Case Studies in Neuroscience: A dissociation of balance and posture demonstrated by camptocormia.

Upright stance in humans requires an intricate exchange between the neural mechanisms that control balance and those that control posture; however, the distinction between these control systems is hard to discern in healthy subjects. By studying balance and postural control of a participant with camptocormia - an involuntary flexion of the trunk during standing that resolves when supine - a divergence between balance and postural control was revealed. A kinematic and kinetic investigation of standing and walking showed a stereotyped flexion of the upper body by almost 80° over a few minutes, and yet the participant's ability to control center of mass within the base of support and to compensate for external perturbations remained intact. This unique case also revealed the involvement of automatic, tonic control of the paraspinal muscles during standing and the effects of attention. Although strength was reduced and MRI showed a reduction in muscle mass, there was sufficient strength to maintain an upright posture under voluntary control and when using geste antagoniste maneuvers or "sensory tricks" from visual, auditory, and haptic biofeedback. Dual tasks that either increased or decreased the attention given to postural alignment would decrease or increase the postural flexion, respectively. The custom-made "twister" device that measured axial resistance to slow passive rotation revealed abnormalities in axial muscle tone distribution during standing. The results suggest that the disorder in this case was due to a disruption in the automatic, tonic drive to the postural muscles and that myogenic changes were secondary. NEW & NOTEWORTHY By studying an idiopathic camptocormia case with a detailed biomechanical and sensorimotor approach, we have demonstrated unique insights into the neural control of human bipedalism 1) balance and postural control cannot be considered the same neural process, as there is a stereotyped abnormal flexed posture, without balance deficits, associated with camptocormia, and 2) posture during standing is controlled by automatic axial tone but "sensory tricks" involving sensory biofeedback to direct voluntary attention to postural alignment can override, when required.

Development of a test grid using Eye Movement Perimetry for screening glaucomatous visual field defects.

BACKGROUND: Eye Movement Perimetry (EMP) uses Saccadic Eye Movement (SEM) responses for visual field evaluation. Previous studies have demonstrated significant delay in initiation of SEMs among glaucoma patients in comparison with healthy subjects. The aim of the current study was to develop an EMP-based screening grid to identify glaucomatous visual field defects. METHODS: An interactive test consisting of 36 locations and two stimulus contrasts (162 cd/m2 and 190 cd/m2 on a background of 140 cd/m2) was evaluated in 54 healthy subjects and 50 primary glaucoma patients. Each subject was presented a central fixation target combined with the random projection of Goldmann size III peripheral targets. Instructions were given to look at each peripheral target on detection and then re-fixate at the central fixation target while the saccades were assessed using an eye tracker. From each seen peripheral target, the Saccadic Reaction Time (SRT) was calculated for contrast level 162 cd/ m2. These values were used to plot Receiver Operating Characteristic (ROC) curves for each test locations and the Area Under the Curve (AUC) values were used to identify the locations with highest susceptibility to glaucomatous damage. Each stimulus location with an AUC less than 0.75 along with its mirrored test location around the horizontal axis were eliminated from the grid. RESULTS: The mean age was 48.1 ± 16.6 years and 50.0 ± 14.5 years for healthy subjects and glaucoma patients respectively. A significant increase of SRT values by 76.5% (p < 0.001) was found in glaucoma patients in comparison with the healthy subjects. From the ROC analysis, ten out of 36 locations meeting the cut-off criteria of AUC were eliminated resulting in a new grid containing 26 test locations. SRT values were significantly different (p < 0.05) between the healthy subjects and glaucoma irrespective of the grids used. CONCLUSIONS: The present study resulted in a screening grid consisting of 26 locations predominantly testing nasal, superior and inferior areas of the visual field. An internal validation of the modified grid showed 90.4% of screening accuracy which makes it a potential approach for population based glaucoma screening.

Compensatory stepping in Parkinson's disease is still a problem after deep brain stimulation randomized to STN or GPi.

The effects of deep brain stimulation (DBS) on balance in people with Parkinson's disease (PD) are not well established. This study examined whether DBS randomized to the subthalamic nucleus (STN; n = 11) or globus pallidus interna (GPi; n = 10) improved compensatory stepping to recover balance after a perturbation. The standing surface translated backward, forcing subjects to take compensatory steps forward. Kinematic and kinetic responses were recorded. PD-DBS subjects were tested off and on their levodopa medication before bilateral DBS surgery and retested 6 mo later off and on DBS, combined with off and on levodopa medication. Responses were compared with PD-control subjects (n = 8) tested over the same timescale and 17 healthy control subjects. Neither DBS nor levodopa improved the stepping response. Compensatory stepping in the best-treated state after surgery (DBS+DOPA) was similar to the best-treated state before surgery (DOPA) for the PD-GPi group and the PD-control group. For the PD-STN group, there were more lateral weight shifts, a delayed foot-off, and a greater number of steps required to recover balance in DBS+DOPA after surgery compared with DOPA before surgery. Within the STN group five subjects who did not fall during the experiment before surgery fell at least once after surgery, whereas the number of falls in the GPi and PD-control groups were unchanged. DBS did not improve the compensatory step response needed to recover from balance perturbations in the GPi group and caused delays in the preparation phase of the step in the STN group.

An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits.

Patients with abetalipoproteinemia, a disease caused by defects in the microsomal triglyceride transfer protein (MTP), do not produce apolipoprotein B-containing lipoproteins. It was hypothesized that small molecule inhibitors of MTP would prevent the assembly and secretion of these atherogenic lipoproteins. To test this hypothesis, two compounds identified in a high-throughput screen for MTP inhibitors were used to direct the synthesis of a highly potent MTP inhibitor. This molecule (compound 9) inhibited the production of lipoprotein particles in rodent models and normalized plasma lipoprotein levels in Watanabe-heritable hyperlipidemic (WHHL) rabbits, which are a model for human homozygous familial hypercholesterolemia. These results suggest that compound 9, or derivatives thereof, has potential applications for the therapeutic lowering of atherogenic lipoprotein levels in humans.

Diurnal intraocular pressure fluctuation and its risk factors in angle-closure and open-angle glaucoma.

PURPOSE: To evaluate intraocular pressure (IOP) fluctuation during office hours and its predictive factors in untreated primary angle-closure suspects (PACS); post-iridotomy primary angle closure (PAC) and primary angle-closure glaucoma (PACG) eyes with or without IOP-lowering medication(s) as appropriate and medically treated primary open-angle glaucoma (POAG) eyes. METHODS: One-hundred seventeen eyes (29 PACS, 30 PAC, 28 PACG, and 30 POAG) of 117 patients were included in this cross-sectional study. The subjects underwent hourly IOP measurements with Goldmann tonometer from 0800 to 1700 hours. Subjects with PAC and PACG had laser peripheral iridotomy at least 2 weeks prior to the inclusion. SD of office-hour IOP readings was the main outcome measure. RESULTS: IOP fluctuation differed between the groups (P=0.01; Kruskal-Wallis Test). Post hoc Mann-Whitney U-tests showed significantly less IOP fluctuation in PACS compared with PACG (P<0.01). Peak office-hour IOP was observed in the morning in untreated subjects and in the early afternoon in treated subjects. A stepwise linear regression model identified the presence of peripheral anterior synechiae (PAS), thickness of lens, large vertical cup-to-disc ratio (VCDR), and PAC category as significant predictive factors associated with office-hour IOP fluctuation. CONCLUSIONS: Diurnal IOP fluctuation in asymptomatic PACSs was less than that in treated PACG subjects and was at least comparable to that in treated PAC and POAG subjects. The greater the amount of PAS, the thicker the lens, the larger the VCDR, the greater was the IOP fluctuation during office hours.

In situ phosphorylation of tyrosine hydroxylase in chromaffin cells: Localization to soluble compartments.

The present studies investigated the subcellular distribution of acetylcholine's effects upon the phosphorylation of tyrosine hydroxylase in isolated purified bovine adrenal chromaffin cells. After labeling the intact chromaffin cells with (32)P(i), over 90% of the [(32)P]tyrosine hydroxylase was found in soluble fractions. Stimulation of the cells with acetylcholine, the natural secretagogue of chromaffin cells, increased the phosphorylation of tyrosine hydroxylase and over 90% of the increase was associated with soluble tyrosine hydroxylase. Homogenates and subcellular fractions from chromaffin cells were also prepared and phosphorylated in vitro in an attempt to optimize detection of tyrosine hydroxylase phosphorylation. In chromaffin cell homogenates, both 8-bromo-cyclic AMP and calcium increased (32)P incorporation into tyrosine hydroxylase, and again over 90% of the increase was observed in soluble fractions. In the particulate fraction, phosphorylation of a band which comigrated with tyrosine hydroxylase in electrophoresis was occasionally detected but only with very long autoradiographic exposures. Tyrosine hydroxylase enzymatic activity in the isolated purified chromaffin cells was also found to be associated predominantly (approx 90%) with soluble fractions. In contrast, a large portion (40-50%) of the tyrosine hydroxylase activity from crude bovine adrenal medullae was associated with the particulate fraction. The data indicate that although tyrosine hydroxylase (and possibly kinases) can associate with particulate fractions when isolated from crude bovine adrenal medullae, the enzyme is predominantly soluble when isolated from the isolated cells. Further, the effects of acetylcholine on the isolated chromaffin cells are predominantly associated with this soluble tyrosine hydroxylase and its attendant kinases.

Pseudoexfoliation in South India.

AIM: To study the profile of pseudoexfoliation in a population based study. METHOD: 2850 consecutive subjects aged 40 years or older from a population based survey in a rural area of southern India underwent complete ophthalmic evaluation including history, visual acuity testing, refraction, slit lamp examination, applanation tonometry, gonioscopy, and dilated examination of the lens (including LOCS II grading of cataract), fundus, and optic disc. Patients with pseudoexfoliation syndrome were identified and their data were analysed with respect to age, sex, intraocular pressure, gonioscopic grading, cataract, and optic neuropathy. RESULTS: 108 subjects had pseudoexfoliation syndrome (3.8 %). There was a significant increase in prevalence with age but no sex predilection. The condition was unilateral in 53 cases (49.1%) and bilateral in 55 cases (50.9%). 18 cases with pseudoexfoliation (16.7%) had high intraocular pressure (>21 mm Hg), 16 cases (14.8%) had occludable angles, and 14 cases (13%) had pseudoexfoliation glaucoma. There was a significantly higher prevalence of cataract among people with pseudoexfoliation compared to those without pseudoexfoliation (p = 0.014). CONCLUSION: The prevalence of pseudoexfoliation syndrome in the rural population of south India was 3.8%. Raised intraocular pressure was seen in 16.7% of people with pseudoexfoliation and glaucoma was present in 13%.

Continuous tissue pH and transcutaneous PO2 measurement as an index of tissue perfusion in critically ill patients.

Measurements of transcutaneous PO2 (tcPO2) and tissue pH (pHt) were compared with arterial values in 28 critically ill patients. Eleven of the patients were undergoing continuous flow cardiopulmonary bypass and the other 17 were admitted to the Intensive Therapy Unit (ITU) suffering from a variety of medical and surgical disorders. A total of 135 observations were made on the 28 patients. The overall correlation between the two sets of measurements was poor. The correlation coefficient (r) between arterial PO2 (Pa,O2) and tcPO2 was 0.41 (P less than 0.01) and between arterial pH (pHa) and pHt 0.67 (P less than 0.01). However, the value varied greatly in different groups of patients. In those patients with cardiopulmonary failure, the tcPO2 and pHt measurements rapidly and accurately reflected changes in peripheral tissue perfusion, by contrast the core-peripheral temperature deficit did not change significantly. It is concluded that the technique can be used as a sensitive index of peripheral blood flow and may have prognostic significance

High frequency oscillations and mucociliary transport.

Mucociliary transport is influenced by high frequency oscillation of air within the lungs. While some studies suggest that high frequency ventilation may be detrimental, with appropriate techniques, there is no doubt that this has potential as a means of improving the clearance of secretions from the lung.

High-risk obstetric patients. Maternal morbidity after cesareans.

OBJECTIVE: To assess maternal morbidity associated with cesarean delivery among high-risk obstetric patients in a private practice setting. STUDY DESIGN: Maternal outcome parameters were prospectively studied in 1,000 consecutively delivered patients over a one-year period. RESULTS: Three hundred forty-one patients (34%) delivered by cesarean; 194 of the procedures were performed without labor. The incidence of febrile morbidity and wound infection in patients undergoing cesarean delivery without labor, 0.5%, was no greater than that of patients who delivered vaginally (P = 1.0). There was a higher incidence of transfusion in patients delivered by cesarean without labor, but these patients were more likely to have preoperative anemia (P = .036). Patients undergoing cesarean with labor or ruptured membranes had an increased incidence of both febrile morbidity (P = .023) and wound seroma (P = .008). CONCLUSION: Maternal morbidity following cesarean delivery in high-risk obstetric patients in a private practice setting is low.

Important characteristics of a director of medical education.

In osteopathic graduate medical education programs, the Director of Medical Education (DME) plays the key leadership role. This article outlines critical characteristics and skills that the DME should possess to successfully perform in this role. Central to this success is a passionate commitment to osteopathic medical education and a commitment to justice and fairness.

Improving productivity in the dental practice: a starting point.

Materials, patients, and information flow through the business, but all must pass through the dentist's hands. Thus they are the constraint within the dental practice. Dentists therefore must pay close attention to streamlining and simplifying clinical processes, delegating administration wherever possible, and outsourcing technical services. It is recommended that techniques such as four-handed dentistry, tray-batching of instruments, computerisation of records, and efficient scheduling of appointments, be adopted to improve through-put. Measures used to assess decision-making and performance-evaluation include the use of a computerised cashbook, appointment-book analysis, comparison of actual versus budgeted income and expenditure, net profit, and return on investment. These measurements are, however, an adjunct to intuition and experience. There must be an awareness that, if patient perceptions fall short of their expectations because of the improvement in clinical efficiencies, such optimisation would be to the detriment of the practice. To achieve on-going improvement, the dentist must create a learning environment where motivated team members are willing to engage in systematic problem solving, experimentation, and the learning and transfer of knowledge.

Establishing a competitive advantage through quality management.

The successful dentist of the future will establish a sustainable competitive advantage in the marketplace by recognising that patients undergoing dental treatment cannot see the result before purchase, and that they therefore look for signs of service quality to reduce uncertainty. Thus the successful dentist will implement a quality programme that recognises not only that quality is defined by meeting patients' needs and expectations, but also that quality service is fundamental to successful business strategy. Finally, the successful dentist of the future will realise that the pursuit of quality is a never-ending process which requires leadership by example.

Dental caries and the microbial ecology of dental plaque: a review of recent advances.

Our understanding of the microbial ecology of dental plaque has rapidly grown with recent developments in the techniques of molecular biology. In particular, knowledge of the mechanisms underlying the acquisition, establishment, pathogenicity, and evolution of the group of organisms responsible for dental caries--the mutans streptococci--has expanded to the point that we can now contemplate new opportunities for caries prevention. These advances reinforce developing concepts of dental plaque as an interdependent, interacting community of specialised organisms with an ability to rapidly adapt conferred by gene structures that facilitate the expeditious modular rearrangement of protein components.

Trunk orientation, stability, and quadrupedalism.

Interesting cases of human quadrupedalism described by Tan and Colleagues (2005-2012) have attracted the attention of geneticists, neurologists, and anthropologists. Since his first publications in 2005, the main attention has focused on the genetic aspects of disorders that lead to quadrupedalism within an evolutionary framework. In recent years this area has undergone a convincing critique (Downey, 2010) and ended with a call "… to move in a different direction … away from thinking solely in terms of genetic abnormality and evolutionary atavism." We consider quadrupedalism as a "natural experiment" that may contribute to our knowledge of the physiological mechanisms underlying our balance system and our tendency toward normal (upright) posture. Bipedalism necessitates a number of characteristics that distinguish us from our ancestors and present-day mammals, including: size and shape of the bones of the foot, structure of the axial and proximal musculature, and the orientation of the human body and head. In this review we address the results of experimental studies on the mechanisms that stabilize the body in healthy people, as well as how these mechanisms may be disturbed in various forms of clinical pathology. These disturbances are related primarily to automatic rather than voluntary control of posture and suggest that human quadrupedalism is a behavior that can result from adaptive processes triggered by disorders in postural tone and environmental cues. These results will serve as a starting point for comparing and contrasting bi- and quadrupedalism.

Body-worn motion sensors detect balance and gait deficits in people with multiple sclerosis who have normal walking speed.

While balance and gait limitations are hallmarks of multiple sclerosis (MS), standard stopwatch-timed measures practical for use in the clinic are insensitive in minimally affected patients. This prevents early detection and intervention for mobility problems. The study sought to determine if body-worn sensors could detect differences in balance and gait between people with MS with normal walking speeds and healthy controls. Thirty-one MS and twenty-eight age- and sex-matched control subjects were tested using body-worn sensors both during quiet stance and gait (Timed Up and Go test, TUG). Results were compared to stopwatch-timed measures. Stopwatch durations of the TUG and Timed 25 Foot Walk tests were not significantly different between groups. However, during quiet stance with eyes closed, people with MS had significantly greater sway acceleration amplitude than controls (p=0.02). During gait, people with MS had greater trunk angular range of motion in roll (medio-lateral flexion, p=0.017) and yaw (axial rotation, p=0.026) planes. Turning duration through 180° was also longer in MS (p=0.031). Thus, body-worn motion sensors detected mobility differences between MS and healthy controls when traditional timed tests could not. This portable technology provides objective and quantitative mobility data previously not obtainable in the clinic, and may prove a useful outcome measure for early mobility changes in MS.

A meta-regression of the long-term effects of deep brain stimulation on balance and gait in PD.

OBJECTIVE: Deep brain stimulation (DBS) alleviates the cardinal Parkinson disease (PD) symptoms of tremor, rigidity, and bradykinesia. However, its effects on postural instability and gait disability (PIGD) are uncertain. Contradictory findings may be due to differences the in stimulation site and the length of time since DBS surgery. This prompted us to conduct the first meta-regression of long-term studies of bilateral DBS in the subthalamic nucleus (STN) and globus pallidus interna (GPi). RESULTS: Eleven articles reported a breakdown of the Unified Parkinson's Disease Rating Scale score before and beyond 3 years postsurgery (mean 4.5 years). Random effects meta-regression revealed that DBS initially improved PIGD compared to the OFF medicated state before surgery, but performance declined over time and extrapolation showed subjects would reach presurgery levels 9 years postsurgery. ON medication, DBS improved PIGD over and above the effect of medication before surgery. Nevertheless, for the STN group, PIGD progressively declined and was worse than presurgery function within 2 years. In contrast, GPi patients showed no significant long-term decline in PIGD in the medicated state. Improvements in cardinal signs with DBS at both sites were maintained across 5 years in the OFF and ON medication states. CONCLUSIONS: DBS alone does not offer the same improvement to PIGD as it does to the cardinal symptoms, suggesting axial and distal control are differentially affected by DBS. GPi DBS in combination with levodopa seemed to preserve PIGD better than did STN DBS, although more studies of GPi DBS and randomized controls are needed.