Life and Environmental Sciences

We present a case of apparent convincing bilateral hilar lymphadenopathy on a chest radiograph, which on further investigation was found to be allergic bronchopulmonary aspergillosis with symmetrical bilateral apical lower lobe infiltrates. This case ...

OBJECTIVETo examine the tissue expression of DNA topoisomerase I (Topo I) and IIα (Topo II), to pursue the possibility of future chemotherapy regimens for squamous cell carcinoma of the penis (SCCP), as high expression of Topo I might indicate sensitivity to the camptothecins, whereas high Topo II might indicate sensitivity to etoposide.To examine the tissue expression of DNA topoisomerase I (Topo I) and IIα (Topo II), to pursue the possibility of future chemotherapy regimens for squamous cell carcinoma of the penis (SCCP), as high expression of Topo I might indicate sensitivity to the camptothecins, whereas high Topo II might indicate sensitivity to etoposide.PATIENTS AND METHODSIn all, 73 patients with SCCP were reviewed and then tissue samples microarrayed. These were then stained with immunohistochemistry for Topo I, Topo II and Ki-67. Tumour stage, grade and type were available.In all, 73 patients with SCCP were reviewed and then tissue samples microarrayed. These were then stained with immunohistochemistry for Topo I, Topo II and Ki-67. Tumour stage, grade and type were available.RESULTSTopo II showed a strong positive correlation with the proliferation index as measured by Ki-67 (P < 0.001) but no correlation with Topo I. There were also strong correlations between tumour grade and Ki-67, and Topo II expression (both P < 0.001). Tumour type was also strongly correlated with Topo II and Ki-67 expression, with the highest expression in basaloid carcinomas and the lowest in verrucous carcinomas. However, Topo I expression was not correlated with any other tumour variable.Topo II showed a strong positive correlation with the proliferation index as measured by Ki-67 (P < 0.001) but no correlation with Topo I. There were also strong correlations between tumour grade and Ki-67, and Topo II expression (both P < 0.001). Tumour type was also strongly correlated with Topo II and Ki-67 expression, with the highest expression in basaloid carcinomas and the lowest in verrucous carcinomas. However, Topo I expression was not correlated with any other tumour variable.CONCLUSIONThe expression of Topo I is grade- and type-independent, and chemotherapy using the camptothecins is unlikely to be effective. The strong positivity of Topo II in high-grade and basaloid SCCPs suggests that treatment with etoposide or other Topo II ‘poisons’ might be a better target for future clinical trials.The expression of Topo I is grade- and type-independent, and chemotherapy using the camptothecins is unlikely to be effective. The strong positivity of Topo II in high-grade and basaloid SCCPs suggests that treatment with etoposide or other Topo II ‘poisons’ might be a better target for future clinical trials.

BackgroundVentricular tachycardia (VT) is associated with increased morbidity and mortality. There is growing evidence for the effectiveness of catheter ablation in improving outcomes in patients with recurrent VT. Consequently the threshold for referral for VT ablation has fallen over recent years, resulting in increased number of procedures.ObjectiveTo evaluate the effectiveness and safety of VT ablation in a real-world tertiary centre setting.MethodsThis is a prospective analysis of all VT ablation cases performed at University Hospital Coventry. Follow-up data were obtained from review of electronic medical records and patient interview. The primary endpoint for normal heart VT was death, cardiovascular hospitalisation and VT recurrence, and for structural heart VT was arrhythmic death, VT storm (&gt;3 episodes within 24 hours) or appropriate shock.ResultsForty-seven patients underwent 53 procedures from January 2012 to January 2018. The mean age ±SD was 57±15 years, 68% were ma...

J Clin Res Pediatr Endocrinol. 2010 March; 2(1): 21–27. ... Published online 2010 February 3. doi: 10.4274/jcrpe.v2i1.21. ... Copyright © Journal of Clinical Research in Pediatric Endocrinology, Published by Galenos Publishing. ... This is an open-access article ...

A 48-year-old lady presented with dyspnoea and chest pain. ECG showed sinus tachycardia with right bundle branch block and right ventricular strain. Echocardiography showed a dilated left ventricle with normal wall thickness and incoordinate septal motion with a globally poor systolic function (ejection fraction of 20%). Coronary angiography revealed normal coronary arteries. Cardiovascular magnetic resonance showed significant delayed enhancement following gadolinium contrast agent …

Administration of the muscarinic cholinergic receptor blocker glycopyrrolate reportedly attenuates the exercise-induced increase in middle cerebral artery mean blood velocity. We sought to determine the cholinergic contribution to blood flow in the internal carotid artery (ICA; duplex Doppler ultrasound) during low (42±9 Watts; mean±SE) and moderate (110±11 Watts) intensity leg cycling in seven young male subjects (21±1 yr). Mean arterial pressure (MAP) and heart rate (HR; ECG) were continuously monitored. Stroke volume (SV) was determined offline using Modelflow and cardiac output calculated (CO=HR×SV). Exercise trials were conducted under control (no drug) conditions and after cholinergic blockade by administration of glycopyrrolate. Cholinergic blockade increased resting CO (6.8±0.4 to 8.7±0.5 L/min; P&lt;0.05) and MAP (79±2 to 89±3 mmHg), while the responses to exercise were similar. ICA blood flow increased similarly from rest during low and moderate intensity exercise under control (271±34, 333±27 and ...

Rheumatoid arthritis (RA) is an inflammatory disorder associated with increased cardiovascular mortality. We sought to determine whether muscle sympathetic nerve activity (MSNA) is heightened, and cardiac baroreflex sensitivity (cBRS) is reduced in patients with RA. Whilst resting supine, blood pressure (BP; Portapres), heart rate (HR; ECG) and MSNA (microneurography) were continuously monitored in 7 chronic RA patients (5 men, 56±4 yr, 28±1 kg/m²; mean±SE), 7 healthy controls (HC: 5 men, 52±5 yr, 26±1 kg/m²) and 7 patients with hypertension as ‘disease’ controls (DC: 5 men, 54±5 yr, 28±1 kg/m²). MSNA burst frequency and spontaneous cardiac baroreflex sensitivity (sequence technique, systolic BP-RR interval) were determined. Mean BP (p=0.001) and HR (p=0.014) were lower in HC group (88±5 mmHg, 55±2 bpm) than RA patients (106±2 mmHg, 70±3 bpm) and the DC group (116±6 mmHg, 63±4 bpm). MSNA burst frequency tended to be higher in RA patients and the DC group (34±4, 37±3 and 26±3 bursts/min in RA, DC, HC; P=0....

The influence of device-guided slow deep breathing (SDB; RESPeRATE) on arterial baroreflex control of the heart and muscle sympathetic nerve activity (MSNA) in essential hypertension patients remains unclear. To address this, respiratory rate, partial pressure of end-tidal carbon dioxide (PETCO2), MSNA (microneurography), heart rate (HR) and blood pressure (BP: Finometer) were monitored in 8 hypertensive patients (55±14 years, BMI 28±3 kg/m2, 152±26/71±11 mmHg [systolic/diastolic BP], duration of hypertension 6.4±6.7 years; mean±SD) during 10 min of normal breathing and 10 min of SDB. Cardiac baroreflex sensitivity (sequence technique) and spontaneous arterial baroreflex control of MSNA burst incidence were calculated offline. As expected, SDB decreased respiratory rate (13±4 to 6±1 breath/min, P=0.001), whereas PETCO2 (P=0.22), and mean BP (98±14 to 97±13 mmHg, P=0.11) were unchanged. MSNA burst incidence tended to fall during SDB (median with interquartile range from 46 [34-56] to 40 [31-48] bur...

We sought to investigate whether device guided slow deep breathing (SDB; RESPeRATE©) influences muscle sympathetic nerve activity (MSNA) and spontaneous baroreflex sensitivity in young healthy individuals. Following a 10 min supine baseline period, 9 men (29±7 years, body mass index 24±2 kg/m2; mean±SD) undertook 10 min of SDB while respiratory frequency (strain gauge pneumobelt), partial pressure of end-tidal carbon dioxide (PETCO2), blood pressure (BP; finger photoplethymography), heart rate (HR; ECG) and MSNA (microneurography) were continuously monitored. Indices of arterial baroreflex control of the heart (sequence technique) and MSNA burst incidence were calculated. Respiratory rate was reduced from 12±2 to 6.2±0.7 breaths/min (P&lt;0.001) during SDB, while PETCO2 (P=0.50), and mean BP (P=0.40) were unchanged. SDB significantly reduced MSNA burst incidence (i.e., percentage of cardiac cycles associated with a MSNA burst) from 25 (20-38) to 20 (18-33) (median and interquartile range; P=0.04). Neither ca...

Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with increased cardiovascular morbidity/mortality and an incompletely understood pathophysiology. In animal studies, central and blood-borne inflammatory cytokines that can be elevated in RA evoke pathogenic increases in sympathetic activity and reductions in baroreflex sensitivity (BRS). We hypothesised that muscle sympathetic nerve activity (MSNA) was increased and BRS decreased in RA. MSNA, blood pressure and heart rate (HR) were recorded in age- and sex-matched RA-normotensive (n = 13), RA-hypertensive patients (RA-HTN; n = 17), normotensive (NC; n = 17) and hypertensive controls (HTN; n = 16). BRS was determined using the modified Oxford technique. Inflammation and pain were determined using serum high sensitivity C-reactive protein (hs-CRP) and a visual analogue scale (VAS), respectively. MSNA was elevated similarly in RA, RA-HTN and HTN patients (32 ± 9, 35 ± 14, 37 ± 8 bursts/min) compared to NC (22 ± 9...