Vagus nerve stimulation for intractable epilepsy: a review

Electrical stimulation of the vagus nerve in the neck by using a programmable stimulator similar to a cardiac pacemaker is being explored as a treatment for epilepsy. There is sound rationale based on studies of animal seizure models for pursuing this treatment modality, and early clinical trials provide support for efficacy in patients with intractable epilepsy at least equivalent to that of some of the new antiepileptic drugs. Safety and tolerability have been demonstrated in >800 patients worldwide since the first implant in 1988. Most of these had partial seizures for which resective epilepsy surgery was not feasible or had failed, but efficacy of vagal stimulation appears to be the same for both partial and generalized epilepsy. Specific selection criteria for this procedure have yet to be established, and further studies are warranted to determine whether vagal stimulation becomes an accepted procedure for epilepsy management.     

Inference, inquiry, evidence censorship, and explanation inconnectionist expert systems

The combination of the techniques of expert systems and neural networks has the potential of producing more powerful systems, for example, expert systems able to learn from experience. In this paper, we address the combinatorial neural model (CNM), a kind of fuzzy neural network able to accommodate in a simple framework the highly desirable property of incremental learning, as well as the usual capabilities of expert systems. We show how an interval-based representation for membership grades makes CNM capable of reasoning with several types of uncertainty: vagueness, ignorance, and relevance commonly found in practical applications. In addition, we show how basic functions of expert systems such as inference, inquiry, censorship of input information, and explanation may be implemented. We also report experimental results of the application of CNM to the problem of deforestation monitoring of the Amazon region using satellite images     

The inactivated plasmid inititator protein RepC/RepC* may have a regulatory role

During replication of the plasmid pT181, the initiator protein RepC is modified by the addition of an oligodeoxynucleotide, giving rise to a new form, RepC*. Here we show that during in vitro replication, RepC* is radioactively labeled, suggesting that the source of the RepC* oligodeoxynucleotide is the newly synthesized pT181 DNA. The RepC/RepC* heterodimer retains its ability to bind the pT181 double-strand origin and, therefore, it may act as a competitive inhibitor of the RepC homodimer during replication.     

Antigenic variants of Plasmodium chabaudi chabaudi AS and the effects of mosquito transmission

Previous results, using a passive transfer assay, have shown that recrudescences of Plasmodium chabaudi chabaudi AS strain are antigenically different from the infecting parental population and also that the recrudescence appears to be a mix of antigenic types. This present study examines further these recrudescent populations using an indirect fluorescent antibody test on live, schizont-infected red blood cells. This analysis shows that ten clones derived from a recrudescence are all antigenically different from the parent population and that some are different from each other. The use of this method to examine the antigenic types of recrudescent clones after transmission through mosquitoes also demonstrates a resulting change in antigenicity. Such results showing a link between mosquito transmission and varying antigenicity may have important implications in terms of immunity and vaccine development.     

Activation of 5-HT2 receptors facilitates depolarization of neocortical neurons by N-methyl-D-aspartate

We prospectively studied 63 children with transient hyperglycemia to determine their risk of acquiring insulin-dependent diabetes mellitus (IDDM) and to evaluate the predictive value of immunologic markers of prediabetes and of the intravenous glucose tolerance test. Children with transient hyperglycemia were identified by a prospective systematic review of the laboratory reports of a large children's hospital and an office-based pediatric practice and by referral from pediatricians. Transient hyperglycemia occurred in 0.46% of children seen in the children's hospital and in 0.013% of children attending a pediatric office practice. Insulin-dependent diabetes mellitus developed within 18 months of identification in 32% of children in whom transient hyperglycemia was discovered in the absence of a serious illness, compared with 2.3% of children identified during a serious illness (relative risk, 13.9; 95% confidence interval, 1.56 to 123.5). Islet cell antibodies and competitive insulin autoantibodies each had a 100% positive predictive value for IDDM; the negative predictive value of islet cell antibodies and competitive insulin autoantibodies was 96% and 98%, respectively. The stimulated insulin release during an intravenous glucose tolerance test, adjusted for age, had the highest overall accuracy of prediction. All children less than 6 years of age with stimulated insulin release levels < 85 pmol/L (12 microU/ml) subsequently had IDDM, as did an 11-year-old child whose stimulated insulin release level was below the 1st percentile of 170 pmol/L (24 microU/ml). To date, no child whose stimulated insulin release level was above the 5th percentile has had IDDM. We conclude that when transient hyperglycemia occurs during a serious intercurrent illness, the risk of progression to IDDM is low. In contrast, one third of children in whom transient hyperglycemia is identified without a serious illness can be expected to have IDDM within 1 year. A combination of islet cell antibodies, competitive insulin autoantibodies, and stimulated insulin release levels during an intravenous glucose tolerance test can accurately distinguish children with prediabetes from those with presumed benign transient increases in plasma glucose concentrations.     

Purification and characterization of a human bradykinin binding protein from inflammatory cells

Bradykinin (BK) is a potent mediator with a broad spectrum of pharmacological and inflammatory actions which are exerted through cell surface receptors. We report here the affinity chromatographic purification of a novel 14 kDa BK binding protein from human blood neutrophils and also peripheral blood mononuclear cells (PBMC), 80% of which are lymphocytes. Radioreceptor crosslinking experiments using bifunctional crosslinkers and radiolabelled BK identified a 14 kDa protein in these cell types both on the cell surface, in glycerol purified plasma membranes and in detergent solubilized cell extracts. Purification by BK affinity chromatography from a variety of BK responsive human cell types i.e. CCD-16Lu lung fibroblasts, HL60 promyelocytes, U937 myelomonocytes and Jurkat T lymphocytes also demonstrated a 14 kDa protein. Purified material obtained from three different BK affinity columns all demonstrated three major proteins at 190, 50 and 14 kDa when eluted with either excess BK or mild acid. Neutrophil fractions from detergent solubilized cell extracts contained an additional 150 kDa protein when eluted with mild acid. Neutrophil and PBMC crude plasma membrane BK affinity column purifications yielded only a single 14 kDa protein. Radioreceptor dot assays of the purified neutrophil eluates containing the 14 kDa protein revealed specific binding to [125I]-BK with a 160 fold excess signal ratio over the original membrane extract. Our data indicates that we have successfully isolated a 14 kDa novel human BK specific binding protein expressed on the surface of inflammatory cells.     

Zidovudine pharmacokinetics in premature infants exposed to human immunodeficiency virus

We used population analysis techniques to determine zidovudine (ZDV) pharmacokinetic parameters in 15 preterm neonates (mean gestational age, 29.4 weeks; mean birth weight, 1,230 g) at a mean age of 5.5 days. The values of the pharmacokinetic parameters were as follows: clearance, 2.53 +/- 0.44 ml/min/kg; volume of distribution, 1.59 +/- 0.51 liters/kg; and half-life, 7.2 +/- 1.5 h. For seven infants studied a second time, at a mean age of 17.7 days, an increase in the mean clearance (2.33 versus 4.35 ml/min/kg; P = 0.024) and a decrease in the half-life (7.3 versus 4.4 h; P = 0.003) were found. The ZDV clearance is low and the half-life is prolonged in premature neonates, but the clearance increases and the half-life decreases with postnatal age. Potentially toxic concentrations may accumulate in serum if the standard dosage for full-term infants is used. We suggest that initial ZDV dosing should be reduced to 1.5 mg every 12 h for preterm neonates.     

Effect of anordrin on the development of mouse preimplantation embryos in vitro

The aim of this study was to establish the feasibility, evaluate the response rate, and assess the impact on local control and survival in locally advanced (bulky nodal) squamous cell carcinoma of the head and neck (SCCHN) patients treated with neoadjuvant chemotherapy consisting of cisplatin followed by continuous infusion of vindesine and fluorouracil with intermittent i.v. folinic acid. Eligibility criteria included histologically proven SCCHN, previously untreated locally advanced stage III-IV with measurable or evaluable disease, no distant metastases, an Eastern Cooperative Oncology Group (ECOG) performance status of less than 2, patient age of at least 18 years, and adequate bone marrow, hepatic, and renal functions. The protocol consisted of three cycles (day 1, day 21, day 42) of Cisplatin (CDDP) 100 mg/m2/day i.v. on day 1 immediately followed by 4 days (96 h) of continuous infusion of vindesine 0.8 mg/m2/day and 5-fluorouracil (5-FU) 600-700 mg/m2/day with folinic acid 150 mg/m2 i.v. every 6 h x 16 doses before locoregional treatment with radiotherapy preceded by radical surgery when appropriate. Twenty-nine patients were enrolled in this study, and 28 were evaluable for activity; an objective response rate of 55% (four complete responses, 12 partial responses) was achieved. Leukopenia and mucositis were the most frequent and severe toxicities. The addition of vindesine did not improve the activity of the CDDP-FU-folinic acid combination, but this may be partly because of the particularly poor prognosis of the present patient population, with 75% of stage IV bulky nodal disease (N2c-N3).