Comorbid posttraumatic stress disorder is associated with suicidality in male veterans with schizophrenia or schizoaffective disorder.

The purpose of this study was to determine if patients with schizophrenia or schizoaffective disorders and comorbid posttraumatic stress disorder (PTSD) are at higher risk for suicidality than patients without comorbid PTSD. Participants were 165 male veterans with primary diagnoses of schizophrenia or schizoaffective disorder. Those with comorbid PTSD reported higher rates of suicidal ideation and suicidal behaviors compared to those without comorbid PTSD. These findings suggest that patients with comorbid PTSD are at higher risk for suicidality. Enhanced screening and targeted interventions may be warranted to address comorbid PTSD and increased suicide risk in this population.

A preliminary study of lamotrigine for the treatment of posttraumatic stress disorder.

BACKGROUND: The anticonvulsant, lamotrigine, may be useful for symptom management in PTSD. METHODS: Subjects enrolled in a 12-week double-blind evaluation of lamotrigine and placebo. Patients were randomized 2:1 to either lamotrigine or placebo. Lamotrigine was initiated at 25 mg/day and slowly titrated every 1 to 2 weeks over 8 weeks to a maximum dosage of 500 mg/day if tolerated. RESULTS: Fifteen subjects entered treatment, fourteen of whom returned for subsequent visits. Of 10 patients who received lamotrigine, 5 (50%) responded according to the DGRP, compared to 1 of 4 (25%) who received placebo. Lamotrigine patients showed improvement on reexperiencing and avoidance/numbing symptoms compared to placebo patients. Treatments were generally well tolerated. CONCLUSIONS: Lamotrigine may be effective as a primary psychopharmacologic treatment in both combat and civilian PTSD and could also be considered as an adjunct to antidepressant therapy used in the treatment of PTSD. These promising results warrant further large sample double-blind, placebo-controlled trials.

Enhanced alpha-adrenoceptor responsiveness and receptor number during global ischaemia in the Langendorff perfused rat heart.

1. Idioventricular rate responses and adrenoceptor number have been examined in normal Langendorff hearts perfused at 70 cmH2O and in 'ischaemic' hearts perfused at 10 cmH2O. 2. In hearts perfused at normal pressure, ventricular rate responses to phenylephrine in the presence of propranolol were biphasic with low concentrations of phenylephrine reducing, and high concentrations increasing, ventricular rate. Both responses were abolished in the presence of prazosin (100 nM). In hearts perfused at low pressure, the negative chronotropic responses to phenylephrine were no longer present and positive chronotropic responses were enhanced compared with those of control tissues. The number of ventricular [3H]-prazosin binding sites was also significantly increased during ischaemia. 3. Idioventricular rate responses to isoprenaline were depressed in ischaemic tissues compared with controls, but [3H]-dihydroalprenolol binding was not altered in these hearts. 4. The incidence and duration of arrhythmias which occurred during 30 min of global ischaemia and reperfusion were not significantly altered in the presence of 100 nM prazosin. 5. These results demonstrate that reducing the perfusion pressure of rat isolated hearts enhances alpha-adrenoceptor-mediated responses and increases alpha-adrenoceptor density. Whether the increase in alpha-adrenoceptor responsiveness during ischaemia is involved in arrhythmogenesis requires further investigation.

Potentiation of alpha-adrenoceptor-mediated responses following chronic beta-adrenoceptor stimulation in the rat heart.

1. Noradrenaline and isoprenaline were infused subcutaneously in rats by use of Alzet osmotic minipumps. The effects of catecholamine infusion on ventricular alpha- and beta-adrenoceptor density and also the responses of isolated cardiac tissues were compared with saline infusion. 2. Noradrenaline (1 mg kg-1) or isoprenaline (40 micrograms kg-1) infused for 3 days resulted in a desensitization of beta-adrenoceptor-mediated responses of isolated left atria and papillary muscles. Concentration-response curves to isoprenaline were shifted to the right in left atria whilst maximum responses were reduced in papillary muscles. Right atrial rate responses were not affected by infusions of catecholamines. 3. Infusions of either noradrenaline or isoprenaline resulted in a supersensitivity of alpha-adrenoceptor-mediated responses in isolated papillary muscles with leftward displacements of concentration-response curves to phenylephrine. 4. The density of both ventricular [3H]-dihydroalprenolol and [3H]-prazosin binding sites was reduced following noradrenaline infusion. Isoprenaline infusion reduced only the density of [3H]-dihydroalprenolol binding sites. 5. Noradrenaline infusion therefore 'down-regulates' both alpha- and beta-adrenoceptors in the rat heart but at the same time ventricular alpha-adrenoceptor-mediated responses are enhanced. Isoprenaline similarly enhances responses to phenylephrine and possible mechanisms for this phenomenon are discussed.

Frame-mounted porcine valve bioprostheses: preparation during aortic-root dilation. Biomechanics and design considerations.

The leaflet geometry and function of frame-mounted porcine bioprostheses prepared with dilation of the aortic root during frame mounting was investigated. The diameter of the porcine aortic root increased by 47% when dilated with a pressure of 120 mm Hg. In the absence of pressure dilation, the ratio of circumferential leaflet length to the radius of the aortic root (S/RA) was 2.7 +/- 0.1, and the angle of inclination of the leaflet to the base of the valve was 17 +/- 4.3 degrees. In this condition, the leaflet geometry was similar to that of some second-generation porcine bioprostheses, which demonstrated high open-leaflet bending strains at the commissures. Dilation of the porcine root with 120 mm Hg reduced the value of S/RA to 1.84 and produced a triangular open-leaflet configuration with minimum open-leaflet bending strains. Open-leaflet bending strains were also reduced in two prototype frame-mounted valves prepared with partial dilation of the aortic root, which had an S/RA ratio of less than 2.3 and a leaflet angle greater than 27 degrees. The study indicates that the next generation of porcine bioprostheses should be prepared with at least 17% dilation of the aortic root during frame mounting and with zero pressure difference across the leaflets during fixation. This can be achieved by applying an equal hydrostatic pressure to both sides of the valve leaflets during fixation and frame mounting.

Atomic quadrupolar photoemission asymmetry parameters from a solid state measurement

A method for measuring the asymmetry parameter gamma arising from dipole-quadrupole interference in core-level photoemission is proposed which is based on condensed thin films and exploits the influence of this asymmetry in photoemission monitoring of x-ray standing wave field absorption. The high density of material in this method offers some advantages over a conventional gas-phase measurement. Results are presented for C, O, and F 1s photoemission at photon energies around 3 keV. The combined nondipole asymmetry factor (delta+gamma/3) for non- s-states can be determined in a similar way.

Effect of inhibition of 5-lipoxygenase metabolism of arachidonic acid on response to endotoxemia in sheep.

We studied the effects of a 5-lipoxygenase inhibitor, L-651,192, on the pulmonary dysfunction caused by endotoxemia in chronically instrumented unanesthetized sheep. The efficacy and selectivity of L-651,392 were tested by measuring in vivo production of leukotriene B4 (LTB4) and cyclooxygenase products of arachidonic acid after endotoxemia before and after pretreatment with L-651,392 and ex vivo from granulocytes and whole blood stimulated with calcium ionophore from sheep before and 24 h after pretreatment with L-651,392. A novel assay for LTB4 by high-performance liquid chromatography/gas chromatography/mass spectrometry techniques was developed as a measure of 5-lipoxygenase metabolism of arachidonic acid. L-651,392 proved to be an effective in vivo 5-lipoxygenase inhibitor in sheep. L-651,392 blocked the increase in LTB4 observed in lung lymph after endotoxemia in vivo in sheep as well as inhibited by 80% the ex vivo production of LTB4 by granulocytes removed from sheep treated 24 h earlier with L-651,392. Although L-651,392 blocked the increase in cyclooxygenase products of arachidonic acid observed in lung lymph after endotoxemia in vivo in sheep, the drug probably did not function directly as a cyclooxygenase inhibitor. L-651,392 did not attenuate the ex vivo production of thromboxane B2 by whole blood from sheep treated 24 h earlier with the drug. L-651,392 attenuated the alterations in pulmonary hemodynamics, lung mechanics, oxygenation, and lung fluid and solute exchange observed after endotoxemia in sheep. We speculate that 5-lipoxygenase products are a major stimulus for cyclooxygenase metabolism of arachidonic acid after endotoxemia in sheep.

Comparative study of the hydrodynamic function of the CarboMedics valve.

The hydrodynamic function of each size of the CarboMedics valve was assessed in a pulsatile flow simulator. The mean pressure difference with respect to forward flow, regurgitant volumes, and total energy loss across each valve were analyzed. The results for the 23-mm aortic and 29-mm mitral CarboMedics valves were compared with those for the St. Jude Medical and Björk-Shiley Monostrut valves. Results showed good hydrodynamic function for each CarboMedics valve, although the pressure difference and total energy loss across the 19-mm aortic valve was high. The hydrodynamic function of the CarboMedics valve was comparable with that of the St. Jude Medical valve. Both valves showed similar leakage volumes, which were significantly larger than that for the Björk-Shiley Monostrut valve. On account of this the total energy loss in the Björk-Shiley valve was significantly less than that for the bileaflet valves in the aortic position. Concern remains for the continuing presence of high closed-valve regurgitation in the bileaflet valves.

Geometry of homograft valve leaflets: effect of dilation of the aorta and the aortic root.

With the increasing interest in aortic homografts as either a free-sewn valve or whole-root replacement, the effect of internal pressure and dilation of the aorta and aortic root on valve leaflet geometry has been studied. Seven aortic homograft roots were studied, six that had been stored in antibiotics and one that had been cryopreserved. The diameter of the aorta was determined as a function of internal pressure and correlated with the stress-strain characteristics of the aortic wall. Three-dimensional leaflet surface geometry was measured in the "neutral" position, and the leaflet was characterized by its radius of curvature and angle of inclination, using a cylindrical model. The diameter of the aorta increased by between 30% and 50% as the dilation pressure increased from 0 to 120 mm Hg. This was consistent with the stress-strain data obtained from strips of the aortic wall in the circumferential direction. The angle of inclination of the leaflet increased from 20 to 80 degrees and the radius of curvature increased from 4 to 17 mm as the internal pressure increased from 0 to 80 mm Hg. The open leaflet configuration showed a triangular orifice with low bending strains for a dilated root, but increased bending strains with reduced dilation pressure. These are important considerations when implanting a free-sewn homograft into the aortic root.

Relation of regional fat distribution to insulin sensitivity in postmenopausal women.

OBJECTIVE: To examine the relation between insulin sensitivity and total and regional body fat in nonobese postmenopausal women. DESIGN: Cross-sectional study. SETTING: A clinical research center. PATIENT(S): Twenty-seven women in the early postmenopausal period, with a mean (+/-SD) age of 50.8 +/- 4.1 years, who had had their last menstrual period 6 months to 3 years before the study. None were taking hormone replacement therapy, and all had an FSH level of >35 mIU/mL, a body mass index of <30 kg/m2, and a waist circumference of <94 cm. INTERVENTION(S): Computed tomography scans at the L4-5 vertebral disk space, dual-photon x-ray absorptiometry scans, and euglycemic hyperinsulinemic clamps were performed. MAIN OUTCOME MEASURE(S): Intraabdominal fat, subcutaneous abdominal fat, sagittal diameter, total body fat, percent body fat, and insulin sensitivity. RESULT(S): The natural log of insulin sensitivity correlated significantly with intraabdominal fat (r = -.39), subcutaneous fat (r = -.43), and sagittal diameter (r = -.48). After adjusting for total fat, sagittal diameter remained significantly related to insulin sensitivity. CONCLUSION(S): Central abdominal fat is inversely and independently related to insulin sensitivity after adjusting for total fat in women in the early postmenopausal period. Efforts to reduce either subcutaneous abdominal fat or intraabdominal fat should be helpful in reducing the risk of noninsulin-dependent diabetes mellitus in postmenopausal women.

Victimization of women and its impact on assessment and treatment in the psychiatric emergency setting.

An understanding of victimization is critical to the practice of emergency psychiatry. Victimization histories are disturbingly common among women presenting to the PES, particularly among frequent service users. The sequelae of victimization are both psychological and physical and often impair health and functioning across numerous domains. PTSD, BPD, and substance-use disorders are often seen among women with victimization histories, which can be particularly challenging for PES providers. Screening for trauma on PES presentation or history should not be overlooked in any person, including severely mentally ill, homeless, disabled, or elderly women. PES clinicians should remember to ask about victimization and pose questions privately in a direct and an open-ended format while conveying empathic validation. Clinical assessment of women with victimization histories in the PES should be guided by the principles of standard emergency psychiatry and be informed by an understanding of trauma. This includes a working knowledge of trauma dynamics, adherence to sound professional boundaries, and care not to retraumatize patients or re-enact perpetrator-victim dynamics. Voyeurism and regression should be avoided, particularly when eliciting trauma history. The PES should be a place for screening and acute intervention, not for conducting intensive trauma therapy. In the PES, the focus should remain on triage and treatment priorities, those of safety and stabilization, and carefully evaluating for substance use and psychosis. The PES ideally provides a "holding environment" that affords a balance of nurturing, limits, consistency, and communication. A basic knowledge of cognitive-behavioral interventions affording "crisis survival strategies," such as DBT, can be particularly useful to PES clinicians. Clinicians also need to monitor issues of countertransference and the potential to be dismissive to these women with complex, comorbid, and chronic problems and diseases. The role for the use of psychotropic medication in PES cohorts with victimization histories should target acute symptoms. Involving regular providers of these decisions is advised to coordinate care and minimize splitting and risks of polypharmacy. Although the SSRIs are effective in symptom management of disorders related to victimization, patients must be reminded of the side-effect profile, particularly sexual dysfunction and withdrawal and discontinuation syndromes.

Olanzapine in the treatment of post-traumatic stress disorder: a pilot study.

Because the atypical antipsychotic olanzapine may be efficacious in treating post-traumatic stress disorder (PTSD) symptoms, we conducted a 10-week, double-blind, placebo-controlled evaluation in which 15 patients were randomized 2:1 to either olanzapine or placebo. The initial dosage was 5 mg/day and was titrated to a maximum of 20 mg/day. Eleven patients completed the study. Patients in both groups showed improvement in PTSD symptoms, but no between-group differences in treatment response were observed and a high placebo response rate was found. Both treatments were tolerated well, although the olanzapine treatment group had more weight gain. Olanzapine fared no better than placebo in this preliminary study in the treatment of PTSD. The lack of difference between olanzapine and placebo may in part be due to olanzapine's not being effective in PTSD or, alternatively, a small sample size, a high placebo response in certain forms of PTSD and the chronicity of PTSD symptoms in some patients.

Fatigue analysis of clinical bioprosthetic heart valves manufactured using photooxidized bovine pericardium.

BACKGROUND AND AIM OF THE STUDY: Recent reports have given details of early clinical failures of bioprosthetic heart valves manufactured using dye-mediated photooxidized bovine pericardium. These failures were attributed to abrasion of the inflow surface of the leaflets against the cloth-covered inner face of the outer valve frame. These failures had not been detected during preclinical testing of such valves. The aim of this study was to determine if such failure modes could be replicated during fatigue testing of the photooxidized valves, and whether lining of the inflow face of the outer frame with pericardium could eliminate these failures. METHODS: The fatigue properties of six lined and six unlined PhotoFix(R) alpha valves was determined using two Rowan Ash fatigue testers which were cycled at 15 Hz for a maximum of 210 million cycles. The closing pressure within in each chamber was 110+/-10 mm Hg. Each valve was inspected every 40 million cycles for any signs of fatigue failure. All valves were tested to at least 210 million cycles. RESULTS: In all six lined PhotoFix alpha valves there was no evidence that wear, tear or abrasion of the inflow aspect of the leaflets adjacent to the inflow face of the outer frame had occurred. Only one unlined valve showed any signs of damage adjacent to the outer frame, as evidenced by loss of loose connective tissue, but this did not have the imprint of the cloth covering, which would have suggested actual wear. Effectively, after 200 million cycles, no fatigue failures of either the lined or the unlined PhotoFix alpha valves had occurred. Moreover, the leaflet tears that had been observed clinically were not replicated in this study. CONCLUSION: Previous studies have shown a good qualitative, quantitative association between fatigue failure in Rowan Ash accelerated fatigue testers, and clinical experience in glutaraldehyde-treated bovine pericardial valves. The accelerated fatigue tester did not provide an adequate model for the prediction of clinical failure for the photooxidized pericardial valves.

A new design for polyurethane heart valves.

BACKGROUND AND AIM OF THE STUDY: The synthetic flexible tri-leaflet heart valve offers considerable potential for improvement in both hydrodynamic and biomechanical performance of replacement heart valves. To date, success with the synthetic leaflet heart valve has been limited, partly due to limitations in the biostability of the polyurethanes used. With the synthesis of new biostable polyurethanes, the integration of advancing technology, and better knowledge of the functional and biomechanical design requirements necessary to increase the long-term durability of the polyurethane heart valve, novel clinical solutions are now in sight. METHODS: This study describes the design characteristics, hydrodynamic and biomechanical performance of a new design of polyurethane heart valve. The function and durability characteristics of this novel design of heart valve, manufactured using a proven durable non-biostable polyurethane, was compared with that of a single AorTech porcine bioprosthetic heart valve and a single tilting disc mechanical heart valve, the Björk-Shiley Monostrut valve (BSM), of similar size. RESULTS: For equivalent sizes of valve, the new polyurethane heart valve design had significantly lower pressure gradients compared with the porcine valve at all flow rates and to the BSM valve at the higher flow rates. The effective orifice area of the polyurethane valve was greater than the other two valves studied; regurgitation and total energy loss were less. The new polyurethane valve design reached over 360 million cycles in an accelerated durability tester, without failure. CONCLUSION: This new design of polyurethane heart valve showed improved hydrodynamic function in comparison with either the porcine bioprosthetic or the BSM mechanical heart valve. The pulsatile flow results showed a lower total energy loss associated with this valve, indicating improved potential patient benefit. The durability of this new design of polyurethane heart valve was demonstrated when manufactured using a medical-grade polyurethane.

The influence of ventricular input impedance on the hydrodynamic performance of bioprosthetic aortic roots in vitro.

BACKGROUND AND AIM OF THE STUDY: Hydrodynamic function testing using pulsatile flow simulators provides a valuable means of comparative assessment of heart valves in vitro. The majority of pulsatile flow simulators consist of modular rigid chambers and a positive displacement pump with an infinite input impedance, in which the inertia of the test fluid results in pressure oscillations when the valves under test are opening and closing. For mechanical and stented bioprosthetic valves these pressure oscillations decay quickly. However, due to the highly compliant nature of tissue roots, the resulting pressure and flow oscillations are extreme and extend throughout systole. With increasing interest in the use of free-sewn roots and valves it is most desirable to improve this hydrodynamic model. The aim of this study was to investigate the influence in changes in ventricular input impedance on the hydrodynamic characteristics of free-sewn aortic roots and stented valves. METHODS: The Leeds pulsatile flow simulator was modified to incorporate additional compliance chambers in the form of a viscoelastic impedance adaptor (VIA) at the pump/ventricular interface. Six 23 mm bioprosthetic aortic roots fixed with 0.5% buffered glutaraldehyde at zero pressure, and a size 23 mm stented porcine aortic bioprosthesis were tested in this modified simulator, at the conditions of maximum and minimum input compliance. RESULTS: The pressure and flow waveforms for the fixed aortic roots showed considerable differences at the conditions of maximum and minimum input compliance. Indeed, the extreme pressure oscillations observed at minimum compliance (infinite input impedance) were not present at maximum compliance, and the forward flow waveform was much smoother. In contrast, for the stented valve, the differences in the pressure and flow waveforms between maximum and minimum input compliance were minimal, but this was expected due to the lack of compliance in the stented valve itself. In addition, the flow and pressure waveforms at maximum compliance in the VIA were comparable for the fixed aortic roots and the stented bioprosthesis, thus allowing direct comparison of the characteristics of these two different devices. Using test conditions of maximum input compliance, effective orifice area for the roots was 1.69 cm2 compared with 1.47 cm2 for the stented valve. CONCLUSION: An appropriate physiological model for the hydrodynamic testing of compliant tissue roots has been established.

Leaflet geometry and function in porcine bioprostheses.

The leaflet geometry and hydrodynamic function of five porcine bioprostheses have been studied and compared to a fresh tissue porcine valve. The neutral leaflet geometries in two high pressure fixed valves (Carpentier Edwards and Hancock) and two low pressure fixed valves (Carpentier Edwards Supra-Annular and Hancock 2) had been modified during fixation and mounting. The leaflets were extended or displaced downwards towards the base of the valve, producing a higher ratio of circumferential leaflet length to inter-commissural spacing than in the fresh tissue valve. This produced high bending strains in the commissural area of the open leaflet in hydrodynamic tests. The leaflet geometry of the fresh tissue porcine valve studied was defined by a cylindrical shell inclined at approximately 27 degrees to the base of the valve and showed reduced open leaflet bending strains. Leaflet opening at low flows was dependent on leaflet geometry. Geometrical changes which are induced during mounting and fixation produced higher bending strains in the commissural area of the open leaflets. These may be contributing factors to tissue degeneration and calcification in this area.

Carbomedics and St. Jude Medical bileaflet valves: an in vitro and in vivo comparison.

The hydrodynamic and haemodynamic function of 29 mm mitral and 23 mm aortic St Jude Medical (SJM) and CarboMedics (CM) heart valves have been compared in a pulsatile flow simulator in the laboratory and by doppler ultrasound in vivo. The laboratory studies showed that there was no significant difference in the pressure drop across the valves. The valves also had similar regurgitant volumes. Doppler ultrasound confirmed these results with a mean pressure drop of 12.9 +/- 5.5 mmHg across the CM aortic valves and 12.6 +/- 5.5 mmHg for the SJM aortic valves. The mean mitral diastolic pressure drops were 3.8 +/- 1.8 and 4.6 +/- 1.4 mmHg for the CM and SJM valves, respectively. Mild aortic regurgitation was detected in 5 of 14 patients in the CM group and 1 out of 6 patients in the SJM group, though none of the cases were clinically significant. Both the in vitro and in vivo results show these valves to have acceptable and comparable function.

The hydrodynamic function and leaflet dynamics of aortic and pulmonary roots and valves: an in vitro study.

Fresh homograft aortic and pulmonary roots were tested in a pulsatile flow simulator to assess their hydrodynamic function and leaflet opening characteristics. Simultaneous flow and pressure measurements were obtained for a range of cardiac outputs. The effective orifice area and regurgitant volumes were calculated. The mean pressure difference across the pulmonary roots was obtained under both left and right side pressures. A video recording of valve leaflet function was also obtained for each valve. A comparison was made with four porcine bioprosthetic heart valves (21 and 23 mm). The mean pressure difference with respect to flow for the 21 mm Hancock II and Intact porcine bioprostheses was significantly higher than that for all aortic roots tested. The 24 mm aortic root showed significantly lower pressure drop compared to all porcine valves tested. The mean pressure difference across each pulmonary root at pulmonary pressures was significantly greater than at systemic pressures. At systemic pressures the fully open leaflets had a triangular orifice with low leaflet open bending strains at the commissures. At the lower internal pressures, with reduced dilation of the root, higher bending strains were noted. These were not as severe as seen in porcine valves.

The relationship between self-rated health and health care service use among women veterans in a primary care clinic.

This study examined whether self-rated health predicted health service use among women in an equal access primary care clinic setting. Women veterans (n = 139), 23-76 years of age were administered the PRIME-MD questionnaire at their outpatient clinic (OPC) visit which included a self-rated health item and assessment of symptoms. Number of prospective OPC visits was the outcome variable. Women who had poor/fair health were significantly more likely (OR = 3.25) to have more (>12) OPC visits than women who reported excellent/very good health. We conclude that poor perception of one's health is an important predictor of health care use among women veterans.

Racial variation in wanting and obtaining mental health services among women veterans in a primary care clinic.

Epidemiologic studies suggest that African-American women may be less likely to obtain mental health services. Racial differences were explored in wanting and obtaining mental health services among women in an equal access primary care clinic setting after adjusting for demographics, mental disorder symptoms, and a history of sexual trauma. Participating in the study were women veterans at a primary care clinic at the Durham Veterans Affairs Medical Center. Consecutive women patients (n = 526) between the ages of 20 and 49 years were screened for a desire to obtain mental health services. Patients were given the Primary Care Evaluation of Mental Disorders questionnaire (PRIME-MD) and a sexual trauma questionnaire. Mental health service utilization was monitored for 12 months. The median age of the women was 35.8 years; 54.4% of them were African-American. African-American women expressed a greater desire for mental health services than whites, yet mental health resources at the clinic were similarly used by both racial groups. African-American women may want more mental health services; however, given an equal access system, there were no racial differences in mental health use.