Development and testing of the Gait Assessment and Intervention Tool (G.A.I.T.): a measure of coordinated gait components.

Recent neuroscience methods have provided the basis upon which to develop effective gait training methods for recovery of the coordinated components of gait after neural injury. We determined that there was not an existing observational measure that was, at once, adequately comprehensive, scored in an objectively-based manner, and capable of assessing incremental improvements in the coordinated components of gait. Therefore, the purpose of this work was to use content valid procedures in order to develop a relatively inexpensive, more comprehensive measure, scored with an objectively-based system, capable of incrementally scoring improvements in given items, and that was both reliable and capable of discriminating treatment response for those who had a stroke. Eight neurorehabilitation specialists developed criteria for the gait measure, item content, and scoring method. In subjects following stroke (>12 months), the new measure was tested for intra- and inter-rater reliability using the Intraclass Correlation Coefficient; capability to detect treatment response using Wilcoxon Signed Ranks Test; and discrimination between treatment groups, using the Plum Ordinal Regression. The Gait Assessment and Intervention Tool (G.A.I.T.) is a 31-item measure of the coordinated movement components of gait and associated gait deficits. It exhibited the following advantages: comprehensive, objective-based scoring method, incremental measurement of improvement within given items. The G.A.I.T. had good intra- and inter-rater reliability (ICC=.98, p=.0001, 95% CI=.95, .99; ICC=.83, p=.007, 95% CI=.32, .96, respectively. The inexperienced clinician who had training, had an inter-rater reliability with an experienced rater of ICC=.99 (p=.0001, CI=.97, .999). The G.A.I.T. detected improvement in response to gait training for two types of interventions: comprehensive gait training (z=-2.93, p=.003); and comprehensive gait training plus functional electrical stimulation (FES; z=-3.3, p=.001). The G.A.I.T. was capable of discriminating between two gait training interventions, showing an additive advantage of FES to otherwise comparable comprehensive gait training (parameter estimate=1.72, p=.021; CI, .25, 3.1).

Performance of an intramuscular electrode during functional neuromuscular stimulation for gait training post stroke.

The goal of rehabilitation for stroke patients in this research was to improve the volitional coordination of the swing phase and stance phases of gait. Functional neuromuscular stimulation (FNS) is a promising rehabilitation tool for restoring motor control. For our gait training protocols, FNS systems with surface electrodes were impractical. For the rehabilitation protocols that we defined, available implantable electrode designs did not meet desired criteria regarding fracture rate, invasiveness of placement procedures, and maintenance of position at the motor point. The criteria for the new intramuscular (IM) electrode design included minimally invasive electrode placement technique, accurate placement of electrodes, good muscle selectivity, consistency of muscle activation, good position maintenance of the electrode at the motor point, comfortable stimulus, and practical donning time for the system. A percutaneous electrode was designed for placement beneath the skin at the motor point of seven paralyzed or paretic muscles in the lower limb. A single-helical coil lead, a double-helical coil electrode, and fine wire barbs were design features that enhanced the anchoring capability of the electrode. A polypropylene core enhanced electrode durability. Implantation tools were custom-designed to enable accurate electrode placement without incision. We studied 17 subjects with a total of 124 electrodes. With the use of IM electrodes, FNS was provided for 1,413.8 electrode months. During this time, no instances of infection occurred. The measure of electrode integrity showed a 99% electrode survival rate. Throughout the treatment protocols, 93% of the electrodes delivered a good muscle response; 7% (nine electrodes) moved from the motor point and delivered a poor muscle response during the treatment protocol. Anchoring performance was higher for electrodes implanted in muscles that moved the hip (96.0%) and ankle joints (97.45%) compared with electrodes implanted in muscles that moved the knee joint (88.5%). Ninety-seven percent of the electrodes delivered a comfortable stimulus. Three percent delivered a stimulus that was uncomfortable at therapeutic levels and therefore were not used. We achieved gains in subject impairment and disability measures. The system proved to be practical for use in both clinical and home environments.

ECT in bipolar and unipolar depression: differences in speed of response.

OBJECTIVES: There is sparse evidence for differences in response to electroconvulsive therapy (ECT) between patients with bipolar or unipolar major depression, with virtually no information on speed of response. We contrasted a large sample of bipolar (BP) and unipolar (UP) depressed patients in likelihood and rapidity of clinical improvement with ECT. METHODS: Over three double-blind treatment protocols, 228 patients met Research Diagnostic Criteria for UP (n = 162) or BP depression (n = 66). Other than lorazepam PRN (3 mg/day), patients were withdrawn from psychotropics prior to the ECT course and until after post-ECT assessments. Patients were randomized to ECT conditions that differed in electrode placement and stimulus intensity. Symptomatic change was evaluated at least twice weekly by a blinded evaluation team, which also determined treatment length. RESULTS: Patients with BP and UP depression did not differ in rates of response or remission following the ECT course, or in response to unilateral or bilateral ECT. Degree of improvement in Hamilton Rating Scale for Depression scores following completion of ECT was also comparable. However, BP patients received significantly fewer ECT treatments than UP patients, and this effect was especially marked among bipolar ECT responders. Both BP I and BP II patients showed especially rapid response to ECT. CONCLUSIONS: The BP/UP distinction had no predictive value in determining ECT outcome. In contrast, there was a large effect for BP patients to show more rapid clinical improvement and require fewer treatments than unipolar patients. The reasons for this difference are unknown, but could reflect a more rapid build up of anticonvulsant effects in BP patients.

Feasibility of gait training for acute stroke patients using FNS with implanted electrodes.

Following stroke, many patients do not regain a normal, safe gait pattern even after receiving conventional physical therapy. One promising technique is functional neuromuscular stimulation (FNS) with intramuscular (IM) electrodes (FNS-IM). Five subjects were admitted into the study at 3 weeks to 3 months following the stroke. For each subject, electrodes were placed intramuscularly at the motor point of up to seven lower extremity paretic muscles. Subjects were treated for 6 months, twice weekly with FNS-IM for exercise and gait training. The stimulator and software provided individualized stimulation patterns, with flexible stimulus parameters and activation timings of multiple muscles. Outcome measures were active joint movement, coordination (Fugl-Meyer scale), balance (Tinetti scale), gait (Tinetti scale), activities of daily living (functional independence measure), and therapist and subject satisfaction (survey instrument). Subjects tolerated well the placement of IM electrodes with no adverse effects, and subjects lost no conventional rehabilitation time. Therapists and subjects were satisfied with the FNS-IM system as a rehabilitation tool. Post treatment, subjects demonstrated improvements in impairment and disability in active joint movement, coordination, balance, gait and activities of daily living. Considered together with prior research for chronic stroke subjects, this research suggests that FNS-IM can be successfully and efficaciously utilized for gait training for those with acute stroke.

Response of prolonged flaccid paralysis to FNS rehabilitation techniques.

PURPOSE: The purpose of this study was to investigate the response of muscles with prolonged flaccid paralysis (a year after stroke) to two types of treatment: (1) functional neuromuscular stimulation (FNS) with surface electrodes; and (2) FNS with intramuscular (IM) electrodes (FNS-IM). A second purpose was to compare FNS-gait versus volitional gait (no FNS activation). METHOD: We used a single case study design; our patient was age 72, with flaccid paralysis of knee flexors and ankle dorsiflexors. RESULTS: Following four months of treatment with surface-stimulation, there was no change in muscle function or gait. Following treatment with FNS-IM, the patient regained partial volitional control of knee flexors and dorsiflexors; untreated muscles did not change. CONCLUSION: FNS-gait provided more normal knee and ankle dorsiflexion during swing phase versus volitional gait swing phase (no FNS activation).

Electrically induced recovery of gait components for older patients with chronic stroke.

OBJECTIVE: To compare the gains for chronic stroke patients in volitional gait pattern attained from treatment with functional neuromuscular stimulation (FNS) and intramuscular electrodes (IM) with gains attained using conventional therapy, including treatment with FNS using surface electrodes (surface-stim). DESIGN: This single-subject research design consisted of a series of two subjects. Three months of conventional therapy and surface-stim were followed by treatment using the FNS-IM system. Two stroke patients had cerebrovascular accident 1 or 4 yr before the study and ambulated with a cane. Interventions consisted of 3 months of conventional exercise and gait training including surface-stim, followed by 7-14 months of treatment with the FNS-IM system. Treatments occurred up to 3 times/wk for 1-hr sessions and a home program. Outcome measures consisted of six kinematic gait components, as measured by a six-camera video-based data-acquisition system. Coordination of isolated joint movement was measured according to the Fugl-Meyer scale. RESULTS: Both subjects improved during conventional therapy to some degree. During FNS-IM treatment, gains were made beyond those attained during conventional therapy. Statistically significant differences were found between conventional and FNS-IM therapy. CONCLUSIONS: For these two subjects, gains in volitional control of gait were made during conventional treatment (including surface-stim); for these two subjects during FNS-IM treatment, additional gains were made in volitional gait pattern, beyond those attained during conventional therapy.

Therapeutic neural effects of electrical stimulation.

The use of a functional neuromuscular stimulation (FNS) device can have therapeutic effects that persist when the device is not in use. Clinicians have reported changes in both voluntary and electrically assisted neuromuscular function and improvements in the condition of soft tissue. Motor recovery has been observed in people with incomplete spinal cord injury, stroke, or traumatic brain injury after the use of motor prostheses. Improvement in voluntary dorsiflexion and overall gait pattern has been reported both in the short term (several hours) and permanently. Electrical stimulation of skin over flexor muscles in the upper limb produced substantial reductions for up to 1 h in the severity of spasticity in brain-injured subjects, as measured by the change in torque generation during ramp-and-hold muscle stretch. There was typically an aggravation of the severity of spasticity when surface stimulation reached intensities sufficient to also excite muscle. Animals were trained to alter the size of the H-reflex to obtain a reward. The plasticity that underlies this operantly conditioned H-reflex change includes changes in the spinal cord itself. Comparable changes appear to occur with acquisition of certain motor skills. Current studies are exploring such changes in humans and animals with spinal cord injuries with the goal of using conditioning methods to assess function after injury and to promote and guide recovery of function. A better understanding of the mechanisms of neural plasticity, achieved through human and animal studies, may help us to design and implement FNS systems that have the potential to produce beneficial changes in the subject's central nervous systems.

Scintigraphic diagnosis of peritoneo-pleural communication in the absence of ascites.

Pleural effusion in the presence of cirrhosis and ascites is well recognized. Peritoneal fluid is thought to enter the pleural cavity either because of overloaded lymphatics or a structural defect between the peritoneal and chest cavities. Pleural effusion rarely occurs in the absence of demonstrable ascites. This report describes the scintigraphic diagnosis of peritoneo-pleural communication in a patient with cryptogenic cirrhosis and pleural effusion without ascites.

Ketamine-xylazine anaesthesia permits a KATP channel antagonist to attenuate preconditioning in rabbit myocardium.

OBJECTIVE: ATP sensitive potassium (KATP) channels have been implicated in the mechanism of ischaemic preconditioning, though apparently not in the pentobarbitone anaesthetised rabbit model. The aim of this study was to test whether potassium channel activation and blockade would alter protection in ketamine-xylazine anaesthetised rabbits. METHODS: In situ rabbit hearts (n = 50) received 30 min regional ischaemia and 3 h reperfusion. Some hearts were preconditioned by 5 min regional ischaemia and 10 min reperfusion prior to the long ischaemia. Infarct size was determined by tetrazolium staining. RESULTS: In rabbits anaesthetised with ketamine-xylazine, brief preconditioning ischaemia continued to produce much smaller infarcts than in non-preconditioned animals [19(SEM 2)% v 47(3)%, p < or = 0.05]. blocking KATP channels by pretreating with glibenclamide resulted in 35(3)% infarction in non-preconditioned hearts and aborted protection in preconditioned hearts [35(4)% infarction]. Substituting the potassium channel activator pinacidil for the short ischaemia caused comparable reductions in infarct size [28(4)%, p < or = 0.05 v non-preconditioned hearts]. This protection, however, could be blocked by concomitant administration of the adenosine receptor blocker 8-(p-sulphophenyl)theophylline (SPT) [44(3)% infarction]. CONCLUSIONS: When ketamine-xylazine anaesthesia was employed, the protective effects of ischaemic preconditioning in the rabbit heart could be blocked by glibenclamide, and pinacidil could mimic the protection of ischaemic preconditioning. Because the protection afforded by pinacidil could be blocked by SPT, however, there is still some question whether the KATP channel is the end effector of preconditioning.

Augmentation of transfers for a quadriplegic patient using an implanted FNS system. Case report.

A 22 year old man with incomplete quadriplegia (C6-7) was unable to perform either a sliding or a pivot transfer. He was instrumented with an implanted functional neuromuscular stimulation (FNS) system, radio frequency-linked to a belt-worn controller. The system activated eight muscles selected from among quadriceps, hamstrings, posterior portion of the adductor magnus, gluteus maximus, and erector spinae, bilaterally. The two-stage implantation procedure included electrode implantation with percutaneous leads followed by stimulator implantation and removal of the percutaneous leads. All implants were well tolerated with no adverse effects. The subject was able independently to put on the external controller portion of the system and to perform a standing pivot transfer with only standby assistance. An unexpected outcome of the FNS system use was increased voluntary upper body strength that resulted in improvement of the sliding transfer from 'inability' to 'independent'.

Cryosurvival of Trichomonas vaginalis during cryopreservation of human semen.

Despite a 90% cryosurvival of Trichomonas vaginalis in their growth medium trypticase yeast maltose (TYM) with DMSO, none of these parasites have previously been observed to survive during cryopreservation of infected human semen with glycerol (Andrologia 18, 323 (1986)). This could have been due to the failure of the culture method used to detect low numbers of survivors. The prospects of possible transmission of T. vaginalis by artificial insemination with cryobanked (-196 degrees C) semen prompted an investigation of the cryosurvival of this parasite in the presence of semen with the cryoprotectant glycerol, using a more sensitive culture method for viability evaluation. Semen and seminal fluid from the same 23 ejaculates, as well as culture medium, were inoculated with small clinical numbers of T. vaginalis and evaluated as to their survival before and after cryopreservation. Results indicated: (i) The highest cryosurvival of T. vaginalis (4.5%) was in cryobanked (glycerolated) semen, (ii) semen, as well as glycerol, shows cryoprotective action, and (iii) glycerol reduced survival of parasites in semen, seminal fluid, and TYM medium during exposure prior to freezing. Clinical information on infectivity of small numbers of T. vaginalis and the data presented here suggests that these organisms could be transmitted by artificial insemination with infected cryobanked human semen.

The effect of ionizing radiation on the viability of Trichomonas vaginalis.

1. The effects of continuous gamma radiation on the viability of Trichomonas vaginalis (ATCC 30001) were assessed by a colony count technique. 2. A triphasic survival curve showed an initial shoulder (Dq) of 3 Gy followed by three linear curves with D0 values of 34, 300, and 90 Gy. 3. Sterilization of 10(6) cells/ml occurred from 1600 to 1800 Gy of radiation. 4. Population growth, subsequent to radiation exposure of 17-100 Gy, showed an increased lag time followed by a faster rate of growth, compared with unirradiated cells. 5. Trichomonas vaginalis is more sensitive to ionizing radiation than free-living protozoa and appears as radiosensitive as those parasitic protozoa examined in radioattenuation experiments.

Difference in effect of dog seminal fluid and human seminal fluid and semen on in vitro survival of Trichomonas vaginalis.

The authors examined the ability of dog seminal fluid to serve as an animal model in order to study survival of Trichomonas vaginalis in human urogenital secretions. Two strains were used: SVI-1, a recent isolate from a male patient, and ATCC 30001, a strain that has been cultured for many years. The authors incubated the T. vaginalis strains in dog seminal fluid, human seminal fluid, and human semen, at 37 degrees C for 6, 12, and 24 hrs. For both strains, survival in dog seminal fluid was much poorer than that in human semen and seminal fluid, zero survival being noted at 24 hrs. The SVI-1 strain survived significantly better than ATCC 30001 in all secretions. Data from experiments using isolates from two female patients, but incubated in human seminal fluid alone, agreed with results obtained with SVI-1. Dog seminal fluid may not be a suitable substitute for human secretions in T. vaginalis studies, and long-term culture may decrease the ability of T. vaginalis to survive in the male urogenital tract.

Refined crystal structure of beta-lactamase from Citrobacter freundii indicates a mechanism for beta-lactam hydrolysis.

Beta-Lactamases (EC 3.5.2.6, 'penicillinases') are a family of enzymes that protect bacteria against the lethal effects of cell-wall synthesis of penicillins, cephalosporins and related antibiotic agents, by hydrolysing the beta-lactam antibiotics to biologically inactive compounds. Their production can, therefore, greatly contribute to the clinical problem of antibiotic resistance. Three classes of beta-lactamases--A, B and C--have been identified on the basis of their amino-acid sequence; class B beta-lactamases are metalloenzymes, and are clearly distinct from members of class A and C beta-lactamases, which both contain an active-site serine residue involved in the formation of an acyl enzyme with beta-lactam substrates during catalysis. It has been predicted that class C beta-lactamases share common structural features with D,D-carboxypeptidases and class A beta-lactamases, and further, suggested that class A and class C beta-lactamases have the same evolutionary origin as other beta-lactam target enzymes. We report here the refined three-dimensional structure of the class C beta-lactamase from Citrobacter freundii at 2.0-A resolution and confirm the predicted structural similarity. The refined structure of the acyl-enzyme formed with the monobactam inhibitor aztreonam at 2.5-A resolution defines the enzyme's active site and, along with molecular modelling, indicates a mechanism for beta-lactam hydrolysis. This leads to the hypothesis that Tyr 150 functions as a general base during catalysis.

Survival of Trichomonas vaginalis in human semen.

Although exposure of Trichomonas vaginalis to human semen is of short duration, any effect that this fluid may have on the urogenital protozoon could affect its transmission, especially if only few trichomonads are present. Small numbers of parasites (about 2500/ml semen) incubated in semen from different donors at 37 degrees C, were found to survive or grow for up to 12 hours in all samples and for up to 24 hours in most. Survival and growth of T vaginalis in semen most resembled that found in Diamond's trypticase, yeast extract, and maltose (TYM) medium without serum supplement, rather than in complete TYM medium and phosphate buffered saline. Contrary to previous reports, semen did not inhibit the survival of T vaginalis, and the presence of trichomonads did not alter motility or numbers of spermatozoa up to 24 hours. The data suggest that semen provides a favourable milieu for transmitting trichomonads.

Circannual incidence of Giardia lamblia.

A circannual rhythm of Giardia lamblia positive stools was found by examination of records from three clinical laboratories in central Arkansas for the period 1980-1986. Cosinor analysis of monthly Giardia incidence based on stool specimen records from approximately 12,000 patients over the 7-year period revealed a circannual rhythm (P less than 0.001) on the basis of percent positive patients/month, with a computive acrophase occurring in late summer and minimum values in the winter. Patients involved in the study were primarily from the central Arkansas metropolitan areas, southern delta regions and northern mountainous regions of the state. Analysis of the data on the basis of total positive Giardia patients/month also revealed a circannual rhythm with the acrophase again occurring in late summer. The overall mean for percent positive stool specimens for the 7-year period was 5.3%, compared with the national average of 3.8% for G. lamblia positive stools. The data indicate that there may be a "Giardia season" in Arkansas since they could not be explained on the basis of day-care age distribution, or geographic origin. Awareness by epidemiologists, public health officials and other health care professionals of this circannual incidence of giardiasis is important for the prevention, diagnosis and treatment of this infectious disorder.