Are release recommendations for NGRI acquittees informed by relevant data?

We conducted a retrospective review of factors involved in clinical recommendations for release of patients adjudicated not guilty by reason of insanity (NGRI). Medical records from 91 patients in a maximum security forensic hospital who participated in a formal hearing process to determine suitability for release were reviewed. The purpose of the study was twofold: (1) to examine the process involved in day to day clinical decision-making regarding release from a maximum security forensic hospital and (2) to determine what factors in a patient's clinical and legal history were related to recommendation decisions.

The use of organic vapor sorption to determine low levels of amorphous content in processed pharmaceutical powders.

Organic dynamic vapor sorption (organic-DVS) was used to characterize amorphous content in known amorphous-crystalline mixtures of lactose and salbutamol sulfate. N-octane was chosen as an apolar probe and measurements were carried out by exposing mixtures of each sample to partial pressures 0-90% p/p(0). A linear relationship between amorphous content and n-octane partial pressure was observed for both lactose and salbutamol sulfate with R(2) values of 0.

NASA returns rocks from a comet.

Cometary particles returned by the Stardust Discovery Mission are primarily silicate materials of solar system origin. Some of the grains were formed at high temperatures close to the Sun, but then transported far out to the Kuiper belt region of the solar system before being incorporated in the comet.

Solar wind neon from Genesis: implications for the lunar noble gas record.

Lunar soils have been thought to contain two solar noble gas components with distinct isotopic composition. One has been identified as implanted solar wind, the other as higher-energy solar particles. The latter was puzzling because its relative amounts were much too large compared with present-day fluxes, suggesting periodic, very high solar activity in the past.

Nicotinamide reverses neurological and neurovascular deficits in streptozotocin diabetic rats.

In diabetes, activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) is an important effector of oxidative-nitrosative injury, which contributes to the development of experimental diabetic peripheral neuropathy (DPN). However, the potential toxicity of complete PARP inhibition necessitates the utilization of weaker PARP inhibitors with additional therapeutic properties. Nicotinamide (vitamin B3) is a weak PARP inhibitor, antioxidant, and calcium modulator and can improve energy status and inhibit cell death in ischemic tissues.

Novel aminobenzimidazoles as selective MCH-R1 antagonists for the treatment of metabolic diseases.

A series of novel aminobenzimidazoles was prepared and evaluated for h-MCH-R1 antagonist properties. Most of the compounds showed excellent h-MCH-R1 binding affinity as well as mouse ex vivo binding. Compounds 9 and 18 were active in mouse DIO studies at 30mpk.

Enhanced low-temperature CO oxidation on a stepped platinum surface for oxygen pressures above 10(-5) Torr.

The rate of CO oxidation has been characterized on the stepped Pt(411) surface for oxygen pressures up to 0.002 Torr, over the 100-1000 K temperature range. CO oxidation was characterized using both temperature-programmed reaction spectroscopy (TPRS) and in situ soft X-ray fluorescence yield near-edge spectroscopy (FYNES).

In situ soft X-ray studies of ethylene oxidation mechanisms and intermediates on the Pt(111) surface.

In situ studies of ethylene oxidation on Pt(111) have been performed using a powerful combination of fluorescence yield soft X-ray methods for temperatures up to 600 K and oxygen pressures up to 0.01 Torr. Absolute carbon coverages have been determined both in steady-state and dynamic catalytic conditions on the Pt(111) surface.

Tetrahydroisoquinolines as MCH-R1 antagonists.

A series of potent and selective inhibitors of h-MCH-R1 has been developed based on the piperidine glycineamide compounds I and II. These structurally more rigid tetrahydroisoquinolines (III and IV) showed better pharmacokinetics. The highly potent compounds 12d and 12g displayed excellent rat pk.

Hydrazides of clozapine: a new class of D1 dopamine receptor subtype selective antagonists.

Acylated and aroylated hydrazinoclozapines are highly potent dopamine D(1) antagonists that show remarkable selectivity over other dopamine receptors. The most potent compound in this series is the 2,6-dimethoxybenzhydrazide 33 with a D(1)K(i) of 1.6 nM and 212-fold selectivity over D(2) receptor.

Prevalence of white matter hyperintensities in a young healthy population.

Background And Purpose: White matter hyperintensities (WMHs) are bright objects observed in the white matter on brain magnetic resonance (MR) imaging. WMHs are often reported as "normal" findings but may represent pathological changes. The prevalence of WMHs appears to increase with increasing age although both the typical timing and clinical significance of their appearance among medically and neurologically healthy persons remains unclear.

Modification of the clozapine structure by parallel synthesis.

A structure-activity study based on the core structure of clozapine 1b was accomplished by utilizing high-throughput synthesis. Several focused libraries were designed and synthesized to quickly develop SAR. The results indicate that by varying different regions of clozapine, both D(1)-selective and D(2)-selective compounds can be obtained.

ISO 15189:2003--quality management, evaluation and continual improvement.

The requirements of ISO 15189:2003 are discussed in the context of a process- and outcome-based quality management model in which the user's needs are the central focus. The requirements of ISO 15189:2003 are examined in terms of organisation and a quality management system, stressing the importance of evidence, document control, and control of records and clinical material. Examples are provided from the areas of resource management, and pre-examination, examination and post-examination processes.

Design and synthesis of orally efficacious benzimidazoles as melanin-concentrating hormone receptor 1 antagonists.

Biaryl urea lead compound 1 was discovered earlier in our MCH antagonist program. Novel benzimidazole analogues with increased chemical stability, devoid of the potential carcinogenic liability associated with a biarylamine moiety, were synthesized and evaluated to be potent MCH R1 antagonists. Two compounds in this series have demonstrated in vivo efficacy in a rodent obesity model.

Synthesis and structure-activity relationships of piperidine-based melanin-concentrating hormone receptor 1 antagonists.

Isosteric replacement of the urea group of lead compound 1 led to novel substituted piperidine phenylamide analogues. SAR on the electron-induced effects of various linkers as well as substituents on the phenyl rings and the piperidine nitrogen has been investigated. Many single-digit nanomolar MCH R1 antagonists have been identified from this series.

Taurine reverses neurological and neurovascular deficits in Zucker diabetic fatty rats.

Increased oxidative stress is implicated in the pathogenesis of diabetic peripheral neuropathy (DPN). However, the efficacy of antioxidant therapy on DPN complicating type 2 diabetes remains unexplored. We therefore determined the ability of the antioxidant taurine to reverse deficits of hind limb sciatic motor and digital sensory nerve conduction velocity (NCV), nerve blood flow (NBF), and sensory thresholds in hyperglycemic Zucker diabetic fatty (ZDF) rats.

Investigating the moisture-induced crystallization kinetics of spray-dried lactose.

Gravimetric water sorption experiments were performed to study the crystallization behavior of amorphous spray-dried lactose over a wide range of temperature and humidity conditions. Experiments performed at 25 degrees C between 48 and 60% relative humidity (RH) showed that the onset time to crystallization increased dramatically with decreasing humidity. At 55% RH and above, crystallization occurred in a single detectable step, while below a two-step process was observed.

Pregnancy outcomes after maternal exposure to simvastatin and lovastatin.

Background: Our objective was to determine the frequency of adverse outcomes after maternal exposure to simvastatin and/or lovastatin during pregnancy in postmarketing experience.

Methods: We reviewed the Merck & Co., Inc.

Tolerance to the miotic effect of sarin vapor in rats after multiple low-level exposures.

Inhibition of acetylcholinesterase (AChE) by the organophosphorous compound sarin (GB) results in the accumulation of acetylcholine and excessive cholinergic stimulation. There are few data in the literature regarding the effects of multiple low-level exposures to GB and other organophosphorous compounds via relevant routes of exposure. Therefore, the present study was undertaken, and is the first, to investigate the effect of low-level repeated whole-body inhalation exposures to GB vapor on pupil size and cholinesterase activity in the eyes and blood.

The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1).

Ezetimibe is a potent inhibitor of cholesterol absorption that has been approved for the treatment of hypercholesterolemia, but its molecular target has been elusive. Using a genetic approach, we recently identified Niemann-Pick C1-Like 1 (NPC1L1) as a critical mediator of cholesterol absorption and an essential component of the ezetimibe-sensitive pathway. To determine whether NPC1L1 is the direct molecular target of ezetimibe, we have developed a binding assay and shown that labeled ezetimibe glucuronide binds specifically to a single site in brush border membranes and to human embryonic kidney 293 cells expressing NPC1L1.

Cathlink 20: a subcutaneous implanted central venous access device used in children with sickle cell disease on long-term erythrocytapheresis--a report of low complication rates.

Background: Experience with the use of central venous access device (CVAD) in children with sickle cell disease (SCD) on hypertransfusion is limited and published studies report wide variability in the rates of CVAD-associated complications.

Procedure: In this study, a total of 18 Cathlink 20 ports (Bard Access systems, Salt Lake City, UT) were implanted in 15 patients aged 7-20 years with SCD for 19, 230 catheter patient days.

Results: No peri-operative complications were observed.

Dopamine D1/D5 receptor antagonists with improved pharmacokinetics: design, synthesis, and biological evaluation of phenol bioisosteric analogues of benzazepine D1/D5 antagonists.

Benzazepines 1 and 2 (SCH 23390 and SCH 39166, respectively) are two classical benzazepine D1/D5 antagonists, with Ki values 1.4 and 1.2 nM, respectively.