Febrile seizures: is the EEG a useful predictor of recurrences?

We examined the predictive value of a paroxysmal EEG in children with febrile seizures seen at the University Pediatric Clinic, Skopje, Macedonia, between 1982 and 1984. This was the only facility providing EEG or neurologic consultation for children in Macedonia, and almost all children in the area who experienced a febrile seizure were referred to this facility. EEGs were classified as epileptiform if they contained spikes and sharp waves or spike wave complexes, which were either focal or generalized, and were considered abnormal for age and state. Nonspecifically abnormal was defined as focal or generalized slowing excessive for age and state. Follow-up visits were scheduled at 6-month intervals; mean follow-up time was approximately 23 months. In order to determine whether clearly abnormal EEG features would predict recurrences, we compared the recurrences in 170 children with initial normal-appearing EEGs with 99 children with initial paroxysmal EEGs. There was no significant difference in risk of recurrence of febrile seizures between the two groups; increase in recurrence risk was determined primarily by younger age. The EEG did not add information regarding the likelihood of recurrence of febrile seizures.

NMR studies of Pi-containing extracellular and cytoplasmic compartments in brain.

The inorganic phosphate (Pi) NMR peak in brain has an irregular shape, which suggests that it represents more than a single homogeneous pool of Pi. To test the ability of the Marquardt-Levenberg (M-L) nonlinear curve fit algorithm software (Peak-Fit) to separate multiple peaks, locate peak centers, and estimate peak heights, we studied simulated Pi spectra with defined peak centers, areas, and signal-to-noise (S/N) ratios ranging from infinity to 5.8. As the S/N ratio decreased below 15, the M-L algorithm located peak centers accurately when they were detected; however, small peaks tended to grow smaller and disappear, whereas the amplitudes of larger peaks increased. We developed an in vitro three-compartment model containing a mixture of Pi buffer, phosphocreatine, phosphate diester, and phosphate monoester (PME), portions of which were adjusted to three different pHs before addition of agar. Weighed samples of each buffered gel together with phospholipid extract and bone chips were placed in an NMR tube and covered with mineral oil. Following baseline correction, it was possible to separate the Pi peaks arising from the three compartments with different pH values if each peak made up 10-35% of total Pi area. In vivo, we identified the plasma compartment by intraarterial infusion of Pi. It was assumed that intracellular compartments contained high-energy phosphates and took up glucose. Based on these assumptions we subjected the brains to complete ischemia and observed that Pi compartments at pH 6.82, 6.92, 7.03, and 7.13 increased markedly in amplitude. If the brain cells took up and phosphorylated 2-deoxyglucose (2-DG), 2-DG-6-phosphate (2-DG-6-P) would appear in the PME portion of the spectrum ionized according to pH. Four 2-DG-6-P peaks with calculated pH values of 6.86, 6.94, 7.04, and 7.15 did appear in the spectrum, thereby confirming that the four larger Pi peaks represented intracellular spaces.

The effect of a free radical scavenger and platelet-activating factor antagonist on FFA accumulation in post-ischemic canine brain.

The effects of the platelet-activating factor antagonist BN 50739 and a free radical scavenger dimethyl sulfoxide on the accumulation of free fatty acids in post-ischemic canine brain are reported. Following 14 min of complete normothermic ischemia and 60 min of reperfusion, the total brain FFAs were approximately 150% higher than in the control group (p < 0.05). Perfusion with the platelet-activating factor antagonist BN50739 in its diluent dimethyl sulfoxide during 60 min of post-ischemic reoxygenation resulted in a 61.8% (p < 0.01) reduction in the total brain free fatty acid accumulation. Palmitic, stearic, oleic, linoleic, and arachidonic acids decreased by 53.8%, 63.5%, 69.0%, 47.4%, and 57.2%, respectively. Although dimethyl sulfoxide alone caused stearic and arachidonic acids to return to the normal concentration range, BN 50739 had a significant influence on recovery of palmitic, oleic, and linoleic acids and was previously shown to provide significant therapeutic protection against damage to brain mitochondria following an ischemic episode. Because free fatty acid accumulation is one of the early phenomena in cerebral ischemia, this study provides evidence to support the hypothesis that both platelet-activating factor and free radicals are involved in initiating cerebral ischemic injury.

Inorganic phosphate compartmentation in the normal isolated canine brain.

In vivo 31P magnetic resonance spectra of 16 isolated dog brains were studied by using a 9.4-T wide-bore superconducting magnet. The observed Pi peak had an irregular shape, which implied that it represented more than one single homogeneous pool of Pi. To evaluate our ability to discriminate between single and multiple peaks and determine peak areas, we designed studies of simulated 31Pi spectra with the signal-to-noise (S/N) ratios ranging from infinity to 4.4 with reference to the simulated Pi peak. For the analysis we used computer programs with a linear prediction algorithm (NMR-Fit) and a Marquardt-Levenberg nonlinear curve-fit algorithm (Peak-Fit). When the simulated data had very high S/N levels, both methods located the peak centers precisely; however, the Marquardt-Levenberg algorithm (M-L algorithm) was the more reliable at low S/N levels. The linear prediction method was poor at determining peak areas; at comparable S/N levels, the M-L algorithm determined all peak areas relatively accurately. Application of the M-L algorithm to the individual experimental in vivo dog brain data resolved the Pi peak into seven or more separate components. A composite spectrum obtained by averaging all spectral data from six of the brains with normal O2 utilization was fitted using the M-L algorithm. The results suggested that there were eight significant peaks with the following chemical shifts: 4.07, 4.29, 4.45, 4.62, 4.75, 4.84, 4.99, and 5.17 parts per million (ppm). Although linear prediction demonstrated the presence of only three peaks, all corresponded to values obtained using the M-L algorithm. The peak indicating a compartment at 5.17 ppm (pH 7.34) was assigned to venous pH on the basis of direct simultaneous electrode-based measurements. On the basis of earlier electrode studies of brain compartmental pH, the peaks at 4.99 ppm (pH 7.16) and 4.84 ppm (pH 7.04) were thought to represent interstitial fluid and the astrocyte cytoplasm, respectively.

Risk factors for febrile seizures in the People's Republic of China: a case control study.

A case control study was conducted to investigate the association of family history of febrile seizures (FS) and history of maternal, pregnancy and delivery, and postnatal factors with FS. Information was gathered by door-to-door survey in six major cities in the People's Republic of China. Factors present before the date of onset of FS were assessed in 182 subjects and in an equal number of controls matched for age, sex, and geographic area. The odds ratio for risk of FS in children with a family history of FS in a first-degree relative was 10.0 (confidence interval 2.7-58.6), confirming other observations that familial factors are an important predisposing characteristic for FS. Maternal acute respiratory infection during the first trimester of pregnancy was slightly more frequent in children with FS (odds ratio, 1.9 confidence interval 1.0-3.9). None of the other examined pregnancy or delivery factors was associated with an increased risk, suggesting that birth history is not an important factor predisposing to FS.

Recovery of postischemic brain metabolism and function following treatment with a free radical scavenger and platelet-activating factor antagonists.

We have studied the metabolic and functional effects of two new platelet-activating factor (PAF) antagonists (BN 50726 and BN 50739) and their diluent (dimethyl sulfoxide; DMSO) during reoxygenation of the 14-min ischemic isolated brain. Blood gases, EEG, auditory evoked potentials, cerebral metabolic rate for glucose (CMRglc), and cerebral metabolic rate for oxygen (CMRO2) were monitored throughout the study. Frozen brain samples were taken for measurement of brain tissue high-energy phosphates, carbohydrate content, and thiobarbituric acid-reactive material (TBAR, an indicator of lipid peroxidation) at the end of the study. Following 60 min of reoxygenation in the nontreated 14-min ischemic brains, lactate, AMP, creatine (Cr), intracellular hydrogen ion concentration [H+]i), and TBAR values were significantly higher and ATP, creatine phosphate (PCr), CMRglc, CMRO2, and energy charge (EC) values were significantly lower than the corresponding normoxic control values. PCr and CMRO2 values were significantly higher, and glycogen, AMP, and [H+]i values were significantly lower in the BN 50726-treated ischemic brains than in DMSO-treated ischemic brains. In brains treated with BN 50739, ATP, ADP, PCr, CMRO2, and EC values were significantly higher, and lactate, AMP, Cr, and [H+]i values were significantly lower than corresponding values in the DMSO-treated ischemic brains. TBAR values were near control levels in all brains exposed to DMSO. There was also marked recovery of EEG and auditory evoked potentials in brains treated with DMSO. Treatment with BN 50726 or BN 50739 in DMSO appeared to improve brain mitochondrial function and energy metabolism partly as the result of DMSO action as a free radical scavenger.(ABSTRACT TRUNCATED AT 250 WORDS)

Does omentectomy prevent malignant small bowel obstruction?

Because the omentum collects and disseminates cancer cells, omentectomy is an integral part of ovarian cancer surgery. We postulate that the omentum serves a similar function in colon cancer and may contribute to post-operative malignant small bowel obstruction (S.B.O.) and that routine omentectomy during colectomy would reduce the incidence of S.B.O. Fischer 344 rats and a transplantable carcinogen-induced rat colon cancer were used to test: (1) whether the omentum is a unique site of intra-abdominal colon tumor implantation which contributes to S.B.O.; and (2) whether omentectomy at the time of tumor implantation would reduce the incidence of S.B.O. Statistical analysis confirmed that animals undergoing omentectomy had a significantly lower incidence of omental tumors and malignant S.B.O. (26 per cent and 16 per cent respectively) when compared with sham operated animals (75 per cent and 85 per cent respectively, P less than 0.001). These data suggest that the omentum is a source of bowel obstruction from implantation and growth of tumour cells in the rat model. Although this could be tested in other animal systems, the addition of routine omentectomy to colectomy is simple, not time-consuming, and may reduce postoperative morbidity.

Relating cerebral ischemia and hypoxia to insult intensity.

The contributions of five variables believed to influence the brain's metabolism of O2 during hypoxia [duration, PaO2, delta CMRO2 (the difference between normal and experimental oxygen uptake), O2 availability (blood O2 content.CBF), and O2 deficit (delta CMRO2.duration)] were assessed by stepwise and multiple linear regression. Levels of brain tissue carbohydrates (lactate, glucose, and glycogen) and energy metabolites [ATP, AMP, and creatine phosphate (CrP)] were significantly influenced by O2 deficit during hypoxia, as was final CMRO2. After 60 min of reoxygenation, levels of tissue lactate, glucose, ATP, and AMP were related statistically to the O2 deficit during hypoxia; however, CMRO2 changes were always associated more significantly with O2 availability during hypoxia. Creatine (Cr) and CrP levels in the brain following reoxygenation were correlated more to delta CMRO2 during hypoxia. Changes in some brain carbohydrate (lactate and glucose), energy metabolite (ATP and AMP) levels, and [H+]i induced by complete ischemia were also influenced by O2 deficit. After 60 min of postischemic reoxygenation, brain carbohydrate (lactate, glucose, and glycogen) and energy metabolite (ATP, AMP, CrP, and Cr) correlated with O2 deficit during ischemia. We conclude that "O2 deficit" is an excellent gauge of insult intensity which is related to observed changes in nearly two-thirds of the brain metabolites we studied during and following hypoxia and ischemia.

Reduced incidence of hepatic metastases by perioperative treatment with recombinant human interleukin-2.

Abdominal operations induce immunosuppression during the time when tumors are manipulated and tumor cells are released into the circulation. The authors tested the hypothesis that the combined effect of these factors may promote the development of metastatic tumor implants and that perioperative treatment with Human Recombinant Interleukin-2 (RIL-2), a known immunostimulant of t, natural killer (NK), and lymphokine activated killer (LAK) cells may reduce the incidence of liver metastases from transplantable rat colon cancers. Hepatic metastases were induced in male Fischer 344 (F344) rats by injecting 10(7) rat colon tumor cells into the portal venous system during laparotomy. Control rats developed tumors by four weeks and were dead by ten weeks. Eleven groups of rats underwent celiotomy with portal vein injection of tumor on day three. Rats received either no RIL-2, RIL-2, or excipient buffer at varying doses on days 1 through 5 or 3 through 7 of these experiments. Animals were assessed for the presence of tumor and the incidence of liver metastases at autopsy (sacrifice and autopsy performed at seven weeks). Eighty-five percent of the rats in the untreated group developed tumor. This compared with only 50 percent of animals receiving 10(3) u/dose (P less than .025) and 42 percent of animals receiving 10(4) u/dose (P less than .01) of Interleukin-2 on days 1 through 5. Animals receiving very high doses of RIL-2 (10(5) or 4 X 10(5) units per dose) had a greater chance of developing tumors than did control rats, or rats receiving lower doses of RIL-2 (P less than .05). It is concluded that the perioperative period may be critical for the implantation and growth of metastatic disease and that perioperative immunostimulation with RIL-2 can decrease the incidence of tumors in these animals. This model may have relevance to the treatment of human colon cancer.

The significance of asymptomatic microhematuria in men 50 or more years old: findings of a home screening study using urinary dipsticks.

In an ongoing home screening study 231 men 50 or more years old without known causes of hematuria have tested their urine each week with a chemical reagent strip for the presence of blood. After 3 months of testing 23 patients have had hematuria at least once. Of these men 5 have had urinary cancers and 5 have had other serious underlying diseases requiring immediate treatment. In only 3 of these 10 men (only 1 with cancer) did hematuria occur in more than a third of the testings or on subsequent microscopic urinalysis. The degree of hematuria was unrelated to the seriousness of its cause. We conclude that in this population hematuria occurs so intermittently that when found on routine urinalysis, regardless of quantity, serious underlying pathological conditions must be ruled out aggressively. Furthermore, regular hematuria home testing appears to offer promise as an economical means to detect urinary cancers and other serious diseases in asymptomatic men 50 or more years old.

Do operations facilitate tumor growth? An experimental model in rats.

Enhancement of tumor growth by operation is a concern often expressed by surgeons and patients anticipating cancer surgery. Two series of experiments were performed in which Fischer 344 rats and a carcinogen-induced transplantable rat colon cancer were used to test whether anesthesia and operation facilitate tumor implantation and growth. In the first experiments two groups of rats were given intraperitoneal tumor cells. One group underwent sham laparotomy; the second did not undergo surgery. In the second set of experiments rats were injected subcutaneously with tumor cells and then divided into four groups. The first group did not undergo laparotomy. The second underwent laparotomy on day 1, the third on day 15, and the fourth on days 15 and 29 after tumor implantation. Animals were followed for the incidence and growth rate of tumors that developed. The initial experiments demonstrated that 89% of the operated versus 49% of the nonoperated animals developed a tumor (p less than 0.001). The second experiment demonstrated that: animals undergoing multiple operations have a higher incidence of subcutaneous tumor nodules than nonoperated animals (p less than 0.05); animals undergoing multiple operations have a higher incidence of subcutaneous tumor nodules than animals undergoing a single operation (p less than 0.05); animals undergoing multiple operations had larger size tumor masses than the nonoperated animals (p less than 0.05) and than animals undergoing only one operation (p less than 0.04). This study supports the hypothesis that multiple operations and anesthesia may enhance tumor implantation and growth of metastases. This should be considered when designing therapy for patients with cancer.