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Biomedical subjects

M A Epstein

Publications and source records attributed to M A Epstein.

At least 19 recordsLinked to original sources

Vascular malformation with radiation vasculopathy after treatment of chiasmatic/hypothalamic glioma.

Chiasmatic/hypothalamic gliomas usually are histologically benign astrocytomas that may recur many years after diagnosis and treatment. Three children with chiasmatic/hypothalamic gliomas who were treated at the authors' institution returned 9.5, 11.5, and 2 years, respectively, after radiation therapy (RT) because visual and neurologic deterioration developed. Neuroradiographic studies, including arteriography in two of the patients, showed large mass lesions. These were presumed to be recurrence of tumor, and chemotherapy was administered. Pathologic examination of two children who died and of the third who had a biopsy revealed only a minimal amount of residual, histologically benign astrocytoma, whereas the bulk of the specimen consisted of numerous vessels of variable size. These probably represented incorporation of the rich vasculature in the chiasmal region into the tumor, which underwent degeneration secondary to RT. Radiographic methods did not distinguish progressive tumor growth from the vasculopathy and led to inappropriate clinical diagnoses and treatment.

Adolescent

Cardiac rhythm during temporal lobe seizures.

We studied the neuroanatomic correlates of ictal tachycardia in 27 seizures from five patients with unilateral temporal lobe epilepsy being evaluated with bilateral temporal lobe depth electrodes and orbitofrontal subdural electrodes. There were 11 complex partial seizures, three simple partial seizures, and 13 subclinical seizures. For all seizures, heart rate (HR) increased in a graded fashion as new cortical regions anywhere in the brain were recruited into the seizure. HR plateaued at the new level despite EEG frequency changes until the next region became involved. Increases in HR did not correlate with increased duration of seizures but rather with volume of brain involved. Restricted amygdaloid seizure activity was generally insufficient to alter HR. We conclude that the amygdala has a limited role in modulating HR during seizures, and ictal tachycardia depends principally on the volume of cerebral structures recruited into a seizure.

Adult

Late-onset globoid cell leukodystrophy mimicking an infiltrating glioma.

A 3 1/2 year old girl who developed a gradual left hemiparesis and hemianopia is reported. Neuroimaging studies demonstrated an infiltrating-like high density lesion which crossed the splenium of the corpus callosum, thought to represent a glioma. Subsequent brain biopsy established the correct diagnosis of globoid cell leukodystrophy (GCL), which suggests that the radiographic appearance of late-onset GCL may mimic that of an infiltrating glioma.

Brain

The boundaries of attention deficit disorder.

This report examines distinctions and interrelationships among attention deficit disorder (ADD) and two closely related conditions: learning disability (LD) and oppositional/conduct (O/C) disorder. To evaluate our hypothesis that some of the difficulty in resolving the relationship between ADD and, particularly, O/C may reflect the consequences of selective referral patterns, we studied groups of children diagnosed as ADD from different referral sources. Results suggest that referral bias does exist and that children referred to mental health settings differ from those referred to pediatricians, child neurologists, or psychologists. Because of the nature of the subjects referred to mental health services, nonrepresentative associations may emerge. Rather than being considered as prototypical of all children with attention disorder, children referred to mental health facilities may represent simply an extreme of the continuum of ADD. Evidence suggests that many children with ADD will be represented by those referred primarily for attentional deficits and learning problems, rather than those with inattention, hyperactivity, or aggression referred for child psychiatric evaluation.

Adolescent

The role of plasmapheresis in childhood Guillain-Barré syndrome.

Plasmapheresis has been advocated in the treatment of childhood Guillain-Barré syndrome under the assumption that the results of adult series can be extrapolated to children. To test this assumption, we retrospectively evaluated the medical charts of all children who were admitted to The Children's Hospital of Philadelphia between January 1984 and March 1989, with the diagnosis of Guillain-Barré syndrome. Of the 30 patients identified, 7 were excluded because they had mild disease. Of the remaining 23, 9 underwent plasmapheresis and 14 served as historic control subjects. The two groups were similar with respect to age, presenting symptoms, findings on initial physical examination, and antecedent illnesses at the time of diagnosis. The mean time to recover to Grade 2 (independent ambulation) was significantly shorter in the plasmapheresis-treated group, 24.0 +/- 25.4 days, compared to 60.2 +/- 43.6 days in control subjects (mean +/- 1 SD). Our results indicate that plasmapheresis diminishes morbidity in childhood Guillain-Barré syndrome by shortening the interval until recovery of independent ambulation.

Adolescent

Cavernous angioma presenting as atypical facial and head pain.

Recurrent headache is a common pediatric problem. As the differential diagnosis of headache is extensive, physicians rely on the mode of presentation to focus any investigation. A report of an adolescent in whom atypical facial and head pain caused by a preexisting cerebellar cavernous angioma is presented. Facial pain and headache resolved following excision of the tumor.

Child

Validation of a first-generation Epstein-Barr virus vaccine preparation suitable for human use.

The efficacy of a new vaccine preparation against Epstein-Barr (EB) virus was investigated in cotton-top tamarins. The vaccine consists of fast protein liquid chromatography-purified EB virus membrane antigen glycoprotein of 340 Kd (MA gp340) mixed with a synthetic muramyl dipeptide adjuvant emulsified in squalane containing a pluronic polymer; it is suitable for both scaled-up batch production and eventual administration to man. Vaccinated tamarins rapidly developed ELISA detectable high titre antibodies to MA gp340, and their sera became strongly EB virus-neutralising. After challenge with a massive 100% carcinogenic dose of EB virus, the vaccinated tamarins had a strikingly low level of circulating EB virus-carrying mononuclear cells, in contrast to a control animal, and remained entirely free of tumours. This first-generation vaccine has thus been validated in experimental animals and the way opened for a phase I human trial.

Acetylmuramyl-Alanyl-Isoglutamine

Large-scale purification of Epstein-Barr virus membrane antigen gp340 with a monoclonal antibody immunoabsorbent.

A purification method has been elaborated to isolate Epstein-Barr (EB) virus membrane antigen, gp340, in milligram amounts. The gp340 was prepared from detergent extracts of B95-8 cells by affinity chromatography with a monoclonal antibody immunoabsorbent. Bound material was eluted and the eluate, consisting of 50% gp340, was then fractionated by gel filtration. The final gp340 product was antigenically active and 95% pure. The purification method was found to be rapid and reproducible with no loss of the ability of the immunoabsorbent to retain gp340 after repeated elution. The procedure provides suitable material to permit the detailed structural analysis of gp340 necessary for both vaccine design and for the investigation of the role of gp340 in immunity to EB virus infection.

Antibodies, Monoclonal

Allospecific T cell recognition of HLA-A2 antigens: evidence for group-specific and subgroup-specific epitopes.

Interleukin 2-dependent alloreactive cytotoxic T cell lines, with activity predominantly directed against the HLA-A2 antigen, have been generated in vitro by stimulating blood mononuclear cells from donors nonimmune to the Epstein-Barr (EB) virus with appropriate numbers of EB virus-transformed B cells from A2-homozygous individuals. Such effector cells were tested against a panel of EB virus-transformed target cell lines all expressing the serologically defined A2 antigen but typed into "common A2" and "variant A2" subgroups on the basis of their recognition by A2-restricted EB virus-specific cytotoxic T cells. "Variant A2" responder cells cocultivated with "common A2"-bearing stimulators gave rise to effector T cell lines which recognized only the "common A2"-bearing subgroup of targets. By contrast, responder cells from A2-negative donors stimulated with "common A2"-bearing cells produced effector T cell lines in which the strong lysis of "common A2"-bearing targets was accompanied by a lower, but still significant, lysis directed against all targets within the "variant A2" subgroup. In both cases, lysis of the target cells was blocked equally well by the anti-A2-specific monoclonal antibody MA2.1 as by the monoclonal antibody W6/32 specific for HLA-A, -B, and -C determinants. This suggests that HLA-A2 molecules possess at least two distinct sets of epitopes capable of inducing alloreactive T cell cytotoxicity: first, epitopes probably associated with T cell-restricting sites, which generate subgroup-specific responses, and second, epitopes shared by all A2 molecules, and perhaps associated with serologically defined sites, which generate "pan A2" group-specific responses.

B-Lymphocytes

Biological and biochemical observations on isolates of EB virus from the malignant epithelial cells of two nasopharyngeal carcinomas.

Foetal, adult seronegative, and cotton-top marmoset lymphocytes have been transformed into cell lines by EB virus from the malignant epithelial cells of two nasopharyngeal carcinomas. The nature of the cell lines was checked by karyotyping and by light and electron microscopy, and the presence of the EB virus genome was demonstrated by immunofluorescence tests. Immunofluorescence also showed the incidence of EB virus-producing cells in each line and this was checked by electron microscopy and the use of a lymphocyte transformation assay. Two foetal-derived lines did not produce virus spontaneously, could not be activated with various inducers, and were found by DNA reassociation kinetics to carry only small numbers of genome copies per cell. An adult-derived line produced virus, could be activated to produce more, and provided enough infectivity to transform marmoset cells. The resulting marmoset line made profuse transforming virus; it thus provides the first abundant source of NPC-derived infectious EB virus for comparative studies. The results are discussed in relation to the interactions with comparable target cells of EB virus from normal individuals and from patients with other diseases.

Animals

Identification of murine endogenous xenotropic retrovirus in cultured multicellular tumour spheroids from nude-mouse-passaged nasopharyngeal carcinoma.

After nude-mouse-passage, a carcinoma of the nasopharynx was found to contain a few scattered C-type retrovirus particles. Culture of this nude-mouse-grown material over solid agar allowed the human tumour cells to grow as multicellular spheroids which increased in number by budding and could be subcultured for up to 6 months. Within the spheroids the human tumour cells expressed increased retrovirus replication and large numbers of C-type particles were observed. Treatment with a halogenated pyrimidine further enhanced the virus production. This tissue culture system provided sufficient virus production for the identification of the retrovirus as an endogenous xenotropic murine leukaemia virus and not a human agent.

Animals

High-resolution determination of the R-R interval.

A preprocessor is described that determines the time interval between successive R waves of the electrocardiogram with an error of less than 0.2 ms. It accomplishes this by sepearting in hardware the function of determining the approximate location of the R wave from the function of localizing with great accuracy the peak of the wave form. With this device it is possible to detect abnormal heart rate patterns characterized by exceedingly small beat-to-beat variability. The approach may be useful for other bioelectric signals.

Electrocardiography

Maturation of ventilation and ventilatory pattern in normal sleeping infants.

Noninvasive studies of ventilation and ventilatory pattern were performed serially in 15 normal infants in the first 4 mo of life during REM and quiet sleep with the barometric method. We measured tidal volume (VT), total respiratory cycle time (Ttot), inspiratory time (Ti), expiratory time (TE), mean inspiratory flow (VT/TI), and respiratory "duty cycle" (TI/Ttot). Vt, Ttot, TI, TE, VT/TI, and VT/Ttot but not TI/Ttot increased with age. In all age groups, Ttot, TI, and TE but not VT/TI were greater in quiet than in REM sleep. In the first 2 mo of life, VT was greater in quiet than in REM sleep; in the older infants, VT/Ttot was smaller in quiet than in REM sleep. TI/Ttot was not dependent on sleep state. Thus, because VT/Ttot = VT/TI X TI/Ttot, the increase in VT/Ttot with age results from an increase in mean inspiratory flow rather than from changes in respiratory "duty cycle". Further, the "on-switching" as well as the "off-switching" of inspiratory activity depends on sleep state.

Aging

The QT interval in aborted sudden infant death syndrome infants.

The QT interval was measured in 12 normal and 7 aborted sudden infant death syndrome (SIDS) infants in rapid eye movement (REM) and quiet sleep at monthly intervals through the age of 4 months. An accuracy of better than 2 msec was assured by high resolution of the digitized signal and calibration of each QT measurement with an accurately generated time code. In contrast to current speculations, the QT index was significantly smaller in the infants with aborted SIDS than in the normal infants in both REM and quiet sleep (P less than 0.05). In addition, as in normal infants, the QTc was smaller in REM than in quiet sleep (P less than 0.01). Although these results offer no support for the hypothesis that SIDS results from prolongation of the QT interval, they suggest that aborted SIDS infants have a functional abnormality in the autonomic nervous system.

Autonomic Nervous System

Effect of sleep state on the QT interval in normal infants.

Twenty QT intervals selected at random from the middle periods of rapid eye movement (REM) and quiet sleep were measured in 12 normal infants studied at 2 weeks and 1, 2, 3, and 4 months of life. A digitizing system, consisting of a precision rotational potentiometer mounted on a pair of calipers and an A/D converter, was used for measurements. An accuracy of +/- 2 msec was achieved by high resolution of the digitized signal and calibration of each QT measurement with an accurately generated time code. Sleep staging was done visually using an electroencephalogram (EEG), an electrooculogram (EOG), a submental electromyogram (EMG), and behavioral criteria. Our results show that the QT index (QTc = QT/square rootRR) was significantly greater during quiet sleep (mean = 0.439) than during REM sleep (mean = 0.433) (P less than 0.01) and that this difference existed at all ages studied.

Electrocardiography