How I do it: endoscopic-microscopic anterior skull base reconstruction.

Reconstruction of the anterior skull base must be secure and watertight. Failure to achieve this places the patient at risk of the development of cerebral sepsis. We have developed the technique of endonasal duraplasty and have achieved a 90% long-term success rate. In this article we described the key elements of our technique starting with radiographic and fluorescein localization of a skull base defect. The main steps in reconstruction and materials used are detailed, together with modifications of our technique for certain difficult situations and tips for success. Attention is drawn to potential pitfalls that have been identified over 25 years of clinical practice.     

Once-daily gentamicin dosing for the preterm and term newborn: proposal for a simple regimen that achieves target levels.

OBJECTIVE: Based on recent safety and efficacy data, combined with the known pharmacokinetic parameters of aminoglycosides in the newborn, once-daily gentamicin should be preferable to the many other dosing regimens currently in use. Although there are growing data to support its use in term newborns, experience with preterm infants is more limited. In our Neonatal Intensive Care Unit, we experienced difficulties regarding complicated dosing regimens, actual dosing errors, and the tendency to check trough and peak levels around the third dose for infants receiving only a 48 hour course. Therefore, we conducted a quality improvement initiative in which we developed and tested a clinical practice guideline for the use of once-daily gentamicin for preterm and term infants that we hoped would yield trough and peak levels in our target range. METHODS: We combined a review of the published English language literature with pharmacokinetic analysis of our own data prior to initiation of this new regimen to design the following dosing regimen: <35 weeks gestation: 3 mg/kg q 24 hours, > or =35 weeks gestation: 4 mg/kg q 24 hours. Our goal serum levels were a trough < or =2 microg/ml and a peak between 6 and 12 microg/ml. We collected and analyzed trough and peak levels from all infants receiving this dosing regimen in the first week of life for at least 72 hours between 3/1/99 and 12/31/00. RESULTS: In total, 214 babies met our inclusion criteria, 75 of whom were <35 weeks gestation. 100% of babies of all gestational ages had a nontoxic trough level. For infants <35 weeks gestation, 79% had a therapeutic peak level, with a mean value of 6.8 microg/ml. For infants of at least 35 weeks gestation, 93% had a therapeutic peak level, with a mean value of 8.4 microg/ml. 92% of nontherapeutic peaks were too low. CONCLUSION: This study of once-daily gentamicin represents the largest sample size of pre-term infants published to date. The proposed regimen is simple and yields a high proportion of desirable levels. We recommend it for use in preterm and term newborns.     

Sites in the brain at which cholecystokinin octapeptide (CCK-8) acts to suppress feeding in rats: a mapping study

In this study, an examination was made of the sites in the brain of the rat at which the injection of cholecystokinin octapeptide (CCK-8) would alter food intake. Rats fasted for 24 hr received intracerebral injections of CCK-8 (1 nmol) or an equal volume of saline (0.5 microliters), into various sites in the brain through permanently implanted stainless steel cannulae. After prior acclimatisation to individual plexiglass compartments, latency to feed, as well as consumption of food and water during 0-20, 20-40 and 40-60 min after the injection, were recorded. The available food was the standard rat pellets, to which the animal otherwise had constant daily access. With this paradigm, active sites at which CCK-8 suppressed feeding were defined as sites at which consumption of food for 0-20 min was reduced by 25% or more, or the latency to feed was increased by 3 min or more after the injection of CCK-8, as compared to the effect of the injection of saline, made at the same site. Such active sites were most densely distributed in the rostral diencephalon, e.g. hypothalamus, the medial pontine area and lateral medulla, in the vicinity of the nucleus tractus solitarii (NTS). By grouping data for injections according to histologically identified sites, statistical analysis of groups of injections confirmed that these three major areas of the brain were active with regard to the suppression of feeding by CCK-8. These data suggest that CCK may not only initiate satiety messages, as a circulating hormone at peripheral sites, but also participate in the conduction of such information to the target in the brain by serving as a neurotransmitter in the lateral medulla (e.g. NTS), medial pontine area (e.g. relay station between the NTS and hypothalamus) and the lateral hypothalamus, where local release of CCK-8 after stomach loading has been observed.     

Anti-idiotypic antibodies against a monoclonal antibody specific for the trichothecene mycotoxin T-2

A BALB/c murine monoclonal antibody against the trichothecene mycotoxin T-2 was generated. The antibody, designated HD11, specifically bound T-2 mycotoxin. The binding of HD11 to T-2 conjugated to bovine serum albumin was inhibited by free T-2 toxin but not by the water-soluble heterocyclic guanidines saxitoxin and tetrodotoxin. The T-2 detection limit in an enzyme-linked immunosorbent assay with HD11 was in the nanogram range. The in vitro cytotoxicity of T-2, as measured by the inhibition of radiolabeled leucine uptake of the human epidermoid carcinoma Hep-2 and KB cell lines, was completely reversed by the addition of HD11. Rabbit anti-idiotypic antibodies specific for HD11 were generated and characterized.     

Heart rate and blood pressure variability as markers of sensory blockade with labour epidural analgesia

PURPOSE: To evaluate the correlation between the progression of somatosensory blockade and changes in autonomic outflow following the onset of labour epidural analgesia. METHODS: Twelve labouring parturients consented to participate in the study. Baseline electrocardiogram, blood pressure (BP) and respiratory rate were recorded for ten minutes. The epidural consisted of 0.125% bupivacaine with 50 microg of fentanyl (total volume 20 mL). Measurements were repeated for ten minutes after initiation of the block. The level of sensory block was measured bilaterally with loss of sensation to ice at two-minute intervals. Wavelet transform was used to obtain heart rate (HR) and BP variability every two minutes following the loading dose of epidural medication. High frequency power of HR variability was used to assess changes in parasympathetic activity. The total power of BP variability was used to assess changes in sympathetic activity. A nonparametric repeated measures ANOVA was used for the variability data, and a Spearman rank correlation test was used to evaluate the relationship between the sensory block and HR and BP variability. RESULTS: The sensory block progressed to T9 at ten minutes post-epidural and was the mirror image of the decrease in total power of BP variability. High frequency power of HR variability increased to a plateau at six minutes post-epidural. A significant correlation was found between the increase in sensory block and the observed decrease in BP variability (r = -1.000, P = 0.0028). CONCLUSION: In this study of labouring parturients, BP variability correlated with the progression of both sympathetic and somatosensory block following epidural anesthesia, while HR variability was shown to be a surrogate marker of increased parasympathetic activity.     

Magnetic susceptibility effects secondary to out-of-plane air in fast MR scanning

Areas of signal loss in brain overlying air-containing structures at the skull base are commonly observed on axial fast MR images. The nature of this effect, which can mimic the appearance of cerebral hemorrhage, is investigated in a phantom study and in a normal volunteer. The magnitude of the signal loss is found to be inversely related to the distance of the scanning plane from the air-containing structure and directly related to the echo time.     

The synthesis and localization of alternatively spliced fibronectin EIIIB in resting and thrombin-treated megakaryocytes

There are several species of alternatively spliced fibronectin (FN). One of these, FN EIIIB, is primarily present in embryonic and in proliferating and migrating cells and is believed to be important for cell maturation. We have studied the synthesis, localization, and secretion of this FN isoform in isolated guinea pig megakaryocytes, nonmegakaryocytic bone marrow cells, and platelets. There was 7.5 times more general FN in megakaryocytes than in nonmegakaryocytic cells based on the analysis of equivalent amounts of protein. FN EIIIB was detected by Western blotting in megakaryocytes but not in nonmegakaryocytic cells present in bone marrow. Neither megakaryocytes nor platelets secreted FN EIIIB, while megakaryocytes secreted 25.3% +/- 4.6% general FN and platelets secreted about 61% general FN in response to thrombin. Analysis of immunostained cells by confocal microscopy revealed that FN EIIIB had been redistributed to the surface of megakaryocytes in response to thrombin. Synthesis was studied by metabolic labeling, and megakaryocytes were shown to synthesize FN and FN EIIIB. Thus, megakaryocytes and platelets are among a small number of adult cells and tissues that synthesize and contain FN EIIIB. The expression of FN EIIIB on the megakaryocyte surface may influence migration and maturation.     

Self-Concept and Satisfaction With Physical Appearance in Youth With and Without Oral Clefts

This study investigated relationships between child/parent dissatisfaction with child facial appearance and the self-concept/social competence of 8- to 15-year-old children with (N = 34) and without (N = 34) oral clefts. Children in both groups had normative psychosocial adjustment, but also reported moderate dissatisfaction with facial appearance. Cleft group parents were more likely to agree with their child's dissatisfaction. When cleft group parents were more dissatisfied with child facial appearance, their children reported better quality of life. Results suggest that parents of children with clefts reporting greater dissatisfaction may respond in positive ways that enhance quality of life.