Panuveitis in association with pseudotumor cerebri

We report a case of an 11-year-old girl with bilateral panuveitis in association with pseudotumor cerebri. The patient underwent complete ophthalmologic, neurologic, and laboratory evaluations and was treated with therapy for pseudotumor cerebri. The patient met the diagnostic criteria for pseudotumor cerebri and also had panuveitis. Symptoms and findings of pseudotumor cerebri and panuveitis improved significantly after combination therapy of oral acetazolamide and weight reduction. The index case illustrates that pseudotumor cerebri can be associated with panuveitis. Therapy for pseudotumor cerebri might also help with the resolution of uveitis.     

Assessment of depression in medically ill children presenting to pediatric specialty clinics

OBJECTIVE: Self-report measures of depression may be inaccurate when applied to medically ill children because of the overlap between medical and psychiatric symptoms. The American Academy of Pediatrics endorses the use of self-reports as diagnostic aids (used in patients who are suspected of having an emotional problem by their pediatricians). This approach has not been validated. We evaluated the diagnostic accuracy of the Children's Depression Inventory (CDI) in medically ill children who were referred for evaluation by their pediatricians. METHOD: The evaluation included the CDI and a best estimate diagnostic procedure that incorporated results from semistructured and other interviews. Evaluators were not aware of the CDI scores when making a diagnostic determination. RESULTS: One hundred twenty-five patients, 8-19 years old, were referred between September 2000 and May 2003. Eighty-one completed the diagnostic procedure. The CDI summary score performed well in identifying best estimate depressive disorder determinations in this cohort. A cutoff of 11 and above correctly identified 80% of cases, with a specificity of 70%. DISCUSSION: A self-report measure of depression (CDI) could be used as a diagnostic aid in medically ill children who are suspected of having an emotional problem by their pediatricians. This finding supports the "two-tier" depression screening approach endorsed by the American Academy of Pediatrics for use in pediatricians' offices.     

Pilot study: fluvoxamine treatment for depression and anxiety disorders in children and adolescents with cancer

OBJECTIVE: To evaluate the safety, tolerability, and benefit of fluvoxamine for the treatment of major depressive disorder or anxiety disorders in children and adolescents with cancer. METHOD: The study was conducted from 2001 to 2004 at a pediatric hematology-oncology center. Fifteen children and adolescents with cancer were treated with fluvoxamine 100 mg/day in an open prospective 8-week trial. Safety and tolerability were evaluated at baseline and at weeks 4 and 8 by blood tests and the Side Effects Checklist. Clinical benefit was assessed with the Clinical Global Impressions-Improvement, the Children's Depression Rating Scale-Revised, and the Pediatric Anxiety Rating Scale. RESULTS: Fluvoxamine was well tolerated by all subjects. Psychiatric symptoms improved significantly. CONCLUSIONS: In this open trial, fluvoxamine appeared to be well tolerated and was associated with a promising reduction in the depression and anxiety symptoms of pediatric patients with cancer.     

Dysregulation of the hypothalamic-pituitary-gonadal axis with menopause and andropause promotes neurodegenerative senescence

Senescence is characterized neurologically by a decline in cognitive function, which we propose is the result of degenerative processes initiated by the dysregulation of the hypothalamic-pituitary-gonadal (HPG) axis with menopause and andropause. Compelling epidemiologic evidence to support this assertion includes the increased prevalence of Alzheimer disease (AD) in women, the correlation of serum HPG hormones with disease and the decreased incidence, and delay in the onset of AD following hormone replacement therapy. Dysregulation of the axis at this time leads to alterations in the concentrations of all serum HPG hormones (decreased neuronal sex steroid signaling, but increased neuronal gonadotropin releasing hormone, luteinizing hormone, and activin signaling). Hormones of the HPG axis, receptors for which are present in the adult brain, are important regulators of cell proliferation and differentiation during growth and development. Based on this, we propose that dysregulated HPG hormone signaling with menopause/andropause leads to the abortive reentry of differentiated neurons into the cell cycle via a process we term "dyosis." Interestingly, the major biochemical and neuropathologic changes reported for the AD brain also are intimately associated with neuron division: altered AbetaPP metabolism, Abeta deposition, tau phosphorylation, mitochondrial alterations, chromosomal replication, synapse loss, and death of differentiated neurons. Recent evidence supports the premise that AD-related biochemical changes are likely the combined result of increased mitotic signaling by gonadotropins and GnRH, decreased differentiative and neuroprotective signaling via sex steroids, and increased differentiative signaling via activins. This results in a hormonal milieu that is permissive of cell cycle reentry but does not allow completion of metaphase. Partial resetting of the axis following administration of normal endogenous sex steroids delays the onset and decreases the incidence of AD. Ideally, supplementation with HPG hormones should mimic closely the serum concentrations of all HPG hormones in reproductive men and cycling women to prevent dyotic signaling and attempted neuron division.     

The Positive and Negative Symptoms Questionnaire: a self-report scale in schizophrenia

The assessment of various symptoms in schizophrenia has received much interest, although few studies have compared evaluations by clinicians to those of their patients. Self-report tools may improve service delivery, data collection, and possibly also treatment adherence. We constructed the Positive and Negative Symptoms Questionnaire (PNS-Q), a self-report measure, after items from the Scale for Assessment of Positive Symptoms (SAPS) and the Scale for Assessment of Negative Symptoms (SANS). The PNS-Q contained 68 items and was administered to 61 schizophrenic inpatients. We examined its psychometric properties and utility as a self-report tool in schizophrenia. The PNS-Q exhibited high internal consistency for both its positive and negative subscales. External validity with the SAPS and SANS was low. The positive symptoms subscale correlated significantly with the SAPS ( r = .341, P < .01), whereas the negative symptoms subscale did not correlate at all with the SANS ( r = -0.086, P > .1). The correlation between patients' insight and scores of the PNS-Q was mixed. A partial correlation analysis failed to confirm a relationship between the rating of the patients' level of insight (measured by the Amador Scale to Assess Unawareness of Mental Disorders [SUMD]) and the disparity between the PNS-Q and the SAPS and SANS. However, the PNS-Q correlated highly with McEvoy's Vignettes, a measure of self-perception of symptoms. The results of this study are discussed in light of current research and methodologic issues. The PNS-Q reflects schizophrenics' self-perception, an important, yet neglected, aspect of schizophrenia. Using this new measure, we believe that clinicians and researchers will be able to gain insight to the inner world of these patients and improve their condition, as well as enhance patients' involvement in treatment planning.     

Primary lymphoma of the aorta presenting as a descending thoracic aortic aneurysm

We describe a case of primary lymphoma of the thoracic aorta that presented as an aneurysm of the descending thoracic aorta. The aortic tumor was successfully resected with 2-year disease-free survival.     

Critical analysis of the discrepancy between V(beta) and V(ss) for drugs exhibiting different two-compartment disposition profiles

It is well known that in the two-compartment open body model the values of apparent volume of distribution (V(beta)) and volume of distribution at steady state (V(ss)) are never identical. There are at least two conditions when V(beta) significantly overestimates V(ss). The first is when most of a drug is eliminated relatively rapidly but a small fraction of the dose persists and gives rise to an extremely long half-life. The second is when a drug is rapidly cleared from the central compartment with a short half-life. The primary purpose of the current paper was to investigate how different two-compartment disposition profiles affect the magnitude of difference between V(beta) and V(ss). Novel equations have been developed that relate the V(beta)/V(ss) ratio to f1 (fraction of drug elimination associated with the distributive phase) and to beta/alpha (ratio of the exponential coefficients). This paper demonstrates mathematically that an increasing value of f1 is associated with a greater divergence between V(beta) and V(ss). A similar relationship was also found for the divergence between the terminal half-life (t(1/2beta)) and the mean residence time (MRT). An increase in the beta/alpha ratio results in a substantial decrease of this discrepancy and provides a maximal possible value, or an upper limit to the V(beta)/V(ss) ratio. The newly derived equations along with their graphical presentation may serve as an excellent predictive tool for checking the accuracy of the experimentally obtained values of V(beta) and V(ss).     

High-affinity epidermal growth factor receptor (EGFR) irreversible inhibitors with diminished chemical reactivities as positron emission tomography (PET)-imaging agent candidates of EGFR overexpressing tumors

Previous studies with the anilinoquinazoline epidermal growth factor receptor (EGFR) irreversible inhibitor [(11)C]-ML03 demonstrated a rapid metabolism of the tracer, which led to its low in vivo accumulation in EGFR overexpressing tumors. To enhance tumor uptake, the chemical structure of the compound was modified, and four new groups of EGFR inhibitors with a wide range of chemical reactivities were synthesized. Chemical reactivity assay of the compounds, performed with reduced glutathione (GSH), revealed that the group C (4-(dimethylamino)-but-2-enoic amide) derivative was the least chemically reactive against the nucleophilic attack of GSH. Nonetheless, it demonstrated a high inhibitory potency and bound irreversibly to the EGFR. Consequently, the blood stability of the group C compound (5a, ML04) labeled with (11)C was studied. In a time frame of 60 min, no radioactive metabolites were detected in blood. The stability of [(11)C]-5a, as indicated both from in vitro blood-stability assays and injection into nude rats, was significantly higher as compared to [(11)C]-ML03. Since group C presented a greater promise for tumor accumulation, it represents, to date, the most suitable candidate for radiolabeling with long-lived positron emission tomography (PET) radioisotopes.     

Widespread use of soy-based formula without clinical indications

OBJECTIVES: In view of reports of the growing popularity of soy-based formula for infants, we examined soy consumption and its possible overuse during early infancy in central Israel. METHODS: Mothers of 1,803 infants aged 2, 4, 6 and 12 months attending well-baby clinics participated in a telephone survey covering background data, rate, duration, and pattern of soy-based formula use and the reasons for its initiation. The reasons were grouped into those based on the recommendations of the medical personnel and those based on mothers' initiative, and evaluated according to infants' age at soy-based formula initiation (0 to 1, 2 to 4 and 5 to 12 months). The symptoms that prompted soy-based formula use were assessed quantitatively. RESULTS: The rate of soy-based formula use was 10.4% at 2 months and 31.5% at 12 months (P<0.001); 70.6%+/- 2.7% of the infants were given soy for>6 months. Regardless of infants' age, the role of the mothers in the decision to use soy-based formula was greater than that of the medical personnel, and increased significantly with age (chi for trend=0.018). A suspicion of cow's milk allergy was responsible for only 10.9% (7/64) of all soy initiations in infants aged 5 to 12 months. In all ages, occasional symptoms, mainly diarrhea (33.3%) and colic (19.8%), were the leading cause for recommending soy-based formula by medical personnel, whereas the personal preference without clinical justification was the leading cause among mothers. CONCLUSIONS: The use of soy-based formula in central Israel is extensive and continues for long periods, with rates far beyond clinical indications. Mothers play a greater role than medical personnel in the decision to initiate soy-based formula.