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Approach to leg edema of unclear etiology.

A common challenge for primary care physicians is to determine the cause and find an effective treatment for leg edema of unclear etiology. We were unable to find existing practice guidelines that address this problem in a comprehensive manner. This article provides clinically oriented recommendations for the management of leg edema in adults. We searched on-line resources, textbooks, and MEDLINE (using the MeSH term, "edema") to find clinically relevant articles on leg edema. We then expanded the search by reviewing articles cited in the initial sources. Our goal was to write a brief, focused review that would answer questions about the management of leg edema. We organized the information to make it rapidly accessible to busy clinicians. The most common cause of leg edema in older adults is venous insufficiency. The most common cause in women between menarche and menopause is idiopathic edema, formerly known as "cyclic" edema. A common but under-recognized cause of edema is pulmonary hypertension, which is often associated with sleep apnea. Venous insufficiency is treated with leg elevation, compressive stockings, and sometimes diuretics. The initial treatment of idiopathic edema is spironolactone. Patients who have findings consistent with sleep apnea, such as daytime somnolence, loud [corrected] snoring, or neck circumference >17 inches, should be evaluated for pulmonary hypertension with an echocardiogram. If time is limited, the physician must decide whether the evaluation can be delayed until a later appointment (eg, an asymptomatic patient with chronic bilateral edema) or must be completed at the current visit (eg, a patient with dyspnea or a patient with acute edema [<72 hours]). If the evaluation should be conducted at the current visit, the algorithm shown in Figure 1 could be used as a guide. If the full evaluation could wait for a subsequent visit, the patient should be examined briefly to rule out an obvious systemic cause and basic laboratory tests should be ordered for later review (complete blood count, urinalysis, electrolytes, creatinine, blood sugar, thyroid stimulating hormone, and albumin).

Algorithms↗

Management of increased intracranial pressure in the critically ill child with an acute neurological injury.

Increased intracranial pressure reflects the presence of mass effect in the brain and is associated with a poor outcome in children with acute neurological injury. If sustained, it has a negative effect on cerebral blood flow and cerebral perfusion pressure, can cause direct compression of vital cerebral structures, and can lead to herniation. The management of the patient with increased intracranial pressure involves the maintenance of an adequate cerebral perfusion pressure, prevention of intracranial hypertension, and optimization of oxygen delivery. This article reviews the neurological assessment, pathophysiology, and management of increased intracranial pressure in the critically ill child who has sustained an acute neurological injury.

Acute Disease↗

Positron emission mammography-guided breast biopsy.

UNLABELLED: Positron emission mammography (PEM) is a technique to obtain planar images of the breast for detection of potentially cancerous, radiotracer-avid tumors. To increase the diagnostic accuracy of this method, use of minimally invasive methods (e.g., core biopsy) may be desirable for obtaining tissue samples from lesions detected with PEM. The purpose of this study was to test the capabilities of a novel method for performing PEM-guided stereotactic breast biopsies. METHODS: The PEM system consisted of 2 square (10 x 10 cm) arrays of discrete scintillator crystals. The detectors were mounted on a stereotactic biopsy table. The stereotactic technique used 2 PEM images acquired at +/-15 degrees and a new trigonometric algorithm. The accuracy and precision of the guidance method was tested by placement of small point sources of (18)F at known locations within the field of view of the imager. The calculated positions of the sources were compared with the known locations. In addition, simulated stereotactic biopsies of a breast phantom consisting of a 10-mm-diameter gelatin sphere containing a concentration of (18)F-FDG consistent with that reported for breast cancer were performed. The simulated lesion was embedded in a 4-cm-thick slab of gelatin containing a commonly reported concentration of FDG, simulating a compressed breast (target-to-background ratio, approximately 8.5:1). An anthropomorphic torso phantom was used to simulate tracer uptake in the organs of a patient 1 h after a 370-MBq injection of FDG. Five trials of the biopsy procedure were performed to assess repeatability. Finally, a method for verifying needle positioning was tested. RESULTS: The positions of the point sources were successfully calculated to within 0.6 mm of their true positions with a mean error of +/-0.4 mm. The biopsy procedures, including the method for verification of needle position, were successful in all 5 trials in acquiring samples from the simulated lesions. CONCLUSION: The success of this new technique shows its potential for guiding the biopsy of breast lesions optimally detected with PEM.

Biopsy, Needle↗

A rapid signal processing technique to remove the effect of dispersion from guided wave signals.

Guided acoustic and ultrasonic waves have been utilized in various manners for non-destructive evaluation and testing. If a guided wave mode is dispersive, a pulse of energy will spread out in space and time as it propagates. For a long-range guided wave inspection application, this constrains the choice of operating point to regions on the dispersion curves where dispersion effects are small. A signal processing technique is presented that enables this constraint on operating point to be relaxed. The technique makes use of a priori knowledge of the dispersion characteristics of a guided wave mode to map signals from the time to distance domains. In the mapping process, dispersed signals are compressed to their original shape. The theoretical basis of the technique is described and an efficient numerical implementation is presented. The robustness of the technique to inaccuracies in the dispersion data is also addressed. The application of the technique to experimental data is shown and the resulting improvement in spatial resolution is demonstrated. The implications of using dispersion compensation in practical systems are briefly discussed.

Algorithms↗

Contemporary endovascular treatment for disease of the superficial femoral and popliteal arteries: an integrated device-based strategy.

Endovascular therapy for disease of the superficial femoral artery (SFA) and the popliteal artery remains controversial. Percutaneous treatment of this arterial segment presents a particular technical challenge, as the extent of disease varies from short, focal, and stenotic to long, diffuse, and occluded lesions. Over the last 2 decades, multiple therapies have been evaluated, including simple balloon angioplasty, directional atherectomy, stenting (both balloon-expandable and self-expanding), and more recently, intra-arterial radiation, laser, and cryotherapy. Regardless of which modality is used, however, endovascular therapy as a revascularization strategy has the potential to improve symptoms and quality of life and, in selected patients, to avoid limb amputation. While percutaneous endovascular treatment has been historically associated with high procedural success and favorable short and intermediate-term patency rates, long-term clinical results have proven disappointing. Conventional balloon angioplasty is limited by elastic recoil, dissection, and restenosis. Balloon-expandable stents (particularly in the distal SFA) are associated with late stent deformation and mechanical compression, with resultant late clinical failure. Newer self-expanding stents have shown improved initial results but have been limited by late mechanical fatigue and associated restenosis. With the development of several newer endovascular techniques in recent years, the possibilities for treating this condition have increased dramatically. Currently, no long-term comparative data exist regarding the role of these alternative technologies. This article summarizes and compares important data about new endovascular options for intervention therapy in SFA and popliteal disease. In addition, based on this analysis, we propose a contemporary treatment strategy, integrating older and newer technologies into a real-world algorithm.

Algorithms↗

Preoperative simulation for microvascular decompression in patients with idiopathic trigeminal neuralgia: visualization with three-dimensional magnetic resonance cisternogram and angiogram fusion imaging.

OBJECTIVE: Precise assessment of the complex nerve-vessel relationship at the root entry zone of the trigeminal nerve is useful for planning microvascular decompression in patients with idiopathic trigeminal neuralgia. We have applied a fusion imaging technique of three-dimensional (3-D) magnetic resonance cisternography and co-registered 3-D magnetic resonance angiography (MRA) that allows virtual reality for the preoperative simulation of the neurovascular conflict at the trigeminal nerve root entry zone. METHODS: Fusion images of 3-D magnetic resonance cisternograms and angiograms were reconstructed by a perspective volume-rendering algorithm from the volumetric data sets of magnetic resonance cisternography, obtained by a T2-weighted 3-D fast spin echo sequence, and co-registered MRA, by a 3-D time-of-flight sequence. Consecutive series of 12 patients with idiopathic trigeminal neuralgia were studied with fusion 3-D magnetic resonance cisternogram and MRA in the preoperative assessment for the microvascular decompression of the affected trigeminal nerve. RESULTS: The complex anatomical relationship of the offending vessels to the trigeminal nerve root entry zone was depicted on the fusion 3-D magnetic resonance cisternogram and MRA. The presence of offending vessels and compressive site of neurovascular conflict was assessed from the various viewpoints within the cistern and was presumed by the preoperative simulation through the surgical access (surgeon's-eye view). The blinded surgical trajectory was discerned by the virtual image through the opposite direction projected from above (bird's-eye view). The 3-D visualization of the nerve-vessel relationship with fusion images was consistent with the intraoperative trajectory and findings. CONCLUSION: Fusion imaging of 3-D magnetic resonance cisternogram and MRA may prove a useful adjunct for the diagnosis and decision-making process to execute the microvascular decompression in patients with idiopathic trigeminal neuralgia.

Adult↗

Treatment of recurrent metatarsalgia by neuroma resection and muscle implantation: case report and proposed algorithm of management for Morton's "neuroma".

This report describes the theoretical basis for an approach to treating a recurrent Morton's "neuroma." The recurrence, being a true, classic neuroma, is treated by a technique validated in the treatment of the upper extremity painful neuroma: neuroma resection and muscle implantation. A plantar approach, implanting into the deep layer of intrinsics, was used. The three year success of this technique in a long-distance runner is reported.

Adolescent↗

Design of salbutamol EOP tablets from pharmacokinetics parameters.

Salbutamol elementary osmotic pump (EOP) tablets were developed, and fundamental variables affecting their release characteristics were evaluated. The effects of film thickness and compression force on drug release from the tablets containing fixed amount of sodium chloride used as osmogent were evaluated. The core tablets were directly compressed at four compression forces and coated with 3% wt/vol cellulose acetate in acetone to levels of 2%, 3%, and 4% wt/wt. Coated tablets were drilled with CO2 laser beam to form drug delivery orifice of approximately 400 microm in diameter. The drug release was found to follow zero order fashion. The release rate decreased with the increased film thickness and was not affected by the compression force or porosity. The tablets coated to 3% and 4% levels exhibited the release rates within the range calculated from pharmacokinetic data. To illustrate the effect of osmogent content, the tablets were prepared at four osmogent levels and compressed at a constant compression force. The core tablets were coated to a level of 3% wt/wt. The release rate was initially increased with osmogent content and then decreased. At higher osmogent contents, the drug fraction in soluble component was decreased and resulted in the reduction of drug release. In conclusion, film thickness and osmogents played important roles in drug release from EOP tablets.

Albuterol↗

Fracturing rigid materials.

We propose a novel approach to fracturing (and denting) brittle materials. To avoid the computational burden imposed by the stringent time step restrictions of explicit methods or with solving nonlinear systems of equations for implicit methods, we treat the material as a fully rigid body in the limit of infinite stiffness. In addition to a triangulated surface mesh and level set volume for collisions, each rigid body is outfitted with a tetrahedral mesh upon which finite element analysis can be carried out to provide a stress map for fracture criteria. We demonstrate that the commonly used stress criteria can lead to arbitrary fracture (especially for stiff materials) and instead propose the notion of a time averaged stress directly into the FEM analysis. When objects fracture, the virtual node algorithm provides new triangle and tetrahedral meshes in a straightforward and robust fashion. Although each new rigid body can be rasterized to obtain a new level set, small shards can be difficult to accurately resolve. Therefore, we propose a novel collision handling technique for treating both rigid bodies and rigid body thin shells represented by only a triangle mesh.

Compressive Strength↗

[Tuberculous spondylodiskitis (Pott's disease): Experience in a general hospital].

BACKGROUND: Pott's disease (PD) is an uncommon extra-pulmonary form of tuberculosis. Dissimilar data about location, diagnosis and treatment from various hospitals and different countries are reported. PATIENTS AND METHOD: We present our experience with Pott's disease at our institution between January 1993 to December 1999, retrospectively, based on clinical bacteriological and pathological research. We found the medical records of 14 patients diagnosed as having PD at our hospital. The following information was obtained: age, sex, symptoms and sings at presentation, PPD tuberculin skin test, imaging techniques, mycobacterium cultures and smear, histopathologic study, treatment and clinical outcome. RESULTS: The number of microbiological diagnosed tuberculosis during the study period was of 1,400 (4 cases per 1,000 admissions). From them, 1,047 cases (74.8%) were pulmonary and 353 cases (25.2%) extra-pulmonary. We found the medical records of 14 patients diagnosed as having PD at our hospital. There was a diagnostic delay between 2 and 720 days. In 5 cases, cultures were positive (1.4% extra-pulmonary). The following information was obtained: age, sex, symptoms and signs at presentation, PPD tuberculin skin test, imaging techniques, mycobacterium cultures and smear, histopathologic study, treatment and clinical outcome. The mean age of the patients was 58 years. Pain and dorsal location were more frequent (8/14). In 6 cases, tuberculosis was diagnosed at other sites. Tuberculin skin test was positive in 7 ases (50%). The diagnosis was confirmed by positive cultures from biopsies in 5 from 8 cases performed and the histology was compatible in 8 from 11 cases performed. Diskitis was presented in 10 cases, soft tissue abscess in 9 cases (psoas abscess in 2); epidural compression in 9 cases and surgery was necessary in 9 cases (diagnostic in 3). CONCLUSIONS: Pott's disease is a rare entity even among HIV-patients in whom extrapulmonar disease has increased. Dorsal location, diskitis and advanced forms of the disease that deserve surgical treatment are frequent.

Aged↗

Three-dimensional modeling of the effects of parathyroid hormone on bone distribution in lumbar vertebrae of ovariectomized cynomolgus macaques.

Biomechanical and quantitative computed tomography (QCT) analyses showed beneficial effects of parathyroid hormone (PTH (1-34)) on lumbar vertebrae from ovariectomized monkeys, even after withdrawal of treatment for 6 months. Adult cynomolgus monkeys were randomized, ovariectomized (except for sham ovariectomy controls), and treated subcutaneously with vehicle (OVX) or 5 micrograms/kg per day PTH (1-34) (PTH5) for 18 months. An additional group was treated subcutaneously with 5 micrograms/kg per day PTH (1-34) (PTH5W) for 12 months and then switched to vehicle for the remaining 6 months. Lumbar vertebrae were excised at necropsy, and L5 were serially scanned by QCT, using 70 x 70 x 500 microns voxels. PTH increased volumetric bone mineral density (BMD, mg/cm3) and bone mineral content (BMC, mg) for both PTH5 and PTH5W compared with OVX and Sham without inducing hypermineralization, without stimulating periosteal expansion, and without significant constriction of the neural canal. BMD values for the voxels were then averaged to create nearly isotropic voxels of 490 x 490 x 500 microns. Serial scans were stacked and a triangular surface mesh generated for each bone, using a 'marching cubes' algorithm. A smoothed version of each surface mesh was used to generate a tetrahedral element for three-dimensional finite element modeling. An isotropic Young's modulus for each tetrahedral element was calculated as a function of the original voxel BMDs. Linear elastic stress analysis was then performed for each finite element model in which a distributed load of 100 newtons (N) was applied to the top surface of the centrum, perpendicular to the bottom surface with the bottom surface constrained in the direction of loading. Analysis of the effective strain showed considerable reduction in vertebral strain for both PTH5 and PTH5W, compared with OVX. Compression testing of the adjacent L3 and L4 confirmed that vertebral strength and stiffness for PTH5 and PTH5W were significantly greater than for OVX. Histogram and QCT analyses showed PTH conversion of low-density bone (trabecular bone) into medium-density bone (more and thicker trabeculae) by stimulating bone apposition. PTH withdrawal induced conversion of medium-density into low-density and high-density bone with the latter higher than in OVX. These data show that even transient PTH treatment improves vertebral architecture and bone quality to reduce the likelihood of fracture, and that transient treatment is better than no PTH treatment at all.

Animals↗

Relationship between the calibre of carotid arteries and the configuration of the circle of Willis in healthy older persons.

AIM: Recent papers have pointed out that the severity of brain damage that follows carotid occlusion is largely influenced by the state of integrity and functionality of the circle of Willis. In spite of this, duplex scanning investigation of carotid arteries has traditionally been focused on the assessment of the degree of the stenosis, while other features, such as the calibre of carotid arteries and their possible asymmetry, have often been neglected. The aim of the present paper was to verify, in a cohort of older persons, whether, based on the calibre of internal carotid arteries and their possible asymmetry, abnormalities of the circle of Willis can be predicted. Such information could be used to identify high risk patients in whom the status of the circle of Willis should be investigated by MR angiography. METHODS: We studied 118 healthy older persons with both duplex scanning investigation of carotid arteries and MR angiography of the circle of Willis. RESULTS: We found that the finding of abnormal internal carotid artery calibres was always associated with abnormalities of the precommunicating segments either of the anterior or of the posterior cerebral arteries. Abnormalities of communicating arteries did not affect the calibre of internal carotid arteries, but abnormalities of anterior communicating arteries could always be detected by contralateral common carotid artery compression manoeuvres. CONCLUSION: In conclusion our findings show that, in healthy older persons, duplex scanning investigation of carotid arteries may provide useful information about the integrity and functionality of the circle of Willis. Future studies should confirm our findings in patients with atherosclerotic lesions of internal carotid arteries.

Aged↗

Loads in the spinal structures during lifting: development of a three-dimensional comprehensive biomechanical model.

Epidemiological studies have shown that loads imposed on the human spine during daily living play a significant role in the onset of low back pain. The loads applied to the lumbar spine are shared by a number of structures: muscles; posterior elements, including facets and ligaments; and the disc of a ligamentous motion segment. In vivo, it is not practical to determine forces in these structures using experimental techniques. Biomechanical models, based on an optimization technique of electromyographic activities of the trunk muscles, have been proposed to predict forces in the load transmitting structures. The mathematical models reported in the literature are based on information collected from a wide variety of sources, of which the subject that takes part in the experiment is only one. The present study describes techniques developed in our laboratory to collect from the subjects themselves all the data needed for the formulation of a biomechanical model. The results demonstrated that back lifting with 0 N (no load), 90 N, and 180 N in the hands created maximum external flexion moments respectively of 109.6 Nm, 137.9 Nm, and 161.7 Nm, at the L3-4 disc level. The corresponding external axial compression forces on the disc were 469.5 N, 511.8 N, and 601.5 N. The predicted disc compression varied from 3.4 to 5.0 times the body weight. In comparison to the static lifting mode, the dynamic lifting task caused an increase in the disc compression force ranging from 15.8% to 39.4% depending on the load being lifted (e.g., 3256 N for the dynamic mode vs. 2516 N for the static mode when the subject lifted 90 N). The salient features of the entire protocol developed by the authors and the need for further improvements are also presented.

Adult↗

Surgery for upper cervical spine instabilities in children.

BACKGROUND: Due to the paucity of existing data with regard to surgical fusion of upper cervical spine instabilities in the paediatric population, we feel encouraged to report the results of our own series to provide additional information to the available body of literature. METHODS: Since 1991 N = 11 children underwent a total of N = 13 surgical procedures for N = 8 posttraumatic, N = 2 congenital and N = 1 postinfectious instabilities at a mean age of 10 years (range: 3-16 years). Transoral odontectomies, ventral odontoid screw-fixations, dorsal wiring or -clamping and transarticular screw-fixations were performed for stabilization and iliac crest bone graft used for fusion. Pain scores, neurological status and radiological results were documented at regular intervals (mean follow-up: 25.4 months). RESULTS: Stable fusion was achieved in all patients as documented on flexion/extension films and tomographies. At the latest follow-up N = 2 patients had improved and N = 9 were equal to their preoperative neurological status. Pain scores were improved in N = 9 patients. N = 2 children developed "bystander-fusion" after C0/2 wiring. N = 3 peri-operative complications occurred as transient neurological deteriorations. In one case this resulted from the resection of a lower brainstem tumour prior to the stabilization procedure. One was attributed to sublaminar wiring in the case of an os odontoideum and one occurred due to slippage of the halo orthosis after transoral odontectomy before definitive dorsal stabilization was carried out. INTERPRETATION: In accordance with the recent literature, we argue for the application of modern screw fixations and treatment algorithms as established for adults in upper cervical spine instabilities of older children. Techniques and indications remain problematic for those younger than 6 years and may have to be individualized in congenital instabilities.

Adolescent↗

Muscle lines-of-action affect predicted forces in optimization-based spine muscle modeling.

This study describes the effects of varied torso muscle geometries commonly assumed in optimization-based muscle force prediction models. Specifically, the sensitivity of predicted muscle and spinal forces to assumed muscle lines-of-action (LOA) is systematically examined. The practical significance of varied muscle LOAs is addressed by determining the relative precision needed for individual muscle LOAs and assessing which muscles are more critical to accurate prediction of spinal forces. To perform this analysis a nonlinear optimization model was used to generate muscle force predictions during combined frontal and sagittal plane moment loadings with an assumed erect posture. The LOAs of the erector spinae, rectus abdominus, internal and external oblique, and latissimus dorsi were systematically varied in the frontal and sagittal planes over an anatomically feasible range. The results indicated that moderate changes in the assumed LOA could substantially alter the magnitudes of predicted muscle and spinal forces. The estimated activity level of a muscle, as well as the predicted active/silent state could be affected by the LOA of that muscle and others. The patterns of predicted muscle activity, with respect to load orientation, underwent only minor alterations with changing LOA. The relative activation of several muscles, however, was dependent on LOA, and frequently led to variations in predicted spinal compression (> 100 N change) and shear forces (> 50 N change). This dependence of estimated spinal forces on assumed muscle geometry was most pronounced for the obliques and minimal for the more vertically oriented muscles and when loads were sagittally symmetric. This study suggests that muscle LOAs are critical inputs when interpreting absolute muscle and spinal force values predicted by models of physical exertions.

Algorithms↗

Immediate spinal cord decompression for cervical spinal cord injury: feasibility and outcome.

BACKGROUND: The effect of immediate surgical spinal cord decompression on neurologic outcome after spinal cord injury is controversial. Experimental models strongly suggest a beneficial effect of early decompression but there is little supportive clinical evidence. This study is designed to evaluate the feasibility and outcome of an immediate spinal cord decompression treatment protocol for cervical spinal cord injury in a tertiary treatment center. METHODS: To address this issue, 91 consecutive patients with acute, traumatic cervical spinal cord injury (1990-1997) were prospectively studied. Sixty-six patients (protocol group) underwent emergency magnetic resonance imaging (MRI) to determine the presence of persistent spinal cord compression followed, if indicated, by immediate operative decompression and stabilization. Twenty-five patients were managed outside the treatment protocol because of contraindication to magnetic resonance imaging, need for other emergency surgical procedures, or admitting surgeon preference (reference group). The protocol and reference groups had similar sex and age distributions, admitting Frankel grades, levels of neurologic injury, and Injury Severity Scores. RESULTS: Twenty-seven percent of patients seen were not enrolled in the treatment protocol because of the need for other emergent surgical treatment, contraindication to MRI, and specific surgeon bias regarding the "futility" of emergent treatment. The neurologic outcome for the patients in the reference group were similar to that in the previously reported literature. Fifty percent of protocol patients, compared with only 24% of reference patients, improved from their admitting Frankel grade. Eight protocol patients (12%), but no reference patients, improved from complete motor quadriplegia (Frankel grade A or B) to independent ambulation (Frankel grade D or E). Protocol patients required shorter intensive care unit stays, and shorter total hospital stays than reference patients. In the treatment protocol group, spinal cord decompression, confirmed by MRI, was achieved with immediate spinal column alignment and skeletal traction in 32 patients (46%). Thirty-four patients (54%) required emergent operative spinal cord decompression because of MRI-documented persistent spinal cord compression. CONCLUSION: We conclude that immediate spinal column stabilization and spinal cord decompression, based on magnetic resonance imaging, may significantly improve neurologic outcome. The feasibility of such a treatment protocol in a tertiary treatment center is well demonstrated. Additional multicenter trials are necessary to achieve definitive conclusions regarding clinical efficacy.

Adolescent↗

Competitive interactions between retinal ganglion axons for tectal targets explain plasticity of retinotectal projection in the servomechanism model of retinotectal mapping.

The mechanism of topographic mapping of retinal ganglion cells to the midbrain was previously elucidated by the servomechanism model, which is based on the fact that cells expressing Eph-receptors respond specifically to surface expressing membrane-bound ephrin-ligands at a critical level. The retina has increased nasal-to-temporal gradient of Eph receptor-density, and the optic tectum/superior colliculus has increased rostral-to-caudal gradient of membrane-bound ephrin-ligand. An axon from the retina has an identification tag of a certain level of Eph-receptor density depending on its retinal position, and adheres to the site on the tectum/superior colliculus expressing ephrin-ligands at a critical ligand-density level. The servomechanism model rigidly defines positions of axon terminals on the midbrain. However, optic nerve regeneration experiments combined with halved retina or tectum show a plastic or flexible mapping (expansion, compression and transposition of tectal projections). To reconcile the discrepancy between the rigid model and the plastic behavior, competition between retinal axon terminals for a target site was introduced to the servomechanism. The servomechanism/competition model succeeded in computer simulations of the plastic mapping of retinal axons on the tectum. Recent experiments of upregulated ligand-density on the tectum during nerve regeneration and the role of axonal competition are discussed.

Algorithms↗

A synthetic segment of surfactant protein A: structure, in vitro surface activity, and in vivo efficacy.

Surfactant protein A (SP-A) is a 248-residue, water-soluble, lipid-associating protein found in lung surfactant. Analysis of the amino acid sequence using the Eisenberg hydrophobic moment algorithm predicts that the SP-A segment spanning residues 114-144 has high hydrophobic moments, typical of lipid-associating amphipathic domains. The secondary structure, in vitro surface activity and in vivo lung activity of this SP-A sequence were studied with a 31-residue synthetic peptide analog (A114-144). Analysis of the secondary structure using circular dichroism and Fourier transform infrared spectroscopy indicated association with lipid dispersions and a dominant helical content. Surface activity measurements of A114-144 with surfactant lipid dispersions and the hydrophobic surfactant proteins B and C (SP-B/C) showed that A114-144 enhances surface activity under conditions of dynamic compression and respreading on a Langmuir/Wilhelmy surface balance. Synthetic surfactant dispersions containing A114-144 improved lung compliance in spontaneously breathing, 28-d premature rabbits to a greater degree than surfactant dispersions with synthetic SP-B/C and synthetic surfactant lipids alone. These observations indicate that inclusion of A114-144 may improve synthetic preparations currently used for surfactant replacement therapy.

Amino Acid Sequence↗