Systematic review of dynamic graciloplasty in the treatment of faecal incontinence.

BACKGROUND: The aim of this systematic review was to compare the safety and efficacy of dynamic graciloplasty with colostomy for the treatment of faecal incontinence. METHODS: Two search strategies were devised to retrieve literature from the Medline, Current Contents, Embase and Cochrane Library databases up until November 1999. Inclusion of papers depended on a predetermined protocol, independent assessments by two reviewers and a final consensus decision. English language papers were selected. Acceptable study designs included randomized controlled trials, controlled clinical trials and case series. Forty papers met the inclusion criteria. They were tabulated and critically appraised in terms of methodology and design, outcomes, and the possible influence of bias, confounding and chance. RESULTS: No high-level evidence was available and there were no comparative studies. Mortality rates were around 2 per cent for both graciloplasty and colostomy. Morbidity rates reported for graciloplasty appear to be higher than those for colostomy. Dynamic graciloplasty was clearly effective at restoring continence in between 42 and 85 per cent of patients, whereas colostomy is, by its design, incapable of restoring continence. However, dynamic graciloplasty is associated with a significant risk of reoperation. CONCLUSION: While dynamic graciloplasty appears to be associated with a higher rate of complications than colostomy, it is clearly a superior intervention for restoring continence in some patients. It is recommended that a comparative, but non-randomized, study be undertaken to evaluate the safety of dynamic graciloplasty in comparison to colostomy, and that the procedure should be performed only in centres where it is carried out routinely.

Laparoscopic-assisted resection of colorectal malignancies: a systematic review.

OBJECTIVE: To compare the safety and efficacy of laparoscopic-assisted resection of colorectal malignancies with open colectomy. METHODS: Two search strategies were devised to retrieve literature from the Medline, Current Contents, Embase, and Cochrane Library databases until July 1999. Inclusion of papers was determined using a predetermined protocol, independent assessments by two reviewers, and a final consensus decision. English language papers were selected. Acceptable study designs included randomized controlled trials, controlled clinical trials, case series, or case reports. Fifty-two papers met the inclusion criteria. They were tabulated and critically appraised in terms of methodology and design, outcomes, and the possible influence of bias, confounding, and chance. RESULTS: Little high-level evidence was available. Laparoscopic resection of colorectal malignancy was more expensive and time-consuming, but little evidence suggests high rates of port site recurrence. The new procedure's advantages revolve around early recovery from surgery and reduced pain. CONCLUSIONS: The evidence base for laparoscopic-assisted resection of colorectal malignancies is inadequate to determine the procedure's safety and efficacy. Because of inadequate evidence detailing circumferential marginal clearance of tumors and the necessity of determining a precise incidence of cardiac and other major complications, along with wound and port site recurrence, it is recommended that a controlled clinical trial, ideally with random allocation to an intervention and control group, be conducted. Long-term survival rates need to be a primary aim of such a trial.

Preliminary report on reduction of esophagitis by amifostine in patients with non-small-cell lung cancer treated with chemoradiotherapy.

Esophagitis is a major toxicity of chemoradiotherapy for lung cancer. Twenty-four patients with non-small-cell lung cancer received induction chemotherapy (paclitaxel/carboplatin) followed by concurrent thoracic irradiation (RT) and weekly paclitaxel. Acute esophagitis was scored weekly. Since a high rate of grade 3 esophagitis was noted in the initial group of 12 patients, amifostine (AMI) 500 mg intravenously twice weekly was added to the regimen in the subsequent 12 patients. Esophagitis Index (EI) was calculated as an area under the curve reflecting esophagitis grade over time. Median number of AMI doses was 12 per patient. AMI was well tolerated. Two patients were not evaluable for esophagitis. The incidence of grade 3 esophagitis was 18% in the initial 11 patients versus 9% in the AMI-treated patients (P = not significant). Mean EI was numerically lower in the AMI-treated patients than in the initial group (5.1 vs. 11.6, P = 0.14). The product of RT dose and length of esophagus in the RT field was larger in the AMI group (934 vs. 761, P = 0.035). Median survival time for all patients was 12.4 months. Esophagitis Index, a novel measure of the severity and duration of acute esophagitis, may be reduced in lung cancer patients receiving twice-weekly AMI with thoracic RT and paclitaxel. Twice weekly AMI did not eliminate grade 3 esophagitis; therefore, dose escalation of AMI is planned. The effect of AMI was not due to the shorter irradiated esophageal length. A phase III randomized trial is now open to assess AMI's effect on esophagitis.

A simulation of muscle force and internal kinematics of extensor carpi radialis brevis during backhand tennis stroke: implications for injury.

OBJECTIVE: The purpose of this work was use a computer simulation of the action of extensor carpi radialis brevis during a typical backhand tennis stroke of novice and advance players to examine a potential mechanism of injury. DESIGN: This study uses established kinematic data in conjunction with a computer model to give a time varying description of muscle force and length changes. BACKGROUND: Lateral epicondylitis or tennis elbow has been attributed to over-exertion of extensor carpi radialis brevis with novice tennis players being particularly susceptible. METHODS: We used a simple Hill-type muscle model to predict muscle force and internal kinematics based on activation and joint angle changes as inputs. Magnetic resonance images were used to determine the morphometric dimensions of extensor carpi radialis brevis which were used to scale the mechanical properties determined from in vivo contractions of flexor pollicis longus. RESULTS: The simulation indicated that the novice group generated considerably less force and the muscle was subjected to a substantial eccentric contraction as a result of racquet-ball impact. This eccentric contraction occurred with the muscle at a very long length with diminishing tension capabilities. CONCLUSION: The observed pattern of activation and joint kinematics of novice tennis players results in substantial eccentric contractions which are likely the cause of repetitive microtrauma leading to tennis elbow injuries. Adopting the technique seen in advanced players would limit the eccentric contractions and reduce the likelihood of injury. RELEVANCE: Lateral epicondylitis can be extremely problematic because of its chronic nature and relatively high incidence. This study offers one aetiology of the condition that results from improper kinematics during the tennis backhand stroke.

Increase of beta(III)- and beta(IVa)-tubulin isotopes in human prostate carcinoma cells as a result of estramustine resistance.

Estramustine (EM), an antimicrotubule agent, is effective against hormone-refractory prostate cancer when used in combination with vinblastine or paclitaxel. To understand the effect of EM on beta-tubulin, a cellular target for this class of drugs, human prostate carcinoma cells (DU-145) were made resistant to EM, and two cell lines were selected at 12- (EM-12) and 15-microMolar (EM-15) concentrations of the drug. These cell lines exhibited 8- to 9-fold resistance to EM and 2- to 4-fold cross-resistance to paclitaxel. Immunofluorescent staining of the cells with beta-tubulin isotype-specific antibodies showed an approximately 6-fold increase in the beta(III)-tubulin levels and moderate increase in overall beta-tubulin levels in EM-resistant cells when compared to DU-145 cells. This increase of beta(III) isotype was confirmed by Western analysis. A reverse transcriptase-PCR assay was also employed using beta-tubulin isotype-specific primers to quantify beta-tubulin isotype RNA. A 4-fold increase in beta(III) and a 3-fold increase in beta(IV alpha) transcript were seen in both EM-resistant cell lines. These results indicate that overexpression of specific beta-tubulin isotypes may play a role in the cellular defense against EM and other antimicrotubule agents.

P-glycoprotein binding and modulation of the multidrug-resistant phenotype by estramustine.

BACKGROUND: Previous preclinical studies of combinations of estramustine and vinblastine or paclitaxel (Taxol) have shown that it is possible to achieve a greater than additive cytotoxicity with these antimicrotubule drug combinations. Phase II studies in hormone-refractory prostate cancer have demonstrated clinical antitumor activity of sufficient magnitude to stimulate further laboratory and clinical studies of these drugs combinations. PURPOSE: Our purpose was to characterize the interactions of estramustine with P-glycoprotein and to determine its effects. METHODS: Standard laboratory techniques were used to study the effects of estramustine on intracellular drug concentrations, cytotoxicity, and induction of messenger RNA (mRNA) for the MDR1 (also known as PGY1) gene. Using a photoaffinity analogue of estramustine 17-0-[[2-[3-(4-azido-3-[125I]-iodophenyl) propionamido]ethyl]-carbamyl]estradiol-3-N-bis(2-chloroethyl)ca rba mate ([125I]AIPP-estramustine), binding to the membrane proteins of human ovarian (SKOV3) and their multidrug-resistant counterpart SKVLB1 cells was studied. Southern-blot analysis was performed on DNA extracted from human prostate carcinoma wild-type DU145, estramustine-resistant cell line (E4), and SKVLB1 cells. RESULTS: Membrane fractions from SKOV3 and SKVLB1 cells were analyzed for proteins that could be photoaffinity labeled with [125I]AIPP-estramustine. Competitive inhibition of this binding was achieved with excess concentrations of (in order of efficacy) estramustine, vinblastine, verapamil, progesterone, and to a lesser degree, by paclitaxel but not with estramustine phosphate, estradiol, and estriol. SKVLB1 cells accumulated much less [3H]vinblastine and [3H]paclitaxel than did SKOV3 cells. Estramustine caused a concentration-dependent enhancement of drug accumulation in the SKVLB1 cells to a maximum of approximately 12-fold. No effect of estramustine was apparent for the wild-type SKOV3 cells. In comparison with verapamil, estramustine was less effective as a modulator; however estramustine demonstrated good chemosensitizing activity in combination with actinomycin D and vinblastine. Neither short-term, low-dose no longer-term, higher concentration were found to produce measurable transcript (mRNA for the MDR1 gene levels. Such data suggest that, at least levels. Such data suggest that, at least for two distinct human cell line (SKOV3 and DU145), estramustine does not induce the overexpression of the MDR1 gene. CONCLUSION: It is apparent from the P-glycoprotein data that estramustine interacts with this efflux pump, altering intracellular drug accumulation. Overall, the nonempiric basis for including estramustine in clinical protocols that contain other multidrug-resistant drugs is strengthened by the present data.

Effects of changes in segmental values and timing of both torque and torque reversal in simulated throws.

An overarm throw in the sagittal plane was simulated using a three-segment model representing the upper arm, forearm and hand plus ball. Torque inputs at each joint were turned on at systematically varied times and maintained constant once initiated. All simulations began from identical initial conditions. The aim was to determine the sequence of onset of joint torques which gave the maximal range which the ball would travel and the maximal velocity of the ball irrespective of direction. Best throws proved to be sequential in that joint torques were turned on in a proximal to distal (P-D) temporal sequence. The P-D sequence was also demonstrated by time of peak joint angular velocities. The P-D sequence also proved to be best when segmental constants and joint torques were changed. As this sequence is a common feature of skilled throwing and striking, it is concluded that the linked segmental nature of the limb, irrespective of normal muscle characteristics, primarily predisposes the system to the use of a P-D sequence. The algebraic sign of the shoulder and elbow torques was reversed instantaneously to represent the use of antagonistic muscles. This led to increased output if performed late in the throw and in a P-D sequence. It is concluded that the use of antagonism leads to beneficial redistributions of angular velocity amongst limb segments.

Cutaneous versus Muscular Perception of Electrically Evoked Tetanic Pain.

This work was supported in part by Laval University (sabbatical leave of Dr. A.Y. Bélanger), the School of Kinesiology at Simon Fraser University, and Medtronic of Canada Inc. There is much speculation in athletic, physical therapy, and sports medicine circles about the relative cutaneous (superficial) vs. muscular (deep) perception of pain felt during maximum electrically evoked tetanic muscle contraction. To date, very few studies have addressed the basic question of whether pain perception during electrical stimulation is more superficial (cutaneous) or deep in muscular tissue. The purpose of this study was to determine, in a group of 10 healthy male subjects, the effect of a complete sensory nerve block at the thigh on the qualities (intensity, sensory, affective) of pain (elicited by electrically induced tetanic muscle contraction) as measured by the Short-Form McGill Pain Questionnaire felt during high amplitude, 50-Hz electrical stimulation (ES) of the vastus lateralis muscle. The findings from this study provide clear evidence that a healthy individual's tolerance level to pain induced during electrically evoked maximum tetanic muscle contraction depends as much on deep muscle stimulation as it does on cutaneous or superficial stimulation. Indeed, the results show a statistically significant decrease of approximately 50% in all three qualities of pain (intensity, sensory, and affective) following the elimination of cutaneous pain pathways via the nerve blocking procedure (p < 0.05). Until it is demonstrated that the same results hold for patients who often experience pain prior to ES treatments, any clinical implications would seem to be premature. For now, clinicians must be aware that muscle, as much as skin, may limit one's ability to tolerate high amplitude ES treatments. Further research is needed on the cutaneous vs. muscular perception of electrically evoked pain in healthy and diseased populations as well as on the issue of subject and patient experience vs. nonexperience with ES. J Orthop Sports Phys Ther 1992;16(4):162-168.

Diabetic BB/Wor rat haptoglobin exhibits a probable structural abnormality in Asn-linked oligosaccharides.

In this study we demonstrate that haptoglobin, a serum glycoprotein secreted by the liver, has altered structure in the BB/Wor diabetic rat. SDS-PAGE of haptoglobin (a tetramer composed of two glycosylated beta-chains each containing two sites for Asn-linked oligosaccharides connected by disulfide bonds with two nonglycosylated alpha-chains) clearly shows that the beta-chain of haptoglobin from diabetic rats is smaller than normal, with a molecular mass of 39 instead of 40 kDa. Both acute and chronic diabetic rats exhibit the defect. Defective haptoglobin appears in the serum within 4 days of onset of the disease, but insulin therapy prevents the defect. Removal of Asn-linked oligosaccharides with peptide: N-glycosidase F from Flavobacterium meningosepticum abolished the size difference between the beta-chains from normal and diabetic haptoglobin, with the molecular mass in both cases shifting to 30 kDa. Haptoglobin from both normal and diabetic rats was resistant to digestion by endoglycosidase H from Streptomyces griseus, which cleaves high mannose-type chains. Removal of sialic acid with neuraminidase treatment resulted in a reduction in the molecular mass in both cases, but without eliminating the size difference between the two. These results demonstrate that haptoglobin from diabetic BB/Wor rats contains a structural abnormality which correlates with onset of the disease. The defect is most likely due to an alteration in Asn-linked oligosaccharides, probably involving a change in the neutral sugars of complex-type oligosaccharide chains. This finding represents the first example of an altered Asn-linked oligosaccharides in diabetes.

Effect of floor conditions upon frictional characteristics of squash court shoes.

Vertical (FN) and horizontal (FH) forces were recorded while four vertically-loaded court shoes were dragged horizontally across six types of floor surface. Variation in coefficient of limiting friction (FH/FN) between floor surfaces was greater than that between shoes. Squash strokes were also performed on the same surfaces during which FH/FN was calculated. Slips occurred on some surfaces either at heel contact or upon attainment of full-sole contact. It is concluded that the coefficient of limiting friction obtained during full-sole contact with the floor is a suitable means of distinguishing between tractional qualities of shoes. Alternatively, this measure is an inadequate predictor of the likelihood of slips in the game of squash racquets. Dusty floor conditions produce poor traction as does a damp sealed floor. As sweat droplets are unavoidable in the game, floors sealed with urethane represent a significant hazard. Bare, clean, wooden flooring which can absorb moisture represents a better surface than a sealed floor from the point of view of traction.

The step height and the stepping distance as important predictors of the maximal knee joint angle in stepping movements - A proposal for the reconditioning of the injured knee@

The strategies of steps negotiation by individuals were investigated with the aim of relating anthropometric variable; step height; and stepping distance to the joint movements at the knee. Measurements of statures and lengths of limb; leg and foot were taken from 30 subjects. Absolute maximal knee angles were obtained separately for each of the subjects - for different step heights and for different stepping distances. Correlation coefficients of anthropometric variables with the knee angle were compared in cases in which the step height was normalised with respect to each of the anthropometric variables. Stature was eventually used to normalize both step height and stepping distance. A regression equation was developed to predict the absolute maximal knee angle for a given relative step height and at a given relative distance

Applied muscle modelling: implementation of muscle-specific models.

Recent work in musculoskeletal modelling has seen the use of models which represent individual muscles in the human system. This paper presents a model of forearm supination in which models generate specific muscular forces to produce external supinator torque. The model output is compared to measured external torque for isometric and dynamic loading conditions. These data are used to construct isometric torque-angle and torque-angular velocity graphs for both model and experimental output. The discussion focuses on specific topics regarding implementation of muscle models in applied situations. These topics are demonstrated by observing the effect of parameter alteration on model output.

Effects of glucose starvation and puromycin treatment on lipid-linked oligosaccharide precursors and biosynthetic enzymes in Chinese hamster ovary cells in vivo and in vitro.

Previous studies from several laboratories have demonstrated that glucose-starved Chinese hamster ovary (CHO) cells and other cells in culture switch from synthesis of the normal Glc3Man9GlcNAc2-P-P-Dol to Man5-GlcNAc2-P-P-Dol. In this study we have investigated this phenomenon in CHO cells in vitro and in vivo in order to determine the possible site of this block. Our results demonstrate that enzymatic activities responsible for Man9GlcNA2 synthesis in vitro are normal in glucose-starved cells. In vivo, however, the pool of GDP-[3H]Man is severely depleted, while [3H]mannose incorporation into lipid-linked and protein-bound Man5GlcNAc2 is increased. This result suggests that the available GDP-Man in starved cells is utilized to synthesize Man5GlcNAc2 preferentially, resulting in a reduction of Dol-P-Man and Man6-Man9 GlcNAc2 synthesis in vivo in glucose-starved cells. Conditions which prevent the depletion of GDP-[3H]Man in glucose-starved cells, such as puromycin or cycloheximide treatment, result in normal synthesis of Man9GlcNAc2 by glucose-starved cells. An unexpected finding in the course of this study is that puromycin or cycloheximide treatment of cells, which is known to inhibit lipid-linked oligosaccharide synthesis in glucose-fed cells, has no such inhibitory effect on glucose-starved cells.

The mechanical response of active human muscle during and after stretch.

Five subjects contracted forearm supinator muscles which were stretched after development of maximal isometric torque. The ratio of torque at the end of stretch over isometric torque at that position was calculated as excess torque. Excess torque increased with stretch velocity and decreased with stretch amplitude, and it was not dependent upon final muscle length. The rate of decay of torque following stretch could not be shown to depend upon stretch variables. The absence of significant changes in myoelectric activity suggested that with high initial forces, reflex activity did not account for the observed changes. Time-constants of decay (0.15 s to 1.8 s) were much greater than time-constants of rise (approx. 0.07 s) of isometric torque at the same muscle length. This indicates that interaction of series elastic and contractile elements is not the sole cause of prolonged torque following stretch. It is concluded that stretch temporarily enhances the intrinsic contractile properties of a group of human muscles in a manner similar to, but quantitatively different from that seen in isolated muscle preparations.

Squash ball mechanics and implications for play.

The purpose of this research was to examine how temperature and velocity affect coefficient of restitution and how temperature affects the force-deformation properties of balls used in the international game of squash. The balls used were the international yellow dot and a newly developed double yellow dot. Coefficient of restitution increased with temperature and decreased with increases in projection velocity. The effect of temperature was most marked at low projection velocities. Coefficient of restitution was smallest for the double yellow dot ball but differences between balls decreased with increases in both temperature and projection velocity. Static tests showed increasing ball stiffness with increases in both force applied and temperature, and the yellow dot ball showed the greatest stiffness. Static tests indicated that standards published by the Canadian Squash Racquets Association are inappropriate. These results are discussed in the contexts of play and testing and design criteria for the balls.

Mechanical output following muscle stretch in forearm supination against inertial loads.

Muscle stretch enhances force produced in both single fibers and voluntarily activated human muscle. This study determined how initial conditions of muscle stretch (and associated eccentric work), muscle length, and load inertia contributed to human concentric muscular output during maximal voluntary forearm supination. Outputs of angular velocity and concentric work over specific displacements and times of motion were calculated. Multiple regression analysis was performed using these outputs and initial conditions as dependent and independent variables, respectively. Initial conditions were shown to be significant and systematic determinants of muscle output in concentric contraction. Evidence of a temporary shift in the force-velocity curve was found and discussed regarding its beneficial contribution to load movement. Greater benefit was considered to be due to the fact that muscle stretch allows time for achievement of maximal muscular recruitment prior to concentric contraction. This produces large forces at the onset of the concentric phase, in comparison with contractions starting from rest. These findings were discussed with regard to both single- and multi-segment movement patterns.

Kinetic sources of lower-limb angular displacement in the recovery phase of sprinting.

One female sprinter was filmed at the 100-m mark (speed 6.5 m X S-1) of a 400-m run. Four moments occurring at each end of the thigh and shank segments during lower-limb recovery were calculated. These were: proximal and distal net muscle moments, a moment due to proximal joint accelerative force and, a moment due to distal joint-force resulting from motion and inertia of the distal connected segment. Individual contributions of each moment to segmental angular displacement were calculated by double integration, and angular velocity at toe-off was multiplied by time to yield its contribution. Contributions of the proximal muscle moments throughout recovery were 21 rad and 7.5 rad for the thigh and shank segments, respectively. Such large angular displacements did not occur because the three remaining moments opposed the proximal muscle moment. These large moments are mutually offsetting and interactive, acceleration of proximal joints provides a substantial moment during contralateral stance, and segmental angular velocity at toe-off is a significant contributor. Consequently, a phenomenon producing a change in any moment (e.g. muscular fatigue, slippery surface) will require modification of other moments for angular displacement to be maintained within reasonable limits.