Risk Factors for a First Febrile Seizure: A Matched Case-Control Study

Summary We conducted a matched casecontrol study to identify risk factors for first febrile seizures, with special emphasis on characteristics of the acute illness episode. Cases were identified through hospital emergency departments; controls were identified through outpatient clinics and emergency departments. Sixtynine children with first febrile seizures and no history of previous unprovoked seizures were matched for age (±6 months), site of routine pediatric care, and date of visit (±weeks) with 1 or 2 febrile controls who had no history of previous febrile or unprovoked seizures. Medical records for the index visit were reviewed, and parents were interviewed by telephone. Illness characteristics examined included height of temperature, type of underlying illness, contact with a physician during the illness but before the index visit, and use of acetaminophen or decongestants. Family history of febrile and of unprovoked seizures, sociodemographic characteristics, daycare use, and selected preand perinatal variables were also studied. On multivariable analysis, significant independent risk factors were height of temperature, history of febrile seizures in a firstor in a higher degree relative. Gastroenteritis as the underlying illness had a significant inverse (i.e., protective) association with febrile seizures. Maternal smoking during pregnancy was a marginally significant predictor of febrile seizures.     

Regulation of CD59 expression on K562 cells: effects of phorbol myristate acetate, cross-linking antibody and non-lethal complement attack.

CD59 is the major membrane attack complex of complement (MAC) inhibiting protein on human cells. Its regulation is therefore an important factor in determining the fate of cells at sites of complement activation. We have chosen the K562 erythroleukaemia cell line as a model for studies of the regulation of CD59 expression, because it has previously been reported that phorbol 12-myristate 13-acetate (PMA) caused a 15-fold up-regulation of CD59 mRNA in these cells, implying a substantial capacity for CD59 synthesis. However, no assessment of CD59 protein expression was made in these studies. We show here that surface expression of CD59, as assessed by flow cytometry, was increased four-fold over a 16-hr incubation with PMA, whereas surface expression of decay-accelerating factor (DAF) (CD55) and membrane cofactor protein (MCP) (CD46) was not altered. The newly expressed CD59 was functionally active and anchored through glycosyl-phosphatidylinositol (GPI). Increased expression was dependent upon de novo protein synthesis. CD59 released into cell supernatant was also increased seven-fold by PMA, this 'secreted' CD59 retained its GPI anchor. Non-lethal complement attack did not alter CD59 expression but antibody cross-linking of CD59 caused a rapid loss of the CD59-antibody complexes. However, CD59 was quickly restored to pre-attack levels. This rapid restoration was not dependent upon protein synthesis, suggesting release from preformed stores.     

A path-analytical approach to differentiate between direct and indirect drug effects on negative symptoms in schizophrenic patients

The hypothesis that differences in drug effects of risperidone and haloperidol on negative symptoms in schizophrenia are secondary to effects on positive, extrapyramidal, and depressive symptoms was investigated by means of an analysis of the data from the USA-Canada risperidone double-blind randomized clinical trial of 523 chronic schizophrenic patients. Regression analyses in the total sample and within treatment groups confirmed a strong relationship between changes in negative symptoms and the other variables studied (R²=0.50–0.51,p<0.001). Only depressive symptoms did not contribute significantly to these results (p>0.10). Path analysis showed that the greater mean change (p<0.05) of negative symptoms with risperidone compared to haloperidol could not be fully explained by correlations with favourable effects on positive and extrapyramidal symptoms. The relationship between shift in extrapyramidal symptoms and shift in negative symptoms failed to reach statistical significance; however, there was a clear tendency in the expected direction in both treatment groups.     

Neuropharmacology and Drug Interactions in Clinical Practice

Summary: Absorption, distribution, and clearance are key pharmacokinetic principles. These parameters can be highly variable among patients and among compounds, and are factors that must be considered in the wide variability in response to medications. Current antiepileptic drugs (AEDs) present many challenges in their administration. However, understanding and utilizing pharmacokinetic principles can assist the clinician in the appropriate optimization of AEds.     

Nutrition and aging: nutritional status of "apparently healthy" elderly (Dutch nutrition surveillance system)

In a nationwide survey the nutritional status was assessed of 539 apparently healthy, independently living elderly aged 65-79 years. Anthropometric data showed no energy deficits. The prevalence of anemia was 4 and 1% among men and women, respectively. Many elderly showed a low level of 25-hydroxyvitamin D in plasma (less than 31 nmol/L: men 35%; women 43%), indicating a marginal status. Although the prevalence of low blood levels of folate, pyridoxal-5'-phosphate, and total carotenoids was higher among the elderly than among younger adults, clear (clinical) signs of nutritional deficiencies were not observed. Prevalence of obesity (13%), hypercholesterolemia (38%), and hypertension (63%) was found to be high, the percentages being higher for women than for men. Several indicators of the nutritional status appeared to differ among age groups. It is concluded that few differences can be considered as being due to physiological aging, which finding should be reflected in reference values for elderly people.     

Decrease of inorganic blood sulfate following treatment with selected antirheumatic drugs: potential consequence for articular cartilage

The elimination kinetics of inorganic blood sulfate in mice was followed for four hours after a single, oral administration of an antirheumatic drug. Sodium salicylate, aspirin, diflunisal and benorylate, all in a dose of 1.25 mmol/kg, reduced the sulfate level to the less than half that of control. This phenomenon was also demonstrated by phenylbutazone, oxyphenbutazone (both 1 mmol/kg), chloroquine diphosphate (0.6 mmol/kg) and tiaprofenic acid (0.02-0.35 mmol/kg). Niflumic acid (1.08 mmol/kg), piroxicam (0.03 mmol/kg), indomethacin (6.10(-3) mmol/kg), diclofenac (5.10(-3) mmol/kg), ketoprofen (0.2 mmol/kg), naproxen (0.08 mmol/kg) and ibuprofen (0.24 mmol/kg) possessed no sulfate lowering properties. The potential relevance of the use of sulfate lowering drugs for articular cartilage integrity is discussed in the light of what is already known about this subject.     

Differential cytokeratin expression in normal, hyperplastic and malignant epithelial cells from human prostate.

Studies were undertaken to define the expression of cytokeratins in normal, hyperplastic and malignant epithelial cells from human prostate. Cytokeratin (CK) polypeptides, separated by two-dimensional electrophoresis, were identified by immunoblotting with CK-specific monoclonal antibodies. CK polypeptides 5, 7, 8, 15, 18 and 19 were identified in fresh normal and hyperplastic prostate. Expression of CK 15 has not been previously reported in human prostate. Analysis of central and peripheral zone tissues from human prostate did not reveal qualitative differences in CK expression between these areas. Epithelial cells harvested from fresh BPH tissue by percoll gradient centrifugation and propagated in vitro using selective culture techniques showed alterations in CK expression compared to intact human prostate. Specifically, CKs 6, 14, 16 and 17 were noted in cultured BPH epithelial cells but not fresh normal prostate or BPH tissue. Immunoblot analysis of the established prostate cancer cell lines PC3, DU145 and LNCAP showed expression of CKs 8 and 18 but not CKs 5, 7 and 15 which were observed in benign prostate. These studies further characterize CK expression in benign and malignant human prostate and provide insights which may be useful in differentiating normal, hyperplastic and malignant epithelial cells in the human prostate gland.     

Effect on cooking time on mutagen formation in smoke, crust and pan residue from pan-broiled pork

The effect of cooking time on mutagenic activity in crust, pan residue and smoke from pan-broiled pork patties was studied in the Ames Salmonella mutagenicity test system. The effect on mutagenicity of reheating the cooked patties and of keeping them warm was also studied. The meat was broiled at 200 degrees C for various times between 2 and 10 min. Broiled meat was reheated up to 5 times at 200 degrees C, each time to a centre temperature of 70 degrees C. Reheating was also performed in a microwave oven for 2 min and in an electric oven at 200 degrees C for 10 min. In addition, broiled patties were kept warm at 60 degrees C in an incubator for up to 9 hr. The mutagenic activity increased rapidly in all fractions except the volatile phase over the first 6 min of cooking, after which time only a slight increase was seen. At cooking times below 4 min no mutagenic activity was detected in the smoke. Reheating or keeping the meat warm for up to 9 hr had very little effect on the mutagenic activity of the meat. Reversed-phase high-performance liquid chromatography mutagenicity profiles of the aerosol, crust and pan-residue extracts showed no major qualitative differences in samples cooked at different times. It is concluded that during pan broiling at 200 degrees C the major part of the mutagenic activity is formed during the first 6 min of cooking. Reheating the meat or keeping it warm does not significantly affect the mutagenic activity. No major additional mutagens are formed during continued heating for up to 25 min.