Bilateral subdural hematomas after lumboperitoneal shunt placement.

BACKGROUND: Lumboperitoneal shunts are commonly placed as treatment for a variety of conditions, and complications can be significant. OBJECTIVES: We discuss a rare complication of these shunts, namely bilateral non-traumatic subdural hematoma formation. CASE REPORT: A patient with a normal neurologic examination but severe nausea, weight loss, and dehydration presented 2 weeks after lumboperitoneal shunt placement for cryptococcal meningitis, and was found to have bilateral subdural hematomas. CONCLUSIONS: Physicians should be aware of this potentially devastating complication of shunt placement so that prompt and appropriate treatment can be initiated.

Characteristics of spacer device use by patients with asthma and COPD.

OBJECTIVE: Spacer devices (SD) in conjunction with metered dose inhalers (MDI) have been shown to be as effective as saline nebulizers for the delivery of beta-agonists. A preliminary study suggests that SDs are not consistently used. The purpose of this study was to investigate patterns of SD ownership and use to identify potential targets for future educational efforts to increase ownership and use of SD. METHODS: Cross-sectional convenience sample survey of patients presenting to an academic Emergency Department (ED) with a history of asthma/COPD (chronic obstructive pulmonary disease). Informed consent was obtained. Survey data included demographics, association with a primary care physician (PCP), SD ownership, patterns of use, opinions of efficacy about SD and disease severity assessed by duration of asthma/COPD, prior ED visits, hospitalizations, and history of prior intubation. Patterns of use are described and univariate and multivariate analyses were used to identify factors associated with SD ownership. RESULTS: Of the 313 patients, 55.9% were female, the mean age was 46.0 years (standard deviation 14.7), 54.3% were white, and 143 patients (45.7%) reported owning a SD. A total of 36.4% reported a prior hospitalization for their condition and 24% reported a history of being intubated. Less than half of patients presenting with asthma or COPD exacerbation that reported owning a SD used it the day of presentation to the ED. Logistic regression identified having a PCP and a history of prior hospitalization for asthma/COPD as factors independently associated with SD ownership (odds ratio [OR] 1.7, 95% confidence interval [CI] 1.1-2.7 and OR 2.2, CI 1.3-3.5, respectively). CONCLUSION: A majority of patients with asthma/COPD do not own a SD. These data suggest that there is significant opportunity for educational efforts directed at a broad range of asthma/COPD patients in hopes of increasing ownership and use of SD.

Structural and regulatory roles of muscle ankyrin repeat protein family in skeletal muscle.

The biological response of muscle to eccentric contractions (ECs) results in strengthening and protection from further injury. However, the cellular basis for this response remains unclear. Previous studies identified the muscle ankyrin repeat protein (MARP) family, consisting of cardiac ankyrin repeat protein (CARP), ankyrin repeat domain 2/ankyrin repeat protein with PEST and proline-rich region (Ankrd2/Arpp), and diabetes-associated ankyrin repeat protein (DARP), as rapidly and specifically upregulated in mice after a single bout of EC. To determine the role of these genes in skeletal muscle, a survey of skeletal muscle structural and functional characteristics was performed on mice lacking all three MARP family members (MKO). There was a slight trend toward MKO muscles having a slower fiber type distribution but no differences in muscle fiber size. Single MKO fibers were less stiff, tended to have longer resting sarcomere lengths, and expressed a longer isoform of titin than their wild-type counterparts, indicating that these proteins may play a role in the passive mechanical behavior of muscle. Finally, MKO mice showed a greater degree of torque loss after a bout of ECs compared with wild-type mice, although they recovered from the injury with the same or even improved time course. This recovery was associated with enhanced expression of the muscle regulatory genes MyoD and muscle LIM protein (MLP), suggesting that the MARP family may play both important structural and gene regulatory roles in skeletal muscle.

Stress-dependent and -independent expression of the myogenic regulatory factors and the MARP genes after eccentric contractions in rats.

The relationship between muscle mechanical conditions and gene expression was investigated by varying both stress and contraction mode imposed upon rat dorsiflexors (n= 25), activating them at high or low frequencies (150 Hz or 40 Hz) either eccentrically or isometrically. Muscle physiological, immunohistochemical and gene expression changes were then measured 24 h after the exercise bout. Peak stress was the best predictor of muscle injury, independent of contraction mode (i.e. eccentric or isometric). When peak stresses were matched, no physiological or immunohistochemical differences were detected between isometric and eccentric contractions. The expression of certain myogenic regulatory and muscle ankyrin repeat protein (MARP) genes (myoD, myogenin, MLP and CARP) depended both on peak muscle stress achieved during contraction and contraction mode. In contrast, Arpp/Ankrd2 was dramatically upregulated only by eccentric contractions, but not by isometric contractions, even though the stress level of the eccentric contractions varied over a three-fold range and overlapped with that of the isometric group. The role that Arpp/Ankrd2 upregulation plays in the biological response to eccentric contraction remains to be determined, as does the control mechanism whereby the expression of certain genes (such as myoD, myogenin, MLP and CARP) is sensitive to muscle stress while another (Arpp/Ankrd2) is sensitive only to contraction mode.

Muscle LIM protein plays both structural and functional roles in skeletal muscle.

Muscle LIM protein (MLP) has been suggested to be an important mediator of mechanical stress in cardiac tissue, but the role that it plays in skeletal muscle remains unclear. Previous studies have shown that it is dramatically upregulated in fast-to-slow fiber-type transformation and also after eccentric contraction (EC)-induced muscle injury. The functional consequences of this upregulation, if any, are unclear. In the present study, we have examined the skeletal muscle phenotype of MLP-knockout (MLPKO) mice in terms of their response to EC-induced muscle injuries. The data suggest that while the MLPKO mice recover completely after EC-induced injury, their torque production lags behind that of heterozygous littermates in the early stages of the recovery process. This lag is accompanied by decreased expression of the muscle regulatory factor MyoD, suggesting that MLP may influence gene expression. In addition, there is evidence of type I fiber atrophy and a shorter resting sarcomere length in the MLPKO mice, but no significant differences in fiber type distribution. In summary, MLP appears to play a subtle role in the maintenance of normal muscle characteristics and in the early events of the recovery process of skeletal muscle to injury, serving both structural and gene-regulatory roles.

Structural and functional changes in spastic skeletal muscle.

This review summarizes current information regarding the changes in structure or function that occur in skeletal muscle secondary to spasticity. Most published studies have reported an increase in fiber size variability in spastic muscle. There is no general agreement regarding any shift in fiber type distribution secondary to spasticity. Mechanical studies in whole limbs as well as in isolated single cells support the notion of an intrinsic change in the passive mechanical properties of muscle after spasticity in addition to the more widely reported neural changes that occur. Evidence is presented for changes within both the muscle cell and extracellular matrix that contribute to the overall changes in the tissue. Taken together, the literature supports the notion that, although spasticity is multifactorial and neural in origin, significant structural alterations in muscle also occur. An understanding of the specific changes that occur in the muscle and extracellular matrix may facilitate the development of new conservative or surgical therapies for this problem.

Rapid muscle-specific gene expression changes after a single bout of eccentric contractions in the mouse.

Eccentric contractions (ECs), in which a muscle is forced to lengthen while activated, result in muscle injury and, eventually, muscle strengthening and prevention of further injury. Although the mechanical basis of EC-induced injury has been studied in detail, the biological response of muscle is less well characterized. This study presents the development of a minimally invasive model of EC injury in the mouse, follows the time course of torque recovery after an injurious bout of ECs, and uses Affymetrix microarrays to compare the gene expression profile 48 h after ECs to both isometrically stimulated muscles and contralateral muscles. Torque dropped by approximately 55% immediately after the exercise bout and recovered to initial levels 7 days later. Thirty-six known genes were upregulated after ECs compared with contralateral and isometrically stimulated muscles, including five muscle-specific genes: muscle LIM protein (MLP), muscle ankyrin repeat proteins (MARP1 and -2; also known as cardiac ankyrin repeat protein and Arpp/Ankrd2, respectively), Xin, and myosin binding protein H. The time courses of MLP and MARP expression after the injury bout (determined by quantitative real-time polymerase chain reaction) indicate that these genes are rapidly induced, reaching a peak expression level of 6-11 times contralateral values 12-24 h after the EC bout and returning to baseline within 72 h. Very little gene induction was seen after either isometric activation or passive stretch, indicating that the MLP and MARP genes may play an important and specific role in the biological response of muscle to EC-induced injury.

Asynchronous functional, cellular and transcriptional changes after a bout of eccentric exercise in the rat.

Thirty eccentric contractions (ECs) were imposed upon rat dorsiflexors (n = 46) by activating the peroneal nerve and plantarflexing the foot ~40 deg, corresponding to a sarcomere length change over the range 2.27-2.39 microm for the tibialis anterior and 2.52-2.66 microm for the extensor digitorum longus. Animals were allowed to recover for one of 10 time periods ranging from 0.5 to 240 h, at which time muscle contractile properties, immunohistochemical labelling and gene expression were measured. Peak isometric torque dropped significantly by ~40 % from an initial level of 0.0530 +/- 0.0009 Nm to 0.0298 +/- 0.0008 Nm (P < 0.0001) immediately after EC, and then recovered in a linear fashion to control levels 168 h later. Immunohistochemical labelling of cellular proteins revealed a generally asynchronous sequence of events at the cellular level, with the earliest event measured being loss of immunostaining for the intermediate filament protein, desmin. Soon after the first signs of desmin loss, infiltration of inflammatory cells occurred, followed by a transient increase in membrane permeability, manifested as inclusion of plasma fibronectin. The quantitative polymerase chain reaction (QPCR) was used to measure transcript levels of desmin, vimentin, embryonic myosin heavy chain (MHC), myostatin, myoD and myogenin. Compared to control levels, myostatin transcripts were significantly elevated after only 0.5 h, myogenic regulatory factors significantly elevated after 3 h and desmin transcripts were significantly increased 12 h after EC. None of the measured parameters provide a mechanistic explanation for muscle force loss after EC. Future studies are required to investigate whether there is a causal relationship among desmin loss, increased cellular permeability, upregulation of the myoD and desmin genes, and, ultimately, an increase in the desmin content per sarcomere of the muscle.

Desmin cytoskeletal modifications after a bout of eccentric exercise in the rat.

Desmin content and immunohistochemical appearance were measured in tibialis anterior muscles of rats subjected to a single bout of 30 eccentric contractions (ECs). Ankle torque was measured before EC and at various recovery times, after which immunohistochemical and immunoblot analyses were performed. Torque decreased by approximately 50% immediately after EC and fully recovered 168 h later (P < 0.001). Loss of desmin staining was maximal 12 h after EC and recovered by 72 h. Immunoblots unexpectedly demonstrated a significant increase in the desmin-to-actin ratio by 72 h after EC (P < 0.01) and was still increasing after 168 h (P < 0.0001). These data demonstrate a relatively rapid qualitative loss of desmin immunostaining immediately after a single EC bout but a tremendous quantitative increase in desmin content 72-168 h later. This dynamic restructuring of the muscle's intermediate filament system may be involved in the mechanism of EC-induced muscle injury and may provide a structural explanation for the protective effects observed in muscle after a single EC bout.