parameters of discharge and the duration, velocity, and amplitude of corresponding MCP extensions. In contrast, relations between discharge and movements of proximal joints were poorly represented, and RNm discharge was not related to the speed of limb transport. Based on our data and those of others, we hypothesize that cerebellar output via RNm is specialized for controlling hand use and conclude that RNm may contribute to the control of hand preshaping during reaching to grasp by activating muscle synergies that produce the appropriate MCP extension at the appropriate phase of limb transport.

Combination gene therapy with adenoviral vector-mediated HSV-tk+GCV and IL-12 in an orthotopic mouse model for prostate cancer.

We previously demonstrated significant therapeutic activities associated with adenoviral vector-mediated Herpes Simplex Virus/thymidine kinase (AdHSV-tk) with ganciclovir (GCV) in situ gene therapy in the RM-1 orthotopic mouse prostate cancer model and interleukin-12 (AdmIL-12) in situ gene therapy in the RM-9 orthotopic mouse prostate model for prostate cancer. In both protocols, local cytotoxicity and activities against pre-established lung metastases were demonstrated. To test whether combined AdHSV-tk+GCV+IL-12 gene therapy would lead to enhanced therapeutic effects when compared to either treatment alone, we used RM-9 mouse prostate cancer cells in both orthotopic and pre-established lung metastases models of prostate cancer. Combined treatment with a single injection of optimal doses of AdHSV-tk+GCV or AdmIL-12 led to significantly increased suppression of orthotopic tumor growth. IL-12 gene therapy alone was more effective than AdHSV-tk+GCV in suppressing spontaneous lymph node metastases and pre-established lung metastases but combination gene therapy did not result in additional anti-metastatic activities. Combination gene therapy also did not achieve significantly better animal survival compared to AdHSV-tk+GCV or AdmIL-12 alone. Analysis of localized antitumor activities demonstrated that AdHSV-tk+GCV therapy induced higher levels of necrosis compared to AdmIL-12 or combination therapy. However, both treatments alone and combination therapy produced similar increases in apoptotic index. To address the possible mechanisms of locally co-operative cytotoxic activities, we analyzed the systemic natural killer (NK) response and the numbers of tumor-infiltrating immune cells using quantitative immunohistochemical analysis. AdHSV-tk+GCV therapy alone led to detectable increases in iNOS-positive cells, CD4+and CD8+T-cells and moderately increased numbers of F4/80 (macrophage selective)-positive cells within treated tumors. In contrast, AdmIL-12 elicited a highly robust pattern of tumor infiltration for all four of these immune cells that was in general mimicked by combination therapy. Further analysis of the accumulation of transforming growth factor-beta1 (TGF-beta1) immunohistochemical staining demonstrated that AdHSV-tk+GCV treatment, but not AdmIL-12 treatment, produced cancer cell-associated increases in this cytokine relative to control Ad-beta-gal injections. Interestingly, local injection with AdHSV-tk+GCV induced significant splenocyte-derived NK cell cytolytic activities with maximal response 7 days following treatment, whereas AdmIL-12 injection produced significantly higher NK activity with maximal response 2 days following injection. The combined treatment produced a higher systemic NK response over the 14-day treatment period. Depletion of NK cells in vivo demonstrated that this immunocyte subpopulation was responsible for early locally cytotoxic activities induced by AdHSV-tk+GCV but not AdmIL-12 and that NK activities were largely responsible for activities against pre-established metastases generated by both gene therapy protocols. Prostate Cancer and Prostatic Diseases (2001) 4, 44-55

Prostate cancer gene therapy: comparison of adenovirus-mediated expression of interleukin 12 with interleukin 12 plus B7-1 for in situ gene therapy and gene-modified, cell-based vaccines.

We have documented previously that adenovirus-mediated interleukin 12 (IL-12) gene therapy is effective for orthotopic tumor control and suppression of pre-established metastases in a preclinical prostate cancer model (Y. Nasu et al., Gene Ther., 6: 338-349, 1999). In this report, we directly compare the effectiveness of an adenovirus that expresses both IL-12 and the costimulatory molecule B7-1 (AdmIL12/B7) with one that expresses IL-12 alone (AdmIL-12) using the poorly immunogenic RM-9 orthotopic murine model of prostate cancer. We document AdmIL-12/B7-mediated secretion of IL-12 and increased surface expression of B7-1 in infected RM-9 tumor cells. A significant reduction in orthotopic tumor size and increased survival was demonstrated in mice treated with a single orthotopic injection of AdmIL-12/B7 compared with AdmIL-12 or controls. Six of 19 animals treated with AdmIL-12/B7 survived long term with apparent eradication of the primary tumor in contrast to one of 38 animals in the AdmIL-12-treated group. Orthotopic treatment of tumors with both vectors led to an infiltration of both CD4+ and CD8+ immunoreactive cells, with AdmIL-12/B7 treatment having a more prolonged infiltration of CD8+ cells. AdmIL-12/B7 was also more effective than AdmIL-12 or controls at suppression of pre-established metastases. We further developed a vaccine model based on s.c. injection of infected, irradiated RM-9 cells and found that both AdmIL-12 and AdmIL-12/B7 are effective at suppressing the development and growth of challenge orthotopic tumors using this protocol.

Effects of fiber composition and hindlimb unloading on the vasodilator properties of skeletal muscle arterioles.

It has been hypothesized that microgravity-induced orthostatic hypotension may result from an exaggerated vasodilatory responsiveness of arteries. The purpose of this study was to determine whether skeletal muscle arterioles exhibit enhanced vasodilation in rats after 2 wk of hindlimb unloading (HU). First-order arterioles isolated from soleus and white gastrocnemius muscles were tested in vitro for vasodilatory responses to isoproterenol (Iso), adenosine (Ado), and sodium nitroprusside (SNP). HU had no effect on responses induced by Iso but diminished maximal vasodilation to Ado and SNP in both muscles. In addition, vasodilatory responses in arterioles from control rats varied between muscle types. Maximal dilations induced by Iso (soleus: 42 +/- 6%; white gastrocnemius: 60 +/- 7%) and Ado (soleus: 51 +/- 8%; white gastrocnemius: 81 +/- 6%) were greater in arterioles from white gastrocnemius muscles. These data do not support the hypothesis that microgravity-induced orthostatic hypotension results from an enhanced vasodilatory responsiveness of skeletal muscle arterioles. Furthermore, the data support the concept that dilatory responsiveness of arterioles varies in muscle composed of different fiber types.

Structural and functional remodeling of skeletal muscle microvasculature is induced by simulated microgravity.

Hindlimb unloading of rats results in a diminished ability of skeletal muscle arterioles to constrict in vitro and elevate vascular resistance in vivo. The purpose of the present study was to determine whether alterations in the mechanical environment (i.e., reduced fluid pressure and blood flow) of the vasculature in hindlimb skeletal muscles from 2-wk hindlimb-unloaded (HU) rats induces a structural remodeling of arterial microvessels that may account for these observations. Transverse cross sections were used to determine media cross-sectional area (CSA), wall thickness, outer perimeter, number of media nuclei, and vessel luminal diameter of feed arteries and first-order (1A) arterioles from soleus and the superficial portion of gastrocnemius muscles. Endothelium-dependent dilation (ACh) was also determined. Media CSA of resistance arteries was diminished by hindlimb unloading as a result of decreased media thickness (gastrocnemius muscle) or reduced vessel diameter (soleus muscle). ACh-induced dilation was diminished by 2 wk of hindlimb unloading in soleus 1A arterioles, but not in gastrocnemius 1A arterioles. These results indicate that structural remodeling and functional adaptations of the arterial microvasculature occur in skeletal muscles of the HU rat; the data suggest that these alterations may be induced by reductions in transmural pressure (gastrocnemius muscle) and wall shear stress (soleus muscle).

Adenovirus-mediated interleukin-12 gene therapy for prostate cancer: suppression of orthotopic tumor growth and pre-established lung metastases in an orthotopic model.

Interleukin-12 (IL-12) can elicit potent antitumoral effects that involve the recruitment of specific immune effector cells. We investigated the efficacy of a single injection of a recombinant adenovirus expressing murine IL-12 (AdmIL-12) directly into orthotopic mouse prostate carcinomas generated from a poorly immunogenic cell line (RM-9) derived from the mouse prostate reconstitution system. Significant growth suppression (> 50% reduction of tumor weight) and increased mean survival time (23.4 to 28.9 days) were observed compared with controls. Suppression of pre-established lung metastases was also observed following the injection of AdmIL-12 into the orthotopic tumor. Cytolytic natural killer cell activity was markedly enhanced 1-2 days after virus injection. Immunohistochemical analysis showed significantly elevated intratumoral infiltration of CD4+ and CD8+ T cells 7 days after virus injection. However, splenocyte-derived cytotoxic T lymphocytes were not detected during the 14 days following treatment. Increased numbers of nitric oxide synthase-positive macrophages were seen in the AdmIL-12 treated group 7 days following injection. Systemic inhibition of natural killer cells with antiasialo-GM1 serum led to increased numbers of lung metastases in AdmIL-12-treated orthotopic tumors but did not affect local tumor growth. In this model system the antitumor effects of a single injection of adenovirus-mediated IL-12 appears to be based to a large extent on the activation of nitric oxide synthase in macrophages and possibly T cell activities, whereas the relatively early cytolytic activity of natural killer cells are largely but not exclusively responsible for the antimetastatic effects.

Elevated levels of circulating interleukin-6 and transforming growth factor-beta1 in patients with metastatic prostatic carcinoma.

PURPOSE: Specific cytokines have been found to be secreted by and influence the growth of prostate cancers in cell culture. Interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), granulocyte macrophage-colony stimulating factor (GM-CSF) and transforming growth factor-beta1 (TGF-beta1) have all been closely associated with prostate cancer. We analyzed the levels of these cytokines in the systemic circulation of patients with varying stages of prostate cancer compared to controls. MATERIALS AND METHODS: Serum IL-6, TNFalpha and GM-CSF were measured using commercially available enzyme linked immunosorbent assays in 5 groups of patients, including controls-19 men presenting to prostate cancer screening with normal digital rectal examination and serum prostate specific antigen (PSA) no greater than 2.0 ng./ml., stage pT2-19 with cancer confined to the prostate in the radical prostatectomy specimen, stage pT3-10 with extraprostatic extension and/or seminal vesicle involvement, stage N1-12 with lymph node metastases at pelvic lymph node dissection, and stage M1-9 with bone metastases. Platelet poor plasma TGF-beta1 was measured using a commercially available enzyme linked immunosorbent assay in controls and patients with stage M1 disease only because it was not available for patients with stages pT2, pT3 and N1 disease. No patient had a history of any other malignancy. All blood specimens were collected before surgery and/or androgen ablation. Statistical analysis was done with the Kruskal-Wallis analysis of variance. RESULTS: Serum IL-6 and platelet poor plasma TGF-beta1 were significantly elevated in patients with clinically evident metastases (p = 0.0008 and 0.0412, respectively) while serum GM-CSF and TNFalpha were not. IL-6 and TGF-beta1 correlated with increasing serum PSA (p = 0.0335 and 0.0386, respectively). GM-CSF did not correlate with PSA or age. In multivariate analysis TNFalpha correlated with age but not PSA. CONCLUSIONS: IL-6 and TGF-beta1 correlate with tumor burden as assessed by serum PSA or clinically evident metastases. Further research is needed to determine the response to androgen ablation as well as the source(s) and actions of these cytokines.

Organization of ascending pathways to the forelimb area of the dorsal accessory olive in the cat.

The purpose of these experiments was to define the topography of cuneate and spinal projections to the forelimb representation in the rostral dorsal accessory olive (rDAO). We were interested in determining whether the spinal and cuneate inputs constitute a homogeneous afferent source, and whether there is evidence that they serve different functional roles. We were also interested in determining whether the somatotopy of rDAO is the result of a point-to-point projection from its afferent sources, or whether the projection suggests a reorganization of afferents at the olive. Single unit recording was used to identify specific regions of rDAO, and the topography of inputs to the identified regions was determined by using wheat germ agglutinin-horseradish peroxidase (WGA-HRP) as a tracer. The results from retrograde tracing were confirmed by using WGA-HRP as an anterograde tracer from input sources. The cuneate and spinal neurons providing input to rDAO constitute two distinct neural populations. One consists of cells in the caudal cuneate nucleus and lamina VI of the rostral two cervical segments, the other consists of cells in the rostral cuneate nucleus. The cells in the caudal cuneate nucleus and the rostral cervical segments are large, multipolar neurons that form a single column of rDAO input cells. The column of cells projects to the contralateral rDAO in a topographic fashion with rostral regions of the column projecting to rostral rDAO, which contains cells that respond to somatosensory stimulation of the contralateral shoulder, trunk, and proximal forelimb. Caudal regions of the column project to caudal rDAO, which contains cells that respond to stimulation of the distal forelimb. Despite this topography, there is a large degree of overlap in the terminations from neighboring regions of the input column, indicating that a major reorganization occurs at the rDAO. The projection from the rostral cuneate nucleus arises from small neurons that project bilaterally to rDAO, and the input from the rostral cuneate nucleus lacks a clear topography. We propose that input from the cell column is responsible for the somatosensory sensitivity of rDAO neurons, whereas input from rostral cuneate is most likely modulatory, probably inhibitory, in nature.

Topography of recurrent inhibitory postsynaptic potentials between individual motoneurons in the cat.

1. The amplitude of recurrent inhibitory postsynaptic potentials (RIPSPs) was examined in pairs of lumbosacral motoneurons that were separated by a known distance and were identified by antidromic stimulation of muscle nerves. One motoneuron was stimulated by injecting depolarizing current pulses, and postsynaptic responses were recorded and averaged in the second motoneuron. Input resistance, rheobase, and conduction velocity were determined for many motoneurons. Most motoneurons innervated extensor muscles. 2. RIPSP values as large as -283 microV were recorded, but most were between -10 and -40 microV. RIPSPs from individual motoneurons of a pool are distributed to several heteronymous motor nuclei and have a range of amplitudes comparable with homonymous RIPSPs. 3. A specific spatial distribution of RIPSP amplitudes was found whereby the largest RIPSP amplitudes (> 40 microV) occurred in motoneurons located within +/- 1.4 mm of the stimulated motoneuron. A significant correlation was found between RIPSP amplitude and the distance between motoneurons for all motoneuron pairs. This correlation was also found within individual groups of motoneuron pairs that innervate the lateral gastrocnemius, medial gastrocnemius, anterior-middle biceps femoris, or soleus muscles. 4. The dependency of RIPSP amplitude on the motoneuron species, which is the particular muscle a motoneuron innervates, is less distinct than the dependency of RIPSP amplitude on topography. Pooling all motoneuron species of close motoneuron pairs indicated that RIPSPs measured in homonymous motoneuron pairs were greater in amplitude than RIPSPs measured in heteronymous pairs. In addition, homonymous RIPSPs of anterior middle biceps femoris or lateral gastrocnemius motoneurons were greater than heteronymous RIPSPs of those motoneurons in all heteronymous combinations. However, homonymous and heteronymous RIPSPs were not significantly different when heteronymous pairs were restricted to individual combinations of species. These findings indicate that RIPSP amplitudes within a set of motor nuclei interconnected by recurrent inhibition are dependent in some cases on the species of motoneurons, but this effect is less important than the effect of topography on RIPSP amplitude. 5. These results indicate that recurrent inhibition in motoneuron pools that innervate hindlimb extensor muscles has a strong topographic organization, such that the strongest recurrent inhibition is produced by each motoneuron in a restricted rostrocaudal zone that includes both homonymous and heteronymous motor nuclei. This suggests that recurrent inhibition is organized for the control of several motor nuclei engaged in common motor activity as well as regulation of activity within individual motor pools.

Spatial and temporal features of recurrent facilitation among motoneurons innervating synergistic muscles of the cat.

1. The temporal features and strength of recurrent facilitatory potentials were examined in pairs of lumbosacral motoneurons that were separated by a known distance and were identified by antidromic stimulation of muscle nerves. One motoneuron was stimulated by injecting depolarizing current pulses, and responses were recorded in the second motoneuron. The distance between motoneurons in pairs was also measured to assess the spatial distribution in strength of recurrent facilitation in motor pools. All motoneurons in these pairs innervated muscles that act as hip or ankle extensors. 2. Recurrent facilitatory potentials were found frequently among motoneurons innervating the hindlimb extensor muscles examined. Several categories of recurrent facilitatory responses were identified. One category was composed of facilitation responses that followed an inhibition response. A second category was composed of facilitation responses that were not preceded by a significant inhibition and consisted of a monophasic response. There was a considerable range of latencies in this category. 3. Responses in which recurrent facilitatory potentials were preceded by recurrent inhibitory postsynaptic potentials (RIPSPs) among close motoneuron pairs demonstrated an inverse correlation between the durations of the facilitatory and the inhibitory phases. In addition, the duration of inhibition responses without facilitation was longer on average, than the duration of inhibitory responses that were followed by facilitation. It was suggested that recurrent facilitation may restrict the time course of RIPSPs. 4. In contrast to the topographic distribution of RIPSPs described in the previous report, amplitudes of monophasic facilitations were directly correlated with the distance separating motoneurons in pairs, rather than inversely correlated as was the case for RIPSP amplitudes.(ABSTRACT TRUNCATED AT 250 WORDS)

Oral anticoagulation monitoring in a community pharmacy.

Efforts by pharmacists to become more involved in patient care move the profession beyond the traditional role of dispenser. These initiatives increase the professionalism of the pharmacist and carry the potential for monetary rewards. Monitoring oral anticoagulation therapy is an area in which pharmacists can use specialized drug knowledge and advances in technology to fulfill a special patient need in the community setting. This article has outlined factors that should be considered in the development of an oral anticoagulation therapy monitoring program. Pharmacists can apply these principles to their individual practice environments to determine whether such a program is feasible, practical, and profitable. Pharmacists interested in this type of program must then prepare themselves for the increased demands of documentation, quality assurance, and patient counseling. By implementing an anticoagulation service, pharmacists can improve patient outcomes and extend their practices into a new frontier of pharmaceutical care.

Spatial overlap of rubrospinal and corticospinal terminals with input to the inferior olive.

Somatosensory responses of cells in the dorsal accessory olive are suppressed following stimulation of the magnocellular red nucleus. Since the magnocellular red nucleus of the cat does not project directly to the dorsal accessory olive, the present experiments were designed to identify indirect pathways that might mediate suppression of olivary responsiveness. Wheat germ agglutinin-horseradish peroxidase was used to compare the location of magnocellular red nucleus terminals with the locations of cells providing input to the rostral dorsal accessory olive. Cells projecting to forelimb rostral dorsal accessory olive can be divided into two main groups: one group comprises a column of large cells located in the ventral caudal cuneate nucleus extending into lamina VI of C1 and C2, and a second group comprises smaller cells located in the ventral rostral cuneate nucleus. Terminations of fibers originating in the magnocellular red nucleus were found to target both groups of cells projecting to the dorsal accessory olive. Therefore, it is possible that the responsiveness of olivary cells is influenced via these terminations. Stimulation of sensorimotor cortex has also been shown to inhibit olivary responsiveness. Terminations from sensorimotor cortex target the same regions of cells that project to the dorsal accessory olive as those of the magnocellular red nucleus, and a similar, perhaps identical, anatomical substrate may serve to modulate olivary sensitivity by the two descending systems.