Hypozincaemia in febrile convulsion

To understand further the role of trace elements in the pathogenesis of febrile convulsions, serum zinc (Zn), copper (Cu), magnesium (Mg) and CSF Zn, Cu, Mg and protein levels were measured by spectrometry in patients with febrile convulsion (n=19), bacterial meningitis (n=9), viral CNS infection (n=16) and in the control groupn=10) which consisted of children with signs of meningeal irritation due to upper respiratory tract infection but normal CSF findings. Samples were obtained within 6 h after admission to hospital. Mean serum and CSF Zn levels in the febrile convulsion group were significantly lower than in the other groups (for serum Zn: 0.66±0.03 mg/l vs 0.98±0.07 mg/l, 1.06±0.08 mg/l, 1.05±0.09 mg/lP<0.05; for CSF Zn: 22.96±1.62 g/l vs 75.47 ±6.9 g/l, 50.32±5.235 g/l, 39.85 ±2.81 g/lP<0.05). A linear relationship was established between serum Zn and CSF Zn levels (P<0.001). Mean CSF Zn, Cu and protein levels in the bacterial meningitis group were significantly higher than in the other groups (for CSF Cu 63.94±6.33 g/l vs 38.77±2.70 g/l, 35.84±3.48 g/l, 33.86±2.88 g/lP<0.05; for CSF protein 0.80 ± 0.12 g/l vs 0.22±0.02 g/l, 0.53±0.08 g/l, 0.19±0.01 g/lP<0.05). In children with meningitis, the elevation of the mean CSF Zn and Cu levels may result from the breakdown of the blood-brain barrier and subsequent leakage of trace elements and protein from serum to CSF. There was no significant difference between the four groups in terms of mean serum Mg and mean CSF Mg levels.Conclusion Serum and CSF Zn levels are decreased in children with febrile seizures. Zinc deprivation may play a role in the pathogenesis of febrile seizures.     

Population-based studies of childhood disability in developing countries: rationale and study design

Infant mortality level has been used for decades to indicate the health and socioeconomic status of populations. Given the relative availability of necessary data, this indicator has proved most viable. As the more glaring aspects of underdevelopment fade into history in some countries, other health status indices should be considered. Childhood disability is proposed as 1 such indicator. Disability is neither subsumed by nor necessarily correlated with declining infant mortality, and may thus be used to help identify solutions for both short- and longterm problems. To employ this indicator, one needs to know how various types of disabilities are spread through populations as well as the correlated risk factors. Methodology must be developed which is capable of rapidly identifying cases and assessing risk factors. A 2-stage method, comprised of screening and clinical evaluation, is described.     

Differentiation-specific increase in ALA-induced protoporphyrin IX accumulation in primary mouse keratinocytes.

A treatment regimen that takes advantage of the induction of intracellular porphyrins such as protoporphyrin IX (PPIX) by exposure to exogenous 5-amino-laevulinic acid (ALA) followed by localized exposure to visible light represents a promising new approach to photodynamic therapy (PDT). Acting upon the suggestion that the effectiveness of ALA-dependent PDT may depend upon the state of cellular differentiation, we investigated the effect of terminal differentiation upon ALA-induced synthesis of and the subsequent phototoxicity attributable to PPIX in primary mouse keratinocytes. Induction of keratinocyte differentiation augmented intracellular PPIX accumulation in cells treated with ALA. These elevated PPIX levels resulted in an enhanced lethal photodynamic sensitization of differentiated cells. The differentiation-dependent increase in cellular PPIX levels resulted from several factors including: (a) increased ALA uptake, (b) enhanced PPIX production and (c) decreased PPIX export into the culture media. Simultaneously, steady-state levels of coproporphyrinogen oxidase mRNA increased but aminolaevulinic acid dehydratase mRNA levels remained unchanged. From experiments using 12-o-tetradecanoylphorbol-13-acetate, transforming growth factor beta 1 and calcimycin we demonstrated that the increase in PPIX concentration in terminally differentiating keratinocytes is calcium- and differentiation specific. Stimulation of the haem synthetic capacity is seen in primary keratinocytes, but not in PAM 212 cells that fail to undergo differentiation. Interestingly, increased PPIX formation and elevated coproporphyrinogen oxidase mRNA levels are not limited to differentiating keratinocytes; these were also elevated in the C2C12 myoblast and the PC12 adrenal cell lines upon induction of differentiation. Overall, the therapeutic implications of these results are that the effectiveness of ALA-dependent PDT depends on the differentiation status of the cell and that this may enable selective targeting of several tissue types.     

Autoassociative MLP in Sleep Spindle Detection

Spindles are one of the most important short-lasting waveforms in sleep EEG. They are the hallmarks of the so-called Stage 2 sleep. Visual spindle scoring is a tedious workload, since there are often a thousand spindles in one all-night recording of some 8 hr. Automated methods for spindle detection typically use some form of fixed spindle amplitude threshold, which is poor with respect to inter-subject variability. In this work a spindle detection system allowing spindle detection without an amplitude threshold was developed. This system can be used for automatic decision making of whether or not a sleep spindle is present in the EEG at a certain point of time. An Autoassociative Multilayer Perceptron (A-MLP) network was employed for the decision making. A novel training procedure was developed to remove inconsistencies from the training data, which was found to improve the system performance significantly.     

Fludarabine in combination with alemtuzumab is effective and feasible in patients with relapsed or refractory B-cell chronic lymphocytic leukemia: results of a phase II trial.

PURPOSE: To determine the efficacy and safety of a newly developed concomitant administration of fludarabine and alemtuzumab (FluCam) in patients with relapsed or refractory B-cell chronic lymphocytic leukemia (B-CLL). PATIENTS AND METHODS: A total of 36 patients were treated in this phase II study (median age, 61.47 years; mean number of prior chemotherapies, 2.6; Binet stage C, n = 28). After an initial dose escalation of alemtuzumab over 3 days, alemtuzumab 30 mg and fludarabine 30 mg/m2 were administered on 3 consecutive days. Treatment was repeated after 28 days for up to six cycles. Restaging (following National Cancer Institute criteria) was carried out after cycles 2 and 4 and 1 month after the end of treatment. RESULTS: The overall response rate was 83% (11 complete responses, 19 partial responses, one stable disease, and five progressive diseases). Two patients with progressive disease developed fungal pneumonias, and one patient died as a result of Escherichia coli sepsis. Two subclinical cytomegalovirus reactivations occurred. CONCLUSION: The new FluCam regimen is effective and feasible in patients with relapsed and refractory B-CLL.     

Heparin octasaccharides inhibit angiogenesis in vivo.

BACKGROUND: In previous experiments, we showed that heparin oligosaccharides inhibit the angiogenic cytokine fibroblast growth factor-2. Here, we present the first in vivo study of size-fractionated heparin oligosaccharides in four models of angiogenesis that are progressively less dependent on fibroblast growth factor-2. EXPERIMENTAL DESIGN: Heparin oligosaccharides were prepared using size-exclusion gel filtration chromatography and characterized through depolymerization and strong anion exchange high-performance liquid chromatography. Size-defined oligosaccharides (20 mg/kg/d) were given to mice bearing s.c. sponges that were injected with fibroblast growth factor-2 (100 ng/d). After 14 days, octasaccharides and decasaccharides reduced the microvessel density to levels below control. In a second experiment, HEC-FGF2 human endometrial cancer cells that overexpress fibroblast growth factor-2 were implanted in a hollow fiber placed s.c. in vivo. Oligosaccharides were given at 20 mg/kg/d for 2 weeks and the data again showed that octasaccharides significantly reduced microvessel density around the fiber (P = 0.03). In a more complex model, where angiogenesis was induced by a broad spectrum of growth factors, including vascular endothelial growth factor, we implanted H460 lung carcinoma cells in hollow fibers and treated the animals with oligosaccharides at 20 mg/kg/d over 3 weeks. Octasaccharides reduced the microvessel density to that of control. Preliminary investigation of 6-O-desulfated heparins showed that these also had antiangiogenic activity. RESULTS: Finally, we examined the inhibitory potential of hexasaccharides and octasaccharides given at 20 mg/kg/d and these inhibited the growth of H460 lung carcinoma in vivo. At clinically attainable concentrations, significant anticoagulation (activated partial thromboplastin time, anti-factor Xa, and anti-factor IIa) was not observed in vitro unless species containing > or =16 saccharide residues were investigated. CONCLUSIONS: Thus, our preclinical data show that heparin octasaccharides represent novel antiangiogenic compounds that can be given without the anticoagulant effects of low molecular weight heparin.     

Determination of the pericardial to serum myoglobin ratio for the early diagnosis of perioperative myocardial infarction after coronary artery bypass grafting.

Pericardial fluid reflect the composition of cardiac interstitium in myocardial ischemia. This study investigated the value of the pericardial and serum myoglobin (MG) measurements for the diagnosis of perioperative myocardial infarction (MI) after coronary artery bypass grafting (CABG). Postoperative arterial and pericardial blood samples were taken in 64 subjects undergoing elective CABG allocated to two groups according to the 12-lead electrocardiogram (ECG) abnormalities observed during the first postoperative 24h. Group 1=normal and nonspecific ECG abnormalities, and Group 2=perioperative Q-wave MI. The occurrence of perioperative MI was associated with a dramatic increase in both serum and pericardial cardiac troponin I (CTnI) and MG concentrations. Pericardial concentrations were higher than serum concentrations during the first postoperative 24h in all subject. However, pericardial/serum CTnI ratio in subjects in Group 2 was not statistically different from Group 1 at the time of admission to the intensive care unit (ICU) and did not significantly change at time intervals. On the other hand, more than two-fold increase in the pericardial/serum MG ratio was determined for all patients who experienced perioperative Q-wave MI with the lowest value as 2.75, whereas only 1 of 59 patients in group 1 had the ratio higher than 2 with the highest value as 2.15 at the time of admission to the ICU. In conclusion, determination of pericardial/serum MG ratio may be a useful tool for the early diagnosis of the perioperative MI after CABG.