Alpha-contingent EEG feedback reduces SPECT rCBF variability.

EEG feedback methods, which link the occurrence of alpha to the presentation of repeated visual stimuli, reduce the relative variability of subsequent, alpha-blocking event durations. The temporal association between electro-cortical field activation and regional cerebral blood flow (rCBF) led us to investigate whether the reduced variability of alpha-blocking durations with feedback is associated with a reduction in rCBF variability. Reduced variability in the rCBF response domain under EEG feedback control might have methodological implications for future brain-imaging studies. Visual stimuli were randomly presented to seven subjects, contingent upon the occurrence of alpha (alpha-contingent stimulation (ACS)) or alpha-blocking (not-alpha-blocking-contingent stimulation (NACS)) events. We employed a within-subjects design. rCBF was measured from multiple, cortical and sub-cortical regions. The primary dependent variables were the Mean, Standard Deviation and the ratio of Mean/Standard Deviation of: 1) the alpha-blocking response durations and 2) the temporally summated rCBF responses within the Visual Associative regions of interest (ROIs). Additional within-subjects rCBF measures were derived to quantify the variance-reducing effects of ACS across multiple, distributed areas of the brain. Both EEG and rCBF measures demonstrated decreased variability under ACS. This improved control was seen for localized as well as anatomically distributed rCBF measures.     

Ultrasensitive analysis of the intestinal absorption and compartmentalization of aluminium in uraemic rats: a 26Al tracer study employing accelerator mass spectrometry

BACKGROUND: Developments in accelerator mass spectrometry (AMS) now permit the determination of femtogram amounts of 26Al in blood and in various tissues with good precision and free of external contamination. METHODS: In the present study we used trace quantities of 26Al to investigate the intestinal absorption and compartmentalization of aluminium in rats with renal failure (Nx, 5/6 nephrectomy) and in pair- fed controls (C). Single oral doses of 20 ng 26Al were administered to six animals in each group and, subsequently, 24-h post-load 26Al was analysed in serum, urine, bone, liver, and spleen by means of AMS. RESULTS: Serum concentrations of 26Al were significantly lower in uraemic rats compared to controls, whereas urinary excretion was comparable (Nx, 7.11 +/- 5.78 pg/day vs C, 9.46 +/- 6.10 pg/day), suggesting a higher fraction of ultrafiltrable serum 26Al in uraemia. The target tissues of cellular transferrin-mediated 26Al uptake, liver and spleen, tended to show a larger degree of aluminium accumulation in controls (0.26 +/- 0.31 pg/g vs Nx, 0.14 +/- 0.10 pg/g and 0.37 +/- 0.27 pg/g vs Nx, 0.25 +/- 0.27 pg/g respectively). In contrast, in bone, a site of extracellular aluminium deposition, 26Al concentrations were more elevated in uraemia (1.22 +/- 0.59 pg/g vs C: 0.68 +/- 0.30 pg/g). Estimated total 26Al accumulation in all measured target tissues was significantly higher in uraemic rats (28.15 +/- 9.90 pg vs C: 17.03 +/- 7.03 pg) and total recovery of 26Al from tissue and urine was 26.58 +/- 6.74 pg in controls and 35.75 +/- 7.03 pg in uraemic animals, suggesting a fractional absorption of 0.133% and 0.175% respectively. CONCLUSIONS: Our data suggest that fractional absorption from a dietary level dose of 26Al is about 0.13%. Compartmentalization occurs in transferrin-dependent target tissues such as liver and spleen; however, in quantitative terms extracellular deposition in bone is more important. Uraemia has a significant effect on the intestinal absorption and compartmentalization of aluminium. It enhances fractional absorption and increases subsequent extracellular deposition of aluminium in bone. However, at the same time uraemia does not increase transferrin-dependent cellular accumulation of aluminium in liver and spleen.      

Use of simple clinical signs to predict pneumonia in young Gambian children: the influence of malnutrition.

The current WHO recommendations for the case management of acute respiratory infections (ARI) in children aged 2 months to 5 years in developing countries use fast breathing (respiratory rate of > or = 50 per minute in children under 12 months and > or = 40 in children aged 12 months to 5 years) and lower chest wall indrawing to determine which child is likely to have pneumonia and should therefore receive antibiotics. We have evaluated these and other physical signs in 487 malnourished children and 255 well nourished children who presented with a cough or breathing difficulty. Pneumonia, defined as definite radiological pneumonia or probable radiological pneumonia associated with crackles on auscultation, was present in 145 (30%) of the malnourished children and 68 (26%) of the well nourished children. The respiratory rate predicted pneumonia equally well in the two groups, but to achieve an appropriate sensitivity and specificity the respiratory rate cut-off required in malnourished children was approximately 5 breaths per minute less than that in well nourished children. Intercostal indrawing was more common and lower chest wall indrawing was less common in the malnourished children, with or without pneumonia. These results suggest that fast breathing, as defined at present by WHO, and lower chest wall indrawing are not sufficiently sensistive as predictors of pneumonia in malnourished children. As the latter are a high-risk group, we should like to recommend that children with malnutrition who present with a cough, fast breathing or difficult breathing should be treated with antibiotics.     

In vivo muscarinic cholinergic receptor imaging in human brain with [11C]scopolamine and positron emission tomography.

Cerebral muscarinic cholinergic receptors were imaged and regionally quantified in vivo in humans with the use of [11C]scopolamine and positron emission tomography. Previous studies in experimental animals have suggested the utility of radiolabeled scopolamine for in vivo measurements, on the bases of its maintained pharmacologic specificity following systemic administration and the exclusion of labeled metabolites from the brain. The present studies describe the cerebral distribution kinetics of [11C]scopolamine in normal subjects following intravenous injection. Scopolamine is initially delivered to brain in a perfusion-directed pattern. After 30 to 60 min, activity is lost preferentially from cerebral structures with low muscarinic receptor density including the cerebellum and thalamus. Activity continues to accumulate throughout a 2 h postinjection period in receptor-rich areas including cerebral cortex and the basal ganglia. The late regional concentration of [11C]scopolamine does not, however, accurately parallel known differences in muscarinic receptor numbers in these receptor-rich areas. Tracer kinetic analysis of the data, performed on the basis of a three-compartment model, provides receptor binding estimates in good agreement with prior in vitro measurements. Kinetic analysis confirms significant contributions of ligand delivery and extraction to the late distribution of [11C]scopolamine, reconciling the discrepancy between receptor levels and tracer concentration. Finally, a novel dual-isotope method for rapid chromatographic processing of arterial blood samples in radiotracer studies is presented. The combination of rapid chromatography and compartmental analysis of tracer distribution should have broad utility in future in vivo studies with short-lived radioligands.     

Regional brain distribution of [18F]GBR 13119, a dopamine uptake inhibitor, in CD-1 and C57BL/6 mice

We have examined the regional brain distribution of [18F]GBR 13119 (18F: beta +, T1/2 = 110 min), a dopamine uptake inhibitor, in CD-1 and C57BL/6 mice. High levels of binding are observed in the striatum of both species, with striatum/cerebellum ratios of 3-4 at 60 min after injection of the radiotracer. Striatum radioactivity and striatum/cerebellum ratios are more than 50% reduced in C57BL/6 mice treated chronically with the neurotoxin MPTP. We conclude mice are an appropriate model for the in vivo study of the dopamine uptake system, and that [18F]GBR 13119 may be a suitable in vivo marker for degeneration of striatal dopaminergic neurons.     

The fate of dienochlor administered orally and dermally to rats

Within four days of receiving a single oral dose (1 mg/kg) of [U-ring-14C]dienochlor [bis(pentachloro-2,4-cyclopentadien-1-yl)] female rats excreted 2 and 88% of the applied 14C in urine and feces, respectively. Metabolites could not be identified and the preponderance of the fecal radioactivity consisted of unextractable 14C-labeled residues. Within 1 day virtually all of the dienochlor had been degraded by rats, with only traces of parent dienochlor in excreta and tissues. After four days only 2% of the applied dose remained in tissues (mainly kidney, liver, and gastrointestinal tract). Pharmacokinetic studies with blood plasma and bile showed dienochlor (and/or its metabolites) to be poorly absorbed. Rats were exposed dermally for 24 hr to [14C]dienochlor formulated as Pentac WP miticide both as an aqueous suspension and as an undiluted wettable powder. Half of the dose adhered to the skin and the other half was found in gauze patches used to protect the treated skin. After a 24-hr exposure over 60% of the radiolabel that adhered to skin was removed by washing with an aqueous soap solution and 86% of this rinsing solution was unmetabolized dienochlor. The dienochlor and its metabolites were transported inefficiently from the application site; only 1% of the applied dose was detected in urine plus feces and less than or equal to 0.2% in tissues. With application rates that simulate field exposure by humans, the actual residue of dienochlor and metabolites in skin (i.e., not removable by washing) is about thirteen times higher following exposure to dienochlor as undiluted wettable powder than as an aqueous suspension.     

Generality of Psychopathy Checklist-Revised factors over prisoners and substance-dependent patients

The Psychopathy Checklist-Revised (PCL-R; R. D. Hare, 1991) is an often-used device for assessment of adult antisociality. This research examined generalizability by replicating the 2-factor model for a sample of 326 male prisoners and assessing its congruence and relative reliability and specificity among 620 substance-dependent patients. Generality was assessed also across addiction subtypes (opioid, cocaine, and alcohol), age, gender, and ethnicity. The 2-factor model was found inappropriate for the substance-dependent samples, whereas a unidimensional model represented by the PCL-R total score was found generalizable across prison and substance-dependent samples.     

Peanut lectin binding sites in transitional cell carcinoma of the urinary bladder

Peanut lectin (PNA) binds to D Gal B (1-3) D Gal NAc which is the purported antigenic determinant of the so-called T blood group antigen (TAg). We used PNA in an indirect immunofluorescent technique to study TAg in transitional cell carcinomas of the bladder (TCC). All 14 control tissues failed to express TAg, whereas all controls (100%) expressed TAg on the cell membrane after prior treatment with neuraminidase. Sixty-nine percent of Stage O TCC expressed TAg, whereas 100% of cases expressed TAg after treatment with neuraminidase. Staining patterns noted were: granular intracytoplasmic, intracytoplasmic globular, and membrane. There was no correlation between TAg positivity or negativity and subsequent muscle wall invasion in the Stage O TCC group. Fifty percent of Stage B or greater TCC expressed TAg, whereas 27 of 30 (90%) cases expressed TAg after neuraminidase treatment. TAg-staining patterns noted in Stage B tumors were: membrane, granular intracytoplasmic, intracytoplasmic globular, and glycocalyx. Only 47% of Grade III TCC expressed TAg compared with 72% of low-grade TCC. The authors conclude that the expression of TAg reflects the neoplastic transformation of bladder epithelium. The data also suggest that in TCC, TAg positivity is most likely due to incomplete synthesis of MN blood group glycoprotein, as evidenced by loss of a terminal sialic acid, and that there is also evidence of cytostructural "relocalization" of TAg.     

Long-term morbidity and mortality following hypoxaemic lower respiratory tract infection in Gambian children

Acute lower respiratory infections (ALRI) are the main cause of death in young children worldwide. We report here the results of a study to determine the long-term survival of children admitted to hospital with severe pneumonia. The study was conducted on 190 Gambian children admitted to hospital in 1992-94 for ALRI who survived to discharge. Of these, 83 children were hypoxaemic and were treated with oxygen, and 107 were not. On follow-up in 1996-97, 62% were traced. Of the children with hypoxaemia, 8 had died, compared with 4 of those without. The mortality rates were 4.8 and, 2.2 deaths per 100 child-years of follow-up for hypoxaemic and non-hypoxaemic children, respectively (P = 0.2). Mortality was higher for children who had been malnourished (Z-score < -2) when seen in hospital (rate ratio = 3.2; 95% confidence interval (CI) = 1.03-10.29; P = 0.045). Children with younger siblings experienced less frequent subsequent respiratory infections (rate ratio for further hospitalization with respiratory illness = 0.15; 95% CI = 0.04-0.50; P = 0.002). Children in Gambia who survive hospital admission with hypoxaemic pneumonia have a good prognosis. Survival depends more on nutritional status than on having been hypoxaemic. Investment in oxygen therapy appears justified, and efforts should be made to improve nutrition in malnourished children with pneumonia.