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Selection of appropriate testing systems depends on the characteristics and needs of the office. Clinical practice needs, work flow needs, and the analyst's ability must be balanced against the level of system complexity, automation, quality characteristics, and cost.
Twenty-four resections under hepatic vascular exclusion (HVE) have been performed in patients with massive liver tumors. The procedure of HVE was used to minimize blood loss and the chance of gas embolism; it included clamping of the portal triad and occlusion of the inferior vena cava above and below the liver. In 12 of these patients the HVE was associated with clamping of the abdominal aorta above the celiac axis (AoC). During the "anhepatic" phase, which lasted 24 to 65 minutes (mean 39 minutes), neither venous shunt nor refrigeration was used. When HVE was associated with AoC, the circulation to the lower part of the body was completely excluded so that the systemic circulation was reduced to a small upper compartment in which the mean arterial pressure increased by 33% while the cardiac index decreased by 40%. The diastolic pulmonary arterial pressure remained unchanged. When HVE was not associated with AoC, the body was divided into an upper vascular compartment with normal venous resistance and a lower vascular compartment with increased resistance to the venous return and increased blood volume. The cardiac index, which was distributed to these two compartments, decreased by 40% to 50% but the mean arterial pressure decreased by only 14%. The good hemodynamic tolerance to HVE without AoC that was observed in these patients confirms the efficiency of collateral venous channels in the circumstances reported. AoC appears to be unnecessary in most patients if accurate fluid volume loading has been achieved before HVE. The study of acid-base balance demonstrates the ability of the human body to correct spontaneously the acidosis that follows the release of the clamps, provided a stable hemodynamic state is maintained. Only minor disorders of coagulation, without abnormal bleeding, were observed, and no prophylactic treatment was necessary. There were no deaths during operation, but a 25% postoperative mortality rate was observed mainly related to the underlying disease and the status of the remnant liver parenchyma. Despite its apparent sophistication, HVE is a simple and safe procedure for performing otherwise hazardous liver resections for tumors of large size or that are located close to the inferior vena cava and the suprahepatic veins. Its hemodynamic and metabolic consequences appear to be moderate.
Maintaining stance stability under varying sensory environment is an essential function in the elderly and among patients. Testing sensory organization ability of standing balance, the Sensory Organization Test (SOT), has become a standard procedure in many clinical and laboratory settings. The stance stability can be quantified by two forceplate measures in the SOT: the equilibrium score (ES) and the sway area (SA). This study compares the validity of the ES and the SA in detecting gender, trial, and sensory effects on stability in twenty (ten male, ten female) healthy young adults. Subjects were tested under six sensory conditions: eyes open (EO), eyes closed (EC), sway-referenced vision (Vs), sway-referenced support surface (Ss), eyes closed sway-referenced support surface (ECSs), and sway-referenced visual surround and support surface (VsSs). A visual surround and/or the support surface were tilted proportionately to the subject's spontaneous sway in the sway-referenced conditions. Three trials, 20-second for each trial, were repeated for each sensory condition. Above results demonstrated that the Pearson correlation coefficients between the ES and the SA were all highly significant (p < .0001) except for the first trial of the EO condition. The consistencies in which the two measures discriminated among sensory conditions were tested by the Kendall's coefficient of concordance. The Kendall's coefficient for the ES (W = .843) and the SA (W = .866) were high and similar. Separate ANOVA procedure for the ES and SA revealed that both measures satisfactorily detected a significant sensory condition and trial effects and insignificant gender effect. We can conclude that ES and SA are valid measures of stance stability during the SOT. Our results confirm that healthy young adults have a poorer postural stability when the visual and somatosensory inputs are simultaneously altered. Moreover, the learning effect is observed during repeated trials within test conditions.
The impetus for this conference comes in large measure from the continuing development of the ICH Viral Safety document concerned with testing and evaluation of the viral safety of biotechnology products derived from characterized cell lines of human or animal origin [1]. My opening remarks for this conference were, I think, suggested by the organizers in the belief that George Santayana's quote, "Those who cannot remember the past are condemned to repeat it" has validity for this effort. In this brief review I have tried to recall some past unfortunate episodes and outline the lessons that they might have for us. I have also attempted to outline a number of issues which I believe are critical to the success of efforts to guarantee, as much as humanly possible, the safety that we seek balanced against our ability to develop and use important new products.
BACKGROUND: older people participate in exercise programmes to reduce the risk of falls but no study has investigated a specific balance strategy training intervention presented in a workstation format for small groups. OBJECTIVE: to determine whether a specific balance strategy training programmeme delivered in a workstation format was superior to a community based exercise class programme for reducing falls. DESIGN: a randomised controlled trial model. SETTING: Neurological Disorders, Ageing and Balance Clinic, Department of Physiotherapy, The University of Queensland. SUBJECTS: 73 males and females over 60 years, living independently in the community and who had fallen in the previous year were recruited. METHODS: all subjects received a falls risk education booklet and completed an incident calendar for the duration of the study. Treatment sessions were once a week for 10 weeks. Subject assessment before and after intervention and at 3 months follow-up included number of falls, co-morbidities, medications, community services and activity level, functional motor ability, clinical and laboratory balance measures and fear of falling. RESULTS: all participants significantly reduced the number of falls (P < 0.000). The specific balance strategy intervention group showed significantly more improvement in functional measures than the control group (P = 0.034). Separate group analyses indicated significantly improved performance in functional motor ability and most clinical balance measures for the balance group (P < 0.04). The control group only improved in TUG and TUGcog. CONCLUSIONS: the results provide evidence that all participants achieved a significant reduction in falls. Specific balance strategy training using workstations is superior to traditional exercise classes for improving function and balance.
OBJECTIVES: To compare the effect of two 10-week balance training programs, Combined Balance and Step Training (CBST) versus tai chi (TC), on balance and stepping measures. DESIGN: Prospective intervention trial. SETTING: Local senior centers and congregate housing facilities. PARTICIPANTS: Aged 65 and older with at least mild impairment in the ability to perform unipedal stance and tandem walk. INTERVENTION: Participants were allocated to TC (n = 107, mean age 78) or CBST, an intervention focused on improving dynamic balance and stepping (n = 106, mean age 78). MEASUREMENTS: At baseline and 10 weeks, participants were tested in their static balance (Unipedal Stance and Tandem Stance (TS)), stepping (Maximum Step Length, Rapid Step Test), and Timed Up and Go (TUG). RESULTS: Performance improved more with CBST than TC, ranging from 5% to 10% for the stepping tests (Maximum Step Length and Rapid Step Test) and 9% for TUG. The improvement in TUG represented an improvement of more than 1 second. Greater improvements were also seen in static balance ability (in TS) with CBST than TC. CONCLUSION: Of the two training programs, in which variants of each program have been proven to reduce falls, CBST results in modest improvements in balance, stepping, and functional mobility versus TC over a 10-week period. Future research should include a prospective comparison of fall rates in response to these two balance training programs.
The ability of a mass-balance algorithm to predict non-steady-state phenytoin concentrations in neurosurgery patients was compared with that of Phenda, a computerized Bayesian regression analysis program. Fifty neurosurgery patients who had had two or more initial phenytoin serum concentrations measured at least 60 hours apart and at least 1 hour after any i.v. doses, with the second concentration being not more than twice and not less than half of the first, and who had had a third or final phenytoin measurement (for use in a prediction analysis) were evaluated. The patients' maximum rates of metabolism were calculated by using the two initial phenytoin concentrations and a mass-balance algorithm, and the third phenytoin concentration was predicted. The patients' demographics and phenytoin dosages and concentrations were entered into Phenda, which was used to predict the third phenytoin concentration. The ability of the two methods to predict the third concentration was evaluated by the method of Sheiner and Beal. Fifty observations from 48 patients were evaluated. The mass-balance algorithm had a positive prediction bias of 2.52 mg/L and a precision error of 5.08 mg/L, compared with 2.30 and 5.30, respectively, for Phenda. The difference in the results between the two methods was not significant. There was no significant difference between the mass-balance algorithm and Phenda in the ability to predict phenytoin concentrations.
NMDA-mediated neurotoxicity and oxidative stress have been implicated in the etiology of a number of degenerative diseases including motor neuron disease. The present study examined the effect of chronic administration of the glycine/NMDA receptor antagonist L-701,324 and the monoamine oxidase B inhibitor (r)-deprenyl on the onset and rate of progression of neurological impairment in the motor neuron degeneration (mnd) mouse, a murine model of neurodegeneration. Neurological assessment of mnd mice revealed an onset of motor deficits at 6 months of age as observed by the loss of hindlimb reflex extension. By 7 months, balance was also markedly impaired as measured by deficits in rotarod performance and ability to remain on balancing beams. At 8 months of age mnd mice exhibited gross abnormalities in walking pattern; animals were unable to flex their hindlimbs and tended to walk in small labored movements. Daily administration of L-701,324 (10 mg/kg p.o.) or r(-)-deprenyl (1 mg/kg p.o.) to mnd mice from 4 to 8 months of age failed to delay the onset of symptoms or slow the rate of deterioration of motor performance. These findings suggest that excessive activation of NMDA receptors may not be involved in the pathological process leading to motor neuron dysfunction in mnd mice and do not suggest a protective effect of deprenyl on motor neurons in these mice.
Beginning in the late 1980s, states and the federal government restricted the ability of physicians to "balance bill" Medicare beneficiaries for charges in excess of the copayment and reimbursement amounts approved by Medicare. In this paper, I provide empirical evidence that this policy change resulted in a 9% reduction in out-of-pocket medical expenditures by elderly households. In spite of the change in marginal reimbursement to physicians, however, I find little evidence that the restrictions affected patterns of care. Thus, this restriction on the prices charged by physicians amounted to a transfer from affected physicians to affected patients.
The ability of fungi to produce both meiospores and mitospores has provided adaptive advantages in survival and dispersal of these organisms. Here we provide evidence of an endogenous mechanism that balances meiospore and mitospore production in the model filamentous fungus Aspergillus nidulans. We have discovered a putative dioxygenase, PpoC, that functions in association with a previously characterized dioxygenase, PpoA, to integrate fatty acid derived oxylipin and spore production. In contrast to PpoA, deletion of ppoC significantly increased meiospore production and decreased mitospore development. Examination of the PpoA and PpoC mutants indicate that this ratio control is associated with two apparent feedback loops. The first loop shows ppoC and ppoA expression is dependent upon, and regulates the expression of, nsdD and brlA, genes encoding transcription factors required for meiospore or mitospore production, respectively. The second loop suggests Ppo oxylipin products antagonistically signal the generation of Ppo substrates. These data support a case for a fungal "oxylipin signature-profile" indicative of relative sexual and asexual spore differentiation.
The authors addressed balance control in children from the perspective of skill development and examined the relationship between specific perceptual and motor skills and static and dynamic balance performance. Fifty 11- to 13-year-old children performed a series of 1-legged balance tasks while standing on a force platform. Postural control was reflected in the maximum displacement of the center of mass in anterior-posterior and mediolateral directions. Simple visual, discrimination, and choice reaction times; sustained attention; visuomotor coordination; kinesthesis; and depth perception were also assessed in a series of perceptual and motor tests. The correlation analysis revealed that balancing under static conditions was strongly associated with the ability to perceive and process visual information, which is important for feedback-based control of balance. On the other hand, when greater task demands were imposed on the system under dynamic balancing conditions, the ability to respond to the destabilizing hip abductions-adductions in order to maintain equilibrium was associated with motor response speed, suggesting the use of a descending, feedforward control strategy. Therefore, like adults, 11- to 13-year-old children have the ability to select varying balance strategies (feedback, feedforward, or both), depending on the constraints of a particular task.
This study examined the effects of the absence of vision from birth on automatic postural responses to platform displacements during stance. Postural responses were induced by producing randomly four types of perturbations which consisted of forward and backward translations, and toe up and down rotations. Nine congenitally totally blind and nine sighted adults served as subjects. EMG signals were recorded from four muscles in the right leg, and reaction time to somatosensory stimuli generated by platform displacements was measured by pushing a hand-held button. To assess the ability to control postural balance, the root mean square (RMS) values for lateral and antero-posterior sway before, during, and after perturbations were calculated. The EMG amplitude in the gastrocnemius muscle of a blind subject was smaller than that of a sighted subject with eyes closed. No significant differences were found between blind and sighted subjects in EMG latencies of the lower extremity muscles in response to perturbations. The blind subjects had significantly faster reaction times to somatosensory stimuli triggered by platform displacements, but in toe down rotations no significant difference was found between blind and sighted subjects. The difference in the EMG latencies and reaction times between the two groups suggests that blindness from birth may not affect the spinal stretch reflex, but may affect a volitional act mediated through the motor cortex. There were also no significant differences in the RMS values for postural sway between blind and sighted subjects with eyes open or closed, although blind subjects swayed more after backward translations than did sighted subjects with eyes open. Results suggest that the ability to control postural balance during perturbations was not affected by vision loss from birth. Our findings suggest that the automatic postural response systems of humans are unaffected by the absence of vision from birth and are rather hard wired.
The diatomic radical nitric oxide has been the focus of numerous studies involved with every facet of cancer. It has been implicated in carcinogenesis, progression, invasion, metastasis, angiogenesis, escape from immune surveillance, and modulation of therapeutic response. In recent years, an increasing number of studies have suggested the possible involvement of nitric oxide in multiple cancer types, including melanoma. It is perhaps not surprising that conflicting viewpoints have arisen as to whether nitric oxide is beneficial or deleterious in cancer. However, it has become clear that nitric oxide possesses modulatory properties in a number of signal transduction pathways that depend on concentration and context. Our laboratory has shown that tumor expression of inducible nitric oxide synthase in melanoma patients results in poor survival. Furthermore, we demonstrated that the removal of endogenous nitric oxide in melanoma cell lines led to increased sensitivity to cisplatin-induced apoptosis in a p53-dependent manner. Others have shown anti-apoptotic properties of NO in melanoma cells. However, several studies also suggest that NO can inhibit metastasis and diminish resistance. Despite the apparently conflicting observations, it is evident that NO is involved in melanoma pathology. The purpose of this review is to summarize the current literature relating to the role of NO in cancer with particular emphasis on its relevance to therapeutic resistance in melanoma. Recent evidence suggests the involvement of an intricate and complex interplay between reactive nitrogen species and reactive oxygen species. The importance of nitric oxide and its balance with other oxidative agents in the regulation of cancer cell response to therapies will be discussed. This balance may serve as an important focal point in determining patient response to therapy. The ability to control this balance could significantly influence outcome.
Hearing impairment and balance disturbances limit the ability to perform certain jobs and may cause accidents at work. Bearing this in mind a need for preventive examinations of young people starting their vocational education was discussed. Main causes as well as simple diagnostic techniques which facilitate to detect hearing and balance disturbances by physicians who certify the ability of students to undertake practical vocational education and employment were presented.
This article presents results from a feasibility study of a video-capture virtual reality (VR) system used with patients who have paraplegic spinal cord injury (SCI) and who need balance training. The advantages of the VR system include providing the user with natural control of movements, the ability to use as many parts of the body as are deemed suitable within the context of therapeutic goals, and flexibility in the way the system can be adapted to suit specific therapeutic objectives. Thirteen participants with SCI experienced three virtual environments (VEs). Their responses to a Short Feedback Questionnaire showed high levels of presence. We compared performance in the environments with a group of 12 nondisabled participants. Response times for the patient group were significantly higher and percentage of success was significantly lower than that for the nondisabled group. In addition, significant moderate correlations were found between performance within a VE and static balance ability as measured by the Functional Reach Test. This study is a first step toward future studies aimed at determining the potential of using this VR system during the rehabilitation of patients with SCI.
The kidney's major role in potassium (K) homeostasis depends on its ability to respond effectively to changes in external K balance and to stabilize the extracellular concentration of K. The correction of deviations from normal plasma K levels and the maintenance of external K balance depend on the intrinsic ability of distal nephron segments to either secrete or reabsorb K. Net K secretion occurs mainly in principal cells while K absorption takes place in intercalated cells. Studies on single tubules and principal and intercalated cells have defined the determinants of K secretion and reabsorption including the electrochemical driving forces, specific carriers, ATPases, and K channels. Recent studies on the properties and molecular identity of renal K channels have also contributed significantly to understanding the renal mechanisms that transport and regulate K excretion.
Sporadic research reports of decreased proprioception and balance problems have been reported in subjects with idiopathic scoliosis, yet these sensory motor deficits have not been addressed in conservative clinical management programs. The purpose of this study was to compare both balance reactions and vibratory sensitivity (as an estimate of proprioception) in patients with idiopathic scoliosis (N = 24) and age-matched controls (N = 24). Balance was measured by the ability to pass a series of simple static and complex sensory-challenged balance tasks. Vibratory thresholds were measured with the Bio-Thesiometer at the cervical spine, wrist, and foot. Compared with age-matched controls, regardless of curve severity or spinal fusion, the subjects with idiopathic scoliosis had similar simple static balance responses when the somatosensory system was stable (with or without vision or head turning), but they were significantly more likely to fail the complex, sensory-challenged balance tasks when the somatosensory system was challenged by an unstable position of the feet, particularly when the eyes were closed. The vibratory thresholds were similar in subjects with scoliosis and their age-matched controls, but individuals with moderate to severe scoliosis (> 25 degrees) had significantly higher vibratory thresholds than those with mild curves. These findings suggest there may be problems with postural righting in patients with idiopathic scoliosis, particularly when the balance task challenges the vestibular pathways. Although vibration sensitivity did not distinguish normal healthy individuals from individuals with idiopathic scoliosis, those with more severe scoliotic curves appear to have a high threshold to vibration. These balance and vibratory differences could either be interpreted as etiologic risk factors or as consequences of spinal asymmetry. In either case, given that curves can continue to progress even into the adult years, improving the ability to right the body with gravity could help maintain the balance of the spine despite structural asymmetry.
We have been studying the consequences of embryonic vestibular dysfunction caused by the monolith (mnl) mutation in zebrafish. mnl is a dominant mutation that specifically inhibits formation of utricular otoliths. However, briefly immobilizing mnl/mnl embryos in agarose with the otic vesicle orientated at certain angles selectively induces or prevents formation of utricular and/or saccular otoliths. With this noninvasive technique, we generated six phenotypic classes of mnl/mnl mutants, designated S-S, U-U, U-S, S-US, U-US, and US-US, depending on which otoliths are present on each side (U, utricular otolith; S, saccular otolith). All mnl/mnl larvae survived through day 10 of development. Thereafter, S-S larvae showed a rapid decline, probably because of starvation, and none survived to adulthood. Survival rates in all other classes of mnl/mnl larvae (those having at least one utricular otolith) were close to normal. The presence or absence of utricular otoliths also correlated with vestibular function during early larval development, as measured by three criteria: First, unlike wild-type larvae, S-S mutant larvae showed almost no detectable counter-rotation of the eyes when tilted tail up or tail down. Second, 95% of S-S mutant larvae never acquired the ability to maintain a balanced dorsal-up posture. Third, although most wild-type larvae responded to gentle prodding by swimming in a straight line, S-S larvae responded by swimming in rapid circles, showing sudden and frequent changes in direction ("zigzagging"), and/or rolling and spiraling. All other phenotypic classes of mnl/mnl larvae behaved normally in these assays. These data demonstrate that bilateral loss of utricular otoliths disrupts the ability to sense gravity, severely impairs balance and motor coordination, and is invariably lethal. The presence of a utricular otolith in at least one inner ear is necessary and sufficient for vestibular function and survival. In contrast, saccular otoliths are dispensable for these functions.