Brain and tissue levels of mercury after chronic methylmercury exposure in the monkey

Estimated half-lives of mercury following methylmercury exposure in humans are 52-93 d for whole body and 49-164 d for blood. In its most recent 1980 review, the World Health Organization concluded that there was no evidence to suggest that brain half-life differed from whole-body half-life. In the present study, female monkeys (Macaca fascicularis) were dosed for at least 1.7 yr with 10, 25, or 50 micrograms/kg.d of mercury as methylmercuric chloride. Dosing was discontinued, and blood half-life was determined to be about 14 d. Approximately 230 d after cessation of dosing, monkeys were sacrificed and organ and regional brain total mercury levels determined. One monkey that died while still being dosed had brain mercury levels three times higher than levels in blood. Theoretical calculations were performed assuming steady-state brain:blood ratios of 3, 5, or 10. Brain mercury levels were at least three orders of magnitude higher than those predicted by assuming the half-life in brain to be the same as that in blood. Estimated half-lives in brain were between 56 (brain:blood ratio of 3) and 38 (brain:blood ratio of 10) d. In addition, there was a dose-dependent difference in half-lives for some brain regions. These data clearly indicate that brain half-life is considerably longer than blood half-life in the monkey under conditions of chronic dosing.     

Models of adult day care: findings from a national survey

We examined a nationally representative sample of 60 adult day care centers to describe the state of this evolving care modality after a decade's growth. Results indicate that day care centers can be categorized into three models of care, each of which serves a distinctive subpopulation. Model appropriateness was tested with analysis of variance of differences in participant characteristics. Services, staffing, costs, and other program features are contrasted among the three models.     

Basic surgical techniques and variations of endoscopic sinus surgery

This article gives complete information on the care of the endoscopic sinus surgery patient. Indications and preoperative evaluations necessary for endoscopic sinus surgery are described. The technique of functional endoscopic sinus surgery is covered in detail. Postoperative care and complications are also described. Various procedures for patients with extensive or unusual disease are discussed.     

An open pilot study of nefazodone in depression with anger attacks: relationship between clinical response and receptor binding

Nefazodone has been widely used as an antidepressant, but it has not been tested for depression with anger attacks. In an open study, we administered nefazodone (maximum 600 mg/day) for 12 weeks to 16 outpatients who had major depression with anger attacks. Assessment instruments comprised the Structured Clinical Interview for DSM-IV (SCID), Anger Attacks Questionnaire (AAQ), 17-item Hamilton Rating Scale for Depression (HAM-D-17), Clinician Global Impression Scale (CGI), Symptom Questionnaire (SQ), Modified Overt Aggression Scale (MOAS), and MOAS-Self-Rated. Three subjects underwent positron emission tomography (PET) with [¹⁸F]-setoperone for 5-HT2 binding potential (BP) and [¹¹C]-SCH-23,390 for D1 BP, both at baseline and after 6 weeks of treatment. Eight subjects underwent PET with [¹⁸F]-setoperone and with [¹¹C]-SCH-23,390 at baseline only. In an examination of whether D1 and 5HT2 (data available in six subjects) receptor BP predicted treatment response, we found significant decreases in the HAM-D-17, CGI-S, weighted MOAS, MOAS verbal scale, OAS Self-Rated verbal, SQ Depression and Anger/Hostility scales after nefazodone; 50% responded to nefazodone (defined as ≥50% decrease in HAM-D-17 score), and 44% reported disappearance of anger attacks. A statistically significant percentage decrease in 5HT2 BP was observed for the right mesial frontal and left parietal regions after 6 weeks of treatment. No significant change was observed in D1 BP in any region. Although CGI-I scores correlated significantly with D1 BP in the left thalamic region, the correlation was not significant after Bonferroni correction. The effectiveness of nefazodone for depression with anger attacks may be related to widespread changes in 5HT2 receptor BP.     

Picture naming in early sequential bilinguals: a 1-year follow-up.

In a previous study, a cross-sectional approach was used to investigate developmental changes in basic-level lexical production and cognitive processing in early sequential bilinguals, exploring the effects of age and years of experience during single-language (Spanish or English) and mixed-language (alternating between Spanish and English) picture naming (K. Kohnert, E. Bates, & A. E. Hernandez, 1999). The current study reports on the performance, 1 year later, of a subgroup of these original study participants (n = 28; mean age = 10.2 years) on the same experimental task. Overall, from Time 1 to Time 2 testing, gains were greater in English than in Spanish and in the high-competition mixed-language processing condition than in the single-language processing condition. These results reinforce previous findings of a shift toward greater strength in L2 with increasing age (and years of language experience), as well as the primary role of cognitive development in control of the dual-language system. In addition, examination of individual performance revealed a complex non-monotonic pattern of L1-L2 change across time within an overall pattern of increasing speed, accuracy, and control of the dual-lexical system.     

Neuropeptide modulation of muscarinic receptors and function in cerebral cortex of young and senescent rats.

The possible influence of several neuropeptides on muscarinic receptor binding and function in fronto-parietal cortex of young and senescent Fischer 344 rats was examined. Low concentrations (100 nM) of cholecystokinin, neurotensin and vasoactive intestinal polypeptide (VIP), added in vitro, enhanced carbachol-stimulated phosphoinositide metabolism in cortical miniprisms from both young and senescent rats, while somatostatin was ineffective. Interestingly, the VIP receptor antagonist [d-parachloro-Phe6,Leu17[VIP shifted the dose-response curve for carbachol significantly to the right, indicating inhibition of phosphoinositide hydrolysis. No direct actions of neuropeptides on the number or affinity of [3H]l-quinuclidinyl benzilate binding sites nor on agonist conformation states of the muscarinic receptor were noted in cortex from young animals. The neuropeptide modulation of phosphoinositide metabolism was selective for muscarinic systems, as norepinephrine-stimulated phosphoinositide hydrolysis was not altered. Pretreatment with hemicholinium-3, an inhibitor of high-affinity choline uptake, did not prevent the neuropeptide effects, indicating the interaction was probably postsynaptic. It is possible that pharmacologic manipulation of peptidergic processes could improve cholinergic neurotransmission in brain.     

Reduced Serum Theophylline Concentrations after Discontinuation of Azithromycin: Evidence for an Unusual Interaction

A 68-year-old man receiving long-term therapy with oral sustained-release theophylline 450 mg twice/day was admitted to the hospital after failing treatment with azithromycin for an acute exacerbation of obstructive lung disease. Peak serum theophylline concentration was 20 μg/ml (normal 10–20 μg/ml). Azithromycin was discontinued and the theophylline dosage reduced by 33%. The subsequent 80% decrease in serum theophylline to 4.6 μg/ml was unexpectedly large. Two rechallenges produced similar transient depressions of serum theophylline concentrations after withdrawal of azithromycin, suggesting an interaction. Withdrawal of azithromycin may leave an increased number of active enzyme sites available as the drug is cleared from the system. In some circumstances, it may be useful for pharmacokinetic interaction studies to continue measuring concentrations after the suspected interacting agent is stopped.     

Cerebral vascular effects of angiotensin II: new insights from genetic models.

Very little is known regarding the mechanisms of action of angiotensin II (Ang II) or the consequences of Ang II-dependent hypertension in the cerebral circulation. We tested the hypothesis that Ang II produces constriction of cerebral arteries that is mediated by activation of AT1A receptors and Rho-kinase. Basilar arteries (baseline diameter approximately 130 microm) from mice were isolated, cannulated and pressurized to measure the vessel diameter. Angiotensin II was a potent constrictor in arteries from male, but not female, mice. Vasoconstriction in response to Ang II was prevented by an inhibitor of Rho-kinase (Y-27632) in control mice, and was reduced by approximately 85% in mice deficient in expression of AT1A receptors. We also examined the chronic effects of Ang II using a model of Ang II-dependent hypertension, mice which overexpress human renin (R+) and angiotensinogen (A+). Responses to the endothelium-dependent agonist acetylcholine were markedly impaired in R+A+ mice (P<0.01) compared with controls, but were restored to normal by a superoxide scavenger (PEG-SOD). A-23187 (another endothelium-dependent agonist) produced vasodilation in control mice, but no response or vasoconstriction in R+A+ mice. In contrast, dilation of the basilar artery in response to a NO donor (NONOate) was similar in R+A+ mice and controls. Thus, Ang II produces potent constriction of cerebral arteries via activation of AT1A receptors and Rho-kinase. There are marked gender differences in cerebral vascular responses to Ang II. Endothelial function is greatly impaired in a genetic model of Ang II-dependent hypertension via a mechanism that involves superoxide.