Simultaneous alterations of retinoblastoma and p53 protein expression in astrocytic tumors

The genetic alterations frequently involved in glial malignancies are in the tumor suppressor genes, Rb and p53. An altered Rb expression or p53 overexpression is thought to indicate defective tumor suppression and subsequently more aggressive tumors. Therefore, to assess the alterations in the conjoint expression of Rb and p53 proteins in formalin fixed paraffin embedded sections, 64 astrocytic tumors were studied (16 astrocytomas,7 gemistocytic astrocytomas, 19 anaplastic astrocytomas and 22 glioblastomas) using the avidin biotin immunoperoxidase technique. Fifty two cases (81.25%) were found to be positive for p53 protein. Seventeen of these showed aberrant heterogenous staining for pRb, of which 7 were glioblastomas. Only one case of astrocytoma showed aberrant expression of both p53 and Rb. Thus, of the 64 tumors, simultaneous aberrant expression of both p53 and Rb was seen in 21.9% of cases. This was more commonly observed among glioblastoma cases (7/22). No statistical difference was found between the survival rate of heterogenous pRb and p53 positivity in different grades of tumors. In glioblastomas, the survival rate appeared to be less in patients expressing heterogenous pRb, but this was not statistically significant. These results lead us to suspect that p53 and pRb pathways are inactivated, either through mutation or as part of the neoplastic process in astrocytic tumors.     

Diffuse epithelial keratopathy following a single instillation of topical lignocaine: the damaging drop

Toxic corneal epitheliopathies are a known occurrence following chronic use of topical anesthetic agents in ophthalmology. We report two cases of diffuse epithelial keratopathy following a single drop of 4% lignocaine in two diabetic patients scheduled for fundus fluorescein angiography.     

Dacrystic seizures: Demographic,semiologic, and etiologic insights from a multicenter study in long‐term video‐EEG monitoring units

Purpose: To provide an estimate of the frequency of dacrystic seizures in video‐electroencephalography (EEG) long‐term monitoring units of tertiary referral epilepsy centers and to describe the clinical presentation of dacrystic seizures in relationship to the underlying etiology. Methods: We screened clinical records and video‐EEG reports for the diagnosis of dacrystic seizures of all patients admitted for video‐EEG long‐term monitoring at five epilepsy referral centers in the United States and Germany. Patients with a potential diagnosis of dacrystic seizures were identified, and their clinical charts and video‐EEG recordings were reviewed. We included only patients with: (1) stereotyped lacrimation, sobbing, grimacing, yelling, or sad facial expression; (2) long‐term video‐EEG recordings (at least 12 h); and (3) at least one brain magnetic resonance imaging (MRI) study. Key Findings: Nine patients (four female) with dacrystic seizures were identified. Dacrystic seizures were identified in 0.06–0.53% of the patients admitted for long‐term video‐EEG monitoring depending on the specific center. Considering our study population as a whole, the frequency was 0.13%. The presence of dacrystic seizures without other accompanying clinical features was found in only one patient. Gelastic seizures accompanied dacrystic seizures in five cases, and a hypothalamic hamartoma was found in all of these five patients. The underlying etiology in the four patients with dacrystic seizures without gelastic seizures was left mesial temporal sclerosis (three patients) and a frontal glioblastoma (one patient). All patients had a difficult‐to‐control epilepsy as demonstrated by the following: (1) at least three different antiepileptic drugs were tried in each patient, (2) epilepsy was well controlled with antiepileptic drugs in only two patients, (3) six patients were considered for epilepsy surgery and three of them underwent a surgical/radiosurgical or radioablative procedure. Regarding outcome, antiepileptic drugs alone achieved seizure freedom in two patients and did not change seizure frequency in another patient. Radiosurgery led to moderately good seizure control in one patient and did not improve seizure control in another patient. Three patients were or are being considered for epilepsy surgery on last follow‐up. One patient remains seizure free 3 years after epilepsy surgery. Significance: Dacrystic seizures are a rare but clinically relevant finding during video‐EEG monitoring. Our data show that when the patient has dacrystic and gelastic seizures, the cause is a hypothalamic hamartoma. In contrast, when dacrystic seizures are not accompanied by gelastic seizures the underlying lesion is most commonly located in the temporal cortex.     

Homozygous PLCB1 deletion associated with malignant migrating partial seizures in infancy

Malignant migrating partial seizures in infancy (MMPEI) is an early onset epileptic encephalopathy with few known etiologies. We sought to identify a novel cause of MMPEI in a child with MMPEI whose healthy parents were consanguineous. We used array comparative genomic hybridization (CGH) to identify copy number variants genome-wide and long-range polymerase chain reaction to further delineate the breakpoints of a deletion found by CGH. The proband had an inherited homozygous deletion of chromosome 20p13, disrupting the promoter region and first three coding exons of the gene PLCB1. Additional MMPEI cases were screened for similar deletions or mutations in PLCB1 but did not harbor mutations. Our results suggest that loss of PLCβ1 function is one cause of MMPEI, consistent with prior studies in a Plcb1 knockout mouse model that develops early onset epilepsy. We provide novel insight into the molecular mechanisms underlying MMPEI and further implicate PLCB1 as a candidate gene for severe childhood epilepsies. This work highlights the importance of pursuing genetic etiologies for severe early onset epilepsy syndromes.     

Effect of yoga on exercise tolerance in normal healthy volunteers

Twelve normal healthy volunteers (6 males and 6 females) undergoing yoga training for 90 days were studied for the effect of yoga on exercise tolerance. Their ages ranged from 18 to 28 years. The volunteers were taught only Pranayama for the first 20 days and later on yogic asanas were added. Sub-maximal exercise tolerance test was done on a motorized treadmill by using Balke's modified protocol, initially, after 20 days (Phase-I) and after 90 days of yoga training (Phase-II). Pyruvate and lactate in venous blood and blood gases in capillary blood were estimated immediately before and after the exercise. Minute ventilation and oxygen consumption were estimated before and during the test. Post exercise blood lactate was elevated significantly during initial and Phase-I, but not in Phase-II. There was significant reduction of minute ventilation and oxygen consumption only in males in Phase-I and II at the time when the volunteers reached their 80% of the predicted heart rate. Female volunteers were able to go to higher loads of exercise in Phase-I and II.     

Cerebroprotective potential of resveratrol through anti-oxidant and anti-inflammatory mechanisms in rats

Oxidative stress and inflammation are two important pathological mechanisms involved in cerebral ischemia and reperfusion injury. In pathological conditions such as cerebral infarction, the free radical production is greater than that of elimination by endogenous anti-oxidant system, by this undesirable effect brain is highly injured. Resveratrol is reported to have anti-oxidant and anti-inflammatory, athero-protective activities. Therefore, the aim of the present study is to evaluate the therapeutic potential of resveratrol against cerebral infarction induced by ischemia and reperfusion injury in Wistar rats. Bi-common carotid occlusion followed by 4 h reperfusion model was used to induce cerebral infarction. Percent infarction, oxidative stress markers (malondialdehyde, catalase, superoxide dismutase) and inflammatory markers (myeloperoxidase, TNF-α, IL-6, ICAM-1 and IL-10) were measured. TNF-α, IL-6, IL-10, and intracellular adhesive molecule-I (ICAM-1) levels were quantified by enzyme-linked immunosorbent assay (ELISA). Resveratrol produced significant dose-dependent reduction in percent cerebral infarct volume. At resveratrol 20 mg/kg dose, there was a significant reduction in oxidative stress and inflammatory markers like malondialdehyde, TNF-α, IL-6, myeloperoxidase and ICAM-I and in contrast there was a significant increase in anti-oxidants and anti-inflammatory markers like superoxide dismutase, catalase and IL-10 levels. Resveratrol showed significant cerebroprotective action mediated by anti-oxidant and anti-inflammatory mechanisms.