Body composition changes after 12 months of FES cycling: case report of a 60-year-old female with paraplegia.

STUDY DESIGN: Single-subject (female, 60 years of age) case. OBJECTIVES: The purpose of this case report is to document body composition changes in a 60-year-old female with chronic paraplegia after 12 months of home-based functional electrical stimulation lower extremities cycling (FES-LEC). SETTING: Home-based FES-LEC with internet connection. Southeastern United States. METHODS: FES-LEC three sessions per week for 12 months in participant's home and monitored by the research staff via internet connection. Pre- and post-exercise program testing for body composition including percent body fat, fat mass (FM), lean mass (LM) and whole-body bone mineral density (BMD) via dual-energy x-ray absorptiometry (DXA). RESULTS: There was a 7.7% increase in total body LM and a 4.1% increase in legs LM. There was a 1.2% decrease in total body FM and a 9.9% decrease in legs FM. Percent body fat decreased from 48.4 to 46.3 and whole-body BMD was increased from 0.934 to 1.023, which resulted in an improvement in the DXA T-score from -2.4 to -1.3. CONCLUSION: Positive body compositional changes during this study support the idea that long-term FES-LEC can help restore healthier ratios of LM and FM and possibly decrease the risk of associated diseases. Increased whole-body BMD provides hope that long-term FES-LEC may be beneficial regarding bone health.

Feasibility of home-based functional electrical stimulation cycling: case report.

STUDY DESIGN: Single-subject (male, 64 years of age) case. OBJECTIVES: To determine the feasibility of a home-based FES-LEC (functional electrical stimulation lower extremities cycling) program and effects on body composition, quality of life (QOL) and seat pressure mapping in an older individual with spinal cord injured (SCI). SETTING: Home-based FES-LEC with internet connection. Southeastern United States. METHODS: FES-LEC three sessions per week for 9 weeks in the participant's home and monitored by the research staff via internet connection. Pre- and post-exercise program testing of seat pressure mapping, QOL and body composition including percent body fat (%BF), fat mass (FM), lean mass (LM) and bone mineral density (BMD). RESULTS: The participant completed 25 of 27 recommended exercise sessions over 9 weeks for a 93% compliance rate. Cycling distance increased from 3.98 to 9.00 km (126%). Total body LM increased from 48.94 to 53.02 kg (8.3%). The %BF decreased from 29.6 to 28.4(-1.2%). Total body weight, FM and BMD remained unchanged. Average static seat pressure decreased from 55.5 to 52.59 mm Hg (5%), whereas maximum seat pressure decreased from 120.76 to 91.5 mm Hg (24%). The psychological domain (perception of body image, appearance and self-esteem) of the QOL questionnaire improved from 12.67 to 14. CONCLUSION: Positive changes in this study regarding body composition, QOL and seat pressure mapping support results of clinical studies using FES-LEC training on younger adults with SCI. The high percentage of exercise adherence and positive results on body composition, QOL and seat pressure provide support for the feasibility of home-based FES-LEC.

The effects of spinal cord injury and exercise on bone mass: a literature review.

INTRODUCTION: Bone loss is a common and often debilitating condition that accompanies spinal cord injury. Because bone loss after spinal cord injury is multifactorial, it can be difficult to assess and treat. This process becomes even more complex as secondary conditions associated with aging are introduced. PURPOSE: There are two purposes of this literature review. The first is to summarize information concerning the mechanisms of bone loss and osteoporosis after spinal cord injury. The second is to summarize existing data concerning the effects of exercise on bone loss after spinal cord injury. METHOD: Literature was reviewed concerning the bone loss process and the non-pharmacological treatment options for ameliorating bone loss after spinal cord injury. RESULTS: (Part One) Osteoporosis is universal in persons with chronic complete spinal cord injury, which increases the risk of bone fracture. Bone loss after spinal cord injury is both sublesional and regional with the greatest areas of bone demineralization being in the sublesional trabecular laden areas of the distal and proximal epiphyses of the femur and tibia. (Part Two) While passive weight bearing of paralyzed lower extremities appears to be ineffective, stressing the bones through muscular contractions initiated by electrical stimulation (FES) have yielded positive results in some cases. The intensity, frequency, and duration of stress to the bones appear to be important determinants of improved bone parameters. Although further quantification of these components is needed, some generalized guidelines can be deduced from completed research. Intensities showing positive results have been loads of one to one and a half times body weight for FES exercise or having participants FES cycle at their highest power output. Safety precautions must be used to decrease risk of bone fracture. Generally, the frequency is effective with three or more weekly exercise sessions. Studies of duration suggest that several months to one or more years of FES are necessary. DISCUSSION: In order to promote healthy and independent aging in patients with spinal cord injury, it is important to understand the processes, consequences and effective treatments involved with bone loss.

Transgenic expression of 15-lipoxygenase 2 (15-LOX2) in mouse prostate leads to hyperplasia and cell senescence.

15-Lipoxygenase 2 (15-LOX2), a lipid-peroxidizing enzyme, is mainly expressed in the luminal compartment of the normal human prostate, and is often decreased or lost in prostate cancer. Previous studies from our lab implicate 15-LOX2 as a functional tumor suppressor. To better understand the biological role of 15-LOX2 in vivo, we generated prostate-specific 15-LOX2 transgenic mice using the ARR2PB promoter. Unexpectedly, transgenic expression of 15-LOX2 or 15-LOX2sv-b, a splice variant that lacks arachidonic acid-metabolizing activity, resulted in age-dependent prostatic hyperplasia and enlargement of the prostate. Prostatic hyperplasia induced by both 15-LOX2 and 15-LOX2sv-b was associated with an increase in luminal and Ki-67(+) cells; however, 15-LOX2-transgenic prostates also showed a prominent increase in basal cells. Microarray analysis revealed distinct gene expression profiles that could help explain the prostate phenotypes. Strikingly, 15-LOX2, but not 15-LOX2sv-b, transgenic prostate showed upregulation of several well-known stem or progenitor cell molecules including Sca-1, Trop2, p63, Nkx3.1 and Psca. Prostatic hyperplasia caused by both 15-LOX2 and 15-LOX2sv-b did not progress to prostatic intraprostate neoplasia or carcinoma and, mechanistically, prostate lobes (especially those of 15-LOX2 mice) showed a dramatic increase in senescent cells as revealed by increased SA-betagal, p27(Kip1) and heterochromatin protein 1gamma staining. Collectively, our results suggest that 15-LOX2 expression in mouse prostate leads to hyperplasia and also induces cell senescence, which may, in turn, function as a barrier to tumor development.

Modulation of actin mechanics by caldesmon and tropomyosin.

The ability of cells to sense and respond to physiological forces relies on the actin cytoskeleton, a dynamic structure that can directly convert forces into biochemical signals. Because of the association of muscle actin-binding proteins (ABPs) may affect F-actin and hence cytoskeleton mechanics, we investigated the effects of several ABPs on the mechanical properties of the actin filaments. The structural interactions between ABPs and helical actin filaments can vary between interstrand interactions that bridge azimuthally adjacent actin monomers between filament strands (i.e. by molecular stapling as proposed for caldesmon) or, intrastrand interactions that reinforce axially adjacent actin monomers along strands (i.e. as in the interaction of tropomyosin with actin). Here, we analyzed thermally driven fluctuations in actin's shape to measure the flexural rigidity of actin filaments with different ABPs bound. We show that the binding of phalloidin increases the persistence length of actin by 1.9-fold. Similarly, the intrastrand reinforcement by smooth and skeletal muscle tropomyosins increases the persistence length 1.5- and 2- fold respectively. We also show that the interstrand crosslinking by the C-terminal actin-binding fragment of caldesmon, H32K, increases persistence length by 1.6-fold. While still remaining bound to actin, phosphorylation of H32K by ERK abolishes the molecular staple (Foster et al. 2004. J Biol Chem 279;53387-53394) and reduces filament rigidity to that of actin with no ABPs bound. Lastly, we show that the effect of binding both smooth muscle tropomyosin and H32K is not additive. The combination of structural and mechanical studies on ABP-actin interactions will help provide information about the biophysical mechanism of force transduction in cells.

Hypertrophic and dilated cardiomyopathy mutations differentially affect the molecular force generation of mouse alpha-cardiac myosin in the laser trap assay.

Point mutations in cardiac myosin, the heart's molecular motor, produce distinct clinical phenotypes: hypertrophic (HCM) and dilated (DCM) cardiomyopathy. Do mutations alter myosin's molecular mechanics in a manner that is predictive of the clinical outcome? We have directly characterized the maximal force-generating capacity (F(max)) of two HCM (R403Q, R453C) and two DCM (S532P, F764L) mutant myosins isolated from homozygous mouse models using a novel load-clamped laser trap assay. F(max) was 50% (R403Q) and 80% (R453C) greater for the HCM mutants compared with the wild type, whereas F(max) was severely depressed for one of the DCM mutants (65% S532P). Although F(max) was normal for the F764L DCM mutant, its actin-activated ATPase activity and actin filament velocity (V(actin)) in a motility assay were significantly reduced (Schmitt JP, Debold EP, Ahmad F, Armstrong A, Frederico A, Conner DA, Mende U, Lohse MJ, Warshaw D, Seidman CE, Seidman JG. Proc Natl Acad Sci USA 103: 14525-14530, 2006.). These F(max) data combined with previous V(actin) measurements suggest that HCM and DCM result from alterations to one or more of myosin's fundamental mechanical properties, with HCM-causing mutations leading to enhanced but DCM-causing mutations leading to depressed function. These mutation-specific changes in mechanical properties must initiate distinct signaling cascades that ultimately lead to the disparate phenotypic responses observed in HCM and DCM.

Investigating sun-damaged skin and actinic keratosis with optical coherence tomography: a pilot study.

Actinic Keratosis (AK) arises from sun-damaged skin and is the first clinical manifestation in the multistep process of skin carcinogenesis to invasive squamous cell carcinoma. Thus, it is an ideal target for chemopreventive efforts. Noninvasive measures of AK severity are needed to assess the efficacy of chemoprevention agents. We performed a pilot study on 20 participants to investigate the OCT appearance of sun-protected skin of the upper inner arm as well as sun-damaged skin and early AKs of the dorsal forearms, and to determine if features or quantitative measures in Optical Coherence Tomography (OCT) images could be used to reliably differentiate between these categories. OCT images of upper inner arm (normal appearing skin) showed skin layers and features (stratum corneum, epidermis, dermis, blood vessels) seen in previous studies; additionally in this participant group the subcutaneous fat layer was usually identified. Sun-damaged skin was characterized by increased signal in the epidermis and rapid attenuation of light. AKs were diverse in appearance but frequently characterized by high surface reflection, the presence of a low-signal band in the stratum corneum, and heterogeneous appearance in the epidermis/dermis. Significant differences were found between skin categories using measures of stratum corneum and epidermal/dermal depths and intensities. The presence of a dark band in the stratum corneum was 79% sensitive and 100% specific for AK. This study indicates that OCT holds promise as a useful technique for identifying and characterizing AKs and monitoring their response to chemoprevention agents.

Myosin V exhibits a high duty cycle and large unitary displacement.

Myosin V is a double-headed unconventional myosin that has been implicated in organelle transport. To perform this role, myosin V may have a high duty cycle. To test this hypothesis and understand the properties of this molecule at the molecular level, we used the laser trap and in vitro motility assay to characterize the mechanics of heavy meromyosin-like fragments of myosin V (M5(HMM)) expressed in the Baculovirus system. The relationship between actin filament velocity and the number of interacting M5(HMM) molecules indicates a duty cycle of > or =50%. This high duty cycle would allow actin filament translocation and thus organelle transport by a few M5(HMM) molecules. Single molecule displacement data showed predominantly single step events of 20 nm and an occasional second step to 37 nm. The 20-nm unitary step represents the myosin V working stroke and is independent of the mode of M5(HMM) attachment to the motility surface or light chain content. The large M5(HMM) working stroke is consistent with the myosin V neck acting as a mechanical lever. The second step is characterized by an increased displacement variance, suggesting a model for how the two heads of myosin V function in processive motion.

The value of diffusion-weighted imaging for prediction of lasting deficit in acute stroke: an analysis of 134 patients with acute neurologic deficits.

Acute stroke is one of the three major causes of death and disability in the United States. Now that new, and possibly effective therapy is becoming available, accurate, rapid diagnosis is important to provide timely treatment, while avoiding the risk of complications from unnecessary intervention. Our objective was to test the hypothesis that use of echo-planar (EPI) diffusion-weighted imaging (DWI) is more accurate than conventional T2 weighted MRI in predicting progression to stroke in patients with acute ischemic neurologic deficits. We studied 134 patients presenting with acute neurologic deficits to a community hospital emergency room with both conventional MRI and DWI within 72 h of the onset of the acute deficit. We found DWI significantly more sensitive to permanent neurologic deficit at discharge (sensitivity 0.81) than conventional MRI (sensitivity 0.41). When available, DWI should be considered for routine use in patients being imaged for acute stroke.

Expression of c-kit (CD117) in benign and malignant human endometrial epithelium.

BACKGROUND: The proto-oncogene c-kit encodes a tyrosine kinase receptor (CD117) with a molecular weight of 145 kd. Previous studies, predominantly utilizing immunohistochemistry, have led to contradictory findings regarding the expression of CD117 in the endometrium. To help resolve this issue, we analyzed a series of benign and malignant endometrial tissues using both immunohistochemistry and Western blot analysis. OBJECTIVE: To examine the expression of CD117 in benign and malignant human endometrial tissues. METHODS: The expression of CD117 in 35 benign endometrial tissues (7 hyperplastic, 14 proliferative, 14 secretory) and 10 endometrioid carcinomas was investigated by immunohistochemistry (clone K45 monoclonal antibody). Immunoprecipitation (clone K69 monoclonal antibody) followed by Western blotting (clone K45 monoclonal antibody and clone 1.D9.3D6 monoclonal antibody) was performed to confirm CD117 expression. RESULTS: Fifty-seven percent of the hyperplasias, 93% of proliferative endometria, and 79% of secretory endometria immunostained positively for CD117. In benign endometria, epithelial staining tended to be more intense in the hyperplastic and proliferative endometria as compared to the secretory endometria, whereas endometrial stromal cells were not immunoreactive. Of the 10 frozen endometrial tissues analyzed by immunohistochemistry, 4 of 9 endometrioid carcinomas and a single case of an endometrioid polyp developing in association with a carcinoma expressed CD117. Immunoprecipitation followed by Western blot analysis confirmed expression of full-length CD117 in an endometrial polyp and carcinoma, and revealed a correlation between levels of immunoprecipitated CD117 and immunohistochemical staining intensity. CONCLUSIONS: Benign and malignant endometrial tissues express CD117. Our data suggest (a) a possible relationship between estrogen and CD117 expression in benign endometrium and (b) potential involvement of this growth factor receptor in endometrial carcinogenesis.

Role of the elastic protein projectin in stretch activation and work output of Drosophila flight muscles.

We examine how the stretch activation response of the Drosophila indirect flight muscles (IFM) is affected by the projectin mutation bentDominant. IFM from flies heterozygous for this mutation (bentD/+) produce approximately 85% full length projectin and approximately 15% truncated projectin lacking the kinase domain and more C-terminal sequences. Passive stiffness and power output of mutant fibers is similar to that of wild-type (+/+) fibers, but the amplitude of the stretch activation response (delayed tension rise) was significantly reduced. Measurement of actomyosin kinetics by sinusoidal analysis revealed that the apparent rate constant of the delayed tension rise (2 pi b) increased in proportion to the decrease in amplitude, accounting for the near wild-type levels of power output and nearly normal flight ability. These results suggest that projectin plays a crucial role in stretch activation, possibly through its protein kinase activity, by modulating crossbridge recruitment and kinetics.

High-resolution diffusion imaging using phase-corrected segmented echo-planar imaging.

Diffusion magnetic resonance imaging (MRI) was performed with a high-resolution segmented echo-planar imaging technique, which provided images with substantially less susceptibility artifacts than images obtained with single-shot echo-planar imaging (EPI). Diffusion imaging performed with any multishot pulse sequence is inherently sensitive to motion artifacts and in order to reduce motion artifacts, the presented method utilizes navigator echo phase corrections, performed after a one-dimensional Fourier transform along the frequency-encoding direction. Navigator echo phases were fitted to a straight line prior to phase correction to avoid errors from internal motion. In vivo imaging was performed using electro cardiographic (ECG) triggering. Apparent diffusion coefficient (ADC) maps were calculated on a pixel-by-pixel basis using up to seven diffusion sensitivities, ranging from b = 0 to 1129 x 10(6) s/m(2).

The effect of removing the N-terminal extension of the Drosophila myosin regulatory light chain upon flight ability and the contractile dynamics of indirect flight muscle.

The Drosophila myosin regulatory light chain (DMLC2) is homologous to MLC2s of vertebrate organisms, except for the presence of a unique 46-amino acid N-terminal extension. To study the role of the DMLC2 N-terminal extension in Drosophila flight muscle, we constructed a truncated form of the Dmlc2 gene lacking amino acids 2-46 (Dmlc2(Delta2-46)). The mutant gene was expressed in vivo, with no wild-type Dmlc2 gene expression, via P-element-mediated germline transformation. Expression of the truncated DMLC2 rescues the recessive lethality and dominant flightless phenotype of the Dmlc2 null, with no discernible effect on indirect flight muscle (IFM) sarcomere assembly. Homozygous Dmlc2(Delta2-46) flies have reduced IFM dynamic stiffness and elastic modulus at the frequency of maximum power output. The viscous modulus, a measure of the fly's ability to perform oscillatory work, was not significantly affected in Dmlc2(Delta2-46) IFM. In vivo flight performance measurements of Dmlc2(Delta2-46) flies using a visual closed-loop flight arena show deficits in maximum metabolic power (P(*)(CO(2))), mechanical power (P(*)(mech)), and flight force. However, mutant flies were capable of generating flight force levels comparable to body weight, thus enabling them to fly, albeit with diminished performance. The reduction in elastic modulus in Dmlc2(Delta2-46) skinned fibers is consistent with the N-terminal extension being a link between the thick and thin filaments that is parallel to the cross-bridges. Removal of this parallel link causes an unfavorable shift in the resonant properties of the flight system, thus leading to attenuated flight performance.

The Drosophila projectin mutant, bentD, has reduced stretch activation and altered indirect flight muscle kinetics.

Projectin is a ca. 900 kDa protein that is a member of the titin protein superfamily. In skeletal muscle titins are involved in the longitudinal reinforcement of the sarcomere by connecting the Z-band to the M-line. In insect indirect flight muscle (IFM), projectin is believed to form the connecting filaments that link the Z-band to the thick filaments and is responsible for the high relaxed stiffness found in this muscle type. The Drosophila mutant bentD (btD) has been shown to have a breakpoint close to the carboxy-terminal kinase domain of the projectin sequence. Homozygotes for btD are embryonic lethal but heterozygotes (btD/+) are viable. Here we show that btD/+ flies have normal flight ability and a slightly elevated wing beat frequency (btD/+ 223+/-13 Hz; +/+ 203+/-5 Hz, mean +/- SD; P < 0.01). Electron microscopy of btD/+ IFM show normal ultrastructure but skinned fiber mechanics show reduced stretch activation and oscillatory work. Although btD/+ IFM power output was at wild-type levels, maximum power was achieved at a higher frequency of applied length perturbation (btD/+ 151+/-6 Hz; +/+ 102+/-14 Hz; P < 0.01). Results were interpreted in the context of a viscoelastic model of the sarcomere and indicate altered cross-bridge kinetics of the power-producing step. These results show that the btD mutation reduces oscillatory work in a way consistent with the proposed role of the connecting filaments in the stretch activation response of IFM.

Nasal cartilage grafts: more than a decade of experience.

From 1985 to 1995, a total of 311 patients underwent nasoplasties. During this time period, the number of patients receiving grafts increased from 94 percent in 1985-1989 to 100 percent in 1993-1995. The donor grafts averaged 72 percent nasal cartilage, 10 percent conchal cartilage, 9 percent fascia, and 9 percent rib allograft. Graft recipient sites averaged 41 percent in the tip, 31 percent in the dorsum, 17 percent in the columella, and 3 percent in the region of the lower lateral cartilage; 8 percent were spreader grafts. During this time frame, tip grafting increased from 34 percent in 1985-1989 to 54 percent in 1993-1995. Reoperation for complications decreased from 17 percent in 1985-1989 to 2 percent in 1993-1995. During the time span examined, the use of rib allografts declined, the use of autologous cartilage increased, the use of onlay tip grafts increased, and the incidence of reoperations declined. Early in the series, 80 percent of the malplaced tips were shield type grafts. With the use of the onlay tip graft, the complication of a malpositioned tip has been substantially diminished. The increased use of crushed cartilage has resulted in improvement in results and patient satisfaction, as it serves to camouflage slight irregularities in the tip and dorsum of the nose.

Phosphorylation-dependent power output of transgenic flies: an integrated study.

We examine how the structure and function of indirect flight muscle (IFM) and the entire flight system of Drosophila melanogaster are affected by phosphorylation of the myosin regulatory light chain (MLC2). This integrated study uses site-directed mutagenesis to examine the relationship between removal of the myosin light chain kinase (MLCK) phosphorylation site, in vivo function of the flight system (flight tests, wing kinematics, metabolism, power output), isolated IFM fiber mechanics, MLC2 isoform pattern, and sarcomeric ultrastructure. The MLC2 mutants exhibit graded impairment of flight ability that correlates with a reduction in both IFM and flight system power output and a reduction in the constitutive level of MLC2 phosphorylation. The MLC2 mutants have wild-type IFM sarcomere and cross-bridge structures, ruling out obvious changes in the ultrastructure as the cause of the reduced performance. We describe a viscoelastic model of cross-bridge dynamics based on sinusoidal length perturbation analysis (Nyquist plots) of skinned IFM fibers. The sinusoidal analysis suggests the high power output of Drosophila IFM required for flight results from a phosphorylation-dependent recruitment of power-generating cross-bridges rather than a change in kinetics of the power generating step. The reduction in cross-bridge number appears to affect the way mutant flies generate flight forces of sufficient magnitude to keep them airborne. In two MLC2 mutant strains that exhibit a reduced IFM power output, flies appear to compensate by lowering wingbeat frequency and by elevating wingstroke amplitude (and presumably muscle strain). This behavioral alteration is not seen in another mutant strain in which the power output and estimated number of recruited cross-bridges is similar to that of wild type.

Correction for distortion of echo-planar images used to calculate the apparent diffusion coefficient.

An algorithm for correcting the distortions that occur in diffusion-weighted echo-planar images due to the strong diffusion-sensitizing gradients is presented. The dominant distortions may be considered to be only changes of scale coupled with a shear and linear translation in the phase-encoding direction. It is then possible to correct for them by using an algorithm in which each line of the image in the phase-encoding direction is considered in turn, with only one parameter (the scale) to be found by searching.

Endoscopic transaxillary submuscular augmentation mammaplasty with textured saline breast implants.

The utility of the endoscope was realized in a retrospective analysis of 92 consecutive patients undergoing augmentation mammaplasty with saline-filled textured implants. The transaxillary submuscular approach was used. All patients received preoperative antibiotics and instillation of methylprednisolone into the saline fill, with inflation to manufacturer-recommended levels. complications included seven implant deflations (3.8%), eight implant malpositions (4.3%), and one capsular contracture (0.6%). Of the eight malpositions, six were corrected using the endoscopic technique without removal of the implant and with early manipulation of the implant within the pocket. We conclude that endoscopic control in augmentation mammaplasty is beneficial in secondary operative procedures and we speculate that the endoscope will lessen the rate of implant malposition observed in this study.

An audit of prophylactic antibiotic treatment following tonsillectomy in children.

A prospective audit study was undertaken to assess the effect of two different management policies following tonsillectomy in children in this hospital, one of which requires a prophylactic five-day course of oral antibiotics and the other doses not. A total of 95 children were entered into the trial: 54 received post-operative antibiotics and 41 did not. The post-operative recovery was assessed by completion of a parent questionnaire which included the following parameters: degree of patient distress, nausea and vomiting, otalgia, halitosis, pharyngeal bleeding, analgesic requirement, day of return to a regular diet and General Practitioner consultation. There was no significant reduction in any of the morbidity measures in patients treated with antibiotics. I fact, the analgesic requirement and the incidence of otalgia and irritability on Days 6 and 7 and secondary haemorrhage were significantly higher in the antibiotic-treated patients. Although the number of patients included in this study are small, the result suggest that post-operative antibiotics do not improve the outcome of uncomplicated tonsillectomy. Our previous practice of routinely administering antibiotics to post-tonsillectomy children has been discontinued as the consequence of this audit.