A matter of life or death: special considerations and heightened practice standards in capital sentencing evaluations.

Mental health evaluations at capital sentencing represent a complex and specialized arena of practice. The moral culpability focus of capital sentencing is distinct from guilt-phase considerations of criminal responsibility, and has a specialized literature. Capital violence risk assessment is uniquely oriented to a prison context, relying on past adjustment to incarceration, as well as group statistical data specific to capital offenders and other inmate groups. Personality testing is a more complex consideration in capital sentencing evaluations. The implications of interviewing the defendant, as well as the parameters and documentation of an interview, make full disclosure and informed consent of particular importance. Defense- and prosecution-retained experts are subject to specific ethical vulnerabilities. These are examined in this paper through the lens of current professional standards.

CD14 employs hydrophilic regions to "capture" lipopolysaccharides.

CD14 participates in the host innate inflammatory response to bacterial LPS obtained from Escherichia coli and other Gram-negative bacteria. Evidence from several laboratories suggests that different regions of the amino-terminal portion of the molecule may be involved in LPS binding. In this report a series of single-residue serine replacement and charge reversal mutations were generated to further elucidate the mechanism by which this protein may bind a multitude of different LPS ligands. Single-residue CD14 mutation proteins were examined for their ability to bind LPS obtained from E. coli, Porphyromonas gingivalis, and Helicobacter pylori and facilitate the activation of E-selectin from human endothelial cells. In addition, the single-residue CD14 mutation proteins were employed to perform monoclonal epitope-mapping studies with three LPS-blocking Abs that bound tertiary epitopes. Evidence that several different hydrophilic regions of the amino-terminal region of CD14 are involved in LPS binding was obtained. Epitope-mapping studies revealed that these hydrophilic regions are located on one side of the protein surface. These studies suggest that CD14 employs a charged surface in a manor similar to the macrophage scavenger receptor to "capture" LPS ligands and "present" them to other components of the innate host defense system.

Escherichia coli and Porphyromonas gingivalis lipopolysaccharide interactions with CD14: implications for myeloid and nonmyeloid cell activation.

Porphyromonas gingivalis, a gram-negative bacterium, is an etiologic agent for adult periodontitis. Lipopolysaccharide (LPS) released from this bacterium can react with numerous host cell types. P. gingivalis LPS stimulates tumor necrosis factor alpha and interleukin-1beta secretion from monocytes (myeloid) but does not elicit E-selectin expression from human endothelial cells (nonmyeloid). In contrast, Escherichia coli LPS facilitates expression of these inflammatory mediators through CD14-dependent pathways on both myeloid and nonmyeloid cells. LPS binding studies have revealed that although P. gingivalis and E. coli LPSs bind to CD14 differently, this fact does not adequately explain the lack of endothelial cell activation by P. gingivalis LPS. Rather, LPS binding site and blocking monoclonal antibody epitope mapping studies have suggested that CD14 presents a charged surface that captures different microbial ligands by electrostatic interactions. We propose that human endothelial cells do not respond to P. gingivalis LPS because of their inability to "recognize" CD14-P. gingivalis LPS complexes.

Antisocial personality disorder and psychopathy: diagnostic dilemmas in classifying patterns of antisocial behavior in sentencing evaluations.

Antisocial Personality Disorder (APD) and PCL-R psychopathy are critically examined regarding their application to sentencing determinations. PCL-R psychopathy is emerging in the literature as a more useful forensic diagnostic construct than APD, which appears flawed by multiple weaknesses. These include shifting diagnostic criteria, innumeracy problems, absence of symptom weighting, temporal instability, and the equivalence of some symptoms with substance abuse disorders. Additionally, APD overdiagnosis may result from inattention to issues of social context, trauma history, and symptom pervasiveness. Neither objective nor projective personality testing reliably differentiates APD. Finally, an APD diagnosis does not always indicate criminal, much less incorrigible criminal behavior. By contrast, PCL-R psychopathy results are strongly predictive of criminal behavior and violent recidivism for Caucasian males through mid-life residing in the community. Emerging research with the PCL-R regarding other important populations and contexts is promising but generalization is currently limited.

Integrating base rate data in violence risk assessments at capital sentencing.

Prediction of violence in capital sentencing has been controversial. In the absence of a scientific basis for risk assessment, mental health professionals offering opinions in the capital sentencing context are prone to errors. Actuarial or group statistical data, known as base rates, have proven far superior to other methods for reducing predictive errors in many contexts, including risk assessment. Actuarial follow-up data on violent recidivism of capital murderers in prison and post release have been compiled and analyzed to demonstrate available base rates for use by mental health experts conducting risk assessments pertaining to capital sentencing. This paper also reviews various methods for individualizing the application of base rates to specific cases.

The effects of restraint using self-locking stanchions on dairy cows in relation to behavior, feed intake, physiological parameters, health, and milk yield.

Holstein cows (n = 64) ranging from peak to end lactation were restrained in self-locking stanchions (i.e., head locks) for approximately 4 h/d for four periods in a modified switchback design. Milk yield, milk fat percentage, somatic cell count, and dry matter intake and dry matter intake were unaffected by restraint. Milk protein percentage was significantly lower for cows that were restrained. Plasma cortisol concentrations and the ratio of neutrophils to mononuclear cells were not significantly different between restrained and unrestrained (control) cows. No difference in the incidence of mastitis or other health concerns was noted. Behaviorally, cows that were locked in the stanchions spent significantly more time lying after release from restraint. For cows that were locked up, eating frequency over 24 h was significantly reduced, but dry matter intake was not affected. Total rumination frequency over 24 h was not significantly different for cows that were restraubed; however, cows that were restrained ruminated less during the day following release. Grooming was considered to be a behavioral need and was significantly increased during all times when cows were not locked up. Grooming was also one of the first behaviors performed following release. Acts of aggression were elevated during all periods following restraint, but oral behaviors, such as tongue playing and chewing on objects, drinking behavior, and resting postures were not affected. The use of self-locking stanchions did not appear to affect substantially the overall well-being of the cow.

Nociceptin/orphanin FQ stimulates extracellular acidification and desensitization of the response involves protein kinase C.

A Chinese hamster ovary (CHO) cell line, CHO-ORL1, stably expressing human opioid receptor-like receptor 1 (ORL1) has been used to determine ORL1-mediated signaling events using microphysiometry. Nociceptin/orphanin FQ (N/OFQ), a specific endogenous agonist of ORL1, induced an increase in extracellular acidification rate (ECAR) in CHO-ORL1 cells. The ECAR response stimulated by N/OFQ was concentration-dependent and pertussis toxin-sensitive. Repeated exposures of the cells to N/OFQ caused desensitization of ORL1. The ECAR response was recovered at the half-life of approximately 12 min after the initial challenge. Pretreatment with inhibitor of cAMP-dependent kinase did not affect desensitization of ORL1. However, specific inhibitors for protein kinase C almost abolished N/OFQ-induced desensitization of extracellular acidification responsiveness, indicating the involvement of protein kinase C in the process.

Identification of CD14 residues involved in specific lipopolysaccharide recognition.

CD14 is a key molecule responsible for the innate host inflammatory response to microbial infection. It is able to bind a wide variety of microbial ligands and facilitate the activation of both myeloid and nonmyeloid cells. However, its specific contribution to the innate recognition of bacteria is not known. Presently there is no information on the contribution of individual CD14 residues to Escherichia coli lipopolysaccharide (LPS) binding or on the molecular basis of the interaction between CD14 and LPS from other bacteria. LPS obtained from Porphyromonas gingivalis, a bacterium associated with chronic inflammatory disease, binds CD14 and activates myeloid cells but does not facilitate the activation of nonmyeloid cells. The transfer and binding of these two LPS species to soluble CD14 recombinant globulin proteins with single point mutations was examined. Functional activity of the mutant proteins was monitored by E-selectin expression on human umbilical cord endothelial cells. The analysis identified a charge reversal mutation in a single residue, E47, that demonstrated selective binding to E. coli LPS but not to P. gingivalis LPS. E-selectin activation assays indicated that proteins with mutations at position E47 maintained their structural integrity. Other mutations, including a charge reversal mutation of residue E58, did not significantly reduce the binding of either LPS ligand or the ability of the molecule to facilitate E-selectin activation. These data demonstrate that CD14 can selectively recognize different LPS ligands.

Helicobacter pylori and Porphyromonas gingivalis lipopolysaccharides are poorly transferred to recombinant soluble CD14.

Helicobacter pylori and Porphyromonas gingivalis are gram-negative bacteria associated with chronic inflammatory diseases. These bacteria possess lipopolysaccharides (LPSs) that are able to activate human monocytes to produce tumor necrosis factor alpha but fail to activate human endothelial cells to express E-selectin. With Escherichia coli LPS, tumor necrosis factor alpha activation requires membrane-bound CD14 and E-selectin expression requires soluble CD14 (sCD14). Therefore, the ability of H. pylori and P. gingivalis LPSs to transfer to and bind sCD14 was examined by using immobilized recombinant sCD14 and human serum or recombinant LPS-binding protein (LBP). H. pylori and P. gingivalis LPSs were transferred to sCD14 when serum or LBP was present. However, the transfer of these LPSs to CD14 in serum was significantly slower than the transfer of E. coli LPS. Quantitation of the transfer rates by Michaelis-Menten kinetics yielded K(m) values of 6 and 0.1 nM for H. pylori and E. coli LPSs, respectively. The amount of P. gingivalis LPS required to obtain half-maximum binding to CD14 was approximately 10-fold greater than the amount of E. coli LPS required. The slower transfer rates displayed by these LPSs can be explained by the poor binding to LBP observed in direct binding assays. These results are consistent with the proportionately lower ability of these LPSs to activate monocytes compared with E. coli LPS. However, the ability of H. pylori and P. gingivalis LPSs to bind LBP and transfer to sCD14 demonstrates that the lack of endothelial cell CD14-dependent cell activation by these LPSs occurs distal to sCD14 binding.

Evidence for pharmacologically distinct GABAB receptors associated with cAMP production in rat brain.

Gamma-Aminobutyric acid-B (GABAB) receptors mediate a variety of cellular functions, suggesting the possibility of pharmacologically and molecularly distinct receptors. To explore this possibility a number of GABAB receptor agonists and antagonists were examined for their ability to influence cAMP production in rat brain cerebral cortical slices. While the agonists did not differentiate between receptors associated with the augmentation of isoproterenol-induced cAMP production and those mediating inhibition of forskolin-stimulated second messenger accumulation, significant differences were noted between the potencies of some antagonists to inhibit these GABAB receptor-mediated responses. The results suggest at least two pharmacologically distinct subclasses of GABAB receptors regulate cAMP production in brain.

The efficacy and safety of KL4-surfactant in preterm infants with respiratory distress syndrome.

The present study was undertaken to determine if a synthetic peptide, KLLLLKLLLLKLLLLKLLLLK (KL4), in which K = lysine and L = leucine, in an aqueous dispersion of phospholipids (DPPC and POPG), would expand pulmonary alveoli and improve gas exchange in premature human infants with respiratory distress syndrome (RDS). The KL4 peptide was synthesized to resemble the amino acid pattern of surfactant protein B (SP-B). Forty-seven infants with RDS were treated within 4 h of birth with the KL4-peptide/phospholipid mixture, called KL4-Surfactant. The average arterial-to-alveolar oxygen tension ratios (a/A O2) of 39 patients included in efficacy analyses rose from pretreatment values of 0.14 +/- 0.02 (mean +/- SEM) to 0.40 +/- 0.04 (normal value > or = 0.40) by 12 h of age. Mean airway pressures and oxygenation index values fell concomitantly, and expansion of the lungs was observed on radiographs. The median duration of mechanical ventilation was 5.0 d. Of the 39 included infants, 29 required only a single dose. Radiographic data indicate that those patients requiring a second instillation of KL4-Surfactant but not showing a sustained rise in a/A O2 ratios did, in fact, exhibit expansion of alveoli in the lung. There were no RDS-related deaths; the incidence of complications was no higher than found in other comparable published studies. The data demonstrate that the synthetic peptide, KL4, which mimics the hydrophobic and hydrophilic pattern of SP-B, when formulated in an aqueous dispersion with the phospholipids DPPC and POPG, creates a strong and durable surfactant activity as judged by expansion of pulmonary alveoli and improvement of gas exchange in infants with RDS.

A novel Escherichia coli lipid A mutant that produces an antiinflammatory lipopolysaccharide.

A unique screen was used to identify mutations in Escherichia coli lipid A biosynthesis that result in a decreased ability to stimulate E-selectin expression by human endothelial cells. A mutation was identified in the msbB gene of E. coli that resulted in lipopolysaccharide (LPS) that lacks the myristoyl fatty acid moiety of the lipid A. Unlike all previously reported lipid A mutants, the msbB mutant was not conditionally lethal for growth. Viable cells or purified LPS from an msbB mutant had a 1000-10,000-fold reduction in the ability to stimulate E-selectin production by human endothelial cells and TNF alpha production by adherent monocytes. The cloned msbB gene was able to functionally complement the msbB mutant, restoring both the LPS to its native composition and the ability of the strain to stimulate immune cells. Nonmyristoylated LPS acted as an antagonist for E-selectin expression when mixed with LPS obtained from the parental strain. These studies demonstrate a significant role for the myristate component of LPS in immune cell activation and antagonism. In addition, the msbB mutant allowed us to directly examine the crucial role that the lipid A structure plays when viable bacteria are presented to host defense cells.

Ability of bacteria associated with chronic inflammatory disease to stimulate E-selectin expression and promote neutrophil adhesion.

Porphyromonas gingivalis, Pseudomonas aeruginosa, and Helicobacter pylori have been shown to be associated with adult periodontal disease, chronic lung infections, and peptic ulcers, respectively. The ability of these bacteria to stimulate E-selectin expression and promote neutrophil adhesion, two components necessary for the recruitment of leukocytes in response to infection, was investigated. Little or no stimulation of E-selectin expression was observed with either P. gingivalis or H. pylori when whole cells, lipopolysaccharide (LPS), or cell wall preparations added to human umbilical cord vein endothelial cells were examined. P. aeruginosa was able to induce E-selectin to near-maximal levels; however, it required approximately 100 to 1,000 times more whole cells or LPS than that required by E. coli. Neutrophil-binding assays revealed that LPS and cell wall preparations obtained from these bacteria did not promote endothelial cell adhesiveness by E-selectin-independent mechanisms. In addition, P. gingivalis LPS blocked E-selectin expression by LPS obtained from other bacteria. We propose that lack of E-selectin stimulation and the inability to promote endothelial cell adhesiveness are two additional indications of low biologically reactive LPS. We suggest that this property of LPS may contribute to host tissue colonization. In addition, the ability of P. gingivalis to inhibit E-selectin expression may represent a new virulence factor for this organism.

Focal intestinal perforation in the extremely-low-birth-weight infant.

The purposes of this report were to (1) document the clinical and laboratory features of 11 extremely-low-birth-weight (ELBW) infants with focal intestinal perforation and (2) investigate the clinical events possibly associated with these perforations by examining matched pairs of infants with and without focal intestinal perforation. During the study period 173 infants with birth weights between 600 and 1000 gm were admitted to the neonatal intensive care nursery. Eleven of these ELBW infants had focal intestinal perforations and formed the study group. These infants were matched with 11 ELBW infants who did not have intestinal perforations or signs of inflammatory bowel disease. The matched pairs were similar in all respects except for a significantly higher percent increase in blood urea nitrogen level after treatment with indomethacin (Wilcoxon signed-rank test, p < 0.02) in infants with intestinal perforation. At laparotomy the perforations were noted to be focal, often multiple, and on the antimesenteric border of the distal ileum. None of the infants showed clinical, radiographic, or intraoperative findings that were consistent with classifications for necrotizing enterocolitis (NEC). The incidence of focal intestinal perforation in ELBW infants was 6% versus 2% for typical NEC. In addition, four of the 11 infants with intestinal perforation had positive cultures for either Staphylococcus epidermidis or Candida albicans, whereas none of the infants without perforation had positive cultures during the study period (Fisher's exact test, p < 0.09). We conclude that the clinical presentation and the characteristic intestinal lesions in this group of ELBW infants are distinct from those in typical cases of NEC.(ABSTRACT TRUNCATED AT 250 WORDS)

Excitatory amino acid receptors: a gallery of new targets for pharmacological intervention.

The excitatory amino acids (EAAs) L-glutamate and L-aspartate are the most abundant amino acids in brain and play a number of roles in maintaining neuronal function. Among these are their use as protein constituents, as key intermediates in ammonia metabolism, and as precursors for other neurotransmitters. Given the widespread distribution of EAA-containing neurons, these transmitters are likely to be involved in virtually all central nervous system functions, with abnormalities in neurotransmission contributing to the symptoms of a host of neurological and psychiatric disorders. Because of the importance of EAAs in maintaining the functional integrity of the central nervous system, efforts are underway to design agents capable of regulating the activity of these transmitters for therapeutic gain. Inasmuch as potential side effects preclude a generalized modification of this system, strategies must be found to alter EAA neurotransmission in selected brain regions. In this regard, pharmacological data suggest several functionally distinct EAA receptors, a finding confirmed by cloning studies which hint at an even larger family of sites. Moreover, it appears that some excitatory amino acid receptor complexes are composed of interacting sites which orchestrate receptor function, and there is evidence that EAA receptors may influence the activity of one another. Thus, there appear to be numerous sites that can be targeted to selectively modify excitatory amino acid neurotransmission in brain. Besides the agonist recognition site for each receptor subtype, other targets include regulatory subunits, ion channels and components of receptor-coupled second messenger systems.

Hemorrhagic adrenal cyst.

Adrenal cysts are uncommon. They may be fatal if they hemorrhage and are not rapidly diagnosed. Most adrenal cysts are small and asymptomatic. When they are symptomatic, it is usually because the cyst has enlarged, causing flank discomfort, gastrointestinal complaints, and hemorrhage. Occasionally, a palpable mass may be found. It is thought that hemorrhage occurs secondary to trauma or some toxic or infectious process. The author describes a case in which a previously healthy man had a sudden hemorrhage within a benign adrenal cyst with infarction of the kidney. A discussion of adrenal cysts follows.