ERP evidence of impaired central nervous system function in virally suppressed HIV patients on antiretroviral therapy.

OBJECTIVE: To examine the effects of human immunodeficiency virus (HIV) on central nervous system (CNS) function in patients receiving antiretroviral therapy (ART) who have suppressed viral loads. METHODS: Event-related brain potentials (ERPs) were recorded from 15 virally suppressed HIV patients and 15 age-, sex-, and education-matched controls while they performed a 3-stimulus auditory oddball task. The amplitude and latency of the P3a, P3b, and early auditory components were examined in HIV patients and controls. RESULTS: Virally suppressed HIV patients on ART were more depressed than controls, as determined by the Beck Depression Inventory (BDI). After controlling for the effects of depression, HIV patients had smaller P2, P3a, and P3b amplitudes and longer P3a and P3b latency than control subjects. BDI scores correlated positively with N1 latency in HIV patients and negatively with P3b amplitude in all subjects. CONCLUSIONS: These electrophysiological results suggest that, even in the absence of detectable levels of HIV in the peripheral blood, viral replication persists in the CNS and continues to cause disease in HIV patients on ART.     

Mercury exposure of different origins among dentists and dental nurses

Mercury exposure was studied among dental personnel with the use of urinary mercury excretion rates and questionnaires. The study covered 314 dentists and dental nurses employed in public clinics and private practices in Stockholm. The obtained urinary mercury excretion rates were analyzed by stepwise regression for assigning them to different origins, such as environmental factors, number of amalgam surfaces, chewing of gum, kind of employment and profession, age, sex, amalgam handling time, and use of amalgam capsules. On the average the occupational contribution to the total urinary mercury excretion rate was small and of the same order as the contribution from their own amalgam fillings (approximately 2 micrograms of mercury/24 h). There were, however, individuals showing excretion rates close to the levels at which effects on the central nervous system and the kidneys have been reported.     

Effect of Medicaid payment levels on access to obstetrical care.

Across the nation, the number of providers serving pregnant Medicaid clients has dropped precipitously. In an effort to retain providers, in 1986 the Maryland Medicaid program tripled reimbursement fees for deliveries. This raised Medicaid payments for perinatal care to levels roughly comparable to those paid by private insurers. Providers' participation can be measured using two criteria: the total number of participating providers in a given country and the number of deliveries performed by targeted providers. The fee increase was associated with an overall stabilization in the number of providers performing deliveries. Providers performed slightly more deliveries after the fee increase, relative to predictions derived from statistical models. One-quarter of all providers increased their participation on a scale commensurate with the fee increase.     

Enkephalinergic involvement in periaqueductal gray control of hypothalamically elicited predatory attack in the cat.

The effects of central infusion of naloxone into the midbrain periaqueductal gray (PAG) upon predatory attack behavior in the cat were studied in 12 cats. Initially, quiet biting attack was elicited by electrical stimulation of sites within the lateral hypothalamus using monopolar electrodes. Then cannula-electrodes were implanted into sites within the PAG from which electrical stimulation facilitated or suppressed the attack response. Following identification of modulatory sites within the PAG, naloxone (1.0 micrograms/0.5 microliter) was microinjected into those sites and the effects upon hypothalamically elicited attack were assessed. At nine of twelve sites in the PAG where suppression was obtained, administration of naloxone served to block those effects. Similarly, at six of eight facilitatory sites within the PAG, naloxone also blocked the modulatory effects of PAG stimulation. However, vehicle (isotonic saline) alone did not alter the modulatory effects of PAG stimulation. Administration of DAME (250 ng/0.3 microliter) into PAG modulatory sites in four cats, two which facilitated and two that suppressed the attack response, reversed the effects of naloxone at these sites. These results demonstrate that opioid peptides within the PAG play a complex role in the expression of predatory attack behavior in the cat.     

高效液相色谱法测定右旋儿茶素血浆浓度及药代动力学参数

本文建立了体液中右旋儿茶素的RP-HPLC测定方法。采用C_(18)键合相硅胶为填料的固相提取柱进行样品预处理,右旋儿茶素的提取回收率为79.8%.应用二极管阵列检测器对色谱峰纯度进行鉴定。该法精密度好,方法回收率近100%,日内、日间的变异系数为2.4～5.6%,血浓69.6～1160 ng/ml范围内呈线性关系,r=0.9993。家兔静注右旋儿茶素18mg/kg,其药代动力学过程符合二室模型,分布相半衰期为0.129 h,消除相半衰期为1.19h。     

Effects of haloperidol on the multitrial partial reinforcement extinction effect (PREE): evidence for neuroleptic drug action on nonreinforcement but not on reinforcement

Two experiments investigated the effects of haloperidol (0.1 mg/kg) on the partial reinforcement extinction effect (PREE). In experiment 1 two groups of rats were trained to run in a straight alley using six trials/day with an intertrial interval (ITI) of 5–8 min. The continuously reinforced (CRF) group received food reward on every trial. The partially reinforced (PRF) group was rewarded on a quasi-random 50% schedule. All animals were then tested in extinction. Haloperidol was administered in a 2 × 2 design, i.e., drug-no drug in acquisition and drug-no drug in extinction. In experiment 2 two groups of rats were trained to press a lever in an operant chamber using a discrete trial procedure of ten trials/day with an ITI of 60 s. The CRF group was rewarded on each trial and the PRF group was rewarded on a quasi-random 50% schedule. Haloperidol was administered for 22 days prior to the start of the PREE procedure as well as throughout acquisition and extinction. The PREE, i.e., increased resistance to extinction of PRF as compared to CRF animals, was obtained in both experiments in all drug conditions. In both experiments haloperidol increased the rate of extinction. Experiment 1 revealed that this effect was entirely dur to the administration of the drug in extinction, independently of the drug condition in acquisition. In contrast to previous results in a one trial/day procedure, the administration of haloperidol to CRF animals did not increase resistance to extinction, failing to support the notion that neuroleptics attenuate the rewarding properties of reinforcement.     

Intravenous labetalol for the control of hypertension following repair of coarctation of the aorta

Paradoxical hypertension is a relatively common complication of surgical repair of coarctation of the aorta. An early phase of systolic hypertension has been ascribed to elevated levels of norepinephrine. Activation of the renin-angiotensin system from sympathetic stimulation has been implicated in a later phase of systolic and diastolic hypertension that can result in mesenteric arteritis. The use of a rapidly acting, titratable intravenous alpha- and beta-adrenergic blocker, such as labetalol hydrochloride, addresses both of these neurohormonal mechanisms. In the intravenous form, it would appear to be an excellent choice for the management of early postoperative hypertension and it can be converted to the oral form in cases of persistent hypertension. We report for the first time the use of labetalol in two young patients for the control of paradoxical hypertension following coarctation repair.     

Tissue collection for correlative studies in childhood cancer clinical trials: ethical considerations and special imperatives.

Federal regulations prescribe distinct protections for children participating in research studies. Procedures for collecting tissue specimens from children solely for research purposes must pose no more than a minor increase over minimum risk, thereby limiting the approvable correlative biologic studies to evaluate molecularly targeted agents in children with cancer. Ethical issues arise when approvable correlative studies are a mandatory component of an early-phase pediatric clinical trial of new anticancer agents. The National Cancer Institute Cancer Therapy Evaluation Program sponsored a workshop in 2002 to discuss tissue collection for correlative biologic studies in early-phase childhood cancer clinical studies of molecularly targeted agents. Workshop participants recommended the following: (1) tissue specimens for correlative studies should provide vital clinical and scientific results to qualify for early-phase pediatric study consideration; (2) parents should receive a realistic appraisal of the risks, requirements, and potential for benefit of phase I protocol participation; (3) investigators should clearly distinguish clinically necessary procedures from research procedures of no benefit to the child to improve correlative study informed consent; and (4) participation in correlative research studies included in clinical trials generally should be voluntary. The need to acquire important biologic data regarding new molecular agents will challenge the ingenuity of pediatric cancer researchers, necessitating the application of highly sensitive laboratory assay methods, new imaging procedures, and preclinical models of childhood cancer. Such innovative methods can allow necessary scientific information to be obtained while simultaneously respecting the protections appropriately afforded to children participating in research studies and minimizing the burden of research participation for children with cancer and their families.