CSF opening pressure in children with optic nerve head edema.

BACKGROUND: We previously reported that an abnormal CSF opening pressure (OP) in children was greater than 28 cm H(2)O. Since elevated intracranial pressure can cause optic nerve head edema (ONHE), we would expect that most patients with ONHE would have an OP greater than 28 cm H(2)O. This study describes the range of OP for children with ONHE and compared them to age-matched controls without ONHE. METHODS: Case subjects were children (1-18 years of age) enrolled in a prospective study of CSF OP that demonstrated ONHE at time of lumbar puncture and that the ONHE later resolved. Patients with ONHE secondary to infectious, inflammatory, or ischemic conditions were excluded. Control subjects from the same study, but without ONHE, were matched to cases. RESULTS: Of the 472 subjects enrolled in the study, 41 OP measurements were obtained from 33 patients with ONHE who did not have any exclusionary criteria and matched to 41 control subjects without ONHE. Case subjects had a significantly higher OP (mean, 41.4 cm H(2)0; range, 22-56) than control subjects (mean, 18.9 cm H(2)O; range, 9-29; p < 0.01). Forty of 41 (97.6%) case subjects and 2 of 41 (4.8%) control subjects had OP measures >28 cm H(2)O. CONCLUSIONS: Children with ONHE not related to infectious, inflammatory, or ischemic causes typically have an OP >28 cm H(2)O, significantly higher than age-matched controls without ONHE. This study provides further support to our previously published findings that suggests an abnormal OP in children is typically above 28 cm H(2)O.

Interictal 99mTc-HMPAO SPECT in temporal lobe epilepsy: relation to clinical variables.

PURPOSE: Factors affecting blood flow observed by interictal single-photon emission computed tomography (SPECT) images in temporal lobe epilepsy (TLE) have not been systematically studied or consistently demonstrated. We evaluated interictal SPECT results with respect to many clinical variables in a large population of TLE patients, all of whom underwent temporal lobectomy. METHODS: Interictal 99mTc-HMPAO SPECT scans from 61 TLE patients were obtained before an anterior temporal lobectomy. SPECT was analyzed using a region of interest analysis (ROI) in the cerebellum, anterior temporal lobe, lateral temporal lobe, mesial temporal lobe, whole temporal lobe, and inferior frontal lobe. Asymmetry indices (AIs) were calculated. Correlative analysis of AIs and clinical variables was performed. RESULTS: The AIs from TLE patients differed significantly from those of controls in the anterior temporal (p < 0.01), lateral temporal (p < 0.001), and whole temporal (p < 0.01) regions. No consistent overall correlation between the AIs and clinical variables existed. In right TLE (RTLE) only, AIs in the lateral and whole temporal lobe were positively correlated with age of onset (r = 0.470, p < 0.05; r = 0.548, p < 0.01, respectively). Similarly, in RTLE only, duration of epilepsy was negatively correlated with the anterior (r = -0.395, p < 0.05) and mesial (r = -0.45, p < 0.05) temporal lobe AI. No correlations were found between clinical variables and AIs in left TLE (LTLE) patients. CONCLUSIONS: Significant correlation of age at onset and duration of epilepsy with AIs in RTLE but not LTLE suggests physiologic processes may be determined in part by laterality of TLE. Clinical applications are problematic.

Ratio-images calculated from interictal positron emission tomography and single-photon emission computed tomography for quantification of the uncoupling of brain metabolism and perfusion in epilepsy.

PURPOSE: Image processing techniques were applied to interictal positron emission tomography (PET) and single-photon emission computed tomography (SPECT) brain images to aid in the localization of epileptogenic foci by calculating a functional image that represents the degree of coupling between perfusion and metabolism. Uncoupling of these two functions has been demonstrated to be a characteristic of epileptogenic tissue in temporal lobe epilepsy and has the potential to serve as a diagnostic measure for localization in other areas as well. METHODS: Interictal PET ((18)F-FDG) and interictal SPECT ((99m)Tc-HMPAO) scans were acquired from 11 epilepsy patients. The metabolism and perfusion images were three-dimensionally spatially registered, and a functional ratio-image was computed. These functional maps are overlaid onto a three-dimensional rendering of the same patient's magnetic resonance imaging anatomy. RESULTS: In all patients, an average uniform perfusion-to-metabolism ratio showed approximately constant values throughout most of the whole brain. However, the epileptogenic area (confirmed on surgery) demonstrated an area of elevated perfusion/metabolism in the grey matter. CONCLUSIONS: Although hypometabolism in the PET image was observed in most of these patients, the calculation of a functional ratio-image demonstrated localized foci that in some cases could not be observed on the PET image alone. The ratio-image also yields a quantitative measure of the uncoupling phenomenon.

The alpha-2A-adrenoceptor agonist, guanfacine, increases regional cerebral blood flow in dorsolateral prefrontal cortex of monkeys performing a spatial working memory task.

Research indicates that norepinephrine enhances the working memory functions of the prefrontal cortex (PFC) through actions at post-synaptic, alpha-2A adrenoceptors. The current study examined the effects of the alpha-2A adrenoreceptor agonist, guanfacine (0.7 mg/kg, i.m.), compared to saline on SPECT measures of regional cerebral blood flow (rCBF) in monkeys performing a spatial working memory task. Animals were infused with the SPECT blood flow tracer, Tcm-99m ECD, through an indwelling intravenous catheter while performing the working memory task. Guanfacine treatment significantly improved cognitive performance of the working memory task, and significantly increased rCBF values in the dorsolateral PFC, the brain region most tightly associated with performance of spatial working memory tasks. In contrast, guanfacine had no significant effect on rCBF in the superior temporal cortex, an auditory association area unrelated to task performance. These data are consistent with the hypothesis that alpha-2A adrenoceptor stimulation preferentially enhances functioning of the PFC.

Decreased cerebral blood flow during seizures with ictal SPECT injections.

Increased regional cerebral blood flow (rCBF) at the epileptogenic site has been consistently reported for single photon emission computed tomography (SPECT) injections made during seizure activity, and the increased rCBF has been shown to remain elevated at the epileptogenic site in some cases, even when SPECT injections are made after seizure termination (postictal). A sustained increase in rCBF after seizure cessation was recently confirmed, but for no more than 100 s from seizure onset [Avery, R.A., Spencer, S.S., Spanaki, M.V., Corsi, M., Seibyl, J.P., Zubal, I.G., 1999. Effect of injection time on postictal SPET perfusion changes in medically refractory epilepsy. Eur. J. Nucl. Med. 26, 830-836]. In the current study, it is examined whether ictal SPECT injections demonstrate a similar change in rCBF around 100 s from seizure onset. Twenty-one patients with medically refractory epilepsy and a known area of seizure onset receiving ictal and interictal 99mTc-Hexamethyl-propyleneamineoxime (HMPAO) SPECT scans were studied. The results of SPECT subtraction analysis which visualize increased and decreased rCBF were compared to seizure duration and HMPAO injection time. Five patients received ictal SPECT injections (during ongoing seizure activity) more than 90 s after seizure onset and demonstrated decreased rCBF. Two of these patients also demonstrated areas of increased rCBF. Decreased rCBF was localized to the epileptogenic lobe in four of the five patients. By examining ictal SPECT injections made 90 s after seizure onset, evidence was found that reduced rCBF may exist during ictus. The change in rCBF around 90 s is also observed in postictal injections, suggesting a common metabolic mechanism may be responsible.

Reproducibility of serial peri-ictal single-photon emission tomography difference images in epilepsy patients undergoing surgical resection.

Peri-ictal single-photon emission tomography (SPET) difference images co-registered to magnetic resonance imaging (MRI) visualize regional cerebral blood flow (rCBF) changes and help localize the epileptogenic area in medically refractory epilepsy. Few reports have examined the reproducibility of SPET difference image results. Epilepsy patients having two peri-ictal and at least one interictal SPET scan who later underwent surgical resection were studied. Localization accuracy of peri-ictal SPET difference images results, interictal electroencephalography (EEG), and ictal EEG from the first (seizure 1) and second (seizure 2) seizure, as well as MRI and positron emission tomography (PET) findings, were compared using surgical resection site as the standard. Thirteen patients underwent surgical resection (11 temporal lobe and 2 extratemporal). SPET results from seizure 1 were localized to the surgical site in 12/13 (92%) patients, while SPET results from seizure 2 were localized in 13/13 (100%) patients. All other modalities were less accurate than the SPET results interictal EEG--seizure 1 6/13 (46%); ictal EEG--seizure 1 5/13 (38%); interictal intracranial EEG--seizure 2 4/9 (44%); ictal intracranial EEG--seizure 2 results 8/9 (89%); MRI 6/13 (46%); PET 9/13 (69%)[. SPET results were reproducible in 12/13 (92%) patients. SPET difference images calculated from two independent peri-ictal scans appear to be reproducible and accurately localize the epileptogenic area. While SPET difference images visualize many areas of rCBF change, the quantification of these results along with consideration of injection time improves the diagnostic interpretation of the results.

Effect of injection time on postictal SPET perfusion changes in medically refractory epilepsy.

Single-photon emission tomography (SPET) brain imaging in epilepsy has become an increasingly important noninvasive tool in localizing the epileptogenic site. Ictal SPET demonstrates the highest localization sensitivity as compared with postictal and interictal SPET. While ictal SPET consistently reveals hyperperfusion at the epileptogenic site, postictal SPET reveals either hyper- or hypoperfusion depending on the timing of radiopharmaceutical injection. Much discussion in the literature exists about exactly when the transition from hyper- to hypoperfusion occurs at the epileptogenic site in postictal SPET. The systematic examination of two clinical variables - time of injection from seizure onset and offset - was useful in understanding postictal perfusion changes. Twenty-seven patients with medically refractory epilepsy receiving postictal and interictal SPET scans were studied. Quantitative SPET difference imaging was used to evaluate perfusion changes in relationship to injection time. Perfusion changes were found to reflect the time of injection in relation to seizure onset, but to be somewhat independent of seizure offset. Thus, the majority of patients (8/12, 67%) receiving postictal injections within 100 s after seizure onset demonstrated hyperperfusion, while all patients (15/15, 100%) receiving postictal injections more than 100 s after seizure onset showed hypoperfusion. The explanation of this phenomenon is unknown but the findings appear to parallel known changes in cerebral lactate levels.

Absence of an apolipoprotein E epsilon4 allele is associated with increased parietal regional cerebral blood flow asymmetry in Alzheimer disease.

BACKGROUND: The apolipoprotein E (Apo E) epsilon4 allele has been associated with parietal metabolic abnormalities and asymmetries in asymptomatic subjects at risk for Alzheimer disease (AD). However, previous research has shown minimal effect of the epsilon4 allele on regional cerebral blood flow (rCBF) and metabolism in patients with probable AD. OBJECTIVE: To determine whether the Apo E epsilon4 allele is associated with parietal rCBF abnormalities and asymmetries in patients with probable AD. PATIENTS AND METHODS: Thirty patients with AD with the epsilon4 allele (epsilon4+ AD), 22 patients with AD without the epsilon4 allele (epsilon4- AD), and 14 healthy control subjects underwent single-photon emission computed tomography (SPECT) scanning with 740 MBq technetium Tc 99m hexamethylpropyleneamine oxime. Ratios of parietal-unaffected regions and a left-right parietal asymmetry index were compared between both patient groups. RESULTS: The group with epsilon4- AD was younger (P = .005, Student t test) and had an earlier age of onset (P = .005) than the group with epsilon4+ AD. Analysis of covariance revealed no significant difference in the parietal rCBF ratio, controlling for age of onset and Mini-Mental State Examination score (F(1,48) = 0.06; P = .81). However, contrary to hypothesis, significantly greater parietal rCBF asymmetry was seen in patients with epsilon4- AD (mean +/- SD, 9.7% +/- 5.5%) than those with epsilon4+ AD (6.3% +/- 4.7%; F(1,50) = 5.89; P = .02; analysis of variance). When number of epsilon4 allele copies was considered, this effect appeared to accrue primarily from a difference between patients with 0 and with 2 epsilon4 allele copies. An exploratory analysis of multiple cortical structures suggested that this asymmetry extended to additional regions (superior temporal) and to combined association cortex. CONCLUSIONS: Greater parietal rCBF asymmetry is involved in epsilon4- AD than in epsilon4+ AD. Lack of the epsilon4 allele may be associated with other (as yet undiscovered) genetic or environmental risk factors, which confer greater neuropathological asymmetry.

Thrombotic thrombocytopenic purpura associated with HIV and visceral Kaposi's sarcoma treated with plasmapheresis and chemotherapy.

We present a case of a patient who is HIV positive and developed both thrombotic thrombocytopenia purpura and visceral Kaposi's sarcoma (KS) with hemorrhage. This case presents a difficult management problem in that the patient's bleeding originated from KS lesions and did not quickly abate with plasmapheresis therapy despite both clinical and laboratory improvement after 2-4 days. Chemotherapy was initiated on day 13 and the patient's condition improved markedly afterward. We believe the addition of chemotherapy to plasmapheresis hastened the improvement of our patient's thrombotic thrombocytopenic purpura (TTP) and KS-related bleeding. Therefore, under similar conditions, we recommend combining plasmapheresis and chemotherapy at the onset of therapy.

Renal medullary carcinoma: clinical and therapeutic aspects of a newly described tumor.

BACKGROUND: Renal medullary carcinoma is a newly described, aggressive kidney tumor. All patients with the disease have been African-American with sickle cell (SC) trait or hemoglobin SC disease. METHODS: Patient information was obtained from individual patient records and from the Department of Defense national data bank, The Defense Enrollment and Eligibility Reporting System. Data were obtained from either personal review of the patient's records or from discussion with the patient's physician. Cytogenetic studies were performed on one patient. RESULTS: Six patients are presented. All had SC trait. Median age was 24.5 years and 1 patient was female. Time from diagnosis to death averaged 3 months (range 1-7 mos). No objective responses were reported to a wide variety of chemo and immunotherapies: cyclophosphamide, doxorubicin, cisplatin; methotrexate, vinblastine, doxorubicin, and cisplatin; single agent interferon; single agent paclitaxel; or single agent vinblastine. Investigational regimens included topotecan, doxorubicin, and filgrastim; alpha-interferon, interleukin-2, and 5-fluorouracil; and single agent paclitaxel. Cytogenetic studies revealed numerous structural, as well as numerical anomalies. Of the cells successfully karyotyped (n=4), 2 contained abnormalities of chromosome 3 and all contained monosomy 11. CONCLUSIONS: Renal medullary carcinoma is an aggressive, chemoresistant tumor. Time from discovery of tumor to patient death is very short and has been altered by a wide variety of chemotherapies and immunotherapies. An unidentified genetic component is likely present.

The effects of amphetamine on recovery of function after cortical damage in the rat depend on the behavioral requirements of the task.

The effects of amphetamine on the recovery of function following unilateral lesions of the rat somatic sensorimotor cortex (SMC) were examined. Rats with large SMC were tested on two measures of locomotor placing: the beam-walking test and the foot-fault test. Amphetamine produced an immediate and enduring facilitation of recovery on the beam-walking test. In contrast, the drug had no effect on the rats' ability to accurately place the forelimbs on the rungs of the elevated grid during locomotion on the foot-fault test. These data suggest that amphetamine may facilitate recovery when the requirements of the task produce a deficit in the initiation of locomotion but not when the animal is required to use somatosensory and proprioceptive cues to guide performance on the task. A second group of rats with smaller SMC lesions was evaluated with tactile-placing tests and the bilateral-tactile stimulation task. The forelimb placing reaction is elicited by unilateral tactile stimulation of the vibrissae or forelimb, whereas the ipsilateral asymmetry observed on the bilateral-tactile stimulation test has been interpreted as an impairment in processing stimuli presented on both sides of the body. On two measures of forelimb placing amphetamine produced a facilitation of recovery, but restoration of function was not observed during the period of drug intoxication. In contrast, amphetamine had no effect on recovery of function on the bilateral-tactile stimulation test. Taken together, these data suggest that the behavioral requirements of the task are an important factor in determining the facilitatory effects of amphetamine on recovery of function.

Dermal photoreceptors regulate basking behavior in the lizard Podarcis muralis.

There is evidence that dermal photic responsiveness can be found in a wide range of animals. Behavioral responses to dermal stimulation by light have been observed in pigeon squabs and new-born rats, and more recently in a sea snake. Here we report that painting the dorsal surface of the lizard (Podarcis muralis) with opaque black paint impairs the animal's ability to position itself beneath a light source containing negligible heat. Experiments using light of different spectra and intensities show that the effect is due to light of wavelengths shorter than 600 nm and of intensity higher than 2.5 mW cm-2. These experiments demonstrate for the first time that overt behavior in a terrestrial vertebrate can be mediated by a dermal light sense.

Growth in reptiles.

This paper reviews the literature on growth in reptiles. The current consensus is that growth data for small and medium-sized reptiles are best fitted by logistic-by-mass equations, data for larger reptiles by the von Bertalanffy equation. Experiments on the relationships between behavioural thermoregulation, food consumption and growth in both the laboratory and field are described, and an account is given of some recent work on individual differences in growth rates and their adaptive significance. In general, it may be said that in almost all areas of biology relating to growth, less is known about reptiles than about equivalent phenomena in fishes.

Zinc deficiency alters the protein composition of the membrane skeleton but not the extractability or oligomeric form of spectrin in rat erythrocyte membranes.

We examined the effect of dietary Zn deficiency on the composition and structure of the rat erythrocyte membrane skeleton. Weanling rats were given free access to egg white-based diets (less than 1.0 mg Zn/kg) for 3 wk. Controls were fed diets (pair-fed or ad libitum) supplemented with 100 mg Zn/kg. Membrane skeleton proteins were extracted from isolated erythrocyte membranes in a low ionic strength buffer. Dietary Zn deficiency did not alter the content of spectrin, the major membrane skeleton protein, in the intact membranes or the percentage of spectrin extracted after 24 or 96 h. Zinc deficiency did not alter the oligomeric form of spectrin in the extracts that were analyzed in the presence or absence of EDTA. However, Zn deficiency resulted in a significant reduction in the relative content of protein R5 in the membrane skeleton extracts. The food restriction associated with dietary Zn deficiency was the major factor in the significant reduction in the relative content of RA (adducin) and R4 (protein 4.1) in the membrane skeleton extracts. Dietary Zn deficiency altered membrane skeleton protein composition but had no effect on the extractability or oligomeric form of spectrin.

The oligomeric state of spectrin in the rat erythrocyte membrane skeleton.

The oligomeric state of spectrin in the erythrocyte membrane skeleton of the rat was investigated following extraction in a low ionic strength buffer for 24 and 96 h. All analyses were quantitatively compared with preparations from human erythrocyte membranes. After nondenaturing agarose-polyacrylamide gel electrophoresis, the human samples revealed their characteristic spectrin oligomer pattern; there were high molecular weight complexes near the origin of the gel, followed by several high order oligomers, tetramers, and dimers. The pattern in the rat membrane skeleton also included tetramers and a high molecular weight complex band, but had only one oligomer and no dimers. With time the high molecular weight complex diminished and oligomers accumulated in both the rat and human, while dimers accumulated only in the human and tetramers accumulated only in the rat. Tetramers decreased with time in the human. Extraction of spectrin increased with time and was greater from rat than the human red cell membrane at both time points. The percentage of spectrin and actin in the low ionic strength extract was similar between species, as analyzed by SDS-polyacrylamide electrophoresis, staining, and densitometry. Proteins 4.1 and 4.9 were present in greater percentages in the human. The only temporal effect on monomeric protein composition was an increase of protein A in the rat. There was no species difference in protein A percentage at 24 h, but at 96 h the rat was greater than the human. The results suggest that there are significant differences in the structural arrangement of the rat and human erythrocyte membrane skeleton.

Effect of dietary zinc deficiency and the associated drop in voluntary food intake on rat erythrocyte membrane polyamines.

The effect of dietary zinc deficiency in the rat on the free (noncovalently bound) polyamine concentrations in erythrocyte membranes, in erythrocyte cytosol and in the blood plasma were determined. Weanling male Wistar rats were fed an egg white-based diet containing less than 1.0 mg Zn/kg diet for 3 wk ad libitum. Control rats were either pair-fed or ad libitum-fed the basal diet supplemented with 100 mg Zn/kg diet. Tissue fractions were extracted with 0.2 M perchloric acid and polyamines were measured in the soluble fraction by dansylation, thin-layer chromatography and fluorescence spectrophotometry of the isolated dansylated polyamines. The depressed food intake associated with dietary zinc deficiency caused significantly (P less than 0.05) lower plasma spermidine, erythrocyte cytosol putrescine, spermidine and spermine and erythrocyte membrane spermidine concentrations. In addition, the depressed food intake caused significantly lower spermidine-spermine ratios in the erythrocyte membrane and cytosol and in blood plasma. Dietary zinc deficiency per se caused significantly (P less than 0.05) higher plasma spermidine and spermine and erythrocyte membrane spermine concentrations and significantly lower spermidine-spermine ratios in erythrocyte membrane and cytosol than in pair-fed, zinc-adequate controls.

Structural integrity of the human albumin gene in congenital analbuminemia.

The human serum albumin gene was analyzed by restriction endonuclease mapping of chromosomal DNA isolated from a patient with congenital analbuminemia. Following digestion with a variety of restriction endonucleases, the DNA from this individual produced the same fragments with homology to a serum albumin cDNA probe as did a control DNA specimen. Therefore, the genetic condition of congenital analbuminemia is not caused by any gross structural rearrangement or deletion of the gene itself, but may result from an abnormality in the gene's fine structure, perhaps affecting regulation or processing of the primary RNA transcript.

Observations on coprophagy and the transmission of Hymenolepis nana infections in mice.

Young, previously uninfected white mice became infected with Hymenolepis nana when exposed in small cages to parasite eggs which had been sprinkled in suspension onto the floor of their cage, or to faeces from mice with patent infections. The mean daily probabilities of infection for individual eggs under these two conditions were 2-9 X 10(-6) and 5-4 X 10(-6) respectively. If the mice were starved for 24 h prior to exposure to faeces, then the mean daily probability of infection increased to 2-6 X 10(-4). These differences in transmission are interpreted as being due to differences in the extent of coprophagy; they are not due to any effect of starvation on the hatchability of eggs.

Clutch size and reproductive effort in the lizard Lacerta vivipara Jacquin.

The ratio clutch weight: body weight in Lacerta vivipara is 0.4; larger lizards produce more eggs, and total clutch weight is isometric with body weight. The clutch represents between 7% and 9% of the estimated annual assimilation of a female lizard, and 23-24% of the assimilation during the period between emergence from hibernation and the establishment of the eggs in the oviducts.