Frontal and frontoparietal injury differentially affect the ipsilateral corticospinal projection from the nonlesioned hemisphere in monkey (Macaca mulatta).

Upper extremity hemiplegia is a common consequence of unilateral cortical stroke. Understanding the role of the unaffected cerebral hemisphere in the motor recovery process has been encouraged, in part, by the presence of ipsilateral corticospinal projections (iCSP). We examined the neuroplastic response of the iCSP from the contralesional primary motor cortex (cM1) hand/arm area to spinal levels C5-T1 after spontaneous long-term recovery from isolated frontal lobe injury and isolated frontoparietal injury. High-resolution tract tracing, stereological, and behavioral methodologies were applied. Recovery from frontal motor injury resulted in enhanced numbers of terminal labeled boutons in the iCSP from cM1 compared with controls. Increases occurred in lamina VIII and the adjacent ventral sectors of lamina VII, which are involved in axial/proximal limb sensorimotor processing. Larger frontal lobe lesions were associated with greater numbers of terminal boutons than smaller frontal lobe lesions. In contrast, frontoparietal injury blocked this response; total bouton number was similar to controls, demonstrating that disruption of somatosensory input to one hemisphere has a suppressive effect on the iCSP from the nonlesioned hemisphere. However, compared with controls, elevated bouton numbers occurred in lamina VIII, at the expense of lamina VII bouton labeling. Lamina IX boutons were also elevated in two frontoparietal lesion cases with extensive cortical injury. Because laminae VIII and IX collectively harbor axial, proximal, and distal motoneurons, therapeutic intervention targeting the ipsilateral corticospinal linkage from cM1 may promote proximal, and possibly distal, upper-limb motor recovery following frontal and frontoparietal injury.

Vulnerability of the medial frontal corticospinal projection accompanies combined lateral frontal and parietal cortex injury in rhesus monkey.

Concurrent damage to the lateral frontal and parietal cortex is common following middle cerebral artery infarction, leading to upper extremity paresis, paresthesia, and sensory loss. Motor recovery is often poor, and the mechanisms that support or impede this process are unclear. Since the medial wall of the cerebral hemisphere is commonly spared following stroke, we investigated the spontaneous long-term (6 and 12 month) effects of lateral frontoparietal injury (F2P2 lesion) on the terminal distribution of the corticospinal projection (CSP) from intact, ipsilesional supplementary motor cortex (M2) at spinal levels C5 to T1. Isolated injury to the frontoparietal arm/hand region resulted in a significant loss of contralateral corticospinal boutons from M2 compared with controls. Specifically, reductions occurred in the medial and lateral parts of lamina VII and the dorsal quadrants of lamina IX. There were no statistical differences in the ipsilateral CSP. Contrary to isolated lateral frontal motor injury (F2 lesion), which results in substantial increases in contralateral M2 labeling in laminae VII and IX (McNeal et al. [2010] J. Comp. Neurol. 518:586-621), the added effect of adjacent parietal cortex injury to the frontal motor lesion (F2P2 lesion) not only impedes a favorable compensatory neuroplastic response but results in a substantial loss of M2 CSP terminals. This dramatic reversal of the CSP response suggests a critical trophic role for cortical somatosensory influence on spared ipsilesional frontal corticospinal projections, and that restoration of a favorable compensatory response will require therapeutic intervention.

Old age affects fingertip forces when restraining an unpredictably loaded object.

We investigated the effects of old age on the fingertip force responses that occurred when a grasped handle was pulled unexpectedly to increase the tangential load at the fingertip. These automatic responses, directed normal to the handle surface, help prevent slips between the handle and finger. Old adults (average age 78 years) responded with large peak fingertip forces compared to young adults (average age 30 years), even though the two subject groups showed similar skin slipperiness. For step-shaped loads the average response latency was the same for young and old subjects (about 80 ms). Thus, these automatic responses are not susceptible to the age-related central delays known for simple reaction-time tasks. For ramp-shaped loads the average response latency was inversely related to load rate. Response latency was 25 ms longer for the Old group versus the Young group for loads of 8 N/s, and this difference increased exponentially to a 110-ms difference for 2-N/s loads. A twofold difference in the tangential force required to evoke a response was predicted from linear regressions and can account for the latency difference (0.2 N vs 0.4 N threshold for young and old, respectively, r=0.93 for both groups). This theoretical elevation in load force threshold is consistent with degraded central information processing in old age, and the deterioration of cutaneous mechanoreceptors.

Mechanisms for age-related changes of fingertip forces during precision gripping and lifting in adults.

We investigated changes across the adult life span of the fingertip forces used to grip and lift objects and their possible causes. Grip force, relative safety margin (grip force exceeding the minimum to avoid slip, as a fraction of slip force), and skin slipperiness increased beginning at age 50 years. Skin slipperiness explained relative safety margin increases until age 60 years. Hence, after age 60 years, additional factors must elevate grip force. We argue that one factor is impaired cutaneous afferent encoding of skin-object frictional properties on the basis of three findings. First, only subjects 60 years and older increased their relative safety margins when the friction of the gripped surfaces was varied randomly versus experiments that varied only object weight. Skin slipperiness did not account for this behavior. Second, these older subjects scaled the initial portion of their force trajectories for the slippery surface during experiments when friction was varied. Third, their grip force adjustments to new surfaces were delayed approximately 100 msec as compared with young subjects. Previous research has demonstrated that friction is signaled locally by fast-adapting afferents (FA I afferents), which decrease in number during old age. By contrast, adjustments triggered by object set-down, an event encoded by FA II afferents throughout the hand and wrist, were not delayed in our old subjects. Other findings included that anticipatory control of fingertip forces using memory of object weight was unimpaired in old age. Finally, old and young adults modulated their fingertip forces with equal smoothness and with similar relative intertrial variability.

Tactile impairments cannot explain the effect of age on a grasp and lift task.

This experiment addressed the often-posed theory that age-related declines in manual dexterity result from diminished tactile function. We measured the time 'young' subjects (n=33; mean=45 years) and 'old' subjects (n=33; mean=74 years) needed to grip (thumb and index finger), lift, and transport a small metal sphere when vision was permitted and when blindfolded. Subjects began each trial by reaching for the sphere and were instructed to complete the entire task quickly. In the absence of visual information, placement of the finger and thumb for a secure grip and lift cannot be performed efficiently without tactile information. If age-related tactile changes are functionally significant for this task, then without visual information the 'old' group should show a disproportionate increase in the duration of the grip and lift phase of the task compared to the 'young' group. Perceptual thresholds for tactile pressure stimuli (Semmes-Weinstein filaments) confirmed well-known age-related changes. Age and vision effects were manifest mainly during the grip-lift phase (time from object contact to lift-off from its support surface), with the expected finding that the 'old' group required more time than 'young' group, regardless of visual condition. The main finding was that the 'grip-lift' duration in the 'no-vision' condition was about twice the duration observed in the 'vision' condition for both age groups (ratios of 2.1 and 2.3 for 'young' and 'old', respectively). This similar relative slowing for the two groups fails to support the hypothesis that old adults' ability to grip and lift the object was limited by changes in the availability or use of tactile information.

Staphylococcus aureus bacteremia: factors predicting hospital mortality.

Among 89 episodes of Staphylococcus aureus bacteremia, factors identified as independent predictors of hospital mortality were Acute Physiology and Chronic Health Evaluation III score > 60 (odds ratio [OR], 3.2; 95% confidence interval [CI95], 1.7 to 5.9) and Lifestyle score > 1 (OR, 2.1; CI95, 1.2 to 3.6). Future studies of S aureus bacteremia should take into consideration acute severity of illness (as well as treatment and source of infection) when evaluating outcome.

Conversion of treatment from cefoxitin to ampicillin/sulbactam: experience in a university teaching hospital.

A 12-month trial, conducted in a 650-bed university teaching hospital, evaluated the conversion from cefoxitin to ampicillin/sulbactam. This report discusses the methodology used to evaluate the feasibility of the change and the challenges encountered during the trial period. The effect of cost and overall therapeutic outcome were other aspects of the evaluation. Results indicate that a conversion from cefoxitin to ampicillin/sulbactam is not only feasible but is also a realistic approach to achieving high-quality, cost-effective care.

Clinical appropriateness, therapeutic equivalence, and cost of conversion of H2 antagonist therapy.

A 12-month drug monitoring program targeting the use of H2 antagonists was initiated at the Erie County Medical Center, a 650-bed academic teaching hospital in Buffalo, NY. Discussed in this article are the development of indicators used to determine appropriateness of therapy, implementation of a H2 antagonist monitoring and screening program, examination of the effect of the program on budgetary expenditures for H2 antagonist therapy, evaluation of adverse effects and potential drug interactions associated with drug use, and measurement of possible drug cost savings resulting from the implementation of the program.