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T cells armed with anti-CD3 x anti-CD20 bispecific antibody enhance killing of CD20+ malignant B cells and bypass complement-mediated rituximab resistance in vitro.

OBJECTIVE: Resistance to rituximab, a chimeric monoclonal antibody that binds to CD20, is a major limitation for the successful treatment of patients with non-Hodgkin lymphoma and other CD20+ B-cell malignancies. To circumvent rituximab resistance in these patient populations, we have constructed a bispecific antibody (BiAb), anti-CD3 x anti-CD20 (CD20Bi), that combines rituximab targeting with non-major histocompatibility complex (non-MHC)-restricted cytotoxicity mediated by activated T cells (ATC). MATERIALS AND METHODS: Activated T cells were obtained from anti-CD3 activated peripheral blood mononuclear cells (PBMC) of normal donors or the leukapheresis products of patients by culturing in the presence of interleukin-2 for 6-14 days. After ATC expansion, the cells were armed with CD20Bi. Killing activity was evaluated by 51Cr-release assay. RESULTS: Arming ATC with as little as 5 ng CD20Bi/10(6) cells significantly increased cytotoxicity above unarmed ATC. CD20Bi-armed ATC (50 ng/10(6) cells) efficiently lysed CD20+ cell lines at E:T of 6.25-50, but not the nonhematologic, CD20- SK-BR-3 cell line. High levels of cytotoxicity mediated by CD20Bi-armed ATC (p < 0.05) could not be blocked by an 8000-fold excess of soluble rituximab. CD20Bi-armed ATC in the presence of complement killed ARH-77 cells, a rituximab-complement pathway-resistant multiple myeloma, significantly (p < 0.05) better than rituximab or unarmed ATC, suggesting that CD20Bi-armed ATC may be clinically effective for treatment of rituximab-resistant CD20+ hematologic malignancies. CONCLUSIONS: Our findings demonstrate that CD20Bi-armed ATC enhance cytotoxicity against CD20+ B-cell lines and circumvent complement-mediated rituximab resistance, providing a strong rationale for this immune-based strategy for the treatment of rituximab-refractory CD20+ B-cell malignancies.

Antibodies, Bispecific↗

Whole-arm translocations between chromosome 1 and acrocentric G chromosomes are associated with a poor prognosis for spermatogenesis: two new cases and review of the literature.

OBJECTIVE: To analyze unusual translocations involving a chromosome 1 whole arm and an acrocentric G chromosome p arm found in two men with azoospermia. DESIGN: Case report with review of the scientific literature. SETTING: Cytogenetics department. PATIENT(S): Two men with azoospermia and normal hormonal levels. INTERVENTIONS(S): Peripheral blood lymphocytes were obtained for karyotype, and metaphases were studied by standard GBG, RBG, and CBG banding procedures. MAIN OUTCOME MEASURE(S): Karyotype GBG, RBG, and CBG banding. RESULT(S): Karyotype revealed balanced translocation involving a chromosome 1 whole arm and an acrocentric G chromosome p arm: 46,XY,t(1;21)(q11;p13) (patient 1) and 46,XY,t(1;22)(q11;p11) (patient 2). CONCLUSION(S): With regard to published cases of whole-arm translocation of human chromosome 1 with an acrocentric p arm and a maternal origin of these abnormalities, we argue for an impairment of meiosis resulting in a high probability of quadrivalent-XY-body interaction. Male factor infertility might be due to two poor prognostic factors, first the involvement of human chromosome 1 (and its heterochromatic region) and second the involvement of an acrocentric chromosome p-arm breakpoint. This probable interaction between the pachytene quadrivalent and XY body might explain azoospermia.

Adult↗

Arm coordination symmetry and breathing effect in front crawl.

This study analysed the relationships among arm coordination symmetry, motor laterality and breathing laterality during a 100-m front crawl, as a function of expertise. Ten elite swimmers (G1), 10 mid-level swimmers (G2), and 8 non-expert swimmers (G3) composed three skill groups, which were distinguished by velocity, stroke rate, stroke length, breathing frequency (BF) and the mean number of strokes between two breaths - the stroke breath (SB) - over a 100-m front crawl. Four stroke phases were identified by video analysis (catch, pull, push and recovery) and the index of coordination (IdC) measured the lag time between the propulsive phases of the two arms. The three modes of coordination are catch-up (IdC<0%), opposition (IdC=0%) and superposition (IdC>0%). The IdC was established as the mean of IdC1 and IdC2, which measured the lag time between the propulsive phases of the left and right arms, respectively. The coordination symmetry was analysed by comparing IdC1 and IdC2, and the breathing effect was studied by distinguishing IdC1 (and IdC2) with and without breathing. Motor laterality was determined by an adaptation of the Edinburgh Handedness Inventory. Breathing laterality was determined by a questionnaire and observation during the 100-m trial. Most of the front crawl swimmers showed asymmetric arm coordination, with propulsive discontinuity on one side and propulsive superposition on the other. This asymmetry was most often related to breathing laterality (a preferential breathing side for a unilateral breathing pattern) and motor laterality (arm dominance), with different profiles noted. More than the breathing laterality itself, the breathing actions of the non-expert swimmers amplified their asymmetric coordination on the breathing side. Conversely, the elite swimmers, who had higher and more stable spatial-temporal parameters (velocity and stroke lengths), a high coordination value (IdC) and lower breathing frequency (BF), managed their race better than the less proficient swimmers and their asymmetric arm coordination was not disturbed by breathing actions. By determining the dominant arm and the preferential breathing side, the coach can obtain a swimmer profile that allows both coach and swimmer to better understand and respond to excessive coordination asymmetry.

Acceleration↗

Phase I study pilot arms of radiotherapy and carmustine with temozolomide for anaplastic astrocytoma (Radiation Therapy Oncology Group 9813): implications for studies testing initial treatment of brain tumors.

PURPOSE: To determine the safety and toxicity of carmustine (BCNU) and temozolomide (TMZ) with radiotherapy (RT) in newly diagnosed anaplastic astrocytoma. METHODS AND MATERIALS: Patients >18 years old with anaplastic astrocytoma, a Karnofsky performance status score of > or =60, and adequate pulmonary function were eligible. All patients provided informed consent. Standard RT started within 5 weeks of diagnosis. In both arms, 150 mg/m(2) of TMZ was given on Days 1-5 of RT. In Arm 1, 200 mg/m(2) of carmustine was given on Day 1 of RT. In Arm 2, 150 mg/m(2) of carmustine was given on Day 5 of RT. After RT, TMZ and carmustine were repeated for a total of six cycles. RESULTS: A total of 15 and 14 patients were enrolled in the two pilot arms. Because of hematologic and pulmonary toxicities, dose reductions by the second cycle of therapy occurred in >70% of the patients in Arm 1 and >50% in Arm 2 despite a reduction in the carmustine dose. CONCLUSION: The results of these pilot studies have implications for the design of studies testing the initial treatment of brain tumors. Because of the poor tolerance of the combination, the multicooperative group Phase III study consists of two randomized arms of single-agent carmustine vs. single-agent TMZ.

Antineoplastic Combined Chemotherapy Protocols↗

The MEPUC concept adapts the C-arm fluoroscope to image-guided surgery.

Image-guided surgery requires surgeons to be able to manipulate the imaging modality themselves and without delay. Intraoperative fluoroscopic imaging does not meet this requirement as the C-arm fluoroscope cannot be operated or positioned by the surgeons themselves. The Motorized Exact Positioning Unit for C-arm (MEPUC) concept aims to optimize the workflow of positioning the C-arm fluoroscope. The hardware component of the MEPUC equips the fluoroscope with electric stepping motors. The software component allows the surgeon to control the fluoroscope's movements. The study presented here showed that translational movements within the x-y plane are most frequently performed when positioning the C-arm fluoroscope. Furthermore, reproducing a former projection was found to be a frequent task during image-guided procedures. In our opinion, the MEPUC concept adapts the fluoroscope to image-guided surgery. The most important improvement being definition of a bidirectional data exchange between the surgeon and the C-arm fluoroscope: positioning data from the surgeon to the C-arm fluoroscope and-subsequently-image information from C-arm fluoroscope to the surgeon.

Femoral Fractures↗

Double-blind placebo-controlled randomised trial of vitamin E and pentoxifylline in patients with chronic arm lymphoedema and fibrosis after surgery and radiotherapy for breast cancer.

BACKGROUND AND PURPOSE: Treatment-induced arm lymphoedema is a common and distressing complication of curative surgery and radiotherapy for early breast cancer. A number of studies testing alpha-tocopherol (vitamin E) and pentoxifylline suggest evidence of clinical regression of superficial radiation-induced fibrosis but there is only very limited evidence from randomised trials. Arm lymphoedema after lymphatic radiotherapy and surgery has been used in the present study as a clinical system for testing these drugs in a double-blind placebo-controlled randomised phase II trial. PATIENTS AND METHODS: Sixty-eight eligible research volunteers with a minimum 20% increase in arm volume at a median 15.5 years (range 2-41) after axillary/supraclavicular radiotherapy (plus axillary surgery in 51/68 (75%) cases) were randomised to active drugs or placebo. All volunteers were given dl-alpha tocopheryl acetate 500 mg twice a day orally plus pentoxifylline 400 mg twice a day orally, or corresponding placebos, for 6 months. The primary endpoint was volume of the ipsilateral limb measured opto-electronically using a perometer and expressed as a percentage of the contralateral limb volume. RESULTS: At 12 months post-randomisation, there was no significant difference between treatment and control groups in terms of arm volume. Absolute change in arm volume at 12 months was 2.5% (95% CI -0.40 to 5.3) in the treatment group compared to 1.2% (95% CI -2.8 to 5.1) in the placebo group. The difference in mean volume change between randomisation groups at 12 months was not statistically significant (P = 0.6), -1.3% (95% CI -6.1 to 3.5), nor was there a significant difference in response at 6 months (P = 0.7), where mean change in arm volume from baseline in the treatment and placebo groups was -2.3% (95% CI -7.9 to 3.4) and -1.1% (95% CI -3.9 to 1.7), respectively. There were no significant differences between randomised groups in terms of secondary endpoints, including tissue induration (fibrosis) in the irradiated breast or chest wall, pectoral fold or supraclavicular fossa, change in photographic breast/chest wall appearance or patient self-assessment of function and Quality of Life at either 6 or 12 months. CONCLUSIONS: The study fails to demonstrate efficacy of dl-alpha tocopheryl acetate plus pentoxifylline in patients with arm lymphoedema following axillary surgery and lymphatic radiotherapy, nor does it suggest any benefits of these drugs in radiation-induced induration (fibrosis) in the breast, chest wall, pectoral fold, axilla or supraclavicular fossa.

Adult↗

Variation of rotation moment arms with hip flexion.

Excessive flexion and internal rotation of the hip is a common gait abnormality among individuals with cerebral palsy. The purpose of this study was to examine the influence of hip flexion on the rotational moment arms of the hip muscles. We hypothesized that flexion of the hip would increase internal rotation moment arms and decrease external rotation moment arms of the primary hip rotators. To test this hypothesis we measured rotational moment arms of the gluteus maximus (six compartments), gluteus medius (four compartments), gluteus minimus (three compartments) iliopsoas, piriformis, quadratus femoris, obturator internus, and obturator externus. Moment arms were measured at hip flexion angles of 0, 20, 45, 60, and 90 degrees in four cadavers. A three-dimensional computer model of the hip muscles was developed and compared to the experimental measurements. The experimental results and the computer model showed that the internal rotation moment arms of some muscles increase with flexion; the external rotation moment arms of other muscles decrease, and some muscles switch from external rotation to internal rotation as the hip is flexed. This trend toward internal rotation with hip flexion was apparent in 15 of the 18 muscle compartments we examined, suggesting that excessive hip flexion may exacerbate internal rotation of the hip. The gluteus maximus was found to have a large capacity for external rotation. Enhancing the activation of the gluteus maximus, a muscle that is frequently underactive in persons with cerebral palsy, may help correct excessive flexion and internal rotation of the hip.

Biomechanical Phenomena↗

In vivo moment arm determination using B-mode ultrasonography.

The tendon excursion of the tibialis anterior (TA) muscle was measured in vivo using B-mode ultrasonography in seven subjects under three force levels (0, 30 and 60% maximal voluntary contraction, MVC). For each force level, the TA moment arm (m) was determined by calculating the derivative of the tendon excursion relative to the ankle angle (a). A dynamometer controlled the ankle angle while force levels were monitored. The parametric model proposed by Miller and Dennis (1996), m = R sin(a + delta), where R is the largest moment arm and delta represents the offset angle of R from 90 degrees, was used in a least-squares fit of the relationship between moment arm and ankle angle. The R values at 0% MVC were significantly smaller than those at 30 and 60% MVC. The values of calculated moment arm at 0% MVC were not considered adequate estimates of the TA moment arm because of the possible confounding effect of the slackness of the relaxed muscle-tendon unit in more dorsiflexed positions. The moment arm values at 30 and 60% MVC were believed to provide reliable estimates of those of TA since the application of tension probably reduced the effects of the slackness of the muscle-tendon unit and tendon elongation on tendon excursion measurement at these force levels. Since the ultrasonographic technique is an in vivo application of the tendon excursion technique and therefore takes the functional meaning into consideration, it can yield more significant moment arms than other in vivo or cadaver techniques.

Adult↗

One-trial tolerance to the effects of chlordiazepoxide in the elevated plus-maze is not due to acquisition of a phobic avoidance of open arms during initial exposure.

A single exposure to the elevated plus-maze (EPM) test of anxiety reduces or abolishes the anxiolytic-like efficacy of benzodiazepines. This phenomenon called one-trial tolerance has been suggested to represent the acquisition of a phobic-like response to the open arms during trial 1. The present study was designed to examine the effects of chlordiazepoxide (5 mg/kg, ip) on the behaviour of rats in a conventional EPM apparatus after previous exposure to a four-open-arm EPM, a four-enclosed arm EPM or a conventional EPM, as well as in naive rats. Chlordiazepoxide had clear-cut anxiolytic-like effects (increased percentage of time spent on the open arms) in a traditional EPM in naive rats and in animals previously exposed to a four-open-arm EPM. However, it was ineffective in rats previously exposed to a traditional or a four-closed-arm EPM. Thus, the phenomenon of one-trial tolerance does not depend upon initial open-arm experience.

Analysis of Variance↗

A 5-arm maze enables parallel measures of sustained visuo-spatial attention and spatial working memory in mice.

A 5-arm maze has been developed to provide parallel tests of sustained visuo-spatial attention and spatial working memory in mice. C57Bl/6 mice were trained to select, either by immediate response (attention) or by delayed-matching response (working memory), one target arm among the five open arms. For attention testing, mice were first trained to acquire the basic task in which one randomly selected baited arm remained lit until a choice was made. Criterion of >80% correct with a response latency <5 s was attained in 52-56 trials. Following this, attention was tested by using trials wherein light signal durations of 2, 1 or 0.5 s were intermixed to vary attentional load. In the working memory test, mice were submitted to a forced visit to a randomly selected baited arm during a presentation phase. Following a variable retention interval (R.I.), mice were replaced into the maze and rewarded for choosing this arm. Criterion of >80% correct was attained in 35-40 trials and mice exhibited high levels of retention for R.I.s up to 4 h. Results validate the 5-arm maze for evaluation of both sustained visuo-spatial attention and spatial working memory in mice. Both the tasks are rapidly acquired and the 20% chance level provides high resolution for evaluating performance. This comparative strategy allows to dissociate attention and memory and to reveal deficits in these processes during ageing or in knockout strains. The high level of retention performance over R.I.s of 4 h enables studies using pharmacological treatments differentially affecting the acquisition, encoding, retention or retrieval phases of working memory. Furthermore, functional brain imaging studies may be used to identify neuronal networks which are differentially activated during these distinct phases.

Animals↗

Arm and trunk posture during work in relation to shoulder and neck pain and trapezius activity.

OBJECTIVE: To investigate work technique in relation to work-related shoulder and neck pain (SNP) and upper trapezius muscle activity. DESIGN: A matched pair, case-control field study of female employees with and without SNP. BACKGROUND: It has proved difficult to distinguish subjects with SNP from those without by vocational electromyographic recordings from the upper trapezius muscle. Other potential risk indicators include psychosocial factors and work technique. This study focuses on the latter. METHODS: Manual (14 pairs) and office workers (24 pairs) were recorded during a 30-min work period. Simultaneous recordings of upper trapezius activity by surface electromyography and arm and upper back postures by inclinometers were analysed. RESULTS: Cases and controls were not differentiated on the basis of arm elevation or of trunk posture in the sagittal plane. No significant correlations were found between variables averaging the muscle activity and the arm elevation over the recording period. Statistically significant correlations were, however, found between these variables when analysing recordings at high time resolution (0.2 s) and adjusting for the delay in arm elevation relative to the upper trapezius muscle activity (r = 0.43, manual group; r = 0.32, office group). CONCLUSIONS: Factors other than arm elevation probably contribute more significantly to the load in the upper trapezius muscle, and to the development of work-related SNP in work situations with moderate arm elevation. RELEVANCE: The study suggests that arm and trunk posture recordings are not a sensitive indicator of risk of shoulder and neck complaints in work with low to moderate biomechanical demands.

Journal Article↗

In vivo determination of the patella tendon and hamstrings moment arms in adult males using videofluoroscopy during submaximal knee extension and flexion.

OBJECTIVE: The determination of patella tendon and hamstrings moment arms. DESIGN: The moment-arms were determined using a videofluoroscopy imaging method. BACKGROUND: The determination of hamstrings and quadriceps moment arms is important for the examination of muscle and joint forces in biomechanical applications. METHODS: Ten males performed one knee extension-flexion movement at a very slow (non-constant) angular velocity in front of the image intensifier screen of a videofluoroscopic system. The image of a calibration phantom with 2 cm squares was also recorded. Thirty five calibration points with known coordinates were digitized for the establishment of the polynomial equations that determined the coordinates of any point in the calibration phantom from its corresponding video coordinates. Fourteen control points were digitized and the difference between the actual and predicted coordinates was measured. The patella tendon and hamstrings (biceps femoris) moment arms to the tibiofemoral contract point were calculated. RESULTS: The mean error in the digitizing of the control points using the image deformation method ranged from 0.182 mm to 0.267 mm. The mean patella tendon moment arm ranged from 36.91 (SD 3.2) mm to 42.63 (SD 4.5) mm. The hamstrings moment arm ranged from 23.93 (SD 2.59) to 28.25 (SD 3.04) mm. CONCLUSION: The patellar tendon and hamstring moment-arms were determined using a videofluoroscopy method with acceptable accuracy. These parameters can be used for the biomechanical analysis of knee joint movements in two dimensional applications.

Adult↗

Changes in the tibialis anterior tendon moment arm from rest to maximum isometric dorsiflexion: in vivo observations in man.

OBJECTIVE: In the present study, we examined the hypothesis that the tibialis anterior tendon moment arm increases during maximum isometric dorsiflexion as compared with rest. BACKGROUND: In musculoskeletal modelling applications, moment arms from passive muscles at rest are assumed representative of those measured during isometric muscle contraction. The validity of this assumption is questionable in musculotendon actuators enclosed by retinacular systems as in tibialis anterior. DESIGN AND METHODS: Sagittal-plane magnetic resonance images of the right ankle were taken in six subjects at rest and during maximum isometric dorsiflexion at six ankle angles between dorsiflexion and plantarflexion having the body placed in the supine position and the knee flexed at 90 degrees. Instant centres of rotation in the tibio-talar joint, tibialis anterior tendon action lines and moment arms were identified in the sagittal plane at ankle angles of -15 degrees, 0 degrees,+15 degrees and +30 degrees at rest and during maximum isometric dorsiflexion. RESULTS: At any given ankle angle, the tibialis anterior tendon moment arm during maximum isometric dorsiflexion increased by 0.9-1.5 cm (P<0.01) compared with rest. This was attributed to a displacement of both tibialis anterior tendon action line by 0.8-1.2 cm (P<0.01) and all instant centres of rotation by 0.3-0.4 cm (P<0. 01) distally in relation to their corresponding resting positions. CONCLUSIONS AND IMPLICATIONS: The assumption that the tibialis anterior tendon moment arm does not change from rest to maximum isometric dorsiflexion is invalid. Erroneous tendon forces, muscle stresses and joint moments by as much as 30% would be calculated using resting tibialis anterior tendon moment arms in the moment equilibrium equation around the ankle joint during maximum isometric dorsiflexion. RELEVANCE: A substantial increase in the tibialis anterior tendon moment arm occurs from rest to maximum isometric dorsiflexion. This needs to be taken into consideration when using planimetric musculoskeletal modelling for analysing maximal static ankle dorsiflexion loads.

Adult↗

[Impact and forecasting of hepatitis A immunization in French armed forces, 1990-2004].

BACKGROUND: Hepatitis A is a public health problem specially for migrants or travellers from industrialized countries with a low hepatitis A endemic level. French armed forces adopted an immunization strategy which first targeted overseas forces and subsequently was extended to all armed forces. In this work we studied the impact of this policy. METHODS: Epidemiological surveillance data from 1990 to 2004 was analyzed by Poisson regression and exponential models of decrease used to forecast future rates. RESULTS: From the 826 cases of hepatitis A reported during the study period, 266 (32.2%) occurred in overseas forces and 560 (67.8%) in forces stationed in France. Three periods could be identified in the decline of annual incidence: before 1994, with an average rate of 23.2 per 100,000; from 1994 to 1998: 10.2; and after 1998: 1.2 for all French armed forces. For overseas armed forces, the average rate was 117 per 100,000 before 1994 and 17.1 from 1994 to 1998 (p<0.001). For armed forces stationed in France, the average rate was 12.2 per 100,000 before 1998 and 0.9 after (p<0.001). For overseas armed forces, models clearly described the declining incidence subsequent to targeted immunization in 1995 and for armed forces stationed in France, the decline with generalized immunization starting in 1998. DISCUSSION: The impact of immunization against hepatitis A virus was significant both in an overseas population and in a population staying in France where the risk level can be considered low due to the low endemic rate in France. These results suggest that immunization should be proposed not only for travellers but also for the general population based on real knowledge of the situation and cost-effectiveness analyses.

Forecasting↗

Shoulder muscle moment arms during horizontal flexion and elevation.

The instantaneous muscle moment arms of 10 shoulder muscles including the three portions of the deltoid and the rotator cuff and scapulohumeral muscle groups during four specified glenohumeral motions were calculated. Moment arm values were derived from a plot of tendon excursion versus glenohumeral joint rotation angle during horizontal flexion along the 90 degrees elevation plane and elevation in the sagittal, scapular, and coronal planes. The deltoid had the largest moment arm in elevation. The anterior deltoid has a larger moment arm in the anterior planes, whereas the midportion is greater in the scapular and coronal planes. The muscles with the largest depressor (adductor) moment arms are the pectoralis major, latissimus dorsi, and teres major. Contrary to the findings of other investigators, the supraspinatus and infraspinatus have a smaller potential elevation torque in the scapular plane than has been previously reported. Furthermore the subscapularis may potentially be a more important elevator in the scapular plane than either the supraspinatus or infraspinatus, especially in the latter phases of motion. The pectoralis major has the largest horizontal flexion moment arm with the humerus elevated 90 degrees, whereas the posterior deltoid and infraspinatus have the largest horizontal extension moment arms in this plane.

Adult↗

Humanistic outcomes in the hypertension and COPD arms of a multicenter outcomes study.

OBJECTIVE: To evaluate the effects of pharmaceutical care on selected humanistic outcomes in patients with hypertension or chronic obstructive pulmonary disease (COPD). DESIGN: Clinic patients with hypertension or COPD were randomly assigned to a treatment group (pharmaceutical care) or a control group (traditional pharmacy care) over a six-month period. Clinical pharmacists and pharmacy residents conducted the protocols. There were 133 evaluable patients (63 treatment, 70 control) in the hypertension study arm and 98 evaluable patients (43 treatment, 55 control) in the COPD study arm. The Pharmaceutical Care Questionnaire evaluated patient satisfaction with care. Tests specific to the disease states assessed disease and disease management knowledge. Quality of life (QOL) was evaluated using the Health Status Questionnaire 2.0 (HSQ 2.0) in the COPD arm; in the hypertension arm, the Hypertension/Lipid TyPE Specification Form 5.1 was used. SETTING: Ambulatory care centers of 10 Department of Veterans Affairs (DVA) medical centers and 1 university medical center. INTERVENTIONS: Patient-centered pharmaceutical care model (employing standardized care) implemented by clinical pharmacy residents. MAIN OUTCOME MEASURES: Satisfaction with pharmaceutical care, disease and disease management knowledge, and QOL. RESULTS: Statistically significant differences in most satisfaction items were found, with treatment patients expressing greater satisfaction. Treatment groups in both arms strongly agreed that pharmacists helped them with confidence in use of their medication and understanding of their illness, gave complete explanations about their medications, made them feel that their care was a priority, and followed up on their questions and concerns. In the hypertension arm, treatment patients demonstrated significant increases in knowledge scores. Trends in QOL were positive for both hypertension groups, with a significant decrease found in number of treatment patients reporting problems with sexual function. In the COPD arm, improvement trends were significantly stronger for treatment patients. CONCLUSION: Although patients were not dissatisfied with traditional pharmacy care, they were more satisfied overall with the pharmaceutical care model.

Aged↗

Prenatal diagnosis and characterization of an unbalanced whole arm translocation resulting in monosomy for 18p.

Monosomy for the short arm of chromosome 18 is one of the most frequent autosomal deletions observed. While most cases result from terminal deletion of 18p, 16% of cases reported were as a result of an unbalanced whole arm translocation resulting in monosomy 18p. The origin and structure of these derivative chromosomes were reported in only a few cases. We report the prenatal diagnosis and characterization of a new case of monosomy 18p as a result of an unbalanced whole arm translocation. Amniocentesis was performed at 15 weeks of gestation on a 34-year-old woman initially referred for advanced maternal age. Holoprosencephaly was identified by ultrasound at the time of amniocentesis. Karyotype analysis showed an unbalanced whole arm translocation between the long arm of one chromosome 18 and the long arm of one chromosome 22, 45,XX,der(18;22)(q10;q10), in all metaphases. In effect, the fetus had monosomy for 18p. Parental karyotypes were normal, suggesting a de novo origin for the der(18;22). Fluorescence in situ hybridization (FISH) analysis was performed with alpha-satellite probes D18Z1 and D14Z1/D22Z1 to identify the origin of the centromere on the der(18;22). Signal was observed with both probes, indicating that the centromere was composed of alpha-satellite DNA from both constituent chromosomes. Genotyping of the fetus and her parents with chromosome 18p STS marker D18S391 showed only the paternal 187 bp allele was present in the fetus, indicating that it was the maternal chromosome 18 involved in the der(18;22). This case and previous reports show that de novo unbalanced whole arm translocations are more likely to retain alpha-satellite sequences from the two chromosomes involved.

Adult↗

Does a cognitive map guide choices in the radial-arm maze?

Fifteen rats performed in a standard radial-arm maze task (Experiment 1) and in a modified task with a set of forced choices and a 15-min retention interval prior to completion of the maze (Experiment 2). In addition to the standard measure of choice in the radial-arm maze, orientation toward arms was measured and considered to constitute go-no-go "microchoice" decisions. Rats investigated but rejected many arms. A model of choice was developed in which it was assumed that choice decisions about arms were made independently and that microchoices were not selectively guided toward baited arms. The model performed nearly as well as the rats. These results place important limitations on the theory that choice behavior in the radial-arm maze is guided by a cognitive map.

Animals↗