Antioxidant-rich diets improve cerebellar physiology and motor learning in aged rats

The free radical theory of aging predicts that reactive oxygen species are involved in the decline in function associated with aging. The present paper reports that diets supplemented with either spinach, strawberries or blueberries, nutritional sources of antioxidants, reverse age-induced declines in beta-adrenergic receptor function in cerebellar Purkinje neurons measured using electrophysiological techniques. In addition the spinach diet improved learning on a runway motor task, previously shown to be modulated by cerebellar norepinephrine. Motor learning is important for adaptation to changes in the environment and is thus critical for rehabilitation following stroke, spinal cord injury, and the onset of some neurodegenerative diseases. These data are the first to indicate that age-related deficits in motor learning and memory can be reversed with nutritional interventions.     

A comparison of spinal, epidural, and general anesthesia for outpatient knee arthroscopy

We compared general, epidural, and spinal anesthesia for outpatient knee arthroscopy (excluding anterior cruciate ligament repairs). Forty-eight patients (ASA physical status I-III) were randomized to receive either propofol-nitrous oxide general anesthesia with a laryngeal mask airway with anesthetic depth titrated to a bispectral index level of 40-60, 15-20 mL of 3% 2-chloroprocaine epidural, or 75 mg of subarachnoid procaine with 20 microg fentanyl. All patients were premedicated with <0.035 mg/kg midazolam and <1 microg/kg fentanyl and received intraarticular bupivacaine and 15-30 mg of IV ketorolac during the procedure. Recovery times, operating room turnover times, and patient satisfaction were recorded by an observer using an objective scale for recovery assessment and a verbal rating scale for satisfaction. Statistical analysis was performed with analysis of variance and chi(2). Postanesthesia care unit discharge times for the general and epidural groups were similar (general = 104+/-31 min, epidural = 92+/-18 min), whereas the spinal group had a longer recovery time (146+/-52 min) (P = 0.0003). Patient satisfaction was equally good in all three groups (P = 0.34). Room turnover times did not differ among groups (P = 0.16). There were no anesthetic failures or serious adverse events in any group. Pruritus was more frequent in the spinal group (7 of 16 required treatment) than in the general or epidural groups (no pruritus) (P<0.001). We conclude that epidural anesthesia with 2-chloroprocaine provides comparable recovery and discharge times to general anesthesia provided with propofol and nitrous oxide. Spinal anesthesia with procaine and fentanyl is an effective alternative and is associated with a longer discharge time and increased side effects. Implications: For outpatient knee arthroscopy, anesthesia can be provided adequately with regional or general anesthesia. Epidural and general anesthesia provide equal recovery times and patient satisfaction, whereas spinal anesthesia may prolong recovery and have increased side effects. The choice of anesthesia may depend primarily on the patient's interest in being alert or asleep during the procedure.     

Advances in computer-assisted single-photon emission computed tomography (SPECT) for epilepsy surgery in children

Epilepsy surgery has emerged as an important option in the treatment of children with epilepsy that is refractory to antiepileptic drug management. The cornerstone of successful surgery is accurate localization of the brain region of seizure onset. Traditional techniques of seizure onset localization, e.g. surface electroencephalography (EEG) recording and magnetic resonance imaging (MRI), allow accurate localization in a significant number of patients. When the focus of seizure onset is not apparent from these non-invasive techniques, other methods of localization, e.g. intracranial EEG recording, may be needed before resection of the focus. Single-photon emission computed tomography (SPECT) is a nuclear medicine blood-flow technique that has been used to identify a region of epileptogenic brain associated with low blood flow in the resting state (interictal SPECT) or increased blood flow at the time of seizure activity (ictal SPECT). This report describes the validation and utility of a computer-assisted method of subtracting the interictal from the ictal SPECT scans and co-registering the difference image on the MRI. This method, called subtraction ictal SPECT co-registered on MRI (SISCOM), is used in guiding the location and the extent of intracranial electrode implantation, or in obviating the need for the implantation in some cases.     

Stereotactic radiosurgery for cavernous malformations

OBJECT: The use of stereotactic radiosurgery to treat cerebral cavernous malformations (CMs) is controversial. To evaluate the efficacy and safety of CM radiosurgery, the authors reviewed the experience at the Mayo Clinic during the past 10 years. METHODS: Seventeen patients underwent radiosurgery for high-surgical-risk CMs in the following sites: thalamus/basal ganglia (four patients), brainstem (12 patients), and corpus callosum (one patient). All patients had experienced at least two documented hemorrhages before undergoing radiosurgery. Stereotactic magnetic resonance (MR) imaging was used for target localization in all cases. The median margin radiation dose was 18 Gy and the median maximum dose was 32 Gy. The median length of follow-up review following radiosurgery was 51 months. The annual hemorrhage rate during the 51 months preceding radiosurgery was 40.1%, compared with 8.8% in the first 2 years following radiosurgery and 2.9% thereafter. In 10 patients (59%) new neurological deficits developed that were associated with regions of increased signal on long-repetition time MR imaging performed a median of 8 months (range 5-16 months) after radiosurgery. Three patients recovered, giving the group a permanent radiation-related morbidity rate of 41%. Compared with 31 patients harboring arteriovenous malformations (AVMs) of sizes and in locations similar to those of the aforementioned CMs, who underwent radiosurgery during the same time period, the patients with CMs were more likely to experience radiation-related complications (any complication, 59% compared with 10%; p < 0.001; permanent complication, 41% compared with 10%; p = 0.02). CONCLUSIONS: It is impossible to conclude that radiosurgery protects patients with CMs against future hemorrhage risk based on the available data, although it appears that some reduction in the bleeding rate occurs after a latency interval of several years. The risk of radiation-related complications after radiosurgery to treat CMs is greater than that found after radiosurgery in AVMs, even when adjusting for lesion size and location and for radiation dose.     

Diet Modification before or during Pregnancy on Maternal and Foetal Outcomes in Rodent Models of Maternal Obesity

The obesity epidemic has serious implications for women of reproductive age; its rising incidence is associated not just with health implications for the mother but also has transgenerational ramifications for the offspring. Increased incidence of diabetes, cardiovascular disease, obesity, and kidney disease are seen in both the mothers and the offspring. Animal models, such as rodent studies, are fundamental to studying maternal obesity and its impact on maternal and offspring health, as human studies lack rigorous controlled experimental design. Furthermore, the short and prolific reproductive potential of rodents enables examination across multiple generations and facilitates the exploration of interventional strategies to mitigate the impact of maternal obesity, both before and during pregnancy. Given that obesity is a major public health concern, it is important to obtain a greater understanding of its pathophysiology and interaction with reproductive health, placental physiology, and foetal development. This narrative review focuses on the known effects of maternal obesity on the mother and the offspring, and the benefits of interventional strategies, including dietary intervention, before or during pregnancy on maternal and foetal outcomes. It further examines the contribution of rodent models of maternal obesity to elucidating pathophysiological pathways of disease development, as well as methods to reduce the impact of obesity on the mothers and the developing foetus. The translation of these findings into the human experience will also be discussed.     

Trams,trains, planes and automobiles: logistics of conducting a statewide audit of medical records

Objective: This paper reports on the logistics of conducting a validation study of a routinely collected dataset against medical records at hospitals to inform planning of similar studies. Method: A stratified random sample of 15 hospitals and two homebirth practitioners was included. Site visits were arranged following consent. In addition to the validation of perinatal data, information was collected regarding logistics. Results: Records at 14 metropolitan and rural hospitals up to 500 km from the research centre, and two homebirth practitioners, were audited. Obtaining consent to participate took between 5 days and 10 months. Auditors visited sites on 101 days, auditing 737 medical record pairs at 16 sites. Median audit time per record was 51.3 minutes; electronic records each took 36 minutes longer than paper. Travel time accounted for nearly one‐quarter of audit time. Conclusions: Delays obtaining consents, long travel times and electronic records prolonged audit duration and expense. Employment of experts maximised use of available audit time. Conducting a validation study is a time‐consuming and expensive exercise; however, confidence in the accuracy of public health data is vital. Implications: Validation studies are unquestionably important. Three alternative strategies have been proposed to make future studies viable.     

ATR inhibition sensitizes liposarcoma to doxorubicin by increasing DNA damage

Liposarcomas account for approximately 20% of all adult sarcomas and have limited therapeutic options outside of surgery. Inhibition of ataxia-telangiectasia and Rad3 related protein kinase (ATR) has emerged as a promising chemotherapeutic strategy in various cancers. However, its activation, expression, and function in liposarcoma remain unkown. In this study, we investigated the expression, function, and potential of ATR as a therapeutic target in liposarcoma. Activation and expression of ATR in liposarcoma was analyzed by immunohistochemistry, which was further explored for correlation with patient clinical characteristics. ATR-specific siRNA and the ATR inhibitor VE-822 were applied to determine the effect of ATR inhibition on liposarcoma cell proliferation and anti-apoptotic activity. Migration activity and clonogenicity were examined using wound healing and clonogenic assays. ATR (p-ATR) was overexpressed in 88.1% of the liposarcoma specimens and correlated with shorter overall survival in patients. Knockdown of ATR via specific siRNA or inhibition with VE-822 suppressed liposarcoma cell growth, proliferation, migration, colony-forming ability, and spheroid growth. Importantly, ATR inhibition significantly and synergistically enhanced liposarcoma cell line chemosensitivity to doxorubicin. Our findings support ATR as critical to liposarcoma proliferation and doxorubicin resistance. Therefore, the addition of ATR inhibition to a standard doxorubicin regimen is a potential treatment strategy for liposarcoma.     

Acute otomastoiditis and its complications: role of CT

Acute bacterial (suppurative) otomastoiditis responds to antibiotic treatment; radiologic study is required only when there is clinical suggestion of coalescent mastoiditis, intracranial complications, or an underlying chronic disease. Computed tomography (CT) is the method of choice for evaluating otogenic intra- or extra-cranial complications. CT scans can show stages of disease progression when infection has spread by way of soft tissue, blood, and bone pathways into the dural venous sinuses, meninges, labyrinth, facial nerves, epidural and other intracranial spaces. When there is clinical suggestion of acute coalescent mastoiditis, a CT scan of the temporal bone can confirm the presence of rarefying osteitis, coalescence of the air cells, and subperiosteal abscess.