Successful diagnosis of penetrating cardiac injury using surgeon-performed sonography

BACKGROUND: Patients with penetrating cardiac injuries have a high mortality. The utilization of sonography in these patients may lead to earlier diagnosis and definitive surgical intervention. METHODS: A retrospective review of all patients admitted to a level I trauma center were examined from March 1996 to March 2001 (17,241 patients). Patients were identified with penetrating thoracic injuries and were evaluated for mechanism of injury, sonographic findings (subxiphoid and parasternal windows), injury severity score, length of stay, and mortality. Surgeons performed all sonography. RESULTS: There were 478 patients who underwent sonography for penetrating thoracic injuries. Twenty-three patients were identified with positive sonographic findings. Subsequently 20 patients had a cardiac injury at surgery. There were no missed injuries. The 3 patients with false positive findings had congestive heart failure (2 patients) and morbid obesity (1 patient). Mean time to operation was 13 minutes. Mean injury severity score was 33. Mean intensive care unit and hospital stay was 3.1 days and 7.2 days respectively. Sonography had a specificity of 99.3% and sensitivity of 100% for identifying penetrating cardiac injury and a positive predictive value of 87% and negative predictive value of 100%. There were no hospital deaths. CONCLUSIONS: Early diagnosis and management using surgeon performed sonography may reduce the high mortality associated with penetrating cardiac injury.     

Enhanced β2-adrenergic receptor (β2AR) signaling by adeno-associated viral (AAV)-mediated gene transfer

Background

The concept of spontaneous- or constitutive-activity has become widely accepted and verified for numerous G protein-coupled receptors and this ligand-independent activity is also acknowledged to play a role in some pathologies. Constitutive activity has been reported for the mu opioid receptor. In some cases the increase in receptor basal activity was induced by chronic morphine administration suggesting that constitutive activity may contribute to the development of drug tolerance and dependence. Constitutively active mutants represent excellent tools for gathering information about the mechanisms of receptor activation and the possible physiological relevance of spontaneous receptor activity. The high basal level of activity of these mutants also allows for easier identification of inverse agonists, defined as ligands able to suppress spontaneous receptor activity, and leads to a better comprehension of their modulatory effects as well as possible in vivo use.

Results

Cysteines 348 and 353 of the human mu opioid receptor (hMOR) were mutated into alanines and Ala^348,353 hMOR was stably expressed in HEK 293 cells. [³⁵S] GTPγS binding experiments revealed that Ala^348,353 hMOR basal activity was significantly higher when compared to hMOR, suggesting that the mutant receptor is constitutively active. [³⁵S] GTPγS binding was decreased by cyprodime or CTOP indicating that both ligands have inverse agonist properties. All tested agonists exhibited binding affinities higher for Ala^348,353 hMOR than for hMOR, with the exception of endogenous opioid peptides. Antagonist affinity remained virtually unchanged except for CTOP and cyprodime that bound the double mutant with higher affinities. The agonists DAMGO and morphine showed enhanced potency for the Ala^348,353 hMOR receptor in [³⁵S] GTPγS experiments. Finally, pretreatment with the antagonists naloxone, cyprodime or CTOP significantly increased Ala^348,353 hMOR expression.

Conclusion

Taken together our data indicate that the double C348/353A mutation results in a constitutively active conformation of hMOR that is still activated by agonists. This is the first report of a stable CAM of hMOR with the potential to screen for inverse agonists.     

Evaluation of an educational program for long-term care nursing assistants

OBJECTIVES: To determine if an educational program can improve knowledge and attitude among ancillary staff on end-of-life care issues in a long-term care facility. DESIGN: A pilot study using a pre- and post-test design prior to and at the completion of an education intervention. SETTING: A long-term care facility in suburban Philadelphia that has 150 assisted living beds and 53 nursing home beds. PARTICIPANTS: Long-term care ancillary staff including certified nursing assistants (called "care managers" at this facility), social workers, recreational therapists, and food service workers. INTERVENTION: The intervention was a novel educational program consisting of five in-service lectures with accompanying take home self-study modules for ancillary staff in long-term care entitled "Dignity in Dementia." MEASUREMENTS: Ancillary staff attitudes and knowledge on end-of-life issues in dementia were assessed with a knowledge and attitude questionnaire pre- and post-intervention. One-year follow-up questionnaires were administered to assess long-term maintenance of knowledge and attitude changes. RESULTS: Thirty-two ancillary staff completed the pre-intervention questionnaires. Twenty-nine ancillary staff completed the post-intervention questionnaires (90.6%). There was a significant change in the end-of-life knowledge level of the ancillary staff (P =.0270). Specifically, there was a significant change in one question dealing with dementia as a terminal disease (P = .006). There were also significant changes in the average attitude scores of the ancillary staff. (P = .0242). One-year follow-up revealed that both knowledge and attitude changes were maintained. CONCLUSIONS: This pilot project demonstrates that a staff educational program on end-of-life care for dementia residents can improve end-of-life knowledge and attitudes among long-term care ancillary staff and that this improvement can be maintained for up to 1 year. This intervention is easily reproducible in the long-term care setting. This project is an important step in helping improve end-of-life care for dementia residents in long-term care settings by improving the knowledge and attitudes of their caregivers.     

Parental grieving after a child dies from cancer: is stress from stem cell transplant a factor?

AIM: to investigate psychological distress, family functioning and complicated grieving in parents whose child had died from cancer, and as a function of whether: (a) the deceased child had also received stem cell transplant (SCT) any time during curative treatment; and (b) the place of the child's death (home or hospital). DESIGN: a cross-sectional case-match design. SAMPLE: Fifty-six Australian bereaved parents in two groups: 28 whose child had also received SCT, matched with 28 (on deceased patient variables) whose child had not received SCT. RESULTS: parents in the 'SCT group' (n = 28) reported relatively higher levels of depression, anxiety and stress, and - for those whose child had also died in hospital - a greater likelihood of meeting the criteria for traumatic grief than those parents whose deceased child had not received SCT. There were no significant group differences in family functioning. CONCLUSION: routine psychosocial screening, especially for families undergoing SCT, may contribute usefully to a proactive model of palliative care in identifying parents at risk for complicated bereavement outcomes.     

Effects of early mobility on shortcut performance in a simulated maze

This experiment compared the shortcut choices of able-bodied teenagers with those of physically disabled teenagers who had varying histories of mobility impairment. In a computer-simulated kite-shaped maze, participants were allowed to explore three arms that connected four rooms. Subsequently they were offered a choice between paths connecting two rooms, one of which was a novel shortcut. Disabled teenagers chose correctly on fewer occasions than their able-bodied counterparts. Despite equivalent current levels of mobility, disabled participants whose mobility was more limited early in development were poorer at the task than those whose mobility had deteriorated with age. The results suggest that early independent exploration is important in the development of spatial knowledge, and suggest that the detrimental effects of limited early exploratory experience may persist into the teenage years.     

Responses and afferent pathways of superficial and deeper c(1)-c(2) spinal cells to intrapericardial algogenic chemicals in rats

Electrical stimulation of vagal afferents or cardiopulmonary sympathetic afferent fibers excites C(1)--C(2) spinal neurons. The purposes of this study were to compare the responses of superficial (depth <0.35 mm) and deeper C(1)--C(2) spinal neurons to noxious chemical stimulation of cardiac afferents and determine the relative contribution of vagal and sympathetic afferent pathways for transmission of noxious cardiac afferent input to C(1)--C(2) neurons. Extracellular potentials of single C(1)--C(2) neurons were recorded in pentobarbital anesthetized and paralyzed male rats. A catheter was placed in the pericardial sac to administer a mixture of algogenic chemicals (0.2 ml) that contained adenosine (10(-3) M), bradykinin, histamine, serotonin, and prostaglandin E(2) (10(-5) M each). Intrapericardial chemicals changed the activity of 20/106 (19%) C(1)--C(2) spinal neurons in the superficial laminae, whereas 76/147 (52%) deeper neurons responded to cardiac noxious input (P < 0.01). Of 96 neurons responsive to cardiac inputs, 48 (50%) were excited (E), 41 (43%) were inhibited (I), and 7 were excited/inhibited (E-I) by intrapericardial chemicals. E or I neurons responsive to intrapericardial chemicals were subdivided into two groups: short-lasting (SL) and long-lasting (LL) response patterns. In superficial gray matter, excitatory responses to cardiac inputs were more likely to be LL-E than SL-E neurons. Mechanical stimulation of the somatic field from the head, neck, and shoulder areas excited 85 of 95 (89%) C(1)--C(2) spinal neurons that responded to intrapericardial chemicals; 31 neurons were classified as wide dynamic range, 49 were high threshold, 5 responded only to joint movement, and no neuron was classified as low threshold. For superficial neurons, 53% had small somatic fields and 21% had bilateral fields. In contrast, 31% of the deeper neurons had small somatic fields and 46% had bilateral fields. Ipsilateral cervical vagotomy interrupted cardiac noxious input to 8/30 (6 E, 2 I) neurons; sequential transection of the contralateral cervical vagus nerve (bilateral vagotomy) eliminated the responses to intrapericardial chemicals in 4/22 (3 E, 1 I) neurons. Spinal transection at C(6)--C(7) segments to interrupt effects of sympathetic afferent input abolished responses to cardiac input in 10/10 (7 E, 3 I) neurons that still responded after bilateral vagotomy. Results of this study support the concept that C(1)-C(2) superficial and deeper spinal neurons play a role in integrating cardiac noxious inputs that travel in both the cervical vagal and/or thoracic sympathetic afferent nerves.