Paroxysmal kinesigenic dyskinesia is an episodic movement disorder caused by dominant mutations in the proline-rich transmembrane protein PRRT2, with onset in childhood and typically with improvement or resolution by middle age. Mutations in the same gene may also cause benign infantile seizures, which begin in the first year of life and typically remit by the age of 2 years. Many details of PRRT2 function at the synapse, and the effects of mutations on neuronal excitability in the pathophysiology of epilepsy and dyskinesia, have emerged through the work of several groups over the last decade. However, the age dependence of the phenotypes has not been explored in detail in transgenic models. Here, we report our findings in heterozygous and homozygous Prrt2 knockout mice that recapitulate the age dependence of dyskinesia seen in the human disease. We show that Prrt2 deletion reduces the levels of synaptic proteins in a dose-dependent manner that is most pronounced at postnatal day 5 (P5), attenuates at P60, and disappears by P180. In a test for foot slippage while crossing a balance beam, transient loss of coordination was most pronounced at P60 and less prominent at age extremes. Slower traverse time was noted in homozygous knockout mice only, consistent with the ataxia seen in rare individuals with biallelic loss of function mutations in Prrt2. We thus identify three age-dependent phenotypic windows in the mouse model, which recapitulate the pattern seen in humans with PRRT2-related diseases.
A retrospective cohort study was preformed aiming to verify the presence of
transient dysfunction of gas exchange in the postoperative period of cardiac
surgery and determine if this disorder is linked to cardiorespiratory
events.
Methods
We included 942 consecutive patients undergoing cardiac surgery and cardiac
procedures who were referred to the Intensive Care Unit between June 2007
and November 2011.
Results
Fifteen patients had acute respiratory distress syndrome (2%), 199 (27.75%)
had mild transient dysfunction of gas exchange, 402 (56.1%) had moderate
transient dysfunction of gas exchange, and 39 (5.4%) had severe transient
dysfunction of gas exchange. Hypertension and cardiogenic shock were
associated with the emergence of moderate transient dysfunction of gas
exchange postoperatively (P=0.02 and
P=0.019, respectively) and were risk factors for this
dysfunction (P=0.0023 and P=0.0017,
respectively). Diabetes mellitus was also a risk factor for transient
dysfunction of gas exchange (P=0.03). Pneumonia was present
in 8.9% of cases and correlated with the presence of moderate transient
dysfunction of gas exchange (P=0.001). Severe transient
dysfunction of gas exchange was associated with patients who had renal
replacement therapy (P=0.0005), hemotherapy
(P=0.0001), enteral nutrition
(P=0.0012), or cardiac arrhythmia
(P=0.0451).
Conclusion
Preoperative hypertension and cardiogenic shock were associated with the
occurrence of postoperative transient dysfunction of gas exchange. The
preoperative risk factors included hypertension, cardiogenic shock, and
diabetes. Postoperatively, pneumonia, ventilator-associated pneumonia, renal
replacement therapy, hemotherapy, and cardiac arrhythmia were associated
with the appearance of some degree of transient dysfunction of gas exchange,
which was a risk factor for reintubation, pneumonia, ventilator-associated
pneumonia, and renal replacement therapy in the postoperative period of
cardiac surgery and cardiac procedures. 相似文献
During the last decades, advances in diagnosis and treatment of congenital heart
disease have allowed many individuals to reach adulthood. Due mainly to the great
diagnostic diversity and to the co-morbidities usually present in this age group,
these patients demand assistance in a multidisciplinary facility if an adequate
attention is aimed. In this paper we reviewed, based in the international literature
and also on the authors’ experience, the structural conditions that should be
available for these patients. We highlighted aspects like the facility
characteristics, the criteria usually adopted for patient transfer from the
paediatric setting, the composition of the medical and para- medical staff taking
into account the specific problems, and also the model of outpatient and in-hospital
assistance. We also emphasized the importance of patient data storage, the
fundamental necessity of institutional support and also the compromise to offer
professional training. The crucial relevance of clinical research is also approached,
particularly the development of multicenter studies as an appropriate methodology for
this heterogeneous patient population. 相似文献
The aim of this study was to evaluate the acute effects of unilateral ankle plantar flexors static-stretching (SS) on the passive range of movement (ROM) of the stretched limb, surface electromyography (sEMG) and single-leg bounce drop jump (SBDJ) performance measures of the ipsilateral stretched and contralateral non-stretched lower limbs. Seventeen young men (24 ± 5 years) performed SBDJ before and after (stretched limb: immediately post-stretch, 10 and 20 minutes and non-stretched limb: immediately post-stretch) unilateral ankle plantar flexor SS (6 sets of 45s/15s, 70-90% point of discomfort). SBDJ performance measures included jump height, impulse, time to reach peak force, contact time as well as the sEMG integral (IEMG) and pre-activation (IEMGpre-activation) of the gastrocnemius lateralis. Ankle dorsiflexion passive ROM increased in the stretched limb after the SS (pre-test: 21 ± 4° and post-test: 26.5 ± 5°, p < 0.001). Post-stretching decreases were observed with peak force (p = 0.029), IEMG (P<0.001), and IEMGpre-activation (p = 0.015) in the stretched limb; as well as impulse (p = 0.03), and jump height (p = 0.032) in the non-stretched limb. In conclusion, SS effectively increased passive ankle ROM of the stretched limb, and transiently (less than 10 minutes) decreased muscle peak force and pre-activation. The decrease of jump height and impulse for the non-stretched limb suggests a SS-induced central nervous system inhibitory effect.
Key points
When considering whether or not to SS prior to athletic activities, one must consider the potential positive effects of increased ankle dorsiflexion motion with the potential deleterious effects of power and muscle activity during a simple jumping task or as part of the rehabilitation process.
Since decreased jump performance measures can persist for 10 minutes in the stretched leg, the timing of SS prior to performance must be taken into consideration.
Athletes, fitness enthusiasts and therapists should also keep in mind that SS one limb has generalized effects upon contralateral limbs as well.
Patients with autoimmune lymphoproliferative syndrome (ALPS) and systemic lupus erythematosis (SLE) have T-cell dysregulation and produce abnormal, activated T lymphocytes and an atypical peripheral T-cell population, termed double negative T cells (DNTs). T-cell functions, including DNT transition in T-cell development and T-cell activation, are critically dependent on Notch signaling. We hypothesized that inhibiting Notch signaling would be effective in ALPS and SLE by reducing the production of abnormal DNTs and by blocking aberrant T-cell activation. We tested this hypothesis using murine models of ALPS and SLE. Mice were randomized to treatment with the notch pathway inhibitor (gamma-secretase inhibitor), N-S-phenyl-glycine-t-butyl ester (DAPT), or vehicle control. Response to treatment was assessed by measurement of DNTs in blood and lymphoid tissue, by monitoring lymph node and spleen size with ultrasound, by quantifying cytokines by bead-array, by ELISA for total IgG and anti-double-stranded DNA (dsDNA) specific antibodies, and by histopathologic assessment for nephritis. We found a profound and statistically significant decrease in all disease parameters, comparing DAPT-treated mice to controls. Using a novel dosing schema, we avoided the reported toxicities of gamma-secretase inhibitors. Inhibiting the Notch signaling pathway may thus present an effective, novel, and well-tolerated treatment for autoimmune and lymphoproliferative diseases. 相似文献
Hypertonic saline has been proposed to modulate the inflammatory cascade in certain experimental conditions, including pulmonary inflammation caused by inhaled gastric contents. The present study aimed to assess the potential anti-inflammatory effects of administering a single intravenous dose of 7.5% hypertonic saline in an experimental model of acute lung injury induced by hydrochloric acid.
METHODS:
Thirty-two pigs were anesthetized and randomly allocated into the following four groups: Sham, which received anesthesia and were observed; HS, which received intravenous 7.5% hypertonic saline solution (4 ml/kg); acute lung injury, which were subjected to acute lung injury with intratracheal hydrochloric acid; and acute lung injury + hypertonic saline, which were subjected to acute lung injury with hydrochloric acid and treated with hypertonic saline. Hemodynamic and ventilatory parameters were recorded over four hours. Subsequently, bronchoalveolar lavage samples were collected at the end of the observation period to measure cytokine levels using an oxidative burst analysis, and lung tissue was collected for a histological analysis.
RESULTS:
Hydrochloric acid instillation caused marked changes in respiratory mechanics as well as blood gas and lung parenchyma parameters. Despite the absence of a significant difference between the acute lung injury and acute lung injury + hypertonic saline groups, the acute lung injury animals presented higher neutrophil and tumor necrosis factor alpha (TNF-α), interleukin (IL)-6 and IL-8 levels in the bronchoalveolar lavage analysis. The histopathological analysis revealed pulmonary edema, congestion and alveolar collapse in both groups; however, the differences between groups were not significant. Despite the lower cytokine and neutrophil levels observed in the acute lung injury + hypertonic saline group, significant differences were not observed among the treated and non-treated groups.
CONCLUSIONS:
Hypertonic saline infusion after intratracheal hydrochloric acid instillation does not have an effect on inflammatory biomarkers or respiratory gas exchange. 相似文献