Effects of L-histidine depletion and L-tyrosine/L-phenylalanine depletion on sensory and motor processes in healthy volunteers

Background and purpose:

Animal studies show that histamine plays a role in cognitive functioning and that histamine H₃-receptor antagonists, which increase histaminergic function through presynaptic receptors, improve cognitive performance in models of clinical cognitive deficits. In order to test such new drugs in humans, a model for cognitive impairments induced by low histaminergic functions would be useful. Studies with histamine H₁-receptor antagonists have shown limitations as a model. Here we evaluated whether depletion of L-histidine, the precursor of histamine, was effective in altering measures associated with histamine in humans and the behavioural and electrophysiological (event-related-potentials) effects.

Experimental approach:

Seventeen healthy volunteers completed a three-way, double-blind, crossover study with L-histidine depletion, L-tyrosine/L-phenylalanine depletion (active control) and placebo as treatments. Interactions with task manipulations in a choice reaction time task were studied. Task demands were increased using visual stimulus degradation and increased response complexity. In addition, subjective and objective measures of sedation and critical tracking task performance were assessed.

Key results:

Measures of sedation and critical tracking task performance were not affected by treatment. L-histidine depletion was effective and enlarged the effect of response complexity as measured with the response-locked lateralized readiness potential onset latency.

Conclusions and implications:

L-histidine depletion affected response- but not stimulus-related processes, in contrast to the effects of H₁-receptor antagonists which were previously found to affect primarily stimulus-related processes. L-histidine depletion is promising as a model for histamine-based cognitive impairment. However, these effects need to be confirmed by further studies.     

Comparison of inhibitors of superoxide generation in vascular smooth muscle cells

Background and purpose:

We compared the dose-dependent reductions in cellular superoxide anion (O₂⁻) by catalytic agents: superoxide dismutase (SOD), polyethylene glycol (PEG)-SOD and the nitroxide 4-hydroxy-2,2,6,6,-tetramethylpiperidine-1-oxyl (tempol) with uncharacterized antioxidants: 5,10,15,20-tetrakis (4-sulphonatophenyl) porphyrinate iron (III)(Fe-TTPS), (-)-cis-3,3′,4′,5,7-pentahydroxyflavane (2R,3R)-2-(3,4-dihydroxyphenyl)-3,4-dihydro-1(2H)-benzopyran-3,5,7-triol (-epicatechin), 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen) and N-acetyl-L-cysteine (NAC) with the spin trap nitroblue tetrazolium (NBT) and with the vitamins or their analogues: ascorbate, α-tocopherol and 6-hydroxy-2,5,7,8-tetramethylkroman-2-carboxy acid (trolox).

Experimental approach:

O₂⁻ was generated in primary cultures of angiotensin II-stimulated preglomerular vascular smooth muscle cells from spontaneously hypertensive rats and detected by lucigenin-enhanced chemiluminescence.

Key results:

SOD, PEG-SOD, NAC and tempol produced a similar maximum inhibition of O₂⁻ of 80–90%. -Epicatechin, NBT, ebselen and Fe-TTPS were significantly (P < 0.0125) less effective (50–70%), whereas trolox, α-tocopherol and ascorbate had little action even over 24 h of incubation (<31%). Effectiveness in disrupted and intact cells was similar for the permeable agents, PEG-SOD and tempol, but was enhanced for SOD. Generation of O₂⁻ was increased by NAC and NBT at low concentrations but reduced at high concentrations.

Conclusions and implications:

Maximum effectiveness against cellular production of O₂⁻ requires cell membrane permeability and catalytic action as exemplified by PEG-SOD or tempol. NAC and NBT have biphasic effects on O₂⁻ production. Vitamins C and E or analogues have low efficacy.     

Prevalence of psychiatric disorders among Toronto hospital workers one to two years after the SARS outbreak

OBJECTIVE: This study aimed to determine the incidence of psychiatric disorders among health care workers in Toronto in the one- to two-year period after the 2003 outbreak of severe acute respiratory syndrome (SARS) and to test predicted risk factors. METHODS: New-onset episodes of psychiatric disorders were assessed among 139 health care workers by using the Structured Clinical Interview for DSM-IV and the Clinician-Administered PTSD Scale. Past history of psychiatric illness, years of health care experience, and the perception of adequate training and support were tested as predictors of the incidence of new-onset episodes of psychiatric disorders after the SARS outbreak. RESULTS: The lifetime prevalence of any depressive, anxiety, or substance use diagnosis was 30%. Only one health care worker who identified the SARS experience as a traumatic event was diagnosed as having PTSD. New episodes of psychiatric disorders occurred among seven health care workers (5%). New episodes of psychiatric disorders were directly associated with a history of having a psychiatric disorder before the SARS outbreak (p=.02) and inversely associated with years of health care experience (p=.03) and the perceived adequacy of training and support (p=.03). CONCLUSIONS: Incidence of new episodes of psychiatric disorders after the SARS outbreak were similar to or lower than community incidence rates, which may indicate the resilience of health care workers who continued to work in hospitals one to two years after the SARS outbreak. In preparation for future events, such as pandemic influenza, training and support may bolster the resilience of health care workers who are at higher risk by virtue of their psychiatric history and fewer years of health care experience.     

Effect of catheter placement on 3-D velocity profiles in curved tubes resembling the human coronary system.

Novel measurement techniques based on intravenous ultrasound (IVUS) technology ('IVUS-Flowmetry') require the location of a catheter inside the coronary bed. The present study quantifies disturbances in the 3-D velocity profile induced by catheter placement inside a tube, applying computational fluid dynamics. Two curved, circular meshes (radius K = 0.025 m and K = 0.035 m) with and without a catheter inside the lumen were applied. The catheter was located at the inner curve, the outer curve and at the top position. Boundary conditions were: no slip on the wall, zero stress at the outlet, uniform inflow with entrance velocities of 0.1, 0.2 and 0.4 m/s. Curvature-associated centrifugal forces shifted the maximal velocity to the outer curve and introduced two symmetrical vortices. Additional catheter placement redistributed the 3-D axial velocity field away from the catheter, which was accompanied by the appearance of multiple low-strength vortices. In addition, peak axial velocity increased, peak secondary velocities decreased, axial pressure drop increased and shear stress increased. Flow calculations simulated to resemble IVUS-based flowmetry changed by only 1% after considering secondary velocity. In conclusion, placement of a catheter inside a curved tube resembling the human coronary system changes the velocity field and reduces secondary patterns. The present study supports the usefulness of catheter-based flowmetry during resting flow conditions. During hyperemic flow conditions, flow measurements might be accompanied by large axial pressure drops because the catheter, itself, might act as a significant stenosis.     

Reducing Diagnostic Errors in Musculoskeletal Trauma by Reviewing Non-Admission Orthopaedic Referrals in the Next-Day Trauma Meeting

INTRODUCTION

Diagnostic errors in orthopaedics are usually caused by missing a fracture or misreading radiographs. The aim of this study was to document the pick-up rate of the wrong diagnoses by reviewing X-rays and casualty notes in the next-day trauma meeting.

PATIENTS AND METHODS

The casualty notes and radiographs of 503 patients were prospectively reviewed in the daily trauma meeting between August 2002 and December 2002 in a district general hospital. The relevant data were collected and analysed by a single assessor.

RESULTS

The false positive rate for making an orthopaedic diagnosis was 12.6% (i.e.) diagnosing a fracture, when none existed). The false negative (missing) rate was 4%, while 2.4% incidental findings were missed, or at least not documented, after reading the X-rays. There were 7.8% wrong diagnoses made. The majority of the patients were seen by the senior house officers.

CONCLUSIONS

The medicolegal significance of false negative diagnosis is obviously greater. In a busy emergency department, where a large number of patients are seen, there is a greater risk. This study shows the importance in a small-to-medium sized accident and emergency unit as well, where there is no senior cover available out-of-hours for final radiological interpretation. A morning trauma meeting which covers reviewing admitted patients as well as non-admission orthopaedic referrals has an effective risk management solution to early detection of missed and wrong diagnoses.     

性腺切除及急性饥饿对大鼠垂体-甲状腺功能的影响

本实验采用性腺摘除或经假摘除手术的两性SD大鼠,其中部分动物分别予以睾酮(T)或雌二醇(E_2),观察它们在急性饥饿或非饥饿状态下血清T_4、TSH与T浓度变化。结果提示急性饥饿可使雄鼠甲状腺合成或分泌T_4和性腺分泌睾酮减少,从而不完全地抑制了雄激素所介导的对垂体TSH分泌的兴奋作用。外源性T替代虽然可以使去势雄鼠血清T浓度恢复正常,但却无兴奋TSH分泌的作用;饥饿组去势雄鼠接受外源性T后血清TSH更为减少。提示外源性T可抑制此组雄鼠垂体TSH合成及(或)释放。     

A clinically integrated curriculum in Evidence-based Medicine for just-in-time learning through on-the-job training: The EU-EBM project

Background

Little research has been conducted to investigate role stress experienced by faculty members in medical schools in developing countries. This becomes even more important when the process of reform in medical education has already taken place, such as the case of Iran. The objectives of this study were to investigate and assess the level and source of role-related stress as well as dimensions of conflict among the faculty members of Iranian medical schools. Variables like the length of academic work, academic rank, employment position, and the departments of affiliation were also taken into consideration in order to determine potentially related factors.

Methods

A survey was conducted at three different ranks of public medical schools. The validated Organizational Role Stress Scale was used to investigate the level of role stress and dimensions of role conflict among medical faculty members. The response rate was 66.5%.

Results

The findings show that role stress was experienced in high level among almost all faculty members. All three studied medical schools with different ranks are threatened with relatively the same levels of role stress. Specific differences were found among faculty members from different disciplines, and academic ranks. Also having permanent position and the length of services had significant correlation with the level of role stress. The major role- related stress and forms of conflict among faculty members were role overload, role expectation conflict, inter-role distance, resource inadequacy, role stagnation, and role isolation.

Conclusion

The most role-related stressors and forms of conflict among faculty members include too many tasks and everyday work load; conflicting demands from colleagues and superiors; incompatible demands from their different personal and organizational roles; inadequate resources for appropriate performance; insufficient competency to meet the demands of their role; inadequate autonomy to make decision on different tasks; and a feeling of underutilization. The findings of this study can assist administrators and policy makers to provide an attractive working climate in order to decrease side effects and consequences of role stress and to increase productivity of faculty members. Furthermore, understanding this situation can help to develop coping strategies in order to reduce role-related stress.