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Initiation of lung immunity: the afferent limb and the role of dendritic cells.

The lung is the largest epithelial surface in the body and constitutes a major portal of entry for microorganisms. Dendritic cells (DCs) are bone marrow-derived cells that populate the respiratory tract from the nasal mucosa to the lung pleura. DCs are dexterous cells playing a role in both the innate and the adaptive immune responses. DCs can respond to dangers in the lung by immediately generating protective cytokines that stimulate natural killer (NK) cells to produce cytokines and kill targets. Direct (by pathogen recognition receptors) and indirect (by inflammatory cytokines) recognition of the infectious agent can also trigger signaling pathways in the DCs that activate an integrated developmental program called maturation, which transforms DCs into efficient antigen-presenting cells (APCs) for naive T cell stimulation. Furthermore, DCs play a role in generating effector B cells in the lymph nodes draining the lung. This review focuses on how DCs sense the health of the lung and translate messages regarding the lung microenvironment to cells of the innate and adaptive immune response to initiate effector functions to clear an invading microorganism [T helper 1 (Th1) or Th2 response] or generate tolerance [T regulatory (Tr), anergy, or deletion] to inhaled antigen when no danger is sensed.

Journal Article↗

Serratus anterior free-tissue transfer: harvest-related morbidity in 34 consecutive cases and a review of the literature.

Donor-site morbidity in serratus anterior free-tissue transfers is investigated in 34 consecutive cases. Nineteen lower-extremity reconstructions and 15 facial reconstructions were retrospectively analyzed. office and hospital charts were reviewed, and patients were given a follow-up questionnaire. The mean operative time was 6.3 hr and the mean estimated blood loss was 441 cc. Transfusion was required in 24 percent of cases. The early complication rate was 21 percent consisting of 6 percent hematomas and 15 percent seromas. Scar appearance, pain, numbness, and shoulder strength and mobility were acceptable. Scapular winging was detectable in 3/9 patients examined, but symptomatic in only one. The number of muscle slips harvested or whether the graft was innervated did not significantly affect this rate. Half of the patients had returned to work or school. None attributed any work disability to their donor sites. They participated in many athletic activities, including those requiring upper extremity strength and dexterity. Previously reported series are discussed, and the morbidity of this donor site is compared with reported series of other free muscle flaps. The authors find this flap useful for facial reanimation and for soft-tissue coverage with minimal bulk. Low rates of operative, perioperative, and long-term morbidity are definite advantages.

Adolescent↗

Congenital hemiplegia in children at school age: assessment of hand function in the non-hemiplegic hand and correlation with MRI.

The aim of this study was to evaluate whether children with congenital hemiplegia show abnormal hand function on the non-hemiplegic side and whether this, if present, can be related to the type and extent of brain lesions on MRI. Twenty-two children with congenital hemiplegia of age ranging between 4.8 and 12.3 years, were assessed with a clinical and MRI assessment. Clinical assessment included a structured neurological examination, assessment of hand grips and the Movement Assessment Battery for Children which also includes one item assessing speed and accuracy in each hand. The results showed that 64% of the children studied showed some degree of functional impairment of the non-hemiplegic hand. Manual dexterity 1 from the Movement ABC was, in our experience, a more sensitive tool to detect minor functional abnormalities than the evaluation of hand grips. The severity of the impairment on the non-hemiplegic side was not significantly related to the severity of impairment in the hemiplegic hand (p > 0.05). In contrast, a significant association was found with the site of lesions as hand function in the non-hemiplegic hand was always normal in children with unilateral lesion and abnormal in the ones with bilateral parenchymal lesions (p < 0.05). Children with predominantly unilateral lesions but with bilateral ventricular dilatation or periventricular changes showed more variable results.

Brain↗

Potential use of autoinjector-packaged antidotes for treatment of pediatric nerve agent toxicity.

STUDY OBJECTIVE: We sought to determine the feasibility of discharging Mark 1 atropine and pralidoxime autoinjectors into small, sterile vials to facilitate the potential intramuscular injection of these antidotes, particularly pralidoxime, on a milligram per kilogram basis to small children. METHODS: Autoinjectors were swabbed with isopropyl alcohol and then discharged into emptied, sterile, plastic 10-mL vials. This was repeated with the investigator garbed in standard personal protective gloves and full face mask and hood. The autoinjector injection surfaces were cultured. RESULTS: The autoinjectors were easily discharged into the vials without need for practice or special dexterity, even when investigators were garbed in protective gear. A small core of rubber stopper might be injected into the vial, and thus, the vial contents need to be withdrawn through a filter needle before reinjection. The autoinjector injection surfaces were sterile after alcohol swabbing. CONCLUSION: Autoinjectors might be a readily available source of concentrated pralidoxime for potential intramuscular use in small children.

Antidotes↗

Quantitative assessment of psychomotor recovery after sedation and analgesia for outpatient EGD.

BACKGROUND: Sedation and analgesia are routinely used to improve patient tolerance for GI endoscopy. Currently, assessment of postprocedure recovery uses cardiovascular and respiratory parameters but not psychomotor function. The two aims of this study were to determine degree of psychomotor recovery after conscious sedation for endoscopy when patients meet established discharge criteria, and to identify a sensitive method of testing psychomotor recovery, and thereby provide meaningful predictions regarding the ability of patients to return to daily activities. METHODS: Outpatients undergoing elective EGD were recruited. Four psychometric tests were used to establish baseline psychomotor function before sedation and analgesia: Critical Tracking, Manual Dexterity, Multiple-Choice Reaction Time, and Letter Cancellation. Meperidine and midazolam were administered intravenously per standard nomogram. The tests were repeated immediately after the procedure and at 15-minute intervals until patients were deemed ready for discharge by recovery room personnel. Discharge criteria included an Aldrete discharge score of 10 and the ability to ambulate unhindered and carry on a simple conversation. Recovery personnel were blinded to psychometric test results. Psychomotor scores at discharge were compared with baseline scores to determine percent recovery. RESULTS: Thirty-one patients (12 men, 19 women; mean age 43 years, range 18-72 years) were enrolled. When Aldrete discharge criteria were met, the average psychomotor recovery was only 60% to 70% compared with baseline. At the time of discharge, average psychomotor recovery was 86.5% of baseline. Letter Cancellation and Multiple-Choice Reaction Time had the highest sensitivity in detecting depression of psychomotor function versus baseline, with mean recovery of, respectively, 64% and 63% (p < 0.0001). CONCLUSIONS: Psychomotor function remains significantly impaired when patients reach an Aldrete discharge score of 10. The Letter Cancellation test was most sensitive in detecting psychomotor impairment and recovery. Incorporating psychometric tests with current discharge criteria may identify patients who are better able to resume normal daily activities without supervision.

Adolescent↗

Testing surgical skills of obstetric and gynecologic residents in a bench laboratory setting: validity and reliability.

OBJECTIVE: Resident surgical skills are acquired mainly through observing and later performing procedures in the operating room. Evaluation of surgical skills has traditionally been done through subjective faculty evaluation, a technique that has poor reliability and unknown validity. Our goal was to develop specific surgical tasks, both laparoscopic and open abdominal, that could be objectively and reliably evaluated in a bench laboratory setting. STUDY DESIGN: The prospective development of a reliable and valid resident surgical skills test in a bench laboratory setting was our goal. A written test of surgical knowledge and 12 skills tests were administered to 36 residents. Laparoscopic bench tasks were simulated with the use of a box and camera with a video display. Six laparoscopic tasks were assessed, including placing pegs on a board, running the bowel simulation, and other tasks that involve hand-eye coordination and manual dexterity. Open abdominal skills simulated incision closure, suturing a vaginal cuff, knot tying, and using a tie on a passer. Residents were timed at each given station and were given a rating score by 2 examiners. RESULTS: Knowledge scores showed a significant improvement by residency level. Assessment of construct validity (the ability to discriminate among residency levels) demonstrated significant differences on the rating of overall performance and individual tasks by level (determined by 1-way analysis of variance). Interrater reliability (agreement between 2 raters) with the use of intraclass correlation was 0.79 for the total score. The cost to administer the bench laboratory test was less than $50 and required 30 hours of faculty time. CONCLUSION: The results of this study suggest that surgical bench laboratory tasks can assess residents' surgical skills with good reliability and validity on most tasks. Our previous study, which used an animal laboratory, was expensive, and the bench laboratory model may provide an alternative means to assess surgical skills.

Clinical Competence↗

Retrieval technique for fractured implant screws.

Fractured screws generally are challenging to remove. The technique described in this article involves the use of inexpensive instruments commonly found in dental offices. The force required to remove the broken screw is minimal provided that the screw threads have not been damaged previously. A high degree of manual dexterity is required, however, to prevent damage to the implant itself; thus, this may not be the procedure of choice for inexperienced practitioners.

Dental Abutments↗

Computer-enhanced "robotic" cardiac surgery: experience in 148 patients.

OBJECTIVE: A computer-enhanced instrumentation system was used in 148 patients to minimize access in cardiac surgical procedures. METHODS: The da Vinci telemanipulation system (Intuitive Surgical, Mountain View, Calif) provides a high-resolution 3-dimensional videoscopic image and allows remote, tremor-free, and scaled control of endoscopic surgical instruments with 6 degrees of freedom. By April 2000, the system had been used in 131 patients for coronary artery bypass grafting and 17 patients for mitral valve repair. In the coronary bypass group, the system was used in one of three ways: (1) to take down the internal thoracic artery followed by a minimally invasive direct coronary bypass procedure (n = 81); (2) to perform the anastomosis between the internal thoracic artery and the left anterior descending coronary artery in standard-sternotomy coronary bypass (n = 15); or (3) for total endoscopic coronary artery bypass grafting to anastomose the left internal thoracic artery to the left anterior descending on the arrested heart (n = 27) or the beating heart (n = 8). In 17 patients with nonischemic mitral valve insufficiency the mitral valve was repaired. Closed-chest cardiopulmonary bypass with cardioplegic arrest (Port-Access technique; Heartport, Inc, Redwood City, Calif) was used for arrested-heart total endoscopic coronary bypass and mitral valve repair. RESULTS: The da Vinci system allows for precise tissue handling and enables the endoscopic performance of cardiac surgical tasks that require a high degree of dexterity (coronary anastomosis, mitral valve repair). No technical mishaps have occurred. The internal thoracic artery was successfully taken down in 79 of 81 patients in the group undergoing minimally invasive coronary bypass and, after a steep learning curve, is currently performed in less than 40 minutes. The postoperative patency rate is 96.3%. Total endoscopic coronary bypass was completed in 22 of 27 cases with 95.4% patency as demonstrated by angiography at 3 months' follow-up. Closed-chest endoscopic beating-heart bypass grafting was successfully performed in 2 out of 8 patients with the use of a new endoscopic stabilizer. In the group having mitral valve repair, primary endoscopic computer-enhanced repair was successfully completed in 14 of 17 patients; three others had to be changed to a standard endoscopic technique, including 1 who required valve replacement. At 3 months' follow-up, 1 additional patient underwent early reoperation for recurrent mitral insufficiency. Overall early and late mortality in this cohort of 148 patients was 2.0% and was not related to the use of the system. CONCLUSION: In conclusion, computer-enhanced endoscopic cardiac surgery can be performed safely in selected patients. Internal thoracic artery takedown is now routinely performed with good results. Total endoscopic coronary bypass is feasible on the arrested heart but does not offer a major benefit over the minimally invasive direct approach because cardiopulmonary bypass is still required. The early clinical experience with closed-chest beating-heart bypass grafting outlines the limitations of this approach despite some procedural success.

Animals↗

Programmable motion and patterning of molecules on solid surfaces.

Adsorbed on a solid surface, a molecule can migrate and carry an electric dipole moment. A nonuniform electric field can direct the motion of the molecule. A collection of the same molecules may aggregate into a monolayer island on the solid surface. Place such molecules on a dielectric substrate surface, beneath which an array of electrodes is buried. By varying the voltages of the electrodes individually, it is possible to program molecular patterning, direct an island to move in a desired trajectory, or merge several islands into a larger one. The dexterity may lead to new technologies, such as reconfigurable molecular patterning and programmable molecular cars. This paper develops a phase field model to simulate the molecular motion and patterning under the combined actions of dipole moments, intermolecular forces, entropy, and electrodes.

Journal Article↗

Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson's disease.

We report that a low-calorie diet can lessen the severity of neurochemical deficits and motor dysfunction in a primate model of Parkinson's disease. Adult male rhesus monkeys were maintained for 6 months on a reduced-calorie diet [30% caloric restriction (CR)] or an ad libitum control diet after which they were subjected to treatment with a neurotoxin to produce a hemiparkinson condition. After neurotoxin treatment, CR monkeys exhibited significantly higher levels of locomotor activity compared with control monkeys as well as higher levels of dopamine (DA) and DA metabolites in the striatal region. Increased survival of DA neurons in the substantia nigra and improved manual dexterity were noted but did not reach statistical significance. Levels of glial cell line-derived neurotrophic factor, which is known to promote the survival of DA neurons, were increased significantly in the caudate nucleus of CR monkeys, suggesting a role for glial cell line-derived neurotrophic factor in the anti-Parkinson's disease effect of the low-calorie diet.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

A trap-and-release integrated microfluidic system for dynamic microarray applications.

Dynamic microarrays hold great promise for advancing research in proteomics, diagnostics and drug discovery. However, this potential has yet to be fully realized due to the lack of reliable multifunctional platforms to transport and immobilize particles, infuse reagents, observe the reaction, and retrieve selected particles. We achieved all these functions in a single integrated device through the combination of hydrodynamic and optical approaches. Hydrodynamic forces allow simultaneous transportation and immobilization of large number of particles, whereas optical-based microbubble technique for bead retrieval gives dexterity in handling individual particles without complicated circuitry. Based on the criterion derived in this paper, the device was designed, and fabricated using standard photolithography and soft lithography methods. We examined the dynamics of bubble formation and dissipation in the device, and parametric studies revealed that higher power settings at short intervals were more efficient than low power settings at longer intervals for bead retrieval. We also demonstrated the capabilities of our device and its potential as a tool for screening methods such as the "one-bead-one-compound" (OBOC) combinatorial library method. Although both approaches, hydrodynamic confinement and optical-based microbubbles, are presented in one device, they can also be separately used for other applications in microchip devices.

Journal Article↗

Modular organization of internal models of tools in the human cerebellum.

Human capabilities in manipulating many different tools with dexterity suggest modular neural organization at functional levels, but anatomical modularity underlying the capabilities has yet to be demonstrated. Although modularity in phylogenetically older parts of the cerebellum is well known, comparable modularity in the lateral cerebellum for cognitive functions remains unknown. We investigated these issues by functional MRI (fMRI) based on our previous findings of a cerebellar internal model of a tool. After subjects intensively learned to manipulate two novel tools (the rotated mouse whose cursor appeared at a rotated position, and the velocity mouse whose cursor velocity was proportional to the mouse position), they could easily switch between the two. The lateral and posterior cerebellar activities for the two different tools were spatially segregated, and their overlaps were <10%, even at low statistical thresholds. Activities of the rotated mouse were more anterior and lateral than the velocity mouse activities. These results were consistent with predictions by the MOdular Selection And Identification Controller (MOSAIC) model that multiple internal models compete to partition sensory-motor experiences and their outputs are linearly combined for a particular context.

Adult↗

Murine bone marrow cell line producing colony-stimulating factor.

A cell line (H-1) derived from the adherent layer of a 14-wk-old Dexter bone marrow culture has been maintained as cloned and uncloned lines through 21 passages at the time of these studies. These cell lines develop many fat droplets as they age and become confluent. The uncloned line produces increasing amounts of colony-stimulating activity as the cells become confluent. Feeder layers or supernatants from the nonconfluent or confluent fat-laden cells stimulate the formation of greater numbers of colonies derived from cultures of colony-forming units (CFU) than does medium from L cell culture containing colony-stimulating factor (CSF). Antibody to the CSF-containing medium from L cell culture neutralizes the colony-stimulating activity, thus showing immunologic similarity to a known molecular species that stimulates colony production in a CFU culture that produces granulocyte or macrophage populations, or both.

Adipose Tissue↗

The collagens of hydra provide insight into the evolution of metazoan extracellular matrices.

A collagen-based extracellular matrix is one defining feature of all Metazoa. The thick sheet-like extracellular matrix (mesoglia) of the diploblast, hydra, has characteristics of both a basement membrane and an interstitial matrix. Several genes associated with mesoglea have been cloned including a basement membrane and fibrillar collagen and an A and B chain of laminin. Here we report the characterization of a further three fibrillar collagen genes (Hcol2, Hcol3, and Hcol5) and the partial sequence of a collagen gene with a unique structural organization consisting of multiple von Willebrand factor A domains interspersed with interrupted collagenous triple helices (Hcol6) from Hydra vulgaris. Hcol2 and -5 have major collagenous domains of classical length ( approximately 1020 amino acid residues), whereas the equivalent domain in Hcol3 is shorter (969 residues). The N-propeptide of Hcol2 contains a whey acid protein four-cysteine repeat (WAP) domain, and the equivalent domain of Hcol3 contains two WAP and two von Willebrand factor A domains. Phylogenetic analyses reveal that the hydra fibrillar collagen genes form a distinct clade that appears related to the protostome/deuterostome A clade of fibrillar collagens. Data base searches reveal Hcol2, -5, and -6 are highly conserved in Hydra magnipapillata, which also provided preliminary evidence for the expression of a B-clade fibrillar collagen. All four of the H. vulgaris collagens are expressed specifically by the ectoderm. The expression pattern for Hcol2 is similar to that previously reported for Hcol1 (Deutzmann, R., Fowler, S., Zhang, X., Boone, K., Dexter, S., Boot-Handford, R. P., Rachel, R., and Sarras, M. P., Jr. (2000) Development 127, 4669-4680) but distinct from the pattern shared by Hcol3 and Hcol5. The characterization of multiple collagen genes in relatively simple diploblastic organisms provides new insights into the molecular evolution of collagens and the origins of the collagen-based extracellular matrix found throughout the multicellular animal kingdom.

Animals↗

Neuropsychological functioning among heart transplant candidates: a case control study.

Neuropsychological performance was examined among a group of patients with end-stage heart disease undergoing routine evaluation for transplantation using a matched case-control design. Heart transplant candidates and controls were matched case by case for gender, race, education and age range. In order to match all 44 controls, a clinical series of 303 heart transplant candidates evaluated between October 1995 through March 1998 were considered. Although not specifically matched on variables of estimated IQ and socioeconomic status, statistical analysis showed no group differences on these variables. A separate analysis of variance on each neuropsychological test indicated that the heart transplant candidates performed significantly worse than controls on tasks of fine motor speed and dexterity (i.e., Grooved Peg Board), psychomotor speed and mental flexibility (i.e., Trail Making Test, Part B), and abstract reasoning and problem solving ability (i.e., Shipley Institute of Living Scale-Abstraction subtest). Implications of the results and future directions are discussed.

Adult↗

Intraindividual variability in physical and emotional functioning: comparison of adults with traumatic brain injuries and healthy adults.

Recent research has shown that individuals with certain neurological conditions demonstrate greater intraindividual variability on cognitive tasks compared to healthy controls. The present study investigated intraindividual variability in the domains of physical functioning and affect/stress in three groups: adults with mild head injuries, adults with moderate/severe head injuries, and healthy adults. Participants were assessed on 10 occasions and results indicated that (a) individuals with head injuries demonstrated greater variability in dominant finger dexterity and right grip strength than the healthy controls; (b) increased variability tended to be associated with poorer performance/report both within and across tasks; and (c) increased variability on one task was associated with increased variability on other tasks. The findings suggest that increased variability in physical function, as well as cognitive function, represents an indicator of neurological compromise.

Adolescent↗

Behavioral Dyscontrol Scale deficits among traumatic brain injury patients, part II: Comparison to other measures of executive functioning.

The clinical utility of the Behavioral Dyscontrol Scale (BDS) was compared to that of verbal fluency, the Trail Making Test, and the Stroop Color-Word Test, as well as measures of processing speed/cognitive efficiency and manual dexterity. The ability of these measures to classify 49 TBI patients into frontal versus nonfrontal and mild to moderate versus severe groups was examined. The results showed that the Fluid Intelligence Factor of the BDS improved classifications above and beyond traditional executive measures, but was particularly successful at classifying patients who sustained mild injuries. In contrast, traditional executive instruments were successful at lesion location classifications only among the patients with severe injuries. Severity classifications were successful both for traditional measures of processing speed/cognitive efficiency and for the Motor Programming Factor of the BDS, but only among patients with nonfrontal injuries. These results demonstrate that severity of injury may be an important moderator of tests' sensitivity to frontal lobe involvement.

Adult↗

The subcortical dementia of Huntington's disease.

An effect size analysis incorporating meta-analytic principles was used to review neuropsychological findings in patients with Huntington's disease (HD). Studies dating back to 1980 were gathered and the neuropsychological test results from a total of 760 patients with HD, and 943 healthy controls were synthesized using effect size analyses. The results indicate that patients with HD are most deficient on tests of delayed recall, followed by performance on measures of memory acquisition, cognitive flexibility and abstraction, manual dexterity, attention/concentration, performance skill, and, finally, verbal skill. However, patients with HD display core deficits in fronto-subcortical circuits that give rise to a multitude of cognitive deficits. A rank-order list of specific neuropsychological tasks and test variables in order of sensitivity to HD is also provided to aid in the interpretation of the quantitative results.

Adult↗