Reflections on Epstein-Barr virus: some recently resolved old uncertainties.

The change over recent decades in perceptions of the role of viruses in human cancer-causation is illustrated by the reception given to the discovery of Epstein-Barr virus (EBV) in 1964 compared to that of Kaposi's sarcoma herpesvirus (KSHV or HHV-8) in 1994. Very new data on EBV-like agents in New World monkeys is considered in relation to the antiquity of the association of proto-EBV with early anthropoids. Although the finding that individuals without B lymphocytes do not seem to be infected with EBV appears to have resolved the controversy regarding the permissive cell type producing infectious virus in the oropharynx, the presence of EBV in certain squamous and other epithelial cells raises continuing problems which are discussed. Among many recent successes of molecular biology applied to EBV, new information from such investigations on the genetic defect in X-linked lymphoproliferative syndrome now explains the cause of the disastrous pathological changes underlying the disease.Finally, current progress with vaccines against EBV is reviewed.

QTc interval prolongation associated with citalopram overdose: a case report and literature review.

Citalopram is a member of the selective serotonin reuptake inhibitor class of antidepressants. In 1998, citalopram was approved by the US Food and Drug Administration for the treatment of major depression. Like the other selective serotonin reuptake inhibitors, citalopram enjoys a relatively benign side effect profile compared with the tricyclic antidepressants and the monoamine oxidase inhibitors. However, citalopram has been associated with electrocardiographic changes and seizures at doses greater than 600 mg per day. Fatalities have occurred with citalopram-only overdoses. We report the case of a healthy 21-year-old woman who developed QTc interval prolongation after ingestion of approximately 400 mg citalopram. We discuss the cardiac effects of citalopram, review previous cases of citalopram overdose, and discuss treatment recommendations.

Historical background.

The persisting ancient view of cancer as a contagious disease ended with 19th century scientific investigations which seemed to show it was not. The resulting dogma against an infectious cause for cancer produced great prejudice in the scientific community against the first report of an oncogenic virus by Rous early in the 20th century and, even in the 1950s, against Gross's finding of a murine leukaemia virus and a murine virus causing solid tumours. The Lucké frog renal carcinoma virus was the first cancer-associated herpesvirus. Intriguingly, an environmental factor, ambient temperature, determines virus genome expression in the poikilothermic frog cells. Although an alpha-herpesvirus, Marek's disease virus of chickens shares some aspects of biological behaviour with Epstein-Barr virus (EBV) of man. Very significantly, its lymphomas are the first naturally occurring malignancy to be controlled by an antiviral vaccine, with implications for human virus-associated cancers. The circumstances and climate of opinion in which successive gamma-herpesviruses were discovered are described. The identification of EBV involved two unconventionalities: its finding in cultured Burkitt's lymphoma cells when no human lymphoid cell had ever been maintained in vitro, and its recognition in the absence of biological activity by the then new technique of electron microscopy. These factors engendered hostility to its acceptance as a new human tumour-associated virus. The EBV-like agents of Old World apes and monkeys and the T-lymphotropic gamma-herpesviruses of New World monkeys were found at about the same time, not long after the discovery of EBV. For many years these were thought to be the only gamma-herpesviruses of non-human primates; however, very recently B-lymphotropic EBV-like agents have been identified in New World species as well. Mouse herpesvirus 68 came to light by chance during a search for arboviruses and has become important as a laboratory model because of its close genetic relatedness to EBV and its comparable biological behaviour. The discovery of Kaposi's sarcoma-associated herpesvirus six years ago was made using unconventional new methods, but, unlike with EBV 30 years before, this did not hinder its acceptance. This contrast is discussed in the context of the great progress in human tumour virology which has been made in recent years.

Security for the digital information age of medicine: issues, applications, and implementation.

Privacy and integrity of medical records is expected by patients. This privacy and integrity is often mandated by regulations. Traditionally, the security of medical records has been based on physical lock and key. As the storage of patient record information shifts from paper to digital, new security concerns arise. Digital cryptographic methods provide solutions to many of these new concerns. In this article we give an overview of new security concerns, new legislation mandating secure medical records and solutions providing security.

Memories of childhood sexual abuse: a survey of young adults.

OBJECTIVE: To explore the prevalence of, characteristics of, and factors associated with forgetting of childhood sexual abuse memories in a large non-clinical sample (N = 1712). METHOD: Using an anonymous survey, we asked respondents about (a) the nature and severity of their childhood abuse; (b) the continuity of their abuse memories; and (c) their experiences with others suggesting to them that they might have been abused. RESULTS: A substantial minority of victims in our sample reported having temporarily forgotten their childhood sexual abuse. Forgetting was largely unassociated with victim or abuse characteristics. Compared to individuals who always remembered their abuse, however, individuals who temporarily forgot were more likely to report that someone had suggested to them that they might have experienced abuse. Those who received such suggestions were particularly likely to suspect that they may have experienced childhood sexual abuse that they do not yet remember. CONCLUSION: Forgetting may be less common than implied by earlier estimates from clinical samples, yet it is not uncommon. Also, a sizable minority of the population is wondering whether they have experienced unremembered abuse, and these suspicions are linked to having encountered suggestions from others. We discuss the implications of these findings for understanding the phenomenon sometimes labeled repression.

Security for the digital information age of medicine: issues, applications, and implementation.

Privacy and integrity of medical records is expected by patients. This privacy and integrity is often mandated by regulations. Traditionally, the security of medical records has been based on physical lock and key. As the storage of patient record information shifts from paper to digital, we find new security concerns. Digital cryptographic methods provide solutions to many of these new concerns. In this paper we discuss the new security concerns, new legislation mandating secure medical records, and solutions providing this security.

Altered responsiveness during hyperventilation-induced EEG slowing: a non-epileptic phenomenon in normal children.

The relation between hyperventilation (HV)-induced high-amplitude rhythmical slowing (HIHARS) and altered responsiveness without generalized spike and wave activity has not been clearly defined. To test whether altered responsiveness is a nonspecific physiologic response rather than a symptom of generalized epilepsy, we assessed verbal recall ability and motor response testing in 12 healthy nonepileptic children (mean age 9.6 years). Both tasks were administered as a baseline before HV, during HV but before onset of EEG slowing, and during HIHARS. Verbal recall and motor responsiveness remained unchanged during baseline and HV before onset of slowing. During HIHARS, all children exhibited impaired verbal recall (p < 0.005) and 8 of 12 failed to respond to repeated auditory clicks (p < 0.005). Our findings indicate that in a normal setting, responsiveness may be impaired during HV in healthy nonepileptic children.

Continuous blood density measurement for hemodynamic monitoring: an analysis of its accuracy and sensitivity.

Continuous measurement of arterial blood density after bolus injection of fluids of different density into the right atrium has been used to measure cardiac output and mean transit time through the central circulation. The transit time distribution for density, however, differs from that for plasma-phase tracers such as indocyanine green. This difference may yield important information about red cell transit times through the microcirculation. We analyzed the potential of the density technique to resolve small changes in transit time distributions. Rayleigh's Method was used to calculate the relationship between density distribution within the U-tube and frequency of oscillation. Fourier integral transformation of a functional representation of indocyanine green dye curves provided an estimate of amplitude versus frequency for likely input density signals. We found that the ability of the densitometer to accurately follow blood density changes depends upon physiologic parameters associated with the experimental animal and upon the physical characteristics of the densitometer itself. Even for small animals, such as a rabbit, the densitometer theoretically has the ability to accurately follow rapid density changes over time.

Inhibition of rat mammary tumorigenesis by voluntary exercise.

In this study, the anti-promoting effect of voluntary (wheel) exercise on 7, 12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumorigenesis was investigated. All rats were fed high fat diets (23% of calories as fat) to mimice the typical western diet. Two doses of DMBA were used to determine if the antipromoting effects of exercise were dependent on the strength of the initiating agent. In addition, tumor estrogen receptors were assayed to determined whether exercise, through an estrogen-suppressing mechanism, selects for estrogen receptor-negative tumors. Female Sprague-Dawley rats were fed a semi-purified 23% fat (corn oil) diet (AIN-76A) and, on day 50 of age administered DMBA by gavage at 5 or 10 mg/rat. Rats were then randomized into 4 groups (n = 30) as follows: 1) low DMBA/sedentary; 2) low DMBA/exercise; 3) high DMBA/-sedentary; and 4) high DMBA/exercise. Active rats were placed in wheel-cage units, which allowed voluntary access to an activity wheel for 133 (low DMBA) and 77 (high DMBA) days, respectively, Sedentary rats were placed in conventional cages. Both active groups exhibited significantly lower total tumor numbers than their sedentary controls: 75 vs 102 (low DMBA) (p < 0.05) and 90 vs 160 (high DMBA) (p < 0.001). Compared to sedentary controls, latency was significantly lengthened in the low but not the high DMBA active groups; multiplicity, in contrast, was significantly decreased in the high, but not the low DMBA exercised group. Exercise had no effect on overall tumor incidence. When segregated into exercise tertiles, total tumor active compared to the least active tertile, particularly in the high DMBA group.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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.

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.

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.