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Background Pulmonary embolism (PE) remains a significant cause of mortality in Europe1. Thrombolytic therapy is often utilised as a therapeutic strategy in massive and sub-massive PE. There is a dearth of research on short term complications and subsequent outcomes in patients who have received thrombolysis for PE in Ireland. Methods This retrospective study examined patients who underwent thrombolysis for acute sub massive PE whilst under the care of the respiratory service in Cork University Hospital (CUH) from 2010-2018. All patients had CTPA done for diagnosis of PE. Alteplase was used as a thrombolytic agent. Patient records were perused. Follow-up pulmonary functions tests (PFTs) and trans-thoracic echocardiogram (TTE) results were assessed for evidence of impairment of diffusing capacity (DLCO) and pulmonary hypertension (PH) respectively. Results Twenty five patients were included in the study. Nine patients (36%) were women and 64% men. Average age was 55.1 years. Four patients suffered complications related to thrombolysis (average age 63.3 years). Twenty-Two patients (88%) underwent a follow-up echocardiography (mean 30 weeks post PE). Three patients (13%) had echocardiographic evidence of possible mild PH (i.e. RVSP40mmhg) at initial follow-up. Fourteen patients (56%) who underwent thrombolysis had follow-up PFTs (mean 11.8 months post PE). The diffusing capacity (DLCO) was normal in all patients. Conclusion Thrombolysis was a relatively safe intervention in this small study.

Background: Pulmonary embolism (PE) remains a significant cause of mortality in Europe1. Thrombolytic therapy is often utilised as a therapeutic strategy in massive and sub-massive PE. There is a dearth of research on short term complications and subsequent outcomes in patients who have received thrombolysis for PE in Ireland. Methods: This retrospective study examined patients who underwent thrombolysis for acute sub massive PE whilst under the care of the respiratory service in Cork University Hospital (CUH) from 2010-2018. All patients had CTPA done for diagnosis of PE. Alteplase was used as a thrombolytic agent. Patient records were perused. Follow-up pulmonary functions tests (PFTs) and trans-thoracic echocardiogram (TTE) results were assessed for evidence of impairment of diffusing capacity (DLCO) and pulmonary hypertension (PH) respectively. Results: Twenty five patients were included in the study. Nine patients (36%) were women and 64% men. Average age was 55.1 years. Four patients suffered complications related to thrombolysis (average age 63.3 years). Twenty-Two patients (88%) underwent a follow-up echocardiography (mean 30 weeks post PE). Three patients (13%) had echocardiographic evidence of possible mild PH (i.e. RVSP >40mmhg) at initial follow-up. Fourteen patients (56%) who underwent thrombolysis had follow-up PFTs (mean 11.8 months post PE). The diffusing capacity (DLCO) was normal in all patients. Conclusion: Thrombolysis was a relatively safe intervention in this small study.

Blunt trauma causing cardiac rupture is usually fatal. We report a patient with blunt cardiac injury that suffered traumatic cardiac arrest in the pre-hospital phase of their care. A cardiac tamponade was confirmed with portable ultrasound in a brief return of circulation. The patient had a further cardiac arrest and subsequently underwent damage control emergency surgery via a clamshell thoracotomy at the scene. The tamponade was released and a clamp was applied to the identified left atrial appendage rupture, a return of circulation then occurred. He was transferred to a cardiothoracic centre where a left atrial appendage rupture was identified and closed. The patient had a complicated recovery in hospital but went on to survive neurologically intact. This is the first documented case report of a neurologically intact survivor of a pre-hospital clamshell thoracotomy for blunt trauma. Although survivors of blunt trauma who have pre-hospital thoracotomy are extremely rare it should be considered in very specific circumstances.

Atrial fibrillation can be managed with anticoagulation and restoration of normal sinus rhythm using direct current cardioversion (DCCV). To reduce the risk of thromboembolism anticoagulation pre-and-post DCCV is recommended. This study investigates the cost effectiveness of using NOACs compared to warfarin to attain therapeutic anticoagulation amongst AF patients pre-and-post DCCV. Propensity score matching revealed no statistically significant difference in outcomes from using NOACs and Warfarin. A cost minimisation study was performed; demonstrating a cost differential of €209 between those administered NOACs and warfarin pre and post DCCV. This study demonstrates how using NOACs compared to warfarin to attain therapeutic anticoagulation amongst AF patients preand-post DCCV is cost effective.

To further develop a multiple stimulus method for the rapid acquisition of auditory brainstem responses (ABRs), a 56-stimulus train was tested in mice. Stimuli in the train were tone bursts spaced at 0.5-octave intervals from 4 to 32 kHz. ABR thresholds, latency-intensity and amplitude-intensity functions were obtained using stimuli presented singly (one at a time) and using the 56-stimulus train. Responses from stimuli presented singly and those obtained using the 56-stimulus train were compared. There were no significant differences in thresholds (0.01 level) and very small differences in response latencies and amplitudes. These findings demonstrate the feasibility of multiple stimulus trains for the rapid acquisition of ABRs.

Although mice of the C3H strain normally respond to bacterial lipopolysaccharide with appropriate immune system activation, mice of the C3H/HeJ substrain do not because of a gene defect. This suggests they may be more susceptible to opportunistic bacterial infections and more likely to have otitis media than a normally responding substrain, such as the C3H/HeSnJ. Therefore these two substrains were evaluated for incidence of spontaneous middle ear disease at 2, 4, 6, 10, 12, 15, and 18 months of age. Auditory brain stem response audiometry to pure tones of 4, 8, 16, 24, and 32 kHz was performed to establish the impact of middle ear disease on auditory function. None of the lipopolysaccharide-responsive C3H/HeSnJ mice demonstrated middle ear disease. However, middle ear disease was present in 33% of the C3H/HeJ mice. The conductive loss caused by the otitis media resulted in auditory brain stem response threshold shifts of 15 to 40 dB SPL, lowered peak amplitudes, and increased latencies. Reduced lipopolysaccharide responsiveness by C3H/HeJ mice makes them less capable of reacting immunologically to bacterial infection and presumably underlies the failure to clear middle ear disease. The C3H/HeJ mouse may provide a valuable model in which to study lipopolysaccharide biologic activity and related middle ear inflammatory or immune mechanisms. (Otolaryngol Head Neck Surg 1997;117:459-64.)

Auditory brainstem response (ABR) thresholds, latency and amplitude functions were obtained in mice using stimuli presented singly and as a multiple stimulus sequence. All stimuli were tone-bursts at frequencies from 4 to 32 kHz. The multiple stimulus consisted of a sequence of 20 tone-bursts of four different frequencies at five intensities separated by 12 ms. A comparison of responses to stimuli presented singly and those obtained with the 20-stimulus train showed no significant difference in thresholds. Also, no differences were found in response latencies or amplitudes, indicating that the responses from multiple stimuli were not adapted or otherwise affected. The use of this 20-stimulus train can result in a significant time savings for data acquisition compared with single stimuli. These findings demonstrate the feasibility of the rapid acquisition of unadapted cochlear and brainstem responses at different frequencies using a sequence of tone-bursts at different frequencies and intensities.

The C3H inbred mouse strain arose in 1920 and includes several substrains, such as the C3H/HeJ and C3H/HeSnJ variants. However, use of these C3H mice in hearing research has been limited because their auditory function has not been described. Therefore, the purpose of this study was to characterize auditory function in two C3H representative substrains. C3H/HeJ and C3H/HeSnJ mice were obtained from Jackson Laboratories for auditory brainstem response (ABR) testing at ages from 2 to 30 months. Animals were tested with tone bursts at frequencies of 4, 8, 16, 24, and 32 kHz. These early responses were evaluated for age-related threshold shifts as an index of peripheral auditory function. Both strains show normal sensitivity up to 14 months of age. Thresholds for both strains were slightly elevated at most frequencies at 18 months. C3H/HeSnJ mice tested at 30 months demonstrated little hearing function due to extensive sensorineural degeneration. Thus, these C3H strains maintain excellent cochlear function past 1 year of age.

Effective objective testing methodology is needed for early detection of the effects of ototoxicity on hearing in patients. The requirements for such testing include responses that are: 1) reliable across test sessions; 2) sensitive to ototoxic change (8 kHz), and 3) recordable in a time-efficient manner. Auditory brainstem responses (ABR) appear well suited to this task however, conventional clicks stimulate primarily mid-frequencies (1-4 kHz) and high frequency tonebursts require too much time. We hypothesized that delivery of a band of high frequencies (a high frequency "click"), would elicit reliable and useful ABRs. In the current study, flat and sloped HF (high frequency) clicks with a bandwidth of 8-14 kHz were used. The purpose was to compare brainstem responses elicited by tonebursts, two HF clicks and conventional clicks. The results show that the reliability of responses to the HF clicks were comparable to the tonebursts and further, both HF clicks produced responses slightly larger than tonebursts.

OBJECTIVE—To assess prospectively the prognostic value of soluble cellular adhesion molecules (CAMs) in patients with unstable angina and non-Q wave myocardial infarction and to compare their prognostic accuracy with that of C reactive protein (CRP). DESIGN AND SETTING—Prospective observational study of patients presenting acutely with unstable angina and non-Q wave myocardial infarction to a single south Dublin hospital. METHODS—Patients with Braunwald IIIA unstable angina and non-Q wave myocardial infarction had serum samples taken at presentation before initiation of antithrombotic treatment and were followed for six months. The primary end point was the occurrence of major adverse cardiovascular events (recurrent unstable angina, non-fatal myocardial infarction, and cardiovascular death) at six months. Concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble endothelial selectin, and soluble platelet selectin were measured using an enzyme linked immunosorbent assay technique. CRP was measured with an immunophelometric assay. RESULTS—91 patients (73 men and 18 women, mean (SD) age 61 (11) years) were studied; 27 patients (30%) had major adverse cardiac events during the six months of follow up. Concentration of CRP were significantly raised in patients who had an ischaemic event (mean (SEM) 11.5 (6.4) mg/l v 5.4 (2.5) mg/l, p 3 mg/l and sVCAM-1 > 780 ng/ml for predicting future events was > 90%. There was no difference in concentrations of sICAM-1, soluble endothelin selectin, or soluble platelet selectin between event and non-event groups. CONCLUSION—Raised concentrations of sVCAM-1 and CRP are predictive of an increased risk of major adverse cardiovascular events six months after presentation with unstable angina and non-Q wave myocardial infarction. These findings suggest that the intensity of the vascular inflammatory process at the time of presentation is a determinant of clinical outcome in unstable coronary artery disease. Keywords: cell adhesion molecules; risk stratification; unstable angina

Heat shock protein 70 (HSP70) has been suggested as the putative cochlear antigen underlying a proposed autoimmune etiology in certain cases of Meniere's disease and idiopathic hearing loss. To determine if antibodies to this cellular protein are capable of altering cochlear function, BALB/c ( N =3) and CBA/J ( N =9) mice were inoculated with bovine HSP70 by intraperitoneal injections (10 μ g in saline) every 10 days for 7 or 10 months, respectively. An equal number of control mice were injected with PBS according to the same schedule. ABR thresholds at 4, 8, 16, and 32 kHz in the HSP70-inoculated mice did not change over the 10 month period and were similar to saline controls. Furthermore, serum immune complexes and antinuclear antibodies did not increase over the inoculation period. ELISA analysis demonstrated the mice created antibodies to the foreign HSP70, but these apparently caused no abnormalities in the auditory or immune systems. It was concluded that foreign HSP70 is antigenic and inoculation with it will raise antibodies, but these antibodies were neither immunopathogenic nor cochleopathic. Therefore, these findings do not support current theories that elevated anti-HSP70 antibodies are the underlying cause of hearing loss in patients with such antibodies present.

Although mice of the C3H strain normally respond to bacterial lipopolysaccharide with appropriate immune system activation, mice of the C3H/HeJ substrain do not because of a gene defect. This suggests they may be more susceptible to opportunistic bacterial infections and more likely to have otitis media than a normally responding substrain, such as the C3H/HeSnJ. Therefore these two substrains were evaluated for incidence of spontaneous middle ear disease at 2, 4, 6, 10, 12, 15, and 18 months of age. Auditory brain stem response audiometry to pure tones of 4, 8, 16, 24, and 32 kHz was performed to establish the impact of middle ear disease on auditory function. None of the lipopolysaccharide-responsive C3H/HeSnJ mice demonstrated middle ear disease. However, middle ear disease was present in 33% of the C3H/HeJ mice. The conductive loss caused by the otitis media resulted in auditory brain stem response threshold shifts of 15 to 40 dB SPL, lowered peak amplitudes, and increased latencies. Reduced lipopolysaccharide responsiveness by C3H/HeJ mice makes them less capable of reacting immunologically to bacterial infection and presumably underlies the failure to clear middle ear disease. The C3H/HeJ mouse may provide a valuable model in which to study lipopolysaccharide biologic activity and related middle ear inflammatory or immune mechanisms.

To better understand autoimmune-related inner ear disease, cochlear structure and function were evaluated in the C3H/lpr autoimmune strain mouse, a model for systemic lupus erythematosus. C3H/lpr mice were examined at ages from 2 to 12 months along with age-matched C3H/HeJ controls. Autoimmune disease onset occurred at 3-4 months of age as serum immune complexes, antinuclear antibodies, and spleen weights were significantly elevated. Auditory brainstem response (ABR) audiometry showed normal auditory thresholds in C3H/lpr mice at 4 months of age, but elevated thresholds by 6 months, particularly in the high frequencies. Examination of the cochleas revealed no apparent loss of hair cells or spiral ganglion neurons, even in those mice with 50 dB SPL threshold shifts. However, changes were observed in the stria vascularis, including edematous spaces, enlarged capillaries, and thickened vessel linings. These findings imply that cochlear dysfunction in the autoimmune disease mice is the result of stria vascularis pathology.

An auditory brainstem response method is described for evoking responses to 4 high-frequency (8, 10, 12 and 14 kHz) tonebursts in the same amount of time normally required to obtain responses to single tonebursts. Reliability of responses to high-frequency toneburst stimuli presented in the conventional manner (one at a time) has been previously documented. In the present study, high-frequency tonebursts were presented to 20 normal-hearing subjects singly and in a 4-stimulus sequence. The reliability of resulting responses did not differ significantly between single- and multiple-stimulus test conditions. It is concluded that this sequenced-stimulus concept could be developed for use in serial monitoring of individuals receiving ototoxic agents as well as being broadly applicable to clinical situations in which patients cannot or will not respond voluntarily.