Advanced ovarian carcinoma presenting with a cerebrovascular accident

An infant and his uncle, both with adrenal hypoplasia congenita, shared the same DAX1 mutation. The adolescent uncle had hypogonadotropic hypogonadism, but the infant had a normal minipuberty of infancy. These observations suggest differences in the physiologic mechanisms regulating the hypothalamic-pituitary-gonadal axis in infancy and adolescence.     

Inhibition of nitric oxide synthase disrupts inhibitory gating of auditory responses in rat hippocampus

The amplitude of the hippocampal evoked response to the second of two identical auditory stimuli is suppressed relative to the response to the first stimulus. This inhibitory gating of sensory response has been linked to alpha-bungarotoxin-sensitive nicotinic receptors, which are found primarily on gamma-amino butyric acid neurons in rat hippocampus. A recent study showed a high level of colocalization of alpha-bungarotoxin binding with immunoreactivity for nitric oxide synthase, the catalytic enzyme which produces nitric oxide, in rat hippocampus. To determine if loss of enzyme activity would alter normal sensory inhibition, Nomega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, was continuously perfused through the ventricular system of anesthetized rats as they were tested for response to paired auditory stimuli. L-NAME, but not Nomega-nitro-D-arginine methyl ester (D-NAME), the inactive enantiomer, produced a loss of sensory inhibition. To determine if the effect of nitric oxide was presynaptic or postsynaptic to nicotinic receptors, rats with lesions of the fimbria/fornix, which removes the medial septal projection to the hippocampus, were tested with nicotine in the presence of L- or D-NAME. Fimbria/fornix lesions normally reduce sensory inhibition, which is restored with systemic nicotine injections. Lesioned rats treated with D-NAME showed normal sensory inhibition upon injection of nicotine; lesioned rats treated with L-NAME did not. These data support the hypothesis that stimulation of a nicotinic receptor releases nitric oxide, which in turn mediates sensory inhibition. The nicotine-induced release of nitric oxide may explain why some of the behavioral effects of nicotine have a longer time course than predicted from desensitization of nicotinic receptors.     

The cytochrome P-450 inhibitor cobalt chloride prevents inhibition of renal Na,K-ATPase and redistribution of apical NHE-3 during acute hypertension

PURPOSE: Many tumors express elevated levels of LDL receptors (apoB, E receptors) on their membranes. Selective delivery of anti-neoplastic drugs to tumors by incorporation of these drugs into LDL or LDL-resembling particles should improve the efficacy of tumor therapy and minimize the severe side-effects. Since the apolipoproteins on the particles are essential for the LDL receptor recognition, drugs should preferably be incorporated into the lipid moiety. Most anti-tumor agents are too hydrophilic for incorporation into these carriers. METHODS: We synthesized LAD, a lipophilic prodrug of daunorubicin, by coupling the drug via a lysosomally degradable peptide spacer to a cholesteryl oleate analog. RESULTS: The overall yield of the synthesis was 50% with a purity of > 90%. Radioactively ([3H]) labeled LAD was obtained via a slightly modified procedure (yield 40%). The octanol/water partition coefficient of LAD is 30-fold higher than that of daunorubicin. LAD could be incorporated into triglyceride-rich lipid emulsions and small liposomes, which, if provided with apoE, have been demonstrated earlier to be cleared in vivo via the LDL receptor. The liposomes contained approximately 10 molecules of LAD per liposomal particle. Analysis of differently sized LAD-containing emulsions suggests that LAD associates with the surface of lipidic particles. In the presence of human serum, LAD did not dissociate from the emulsion particles, indicating a firm association of LAD with the carrier. CONCLUSIONS: The coupling of a cholesterol ester analog to daunorubicin results in a lipophilic prodrug that can be firmly anchored into lipidic carries. LAD-loaded emulsions and liposomes provided with recombinant apoE will be tested in the near future for their ability to deliver LAD to tumor tissue in vivo via the LDL receptor.     

A dummy orbit for training in diagnostic procedures and laser surgery with enucleated eyes

OBJECTIVES: The purpose of this study was to analyze duration of coverage among new Medicaid enrollees. METHODS: The 1991 Survey of Income and Program Participation was used to examined the duration of coverage for individuals who did not have Medicaid in January 1991 and obtained coverage by May 1993. RESULTS: Of new Medicaid enrollees, 38% (90% confidence interval [CI] = 34%, 42%) remained covered 1 year later; 26% (90% CI = 21%, 31%) remained covered at 28 months. Of those older than 65 years, 54% (90% CI = 31%, 77%) retained Medicaid for 28 months, vs 20% (90% CI = 14%, 26%) of children. Of people who lost Medicaid, 54% (90% CI = 31%, 77%) had no insurance the following month. CONCLUSIONS: Almost two thirds of new Medicaid recipients lose coverage within 12 months. It is unlikely that Medicaid managed care will enhance continuity of care for new recipients.     

Technetium-99m-MDP uptake in hilar lymph nodes in sarcoidosis

We describe a patient with unexplained hypercalcemia who under went bone scintigraphy, which demonstrated marked tracer uptake within the hilar lymph nodes. The pattern strongly suggested sarcoidosis, which was subsequently confirmed by bronchoscopy-directed biopsy.     

Letter and category fluency in schizophrenic patients: a meta-analysis

Patients with schizophrenia typically demonstrate impairments on semantic and letter fluency tasks but it is possible that these tests demand subtly different cognitive processing: a lexical search based on phonology or orthography or a semantic search based on organization of semantic networks by dimension or attribute. Differences in the performance between these two tasks may imply whether deficits involve difficulties in accessing or traversing connectivities in the semantic system, as opposed to those based on linguistic units. In this meta-analysis, we reviewed 13 studies (N=915) in an attempt to clarify whether schizophrenic patients are in fact differentially impaired in semantic fluency. Results from analyses indicated that schizophrenic patients are disproportionately deficient in category fluency (d=1.23 for semantic and 1.01 for letter fluency with minimal overlap of confidence intervals of weighted d's) suggesting that compromises the semantic system may be present in schizophrenia and perhaps play a role in the symptomatic anomalies exhibited in this patient population.     

Neural activity in areas V1, V2 and V4 during free viewing of natural scenes compared to controlled viewing

Under natural viewing conditions primates make frequent exploratory eye movements across complex scenes. We recorded neural activity of 62 cells in visual areas V1, V2 and V4 in an awake behaving monkey that freely viewed natural images. About half of the cells studied showed a modulation in firing rate following some of the eye movements made during free viewing, though the proportions showing a discernible modulation varied across areas. These cells were also examined under controlled viewing conditions in which gratings or natural image patches were flashed in and around the classical receptive field while the animal performed a fixation task. Activity rates were generally highest with flashed gratings and lowest during free viewing. Flashed natural image patches evoked responses between these two extremes, and the responses were higher when the patches were confined to the classical receptive field than when they extended into the non-classical surround. Thus the reduction of activity during free viewing relative to that obtained with flashed gratings is partly attributable to natural images being less effective stimuli and partly to suppressive spatio-temporal neural mechanisms that are important during natural vision.     

Development of self-handicapping tendencies

This study was undertaken to determine when U.S. children begin to self-handicap, that is, to reduce preparation effort before evaluations rather than applying themselves to do their best. The personal variables examined for their impact on practice behavior were gender, grade level, and self-esteem. The situational variables were time of the self-esteem test (before or after the evaluation task) and importance of the evaluation task. The results showed that (a) the 6th-grade boys were more likely than the 6th-grade girls to self-handicap, (b) the 3rd-grade children were not as affected as the 6th-grade children by the self-evaluation implications of performance evaluations, (c) self-handicapping by low-self-esteem and high-self-esteem 6th graders depended on recent experiences, and (d) the self-affirming experience of a self-esteem test reduced the motivation to self-handicap among high-self-esteem 6th-grade boys.     

Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part 3: A novel mechanism for the inhibition of biological membrane lipid peroxidation by dioxygenated 4-methylcoumarins mediated by the formation of a stable ADP-Fe-inhibitor mixed ligand complex

7,8-Dihydroxy-4-methylcoumarin (DHMC) and 7,8-diacetoxy-4-methylcoumarin (DAMC) have been reported to effectively inhibit in-vivo lipid peroxidation in rat tissues induced by CCl4 and paraquat. DHMC was found to readily impart green colour to the lipid peroxidation incubation mixture containing ADP and Fe3+, whereas DAMC formed green complex only upon incubation with liver microsomes, confirming our earlier observation that liver microsomal deacetylase hydrolyses DAMC to DHMC. Sensitive pH metric technique revealed the formation of ADP-Fe-DHMC ternary complex with highest stability, while Fe-DHMC and ADP-DHMC had negligible stabilities concluding that ADP-perferryl ion formation is prevented by DHMC resulting in the production of stable ternary mixed ligand complex (ADP-Fe-DHMC), thereby inhibiting the formation of O2-, and eventually other reactive oxygen species (ROS) responsible for membrane lipid peroxidation.