Inhalational anesthetics inhibit spreading depression: relevance to migraine

Cortical spreading depression (SD) has not been shown in the human neocortex by direct cortical recordings. However, animal studies suggest that cortical injury, such as that occurring during neurosurgical procedures, should result in the initiation of SD. It is possible that inhibition of SD by volatile anesthetic agents may partially explain the failure to observe SD in the human neocortex during surgery. This study examines the effect of the anesthetic agents α-chloralose, halothane, nitrous oxide and isoflurane on the initiation of cortical SD in the cat neocortex. SD was seen in 100% of cats anesthetized with α-chloralose ( n = 15), in 3 of 7 (42%) animals anesthetized with isoflurane ( p < 0.05, χ² with Yates correction) and none of the animals ( n = 4, 6 hemispheric preparations) anesthetized with halothane ( p < 0.005, χ² with Yates correction, halothane vs α-chloralose group). In all cases this inhibitory effect was reversible. In four animals the administration of nitrous oxide (66%) reduced the inspired concentration of isoflurane required to inhibit SD by 0.75%. This study suggests that halothane, and to a lesser extent isoflurane and nitrous oxide, protect against the initiation of cortical SD. This observation may partially explain why SD has not been demonstrated in human neocortex during surgery. Further studies are needed to determine if SD may occur under pathological conditions, such as during migraine with aura, where the cortex may be predisposed to SD.     

Rate-Responsive Pacing by Means of Activity Sensing Versus Single Rate Ventricular Pacing: A Double-Blind Cross-Over Study

The clinical appiicabiJity of rate-responsive pacing (RRP) by means of activity sensing has been tested in 15 patients. The patients (ages 24–85) had sinus node dysfunction (2), atrial fibrillation (7), or sinus rhythm (6) combined with complete atrioventricular block. Exercise capacity was investigated on a bicycle ergometer and on a treadmill in a double-blind cross-over study design following one week each of fixed rate ventricu/ar pacing (70 bpm) and rate-responsive pacing (60/125–150 bpm). The patients answered a questionnaire concerning subjective symptoms. A Holter ECG was recorded during 24 hours of all day activity on rate-responsive pacing. During exercise in the rate-responsive mode, heart rate increased more on the treadmill than on the bicycle. A majority of the patients (13 of 15) preferred rate-responsive pacing mainly due to less dyspnea and tiredness. Exercise capacity improved significantly both on bicycle (+7%; p < 0.01) and on treadmill (+19%; p < 0.01) during rate-responsive pacing. There were no complications during the follow-up period. In conclusion, the activitysensing pacemaker is a valuable supplement to existing types o/ pacemakers. It should be used in patients in whom an atrial electrogram cannot be used for rate triggering.     

Survivors of childhood cancer: long-term edocrine and metabolic problems dwarf the growth distrubance

The long-term effects of radiotherapy and chemotherapy are becoming increasingly reconginzed as the cure rates of certain childhood malignancies improve. The endocrine system is particularly sensitive to cancer therapies. Long-term survivors of childhood cancer who received cranial irradiation have been shown to have lower than predicted height, an increased prevalence of obesity and redutions in strength, exercise tolerance, bone mineral density, quality of life and academic achievement. Growth hormone deficiency (GHD) is the most frequent endocrine deficiency observed following cranial irradiation. Adults with GHD resulting from primary hypothalamic-pituitary disease during childhood have been shown to exhibit a clinical picture similar to that described in long-term survivors of childhood cancer: increased fat mass and reduced lean mass, strength, exercise tolerance, bone mineral density and quality of life. This review considers the possible contributin of GHD to the adverse sequelae observed in long-term survivors of childhood malignancy and includes our preliminary experience in treating 14 adults with GHD resulting from the treatment of childhood malignancies.     

Predominance of null mutations in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, ATM, was recently identified by positional cloning and found to encode a putative 350 kDa protein with a Pl 3-kinase-like domain, presumably involved in mediating cell cycle arrest in response to radiation-induced DNA damage. The nature and location of A-T mutations should provide insight into the function of the ATM protein and the molecular basis of this pleiotropic disease. Of 44 A-T mutations identified by us to date, 39 (89%) are expected to inactivate the ATM protein by truncating it, by abolishing correct initiation or termination of translation, or by deleting large segments. Additional mutations are four smaller in-frame deletions and insertions, and one substitution of a highly conserved amino acid at the Pl 3-kinase domain. The emerging profile of mutations causing A-T is thus dominated by those expected to completely inactivate the ATM protein. ATM mutations with milder effects may result in phenotypes related, but not identical, to A-T.      

Multicenter assessment of HIV-1 RNA quantitation in semen in the CREAThE network

Detection of HIV-1 RNA in semen is used commonly to determine the safety of semen processing procedures before assisted reproductive technology (ART). Using two panels of prepared semen samples containing HIV-1 the performances of protocols from 14 centers have been compared. No false-positive results were detected but false-negative results were frequent when the concentration was below 500 HIV-1 RNA copies/ml of seminal plasma. Frequency of HIV-1 RNA detection was higher on seminal cells than on seminal plasma. Assays (or protocols) for quantifying HIV-1 RNA in semen performed less well than standardized blood plasma assays. The HIV load in seminal plasma could be a useful marker of the risk of sexual transmission of the virus. Its use as a marker of global HAART efficiency in the HIV reservoir needs further study. Standardized assays are required for detection and measurement of HIV-1 RNA in semen samples.     

Emergence of mupirocin-resistant MRSA among Iranian clinical isolates

Mupirocin is a topical antimicrobial agent which is increasingly used for the treatment and eradication of Staphylococcus aureus colonization from the noses of patients and hospital staff. However, the extensive use of this antibiotic has given rise to mupirocin resistance in S. aureus. The present study evaluated the rate of mupirocin resistance in S. aureus clinical isolates from burns patients. A total of 125 S. aureus nonduplicate consecutive clinical isolates were collected from the burns patients in Iranian Burns Hospital, and the presence of mecA and mupA genes was assessed through polymerase chain reaction. From the 125 isolates, 107 (85.6 %) and 40 (32 %) had the mecA and mupA genes, respectively. The high prevalence of mupirocin-resistant S. aureus in this burns hospital in comparison with other general hospitals in Iran requires revision in the current mupirocin therapy strategies. In tandem with other countries, the rate of mupirocin resistance is increasing in Iran, which necessitates regular monitoring.