Integrating Decision Making and Mental Health Interventions Research: Research Directions

The importance of incorporating patient and provider decision-making processes is in the forefront of the National Institute of Mental Health (NIMH) agenda for improving mental health interventions and services. Key concepts in patient decision making are highlighted within a simplified model of patient decision making that links patient-level/"micro" variables to services-level/"macro" variables via the decision-making process that is a target for interventions. The prospective agenda for incorporating decision-making concepts in mental health research includes (a) improved measures for characterizing decision-making processes that are matched to study populations, complexity, and types of decision making; (b) testing decision aids in effectiveness research for diverse populations and clinical settings; and (c) improving the understanding and incorporation of preference concepts in enhanced intervention designs.     

Peritoneal Desmoplastic Small Round Cell Tumors with Divergent Differentiation: A Review

Peritoneal desmoplastic small round cell tumors with divergent differentiation are recently described highly aggressive neoplasms with characteristic clinical, morphologic, and immunohistochemical features. This review covers 38 cases that have been reported in the literature. The average age of patients is 18.4 years, and males are affected twice as frequently as females. Tumors generally present as multiple peritoneal nodules without obvious organ involvement. Histology shows islands of small cells set in dense desmoplastic stroma. Immunohistochemical stains are usually positive for cytokeratins, epithelial membrane antigen, desmin, and vimentin. Many cases also stain for neuron-specific enolase but rarely for other neuroepithelial markers. Ultrastructural appearances range from undifferentiated small cells to larger epithelial elements. Paranuclear aggregates of intermediate filaments are characteristic. Dense-core granules and other neuroendocrine features have been described in a minority of cases. Some tumors respond to chemotherapy, but most patients die within months to a few years. The histogenesis of these tumors is uncertain.     

Characterization of the sleep-wake patterns in mice lacking fatty acid amide hydrolase

STUDY OBJECTIVES: Oleamide and anandamide are fatty acid amides implicated in the regulatory mechanisms of sleep processes. However, due to their prompt catabolism by fatty acid amide hydrolase (FAAH), their pharmacologic and behavioral effects, in vivo, disappear rapidly. To determine if, in the absence of FAAH, the hypnogenic fatty acid amides induce an increase of sleep, we characterized the sleep-wake patters in FAAH-knockout mice [FAAH (-/-)] before and after sleep deprivation. DESIGN: FAAH (-/-), FAAH (+/-), and FAAH (+/+) mice were implanted chronically for sleep, body temperature (Tb), and locomotor activity (LMA) recordings. Sleep-wake states were recorded during a 24-hour baseline session followed by 8 hours of sleep deprivation. Recovery recordings were done during the 16 hours following sleep deprivation. Total amount of wake, slow-wave sleep, and rapid eye movement sleep were calculated and compared between genotypes. The electroencephalographic spectral analysis was performed by fast Fourier transform analysis. Telemetry recordings of Tb and LMA were carried out continuously during 4 days under baseline conditions. SETTING: N/A. PATIENTS OR PARTICIPANTS: FAAH (-/-) mice and their heterozygote (+/-) and control (+/+) littermates were used. INTERVENTIONS: Sleep deprivation. MEASUREMENTS AND RESULTS: FAAH (-/-) mice possess higher values of slow-wave sleep and more intense episodes of slow-wave sleep than do control littermates under baseline conditions that are not related to differences in Tb and LMA. A rebound of slow-wave sleep and rapid eye movement sleep as well an increase in the levels of slow-wave activity were observed after sleep deprivation in all genotypes. CONCLUSION: These findings support the role of fatty acid amides as possible modulators of sleep and indicate that the homeostatic mechanisms of sleep in FAAH (-/-) mice are not disrupted.     

Large clonal expansions of human virus-specific memory cytotoxic T lymphocytes within the CD57+ CD28- CD8+ T-cell population

The proportion of human peripheral blood CD8+ T cells that are CD57+ CD28- is low at birth but increases with age and in individuals infected with human cytomegalovirus (HCMV) or human immunodeficiency virus (HIV). These CD57+ CD28- CD8+ T cells contain large oligoclonal T-cell expansions whose antigen specificity is unknown. We identified clonal expansions of virus-specific memory cytotoxic T-lymphocyte precursors (CTLp) in both healthy carriers of HCMV and in asymptomatic HIV-infected subjects. In each subject, from the T-cell receptor (TCR) beta-chain hypervariable sequence of each immunodominant CTL clone, we designed complementary oligonucleotide probes to quantify the size and phenotypic segregation of individual virus-specific CTL clones in highly purified populations of peripheral blood CD8+ T cells. We found large clonal expansions of virus-specific CTL clonotypes in CD57+ CD28- CD8+ T cells. Using limiting dilution analysis, we found functional peptide-specific CTLp at high frequency in CD57+ CD28- cells. Thus, memory CTL specific for persistent viruses account for many oligoclonal expansions within CD57+ CD28- CD8+ T cells.     

Amiloride-sensitive Na+ transport across cultured renal (A6) epithelium: evidence for large currents and high NaK selectivity

Electrical techniques were used to determine the NaK selectivity of the amiloride-sensitive pathway and to characterize cellular and paracellular properties of A6 epithelium. Under control conditions, the mean transepithelial voltage (V _T) was –57±5 mV, the short-circuit current (I _sc) averaged 23±2 A/cm² and the transepithelial resistance (R _T) was 2.8±0.3 kcm² (n=13). V _T and I _sc were larger than reported in previous studies and were increased by aldosterone. The conductance of the amiloride-sensitive pathway (G _amil) was assessed before and after replacement of Na⁺ in the mucosal bath by K⁺, using two independent measurements: (1) the slope conductance (G _T), determined from current-voltage (I-V) relationships for control and amiloride-treated tissues and (2) the maximum amiloride-sensitive conductance (G _max) calculated from the amiloride dose-response relationship. The ratio of G _amil in mucosal Na⁺ solutions to G _amil for mucosal K⁺ solutions was 22±6 for G _T measurements and 15±2 for G _max data. Serosal ion replacements in tissues treated with mucosal nystatin indicated a potassium conductance in the basolateral membrane. Equivalent circuit analyses of nystatin and amiloride data were used to resolve the cellular (E _c) and paracellular (R _j) resistances (5 kcm² and 8–9 kcm², respectively). Analysis I-V relationships for tissues depolarized with serosal K⁺ solutions revealed that the amiloride-sensitive pathway could be described as a Na⁺ conductance with a permeability coefficient (P _Na)=1.5±0.2× 10^–6 cm/s and the intracellular Na⁺ concentration (Na_i)=5±1 mM (n=5), similar to values from other tight epithelia. We conclude that A6 epithelia are capable of expressing large amiloride-sensitive currents which are highly Na⁺ selective.     

Misaligned spinal rods can induce high internal forces consistent with those observed to cause screw pullout and disc degeneration

BACKGROUND CONTEXTManual contouring of spinal rods is often required intraoperatively for proper alignment of the rods within the pedicle screw heads. Residual misalignments are frequently reduced by using dedicated reduction devices. The forces exerted by these devices, however, are uncontrolled and may lead to excessive reaction forces. As a consequence, screw pullout might be provoked and surrounding tissue may experience unfavorable biomechanical loads. The corresponding loads and induced tissue deformations are however not well identified. Additionally, whether the forced reduction alters the biomechanical behavior of the lumbar spine during physiological movements postoperatively, remains unexplored.PURPOSETo predict whether the reduction of misaligned posterior instrumentation might result in clinical complications directly after reduction and during a subsequent physiological flexion movement.STUDY DESIGNFinite element analysis.METHODSA patient-specific, total lumbar (L1–S1) spine finite element model was available from previous research. The model consists of poro-elastic intervertebral discs with Pfirrmann grade-dependent material parameters, with linear elastic bone tissue with stiffness values related to the local bone density, and with the seven major ligaments per spinal motion segment described as nonlinear materials. Titanium instrumentation was implemented in this model to simulate a L4, L5, and S1 posterolateral fusion. Next, coronal and sagittal misalignments of 6 mm each were introduced between the rod and the screw head at L4. These misalignments were computationally reduced and a physiological flexion movement of 15° was prescribed. Non-instrumented and well-aligned instrumented models were used as control groups.RESULTSPulling forces up to 1.0 kN were required to correct the induced misalignments of 6 mm. These forces affected the posture of the total lumbar spine, as motion segments were predicted to rotate up to 3 degrees and rotations propagated proximally to and even affect the L1–2 level. The facet contact pressures in the corrected misaligned models were asymmetrical suggesting non-physiological joint loading in the misaligned models. In addition, the discs and vertebrae experienced abnormally high forces as a result of the correction procedure. These effects were more pronounced after a 15° flexion movement following forced reduction.CONCLUSIONSThe results of this study indicate that the correction of misaligned posterior instrumentation can result in high forces at the screws consistent with those reported to cause screw pullout, and may cause high-tissue strains in adjacent and downstream spinal segments.CLINICAL SIGNIFICANCEProper alignment of spinal posterior instrumentation may reduce clinical complications secondary to unfavorable biomechanics.     

How often are diagnostic features missed with less extensive histologic sampling of prostate needle biopsy specimens?

The authors determined whether clinically relevant diagnostic information would be lost by examination of <3 levels per tissue core in prostate needle biopsy specimens. They evaluated 439 consecutive sextant biopsy specimens for the following three histopathologic features: presence of adenocarcinoma involving one core, Gleason pattern 4 in cases of grade 3 + 4 = 7 adenocarcinoma, and perineural invasion (PNI) by carcinoma. For all cases, 3 levels from each involved core were reviewed for the presence or absence of these three features. In 50 cases with adenocarcinoma involving only 1 core, diagnostic carcinoma was present on all 3 levels in 43 cores (86%). Carcinoma was present on only 2 levels in 3 cores (6%), present only on 1 level in 3 cores (6%), and present only on additional cut-downs, not on the original 3 levels in 1 core (2%). Among 32 cases, 51 cores were identified that contained Gleason grade 3 + 4 = 7 adenocarcinoma. In 41 cores (80%), pattern 4 was identified in all 3 levels. In 5 cores (10%), pattern 4 was identified on only 2 levels, and in another 5 cores (10%), pattern 4 was present on only 1 level. Among 36 cases, 69 tissue cores were identified that contained perineural invasion (PNI). In 54 cores (78%), PNI was present on all 3 levels. In 7 cores (10%), PNI was present on only 2 of 3 levels, while in 7 other cores (10%), PNI was present on only 1 of 3 levels. In 1 core (1.5%), PNI was noted only on additional cutdowns, not on the original 3 levels. We estimated that reducing the number of levels to 1 per core could result in the misdiagnosis of PNI, grading, or carcinoma in approximately 8-11% of cores with these features and could have changed the case diagnosis in 9 of 439 cases. If only 2 levels were reviewed, we predict misdiagnosis in 5% to 6% of cores with these features and a change in the case diagnosis in 5 of 439 cases. Misdiagnosis of clinically relevant features on prostate biopsy specimens can be minimized with histologic review of 3 levels per tissue core.     

Chagas' disease in an obstetrical patient

We report a case of a parturient with documented chronic Chagas' disease with cardiac manifestations presenting for labor management and complicated by the need for emergent hysterectomy after delivery. Chagas' disease is a common human hematogenous trypanosomiasis in Central and South America which is now, because of population migration, appearing in the USA. This disease predominantly affects the heart and the gastrointestinal system. This report discusses the parasite, the acute and chronic phases of Chagas' disease and highlights its medical implications, including maternal-fetal transfer of Trypanosoma cruzi.