Cervical spine clearance in blunt trauma: evaluation of a computed tomography-based protocol.

BACKGROUND: Prompt identification of cervical spine injuries has been a critical issue in trauma management. In 1998, the authors developed a new protocol to evaluate cervical spines in blunt trauma. This protocol relies on clinical clearance for appropriate patients and helical computed tomography instead of plain radiographs for patients who cannot be clinically cleared. The authors then prospectively collected data on all cervical spine evaluations to assess the sensitivity and specificity of their approach. METHODS: Any patient without clinical evidence of neurologic injury, alcohol or drug intoxication, or distracting injury underwent cervical spine evaluation by clinical examination. Patients who did not meet these criteria underwent helical computed tomographic scanning of the entire cervical spine. For patients who had neurologic deficits, a magnetic resonance image was obtained. If the patient was not evaluable secondary to coma, the computed tomographic scan was without abnormality, and the patient was moving all four extremities at arrival in the emergency department, the cervical spine was cleared, and spinal precautions were removed. Data were collected for all patients admitted to Santa Barbara Cottage Hospital trauma service between 1999 and 2002. The authors selected for analysis patients with blunt trauma and further identified those with closed head injuries (Glasgow Coma Scale score < 15 and loss of consciousness). In addition, all blunt cervical spine injuries were reviewed. RESULTS: During the period of study, 2,854 trauma patients were admitted, of whom 2,603 (91%) had blunt trauma. Of these, 1,462 (56%) had closed head injuries. One hundred patients (7% of patients admitted for blunt trauma) had cervical spine or spinal cord injuries, of which 99 were identified by the authors' protocol. Only one injury was not appreciated in a patient with syringomyelia. Fifteen percent of patients with spinal cord injury had no radiographic abnormality; all of these patients presented with neurologic deficits. The sensitivity for detecting cervical spine injury was thus 99%, and the specificity was 100%. The risk of missing a cervical spine injury in these blunt trauma patients was 0.04%. The authors missed no spine injuries in patients with head injuries. CONCLUSION: The use of the authors' protocol resulted in excellent sensitivity and specificity in detecting cervical spine injuries. In addition, it allowed early removal of spinal precautions.

Magnetic resonance imaging is not needed to clear cervical spines in blunt trauma patients with normal computed tomographic results and no motor deficits.

HYPOTHESIS: Trauma patients with normal motor examination results and normal cervical spine helical computed tomographic (CT) scans with sagittal reconstructions do not have significant cervical spine injury. DESIGN: Prospectively collected registry data. SETTING: Level II community-based trauma center. PATIENTS: All patients admitted to the trauma service from January 1, 1999, to December 31, 2003. MAIN OUTCOME MEASURES: Injury detected by CT and/or magnetic resonance imaging (MRI) of the cervical spine. Neurologic examination and need for surgery were secondary outcomes. RESULTS: During the study period, 2854 trauma patients were admitted, of whom 91.2% had blunt trauma. Of these patients, 56.2% had a closed head injury. One hundred patients had cervical spine and/or spinal cord injuries. Eighty-five patients had a cervical spine injury diagnosed by CT. Fifteen patients had admission neurologic deficits not seen on CT, and 7 of these patients had non-bony abnormalities on MRI. Ninety-three patients had a normal admission motor examination result, a CT result negative for trauma, and persistent cervical spine pain, and were examined with MRI. All MRI examination results were negative for clinically significant injury. Seventeen patients had MRIs that showed degenerative disc disease, and 6 had spinal canal stenosis secondary to ossification. Twelve comatose patients (Glasgow Coma Scale score, <9), moving all 4 extremities on arrival, with normal CT results of the cervical spine, were examined with MRI. All of these MRI examination results were negative for injury. None of the patients experienced neurologic deterioration. No patient required operative management of spinal injury. CONCLUSION: Blunt trauma patients with normal motor examination results and normal CT results of the cervical spine do not require further radiologic examination before clearing the cervical spine.

Synthesis of 1,7-annulated indoles and their applications in the studies of cyclin dependent kinase inhibitors.

The synthesis of a novel series of 1,7-annulated indolocarbazoles 2 and 16 is described. These compounds were found to be potent cyclin dependent kinase inhibitors with good antiproliferative activity against two human carcinoma cell lines. These inhibitors also arrested tumor cells at the G1 phase and inhibited pRb phosphorylation.

Novel, potent and selective cyclin D1/CDK4 inhibitors: indolo[6,7-a]pyrrolo[3,4-c]carbazoles.

The synthesis and CDK inhibitory properties of a series of indolo[6,7-a]pyrrolo[3,4-c]carbazoles is reported. In addition to their potent CDK activity, the compounds display antiproliferative activity against two human cancer cell lines. These inhibitors also effect strong G1 arrest in these cell lines and inhibit Rb phosphorylation at Ser780 consistent with inhibition of cyclin D1/CDK4.

Synthesis, structure-activity relationship, and biological studies of indolocarbazoles as potent cyclin D1-CDK4 inhibitors.

Novel substituted indolocarbazoles were synthesized, and their kinase inhibitory capability was evaluated in vitro. 6-Substituted indolocarbazoles 4 were found to be potent and selective D1/CDK4 inhibitors. 4d and 4h exhibited potent and ATP-competitive D1/CDK4 activities with IC50 values of 76 and 42 nM, respectively. Both compounds had high selectivity against the other kinases. These D1/CDK4 inhibitors inhibited tumor cell growth, arrested tumor cells at the G1 phase, and inhibited pRb phosphorylation.

Synthesis of quinolinyl/isoquinolinyl[a]pyrrolo [3,4-c] carbazoles as cyclin D1/CDK4 inhibitors.

A novel series of pyrrolo[3,4-c] carbazoles fused with a quinolinyl/isoquinolinyl moiety were synthesized and their D1/CDK4 inhibitory and antiproliferative activity were evaluated. Compound 8H, 14H-isoquinolinyl[6,5-a]-pyrrolo[3,4-c]carbazole-7,9-dione (1d) was found to be a highly potent D1/CDK4 inhibitor with an IC(50) of 69 nM. Compound 1d also inhibited tumor cell growth, arrested tumor cells in G1 phase and inhibited pRb phosphorylation.

Synthesis and evaluation of potent pyrrolidine H(3) antagonists.

The synthesis and biological evaluation of novel antagonists of the rat H(3) receptor are described. These compounds differ from prototypical H(3) antagonists in that they do not contain an imidazole moiety, but rather a substituted aminopyrrolidine moiety. A systematic modification of the substituents on the aminopyrrolidine ring was performed using pre-formatted precursor sets, where applicable, to afford several compounds with high affinity and selectivity for the H(3) receptor.

Aminoalkoxybiphenylnitriles as histamine-3 receptor ligands.

Biaryl nitrile amines were prepared and found to have high affinity and selectivity for human and rat histamine H(3) receptors.