Long-term course of epilepsy in a large cohort of intellectually disabled patients.

This study was designed to describe the course of epilepsy (in terms of seizure frequency) and to assess the variables (antiepileptic therapy regimens and others) correlated to improvement. Seizure frequency (categories: seizure free, more than one seizure/year, monthly seizures, weekly seizures and daily seizures) and antiepileptic medication were retrospectively compared between 1992 and 2002 in a large cohort of 550 inpatients with chronic epilepsy and different degrees of intellectual disability or multiple handicaps. RESULTS: Seizure frequency decreased significantly (p<0.001). 218 of the 394 patients (55.3%) not seizure free in 1992 improved (changed into a better frequency category). The improvement rate was marginally higher in patients who had undergone a medication change (p=0.08). A high seizure frequency in 1992 (p=0.016) and older age (p=0.006), but not epilepsy syndrome or degree of intellectual disability, were predictors for improvement (stepwise logistic regression analysis). 56.4% of the improved patients were on combinations of two AEDs (17.4%, monotherapy; 20.2%, triple therapy). The most frequent therapy regimens in the improved patients were lamotrigine/valproate (48 patients), carbamazepine/phenobarbital (21) and carbamazepine only (19). Lamotrigine/valproate was effective in all kinds of epileptic syndromes. Most patients on lamotrigine had serum concentrations above 10microg/ml, approximately one half had dosages above 200mg/day. The rate of seizure freedom increased from 28.4 to 37.6%. The 84% of the patients seizure free in 1992 remained seizure free. Predictors for seizure freedom in 2002 were higher age (stepwise logistic regression, p<0.0005) and seizure freedom in 1992 (p<0.0005). CONCLUSIONS: Substantial improvement can be achieved even in intellectually disabled patients with chronic epilepsy. Although the rate of seizure freedom is reduced in comparison with a non-ID population, once seizure freedom has been achieved it is most likely to continue. For a majority of this patient population, monotherapy may not be sufficient. Lamotrigine/valproate appears to be a major therapeutic innovation.     

A population-based assessment of the disease burden of consolidated pneumonia in hospitalized children under five years of age.

BACKGROUND: Population-based studies on childhood community-acquired pneumonia are scarce in Latin America. Pneumococcal epidemiology is poorly defined, hence the World Health Organization recommended standardized chest radiograph interpretation to improve the approach to bacterial pneumonia. Therefore, our study aimed to estimate the burden of pneumonia in hospitalized children. METHODS: A three-year surveillance study was carried out in four hospitals covering a population of 229,128 inhabitants of whom 10.2% were under five years of age. Clinical records and digitization of their chest radiographs were obtained. A pediatrician and a pediatric radiologist blinded to the clinical diagnosis interpreted the digital images. RESULTS: Of 2034 patients, 826 (40.6%) had consolidated pneumonia, 941 (46.3%) had non-consolidated pneumonia, and 267 (13.1%) had no pneumonia. Children under two years of age predominated (66.9%). The average annual incidence rate for consolidated pneumonia over the three-year study period was 1175/10(5). Eighteen invasive Streptococcus pneumoniae were isolated from patients with consolidated pneumonia and two from those with non-consolidated pneumonia. Respiratory syncytial virus was evenly distributed between both X-ray groups. CONCLUSIONS: Patients younger than two years of age predominated, being the main targets for anti-pneumococcal conjugated vaccines. Incidence rates provided evidence of the burden of consolidated pneumonia for childhood, estimating the potential benefits of vaccination.     

Reciprocal regulation of the nitric oxide synthase/arginase balance in mouse bone marrow-derived macrophages by TH 1 and TH 2 cytokines

Activation with lipopolysaccharide induces macrophages to produce the enzymes arginase and nitric oxide (NO) synthase. Both enzymes use as a substrate the amino acid L-arginine, which can be either hydrolyzed by arginase to urea and ornithine or oxidized by NO synthase to NO and citrulline. NO is important in the bactericidal and cytotoxic activities of macrophages. An equivalent functional role of arginase and its products is not known. We tested the induction of arginase in bone marrow-derived macrophages by endogenous mediators that are known to induce NO synthase, such as interferon-γ (IFN-γ), or suppress the induction of this enzyme, such as interleukin (IL)-4, IL-10, and prostaglandin E₂ (PGE₂). We find that PGE₂ and the TH2 cytokines IL-4 and IL-10 are potent inducers of arginase. In contrast, the TH 1 cytokine IFN-γ does not induce arginase. Simultaneous application of both types of mediators leads to reduced induction of both arginase and NO synthase. Exposure of macrophage cultures to inducers of NO synthase exhausts their ability to respond subsequently to inducers of arginase. Conversely, exposure of the cells to inducers of arginase exhausts their ability to respond subsequently to inducers of NO synthase. The results are consistent with a competition of both enzymes for their substrate, L-arginine, with a reciprocal inhibition in the induction of both enzymes, or a combination of both phenomena. The enzymes NO synthase and arginase appear to define two alternate functional states of macrophages, induced by TH 1 and TH 2 cytokines, respectively.     

Determinants of acute respiratory infections in Soweto--a population-based birth cohort.

BACKGROUND: Acute respiratory infections (ARIs) are an important cause of infant morbidity in both developing and developed countries, and they are the leading cause of death in poorer parts of the world. Respiratory viruses appear to be the most frequent microbiological pathogens, especially respiratory syncytial virus. It has been suggested that factors such as being male, overcrowding, poor access to medical care, low level of maternal education, and passive smoking are associated with contracting ARIs. DESIGN: A fixed birth cohort of 571 children was followed from birth to 1 year of age. The children were monitored for symptoms of ARIs during regular home visits. SETTING: An urban low-income setting in Soweto, a township outside Johannesburg with an estimated 1.2 million inhabitants, including an estimated 45,000 children under 2 years of age. SUBJECTS: A total of 571 children were observed for 118,650 days. OUTCOME MEASURES: The incidence rate of ARIs. The determinants birth weight, breastfeeding, gender, crowding, passive smoking, indoor pollution, and sanitary facilities were analysed. RESULTS: A total of 489 episodes of coughing or coughing and nasal discharge combined were recorded. Only the father's level of education and the number of people living in the household remained significant in the multivariate analyses. The incidence of severe ARIs was reduced among breastfed infants. CONCLUSIONS: Our study supports previous observations suggesting that crowding and communal living conditions are important determinants of ARIs. Breastfeeding seemed protective against severe ARI. The lack of association with well-described risk factors such as low level of maternal education, gender and passive smoking could be due to lack of statistical power in this rather uniform population.     

Myocardial metabolic imaging by means of fluorine-18 deoxyglucose/technetium-99m sestamibi dual-isotope single-photon emission tomography

The detection of preserved glucose uptake in hypoperfused dysfunctional myocardium by fluorine-18 deoxyglucose (FDG) positron emission tomography (PET) represents the method of choice in myocardial viability diagnostics. As the technique is not available for the majority of patients due to cost and the limited capacity of the PET centres, it was the aim of the present work to develop and test FDG single-photon emission tomography (SPET) with the means of conventional nuclear medicine. The perfusion marker sestamibi (MIBI) was used together with the metabolic tracer FDG in dual-isotope acquisition. A conventional SPET camera was equipped with a 511-keV collimator and designed to operate with simultaneous four-channel acquisition. In this way, the scatter of 18F into the technetium-99m energy window could be taken into account by a novel method of scatter correction. Thirty patients with regional wall motion abnormalities at rest were investigated. The results of visual wall motion analysis by contrast cine-ventriculography in nine segments/heart were compared with the results of quantitative scintigraphy. The scintigraphic patterns of MIBI and FDG tracer accumulation were defined as normal, matched defects and perfusion-metabolism mismatches. Spatial resolution of the system was satisfactory, with a full width at half maximum (FWHM) of 15.2 mm for ¹⁸F and 14.0 mm for ^99mTe, as measured by planar imaging in air at 5 cm distance from the collimator. Image quality allowed interpretation in all 30 patients. 88% of segments without relevant wall motion abnormalities presented normal scintigraphic results. Seventy-five akinetic segments showed mismatches in 27%, matched defects in 44% and normal perfusion in 29%. We conclude that FDG-MIBI dual-isotope SPET is technically feasible with the means of conventional nuclear medicine. Thus, the method is potentially available for widespread application in patient care and may represent an alternative to the ²⁰¹T1 reinjection technique.     

Current determinants of 30-day and 3-month mortality in over 2000 aortic valve replacements: Impact of routine laboratory parameters.

OBJECTIVE: Haematological and biochemical measurements are performed routinely before surgery to exclude organ malfunction and blood cell and coagulation abnormalities. We aimed to test routinely obtained laboratory data as factors predicting operative risk. METHODS: Between 1996 and 2003, 2198 patients underwent aortic valve replacement (AVR) (908 of them with concomitant CABG) in our institute. The mean age of the study population was 69+/-11 years (range 13-91, 43% female). Clinical and laboratory parameters based on the consolidated data mart set were evaluated by multiple logistic regression analysis. RESULTS: The overall operative mortality (within 30 days) was 3.8% and the mortality after 3 months was 5.9%. In addition to clinical characteristics, the following laboratory values were identified as independent predictors of 30-day mortality: fasting blood glucose, antithrombine III, partial thromboplastine time and creatinine kinase. As independent predictors of 3-month mortality, the following laboratory values were indentified: fasting blood glucose, serum creatinine, antithrombine III, partial thromboplastine time, lactate dehydrogenase, sodium concentration and serum proteins. The discriminative power of the models increased if laboratory parameters were included in addition to preoperative clinical characteristics (from 0.75 to 0.79 and from 0.75 to 0.78 for 30-day and 3-month mortality, respectively). The discriminative power using the logistic EuroScore was lower (0.71 and 0.7, for 30-day and 3-month mortality, respectively). CONCLUSIONS: Laboratory parameters as objective markers for organ function and nutritional status are useful data for the prediction of 30-day and 3-month mortality after aortic valve replacement. Using modern methods of information technology, these valuable data which are stored electronically in most hospitals, can be used efficiently for research and quality control.     

18F-FDG PET for mediastinal staging of lung cancer: which SUV threshold makes sense?

(18)F-FDG PET is the most accurate noninvasive modality for staging mediastinal lymph nodes in lung cancer. Besides using visual image interpretation, some institutions use standardized uptake value (SUV) measurements in lymph nodes. Mostly, an SUV of 2.5 is used as the cutoff, but this choice was never deduced from respective studies. Receiver operating characteristic (ROC) analyses demonstrated that SUV thresholds of more than 4 resulted in the highest accuracy. But these high cutoffs imply high false-negative rates (FNRs). The aim of our evaluation was to determine an optimal SUV threshold and to compare its diagnostic performance with the results of visual interpretation. METHODS: This retrospective study included 95 patients with suspected lung cancer who underwent mediastinoscopy/mediastinal lymphadenectomy after (18)F-FDG PET (90-150 min after 250 MBq of (18)F-FDG). Maximum SUV was measured in 371 lymph node regions biopsied afterward and visually interpreted using a 6-level score (- - - through + + +). Diagnostic performance was assessed by ROC analysis. FNR and false-positive rate (FPR), the sum of both error rates (FNR + FPR), and diagnostic accuracy were plotted against a hypothetical SUV threshold to determine the optimum SUV threshold. RESULTS: SUVs in metastatic lymph nodes were higher (mean +/- SD, 7.1 +/- 4.5; range, 1.4-26.9; n = 70) than in tumor-free lymph node stations (2.4 +/- 1.7; range, 0.6-14.9; n = 301; P < 0.01). Inflammatory lymph nodes exhibited slightly increased SUVs (2.7 +/- 2.0; range, 0.8-14.9; n = 146). The plot of error rates featured a minimum of the sum FNR + FPR for an SUV of 2.5. With increasing SUV threshold, the FPR decreased most prominently up to that value whereas a continuous rise of FNR was noticed. Highest diagnostic accuracy was achieved with an SUV of 4.5. The areas under the ROC curves demonstrated that visual interpretation tends to be more accurate than SUV quantification (visual, 0.930 +/- 0.022; SUV, 0.899 +/- 0.025; P = 0.241). Using an SUV of 2.5 as the threshold, the resulting sensitivity, specificity, and negative predictive value were 89%, 84%, and 96%, respectively. CONCLUSION: For mediastinal staging, the choice of an SUV of 2.5 as the threshold is justified because FNR + FPR is minimized. The resulting high negative predictive value of 96% allows the omission of mediastinoscopy in patients with negative mediastinal findings on (18)F-FDG PET images. For the experienced observer, visual analysis should be relied on primarily, with calculation of the SUV used, at most, as a secondary aid. For the less experienced observer, the SUV may be of greater value.