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Biomedical subjects

L M Frank

Publications and source records attributed to L M Frank.

At least 19 recordsLinked to original sources
PubMed2002

Children's ibuprofen suspension for the acute treatment of pediatric migraine.

OBJECTIVE: To compare the efficacy of a single over-the-counter dose (7.5 mg/kg, p.o.) of children's ibuprofen suspension vs. placebo for the acute treatment of pediatric migraine. BACKGROUND: Migraine occurs in 4% of young children. There is a paucity of controlled clinical research in the treatment of childhood migraine and there are currently no approved drugs in the USA for treatment of migraine in children < or = 12 years of age. The purpose of this study is to assess the efficacy and tolerability of a single OTC dose of ibuprofen suspension for the acute treatment of childhood migraine. METHODS: Prospective, double-blind, placebo-controlled, parallel group, randomized study of children 6-12 yrs with migraine (I.H.S.-R 1997) treating 1 attack with a 7.5 mg/kg liq. ibuprofen vs matching placebo. Efficacy measures: (1). Headache severity based upon a 4 pt scale (severe, mod., mild, no headache) at 30, 60, 90, 120, 180 and 240 minutes post dose, and (2). nausea, vomiting, and photo/phonophobia at 120 min. The 1 degrees endpoint was cumulative % of responders (severe or mod. headache reduced to mild or none) by 120 minutes. Secondary endpoints were headache recurrence within 4-24 hours and need for rescue medicines within 4 hours. RESULTS: 138 enrolled; 84 treated/completed diary. 45 active agent, 39 placebo. The 2 groups were comparable (active: placebo) - Ages: 9: 9.1, gender boy/girl - 1.25: 1.6, and diagnosis: migraine w/o aura - 86%: 79%. Concomitant use of prophylactic Rx: 24%: 10% (Table 3). Nausea was eliminated in 60% of the ibuprofen treated patients and 39% of the placebo group (p<0.001). Vomiting, photophobia and phonophobia had marginal, but not statistically significant, decreases at 2 hours. A striking gender difference was noted (Table 4): No AE's were reported. CONCLUSION: Children's ibuprofen suspension at an OTC dose of 7.5 mg/kg is an effective and well-tolerated agent for pain relief in the acute treatment of childhood migraine, particularly in boys. There is a striking difference in gender response rates and placebo responder rates between girls and boys. The boys responded at a statistically significant rate, and girls failed to do so because of a very high placebo responder rate. Multi-center trials are recommended.

Acute Disease↗
PubMed2001

An analysis of neural receptive field plasticity by point process adaptive filtering.

Neural receptive fields are plastic: with experience, neurons in many brain regions change their spiking responses to relevant stimuli. Analysis of receptive field plasticity from experimental measurements is crucial for understanding how neural systems adapt their representations of relevant biological information. Current analysis methods using histogram estimates of spike rate functions in nonoverlapping temporal windows do not track the evolution of receptive field plasticity on a fine time scale. Adaptive signal processing is an established engineering paradigm for estimating time-varying system parameters from experimental measurements. We present an adaptive filter algorithm for tracking neural receptive field plasticity based on point process models of spike train activity. We derive an instantaneous steepest descent algorithm by using as the criterion function the instantaneous log likelihood of a point process spike train model. We apply the point process adaptive filter algorithm in a study of spatial (place) receptive field properties of simulated and actual spike train data from rat CA1 hippocampal neurons. A stability analysis of the algorithm is sketched in the. The adaptive algorithm can update the place field parameter estimates on a millisecond time scale. It reliably tracked the migration, changes in scale, and changes in maximum firing rate characteristic of hippocampal place fields in a rat running on a linear track. Point process adaptive filtering offers an analytic method for studying the dynamics of neural receptive fields.

Adaptation, Physiological↗
PubMed2001

Construction and analysis of non-Poisson stimulus-response models of neural spiking activity.

A paradigm for constructing and analyzing non-Poisson stimulus-response models of neural spike train activity is presented. Inhomogeneous gamma (IG) and inverse Gaussian (IIG) probability models are constructed by generalizing the derivation of the inhomogeneous Poisson (IP) model from the exponential probability density. The resultant spike train models have Markov dependence. Quantile-quantile (Q-Q) plots and Kolmogorov-Smirnov (K-S) plots are developed based on the rate-rescaling theorem to assess model goodness-of-fit. The analysis also expresses the spike rate function of the neuron directly in terms of its interspike interval (ISI) distribution. The methods are illustrated with an analysis of 34 spike trains from rat CA1 hippocampal pyramidal neurons recorded while the animal executed a behavioral task. The stimulus in these experiments is the animal's position in its environment and the response is the neural spiking activity. For all 34 pyramidal cells, the IG and IIG models gave better fits to the spike trains than the IP. The IG model more accurately described the frequency of longer ISIs, whereas the IIG model gave the best description of the burst frequency, i.e. ISIs < or = 20 ms. The findings suggest that bursts are a significant component of place cell spiking activity even when position and the background variable, theta phase, are taken into account. Unlike the Poisson model, the spatial and temporal rate maps of the IG and IIG models depend directly on the spiking history of the neurons. These rate maps are more physiologically plausible since the interaction between space and time determines local spiking propensity. While this statistical paradigm is being developed to study information encoding by rat hippocampal neurons, the framework should be applicable to stimulus-response experiments performed in other neural systems.

Action Potentials↗
PubMed2001

A comparison of the firing properties of putative excitatory and inhibitory neurons from CA1 and the entorhinal cortex.

The superficial layers of the entorhinal cortex (EC) provide the majority of the neocortical input to the hippocampus, and the deep layers of the EC receive the majority of neocortically bound hippocampal outputs. To characterize information transmission through the hippocampal and EC circuitry, we recorded simultaneously from neurons in the superficial EC, the CA1 region of hippocampus, and the deep EC while rodents ran for food reward in two environments. Spike waveform analysis allowed us to classify units as fast-spiking (FS) putative inhibitory cells or putative excitatory (PE) cells. PE and FS units' firing were often strongly correlated at short time scales, suggesting the presence a monosynaptic connection from the PE to FS units. EC PE units, unlike those found in CA1, showed little or no tendency to fire in bursts. We also found that the firing of FS and PE units from all regions was modulated by the approximately 8 Hz theta rhythm, although the firing of deep EC FS units tended to be less strongly modulated than that of the other types of units. When we examined the spatial specificity of FS units, we determined that FS units in all three regions showed low specificity. At the same time, retrospective coding, in which firing rates were related to past position, was present in FS units from all three regions and deep EC FS units often fired in a "path equivalent" manner in that they were active in physically different, but behaviorally related positions both within and across environments. Our results suggest that while the firing of FS units from CA1 and the EC show similarly low levels of position specificity, FS units from each region differ from one another in that they mirrored the associated PE units in terms of their tendency to show more complex positional firing properties like retrospective coding and path equivalence.

Action Potentials↗
PubMed2000

Adjunctive therapy with oxcarbazepine in children with partial seizures. The Oxcarbazepine Pediatric Study Group.

OBJECTIVE: To evaluate the safety and efficacy of oxcarbazepine (OXC) as adjunctive therapy in children with inadequately controlled partial seizures on one or two concomitant antiepileptic drugs (AEDs). BACKGROUND: OXC has shown antiepileptic activity in several comparative monotherapy trials in newly diagnosed patients with epilepsy, and in a placebo-controlled monotherapy trial in hospitalized patients evaluated for epilepsy surgery. DESIGN: A total of 267 patients were evaluated in a multicenter, randomized, placebo-controlled trial consisting of three phases: 1) a 56-day baseline phase (patients maintained on their current AEDs); 2) a 112-day double-blind treatment phase (patients received either OXC 30-46 mg/kg/day orally or placebo); and 3) an open-label extension phase. Data are reported only from the double-blind treatment phase; the open-label extension phase is ongoing. METHODS: Children (3 to 17 years old) with inadequately controlled partial seizures (simple, complex, and partial seizures evolving to secondarily generalized seizures) were enrolled. RESULTS: Patients treated with OXC experienced a significantly greater median percent reduction from baseline in partial seizure frequency than patients treated with placebo (p = 0.0001; 35% versus 9%, respectively). Forty-one percent of patients treated with OXC experienced a > or =50% reduction from baseline in partial seizure frequency per 28 days compared with 22% of patients treated with placebo (p = 0.0005). Ninety-one percent of the group treated with OXC and 82% of the group treated with placebo reported > or =1 adverse event; vomiting, somnolence, dizziness, and nausea occurred more frequently (twofold or greater) in the group treated with OXC. CONCLUSION: OXC adjunctive therapy administered in a dose range of 6 to 51 mg/kg/day (median 31.4 mg/kg/day) is safe, effective, and well tolerated in children with partial seizures.

Adolescent↗
PubMed2000

Trajectory encoding in the hippocampus and entorhinal cortex.

We recorded from single neurons in the hippocampus and entorhinal cortex (EC) of rats to investigate the role of these structures in navigation and memory representation. Our results revealed two novel phenomena: first, many cells in CA1 and the EC fired at significantly different rates when the animal was in the same position depending on where the animal had come from or where it was going. Second, cells in deep layers of the EC, the targets of hippocampal outputs, appeared to represent the similarities between locations on spatially distinct trajectories through the environment. Our findings suggest that the hippocampus represents the animal's position in the context of a trajectory through space and that the EC represents regularities across different trajectories that could allow for generalization across experiences.

Algorithms↗
PubMed1999

Lamictal (lamotrigine) monotherapy for typical absence seizures in children.

PURPOSE: To investigate whether lamotrigine (LTG) monotherapy is effective and safe for newly diagnosed typical absence seizures in children and adolescents (aged 3-15 years, n = 45). METHODS: A "responder-enriched" study design was used: open-label dose escalation was followed by placebo-controlled, double-blind testing of LTG. Conventional hyperventilation testing with EEG recording was used to confirm diagnoses and assess treatment success defined as complete freedom from seizures. Ambulatory 24-h EEG recordings provided supporting evidence of effectiveness. Safety was assessed by evaluation of adverse events, vital signs, and physical, neurologic, and laboratory examinations. Plasma samples were taken to evaluate the pharmacokinetics of LTG. RESULTS: During initial open-label dose escalation, 71.4% of patients (intent-to-treat) or 82% (per protocol analysis) became seizure free; individual patients responded at doses ranging from 2 to 15 mg/kg/day (median, 5.0). In the placebo-controlled, double-blind phase of the study, statistically significantly more patients remained seizure free when treated with LTG (62%) than with placebo (21%; p < 0.02; for the intent-to-treat analysis). Mean plasma concentrations of LTG, were linearly related to dose, although there was substantial interindividual variation. No patients were withdrawn from the study for any safety-related reason. CONCLUSIONS: LTG monotherapy is effective for typical absence seizures in children and is generally well tolerated.

Adolescent↗
PubMed1998

A statistical paradigm for neural spike train decoding applied to position prediction from ensemble firing patterns of rat hippocampal place cells.

The problem of predicting the position of a freely foraging rat based on the ensemble firing patterns of place cells recorded from the CA1 region of its hippocampus is used to develop a two-stage statistical paradigm for neural spike train decoding. In the first, or encoding stage, place cell spiking activity is modeled as an inhomogeneous Poisson process whose instantaneous rate is a function of the animal's position in space and phase of its theta rhythm. The animal's path is modeled as a Gaussian random walk. In the second, or decoding stage, a Bayesian statistical paradigm is used to derive a nonlinear recursive causal filter algorithm for predicting the position of the animal from the place cell ensemble firing patterns. The algebra of the decoding algorithm defines an explicit map of the discrete spike trains into the position prediction. The confidence regions for the position predictions quantify spike train information in terms of the most probable locations of the animal given the ensemble firing pattern. Under our inhomogeneous Poisson model position was a three to five times stronger modulator of the place cell spiking activity than theta phase in an open circular environment. For animal 1 (2) the median decoding error based on 34 (33) place cells recorded during 10 min of foraging was 8.0 (7.7) cm. Our statistical paradigm provides a reliable approach for quantifying the spatial information in the ensemble place cell firing patterns and defines a generally applicable framework for studying information encoding in neural systems.

Action Potentials↗
PubMed1995

Spin-spin relaxation of brain tissues in systemic lupus erythematosus. A method for increasing the sensitivity of magnetic resonance imaging for neuropsychiatric lupus.

OBJECTIVE: To correlate the spin-spin relaxation time (T2) of brain tissue in neuropsychiatric systemic lupus erythematosus (NPSLE) with the patient's clinical condition. METHODS: T2 values were determined in 54 SLE patients and 45 non-SLE controls at 1.5 Tesla, using intensity from multi-echo magnetic resonance (MR) images fitted to an exponential decay curve with rate-constant T2. RESULTS: The T2 of white matter was increased in SLE patients compared with controls (P = 0.01) and was increased in those patients who had previously experienced major NPSLE: Patients with acute diffuse neurologic manifestations (seizures, psychosis, coma) demonstrated a longer T2 of the gray matter (mean +/- SD 92.75 +/- 6.35 ms, n = 10) than did other SLE patients (mean +/- SD 79.61 +/- 5.04 ms, n = 44) (P = 0.02 by t-test), which suggests acute cerebral edema. The mean T2 values of reversible and nonreversible focal lesions were significantly different (P < 0.02), indicating different microenvironments and micropathology. CONCLUSION: Quantitative T2 measurement extends the utility and sensitivity of conventional MR imaging for evaluating NPSLE:

Adolescent↗
PubMed1989

Congenital malformations and psychosocial development in children conceived by in vitro fertilization.

To determine whether in vitro fertilization (IVF) as a method of conception is associated with an increased risk for congenital malformations or developmental dysfunction, we performed a general physical examination for malformations, neurologic examination, developmental examination (Bayley Scales), echocardiography, electrocardiography, abdominal ultrasound study, and, when possible, cranial ultrasound examination on a cohort of 83 IVF children and 93 matched non-IVF children. Major malformations were found in two IVF and one non-IVF subject; the rates were not significantly different. The mean Mental Development Index scores for IVF subjects and the comparison group were 115 +/- 13 and 111 +/- 13, respectively (p = 0.12). The mean Psychomotor Development Index scores were 114 +/- 14 and 108 +/- 15 (p = 0.04). Based on these small numbers but extensive evaluation, we found no association between conception by IVF and an increased risk for congenital malformations. Likewise, children conceived by IVF showed no evidence of developmental delay. Their high average achievement on the Bayley tests probably resulted from the exceptional motivation of their parents ("wantedness") and their generally high socioeconomic status.

Child Development↗
PubMed1989

Neurosonographic features of central nervous system infections in infancy and childhood.

Infections of the central nervous system (CNS) are a serious threat to the developing brain and are a major cause of neurologic handicap in the young. Of the neuroimaging modalities available, cranial ultrasonography has become an important technique in providing information about intracranial infection because of its portability, low cost, minimal morbidity, and diagnostic image quality. Authors of recent reports described ultrasonographic changes in brain parenchyma, extracerebral fluid, and ventricles. Parenchymal changes have been observed with cerebritis, edema, hemorrhage, infarction, and abscess formation; changes in extracerebral fluid include effusion and empyema; and ventricular changes associated with ventriculitis and hydrocephalus have been reliably described. By identifying changes associated with intracranial infections, ultrasonography has emerged as a technique that provides valuable information in making the diagnosis, identifying complications, and directing decisions in management of CNS infection.

Bacterial Infections↗
PubMed1985

Autosomal recessive congenital cerebellar hypoplasia.

We report three sibling pairs with congenital cerebellar hypoplasia. All six children presented in the first years of life with delays in motor and language development. All patients showed cerebellar and/or vermal dysfunction and, on formal psychometric testing, cognitive abilities ranged from normal to moderately retarded. Abnormalities on CT scan ranged from prominent valleculla to an enlarged cisterna magna with hypoplasia of the cerebellar hemispheres and vermis. The pedigrees are consistent with autosomal recessive inheritance.

Adolescent↗
PubMed1985

Prediction of chronic vegetative state in children using evoked potentials.

Absence of median nerve vertex referenced parietal somatosensory evoked potentials with preservation of the brainstem auditory evoked potential correlated with loss of cortical function and preservation of brainstem function in five children sustaining hypoxic insults who developed a chronic vegetative state. Evoked potential studies were more reliable than either the clinical exam or EEG, which were often misleadingly optimistic in prediction of outcome.

Brain Death↗
PubMed1984

Increased intracranial pressure in adrenoleukodystrophy.

Increased intracranial pressure developed as a terminal event in a 5-year-old boy with adrenoleukodystrophy. The CSF protein concentration was 420 mg/dL. Computed tomography showed extensive areas of decreased density in the posterior cerebral white matter. At autopsy, brain weight exceeded the expected value by 20%, and white matter water content was 87.6% (expected value, 72.5%). In rare instances, brain edema may contribute to the development of increased intracranial pressure in adrenoleukodystrophy.

Adrenoleukodystrophy↗
PubMed1984

Prediction of cerebral death by cranial sector scan.

Real-time cranial ultrasonography (cranial sector [CS] scan) was prospectively evaluated for its usefulness in identifying irreversible cerebral injury in critically ill children admitted to the neonatal and pediatric ICUs at our institution. Absence of pulsatile movement of the anterior and middle cerebral arteries was determined to represent absent cerebral perfusion and thus profound irreversible injury. Of 800 consecutive patients representing 1900 CS scans, 12 met the criteria. Six were neonates and 6 were older infants. Mechanisms of injury included severe hypoxia, head trauma, and CNS infection. Absence of brain function by clinical examination and EEG confirmed CS findings in 11 who expired. One neonate survived with intact brainstem function but no identifiable cerebral function or growth. No false positives were demonstrated. We found the CS scan to be a reliable bedside adjunct in the determination of irreversible cerebral injury or cerebral death.

Brain Death↗