Incomplete resection of focal cortical dysplasia is the main predictor of poor postsurgical outcome.

BACKGROUND: Focal cortical dysplasia (FCD) is recognized as the major cause of focal intractable epilepsy in childhood. Various factors influencing postsurgical seizure outcome in pediatric patients with FCD have been reported. OBJECTIVE: To analyze different variables in relation to seizure outcome in order to identify prognostic factors for selection of pediatric patients with FCD for epilepsy surgery. METHODS: A cohort of 149 patients with histologically confirmed mild malformations of cortical development or FCD with at least 2 years of postoperative follow-up was retrospectively studied; 113 subjects had at least 5 years of postoperative follow-up. Twenty-eight clinical, EEG, MRI, neuropsychological, surgical, and histopathologic parameters were evaluated. RESULTS: The only significant predictor of surgical success was completeness of surgical resection, defined as complete removal of the structural MRI lesion (if present) and the cortical region exhibiting prominent ictal and interictal abnormalities on intracranial EEG. Unfavorable surgical outcomes are mostly caused by overlap of dysplastic and eloquent cortical regions. There were nonsignificant trends toward better outcomes in patients with normal intelligence, after hemispherectomy and with FCD type II. Other factors such as age at seizure onset, duration of epilepsy, seizure frequency, associated pathologies including hippocampal sclerosis, extent of EEG and MRI abnormalities, as well as extent and localization of resections did not influence outcome. Twenty-five percent of patients changed Engel's class of seizure outcome after the second postoperative year. CONCLUSIONS: The ability to define and fully excise the entire region of dysplastic cortex is the most powerful variable influencing outcome in pediatric patients with focal cortical dysplasia.

Variant form of STAT4 is associated with primary Sjögren's syndrome.

Single nucleotide polymorphisms in the STAT4 gene have recently been shown to be associated with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Primary Sjögren's syndrome (pSS) is a related autoimmune disease thought to have a pathogenesis similar to these diseases. To test the hypothesis that the variant haplotype of STAT4 seen in RA and SLE is also associated with pSS, we genotyped rs7574865, the most strongly disease-associated SNP in the variant STAT4 haplotype, in 124 Caucasian pSS subjects and compared them to 1143 Caucasian controls. The disease-associated T allele was more common in chromosomes of the pSS patients (29.6%) than in controls (22.3%), leading to a P-value for association of 0.01. These results implicate polymorphisms in the STAT4 gene in the pathogenesis of pSS.

Rapid attainment of steady-state plasma drug concentrations within precise limits in multicompartment mammillary systems.

We have previously described a method of rapidly obtaining a specified steady-state plasma concentration of an intravenous drug within precise limits. However the method is limited to drugs whose disposition may be characterized by an open two-compartment system. In this paper, we illustrate how the method can be extended to drugs whose disposition may be characterized by a mammillary model with any number of compartments. Refinements of our previous technique are also described.

Rapid attainment of steady state plasma drug concentrations within precise limits.

We describe a method of rapidly obtaining a specified steady state plasma concentration of an intravenous drug within precise limits. The technique requires an initial bolus to raise the plasma concentration to the upper limit followed by a series of constant-rate infusions each of which is associated with a minimum plasma concentration equal to the lower limit. The infusion rate is stepped down when the plasma concentration returns to the upper limit. Computer simulation, based on the method, is used to generate plasma concentration-time curves with fluctuations of up to 10% about selected steady state concentrations of amrinone, esmolol, lidocaine, midazolam, propofol, and theophylline. The utility of this general approach to intravenous dosing and potential limitations of the method are discussed.

Concentration and second-gas effects in the water analogue.

The water analogue provides a visual model of the process of anaesthetic exchange. In the standard version, a single pipe connects the mouth container to the lung container and the conductance of this mouth-lung pipe is proportional to alveolar ventilation. This implies that inspired and expired ventilations are equal. In fact, with high inspired concentrations of nitrous oxide, early rapid uptake of gas by solution leads to a substantial difference between inspired and expired ventilation which in turn leads to concentration and second-gas effects. It is shown that by representing inspired and expired ventilations separately, and keeping one of them constant while varying the other to compensate for rapid uptake, concentration and second-gas effects are reproduced in the water analogue. Other means of reproducing the effects are reported but we believe that the first method is the most realistic and the most appropriate for teaching.

Concentration and second gas effects: can the accepted explanation be improved?

During induction with high inspired concentrations of nitrous oxide, net uptake of gas produces a contraction in volume and a concentrating effect. In turn, this results in concentration and second gas effects. Most explanations of these effects are based on the common "rectangle" diagram devised by Stoelting and Eger and contain several inconsistencies which are explored here in order to produce a more accurate description. It is shown that in the standard diagram gas uptake is incomplete, there is ambiguity over functional residual capacity (FRC), equilibration with blood is inadequately represented and there is no representation of recirculation of anaesthetic. Compensation for loss of volume may be by means of an increased inspired ventilation, decreased expired ventilation or reduction in lung volume. Numerous accounts in the literature (including those based on the standard diagram) focus on the former mechanism at constant FRC. This has produced an unbalanced picture in which it is often implied that extra gas is routinely drawn into the lungs to replace that taken up. Significant compensation by this means cannot occur, for example when a constant volume ventilator is used. In discussing concentration and second gas effects, it is necessary to give a balanced view of the alternative mechanisms of compensation or to revert, as above, to a simple statement of the principle of conservation of volume.

Steroids and postoperative analgesia.

The postoperative analgesic requirements of a group of patients receiving high doses of corticosteroids for 48 hours postoperatively were studied. It was found that the opioid requirement of the group was significantly less than that of a control group undergoing similar surgery but not receiving steroids (p less than 0.001). The steroid group required approximately half the opioid dose of the control group. Possible explanations of the effect include the anti-inflammatory action of steroids and competitive inhibition of a common metabolic pathway in the liver.

Chemistry of halothane-enflurane mixtures applied to anesthesia.

The authors obtained boiling point-composition data and vapor pressure-composition data for the halothane-enflurane system at 20 degrees C and 25 degrees C. This was used to demonstrate the existence of an azeotropic mixture of halothane and enflurane and to predict the output of an enflurane vaporizer contaminated with different amounts of halothane and a halothane vaporizer contaminated with different amounts of enflurane. The study was undertaken because the information allows a comprehensive description of the behavior of a contaminated vaporizer and the required data were not previously available. It was shown that an enflurane vaporizer contaminated with halothane delivers potentially dangerous mixtures of the two agents, whereas an enflurane-contaminated halothane vaporizer does not pose a serious problem. It was concluded that when halothane and enflurane vaporizers are mounted in series, the halothane should be downstream. It is explained why the halothane-enflurane azeotrope is unlikely to be useful clinically.

Densities of liquid halothane, methoxyflurane, and enflurane between 0 degrees and 35 degrees C.

The authors determined the densities of liquid halothane, methoxyflurane, and enflurane over the temperature range of 0 to 35 degrees C. The measurements were undertaken because detailed information of this type is useful in, for example, the preparations of chromatography standards, and no previous comparable study has been published. The densities of the liquid agents at different temperatures were described by regression equations. Calculated values using these equations compared favorably with isolated values reported in the literature.

Second trimester septic abortion and the Dalkon shield.

The Dalkon shield was withdrawn from the market in the United States of America last year because of the reports of 11 maternal deaths and 209 cases of septic midtrimester abortions associated with the device in situ. Four cases of late midtrimester septic abortions resulting in neonatal deaths are presented. In one of these, the mother developed septicaemic shock and almost died. The true pregnancy rate with the Dalkon shield is much higher than was initially claimed, particularly if it is inserted in the puerperium. Surveys on the outcome of the pregnancy indicate that 50% end in spontaneous abortion and one in 20 pregnancies are ectopic. A high percentage of the abortions are septic. The Dalkon shield, therefore, has no advantages over other intrauterine contraceptive devices and it remains to be seen whether the recent modification of the device has overcome the disadvantages of the earlier version. If pregnancy is diagnosed with the device in situ, it should be removed if the string is visible. If pregnancy continues with the shield in place, the patient should be observed closely. Should septic abortion occur, active management is indicated and early evacuation of the uterus is recommended.