The mitochondrial K(ATP) channel opener BMS-191095 reduces neuronal damage after transient focal cerebral ischemia in rats.

Activation of mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels protects the brain against ischemic or chemical challenge. Unfortunately, the prototype mitoK(ATP) channel opener, diazoxide, has mitoK(ATP) channel-independent actions. We examined the effects of BMS-191095, a novel selective mitoK(ATP) channel opener, on transient ischemia induced by middle cerebral artery occlusion (MCAO) in rats. Male Wister rats were subjected to 90 mins of MCAO. BMS-191095 (25 microg; estimated brain concentration of 40 micromol/L) or vehicle was infused intraventricularly before the onset of ischemia. In addition, the effects of BMS-191095 on plasma and mitochondrial membrane potentials and reactive oxygen species (ROS) production in cultured neurons were examined. Finally, we determined the effects of BMS-191095 on cerebral blood flow (CBF) and potassium currents in cerebrovascular myocytes. Treatment with BMS-191095 24 h before the onset of ischemia reduced total infarct volume by 32% and cortical infarct volume by 38%. However, BMS-191095 administered 30 or 60 mins before MCAO had no effect. The protective effects of BMS-191095 were prevented by co-treatment with 5-hydroxydecanoate (5-HD), a mitoK(ATP) channel antagonist. In cultured neurons, BMS-191095 (40 micromol/L) depolarized the mitochondria without affecting ROS levels, and this effect was inhibited by 5-HD. BMS-191095, similar to the vehicle, caused an unexplained but modest reduction in the CBF. Importantly, BMS-191095 did not affect either the potassium currents in cerebrovascular myocytes or the plasma membrane potential of neurons. Thus, BMS-191095 afforded protection against cerebral ischemia by delayed preconditioning via selective opening of mitoK(ATP) channels and without ROS generation.     

Defecography as part of the evaluation of anorectal dysfunction

Defecography is the evaluation of the anus and rectum during the act of defecation. We have devised a very simple method of performing this examination in conjunction with the Radiology Department. The entire procedure takes less than 15 minutes from start to finish. In our hospital, we have performed over 130 of these tests. A high level of patient cooperation has been noted in our experience. For the most part, the entire procedure from bowel preparation to final films is well tolerated.     

Questionnaire analysis of the swallowing‐related outcomes following total laryngectomy

Objective: To determine the effects of a total laryngectomy on the swallow and subsequent quality of life in head and neck cancer patients. Design: Cross‐sectional single centre cohort study. Setting: Head and Neck Oncology Unit, Tertiary Referral Unit. Patients: Sixty‐two patients who underwent total laryngectomy at our centre participated in the study. Methods: Subjects were stratified by age, sex, tumour stage, other procedures such as myotomy and nerve re‐implantation. Pharyngectomy, glossectomy, flap reconstruction, neck dissection and previous radio‐ and chemotherapy were also assessed to see if they affected swallow and subsequent quality of life. Main outcome was measured using the MD Anderson Dysphagia Inventory questionnaire. Results: Responses were received from 46 males and 16 females (response rate of 80.5%) with a mean age of 64.7 years (SD 9.4). Median follow‐up in patients was 90 months (range 1–276). The mean MD Anderson Dysphagia Inventory total score in our series of patients was 77.7 (SD 16.6). MD Anderson Dysphagia Inventory global score was 79.4 (SD 22.6), Emotional score was 77.7 (SD 17.8), Functional score 81.3 (SD 15.9) and Physical score was 74.1(SD 18). Statistically significant differences were seen between the emotional scores of glossectomised and non‐glossectomised patients (Mann Whitney, P = 0.04). No significant correlation was seen between the subscale scores and the remaining treatment variables such as age, gender, site, tumour stage, myotomy, nerve implantation, radiotherapy, reconstruction and major complications. Conclusion: This questionnaire study is the largest of its type to assess the swallow of patients who have undergone laryngectomy at a single centre. The overall result confirmed that most patients had a subjectively good swallow. Only glossectomy and the method of PE segment closure were shown to significantly affect swallowing outcomes following surgery. We recommend further work especially prospective studies pre and post surgery using this or similarly validated instruments to fully assess swallow in the laryngectomy population.     

The intraocular pressure and diabetes--a correlative study

In the present study 60 diabetics were examined for intraocular pressure, scleral rigidity and facility of outflow. The intraocular pressure was found higher than in the general population except in patients with proliferative retinopathy. There was no marked difference in scleral rigidity in diabetics. The facility of outflow was lower in diabetic patients.     

Postcoital contraception with levonorgestrel during the peri-ovulatory phase of the menstrual cycle. Task Force on Post-ovulatory Methods for Fertility Regulation

The contraceptive efficacy and side effects of postcoital levonorgestrel used repeatedly during the peri-ovulatory period of one cycle was examined in 259 women. All subjects were of proven fertility in their present union and had ovulatory cycles as assessed from pre-treatment BBT charts. The mean number of coital acts during the treatment cycle was 7.5 (SD:2.6) and the mean number of 0.75 mg levonorgestrel tablets taken during the peri-ovulatory period was 4.0 (SD:1.2). Two pregnancies, both considered to be method failures, occurred, giving a failure rate of 0.8% per treated cycle. Although the overall effect of levonorgestrel on menstrual cycle length was small and insignificant, menstrual cycle disturbances were not uncommon. Intermenstrual bleeding or spotting occurred in 8.5% of the treated cycles and 12.5% of the cycles were less than 20 or more than 35 days. Other side effects, mainly nausea, headache and dizziness, were reported by about 20% of the subjects but the apparent incidence of these complaints varied markedly between the nine participating centres from 0% to just over 50%. The data suggest that repeated postcoital use of levonorgestrel is probably not a viable approach to fertility regulation for the majority of women who have regular intercourse and wish to limit the number of their pregnancies.     

Extent of ictal origin in mesial temporal sclerosis patients monitored with subdural intracranial electrodes predicts outcome.

In patients with mesiotemporal sclerosis, posterior hippocampal involvement at the ictal onset is not associated with an excellent outcome. A study confirmed that ictal onset in the posterior parahippocampal gyrus is associated with a less favorable outcome compared with ictal onset in the anterior parahippocampal gyrus in patients with mesiobasal temporal lobe epilepsy who are undergoing foramen ovale recording. The authors hypothesized that involvement of the two medial contact points of posterior basal temporal subdural (SD) strip at the ictal onset, representing ictal onset in the posterior parahippocampal gyrus, may also adversely influence the surgical outcome. With this objective, the authors assessed the incidence of posterior basal temporal SD strip (the two medial contact points) involvement at the ictal onset in patients with mesiotemporal sclerosis and determined whether presence of this finding influenced surgical outcome. Thirty-six patients with mesiotemporal sclerosis underwent a single SD grid (lateral frontotemporal) and strips (three basal temporal and one orbitosubfrontal) monitoring. Based on the earliest involvement of basal temporal strips (the two medial contact points) during the seizure, patients were classified into (1) anterior and/or middle basal temporal, or (2) posterior basal temporal (with or without involvement of anterior and/or middle basal temporal) ictal onset groups. A temporal lobectomy with adequate resection of the ictal onset zone was performed in all patients. Surgical outcome was based on Engel's classification. Six of 36 (17%) patients were classified into the posterior basal temporal ictal onset group. Only two patients from the posterior basal temporal ictal onset group experienced a good outcome compared with 26 of 30 patients from anterior and/or middle basal temporal ictal onset group (P = 0.01). In patients with mesiotemporal sclerosis who were monitored with SD electrodes, involvement of the two medial contact points of posterior basal temporal strip at the ictal onset (representing ictal onset in the posterior parahippocampal gyrus) occurred in 17% of the patients. These patients might not experience an excellent surgical outcome despite including the ictal onset zone in resection. These findings may be useful in presurgical counseling of patients with mesiotemporal sclerosis who undergo intracranial SD monitoring.     

Video-EEG study in an adult and a child with eyelid myoclonia with absences.

Two patients with eyelid myoclonia with absences (EMA) are described. Videotape of the eyelid myoclonia in one patient is presented. An interesting feature in one patient was the induction of clinical seizures only with daylight, and in another the presence of rare, focal, epileptiform discharges during drowsiness. Valproic acid only partially controlled eyelid myoclonia in both cases. Lamotrigine, alone or in combination with valproate, can be used as an alternative but was ineffective in our cases. [Published with video sequences].