Platelet and leukocyte activation, atherosclerosis and inflammation in European and South Asian men.

BACKGROUND: Increased platelet activation occurs in ischemic heart disease (IHD), but increased platelet activation is also seen in cerebrovascular atherosclerosis and peripheral artery disease. It is not clear therefore whether platelet activation is an indicator of IHD or a marker of generalized atherosclerosis and inflammation. South Asian subjects are at high risk of IHD, but little is known regarding differences in platelet and leukocyte function between European and South Asian subjects. METHODS: Fifty-four male subjects (age 49-79 years) had coronary artery calcification measured by multislice computed tomography (CT), aortic atherosclerosis assessed by measurement of carotid-femoral pulse wave velocity (aortic PWV), and femoral and carotid atherosclerosis measured by B-mode ultrasound. Platelet and leukocyte activation was assessed by flow cytometry of platelet-monocyte complexes (PMC), platelet expression of PAC-1 binding site and CD62P, and expression of L-selectin on leukocytes. RESULTS: Elevated circulating PMC correlated significantly with elevated aortic PWV and PMC were higher in subjects with femoral plaques. In contrast PMC did not differ by increasing coronary artery calcification category or presence of carotid plaques. Higher numbers of PMC were independently related to elevated levels of C-reactive protein (CRP), higher aortic PWV, hypertension and smoking in a multivariate model. Markers of platelet and leukocyte activation did not differ significantly by ethnicity. CONCLUSIONS: Increased PMC are related to the extent of aortic and femoral atherosclerosis rather than coronary or carotid atherosclerosis. The association between elevated CRP and increased PMC suggests that inflammation in relation to generalized atherosclerosis may play an important role in PMC activation.

Concurrent granulomatous Pneumocystis carinii and Mycobacterium xenopi pneumonia: an unusual manifestation of HIV immune reconstitution disease.

This report of concurrent granulomatous Pneumocystis carinii pneumonia (GPCP) and Mycobacterium xenopi pneumonia (MXIP) in a patient with advanced HIV disease 3-5 weeks after commencing antiretroviral therapy (ART) fits the syndrome of HIV immune reconstitution/restoration disease (IRD). It may also be a unique window into the immunology of granulomatous inflammation.

Imaging of the thorax in the management of germ cell testicular tumours.

AIM: To evaluate role of chest computed tomography (CTC) and chest radiography (CXR) in management of patients with testicular germ cell tumours (GCT). PATIENTS AND METHODS: An analysis was undertaken of staging and re-assessment CTC and CXR examinations performed on patients with GCT over a 4.5-year period. Data were obtained on clinical presentation, tumour histology, tumour marker levels and clinical course. Consensus review interpretation was combined with these data to obtain a 'standard of reference'. Sensitivity, specificity and predictive values were derived by comparison of original imaging reports to 'standard of reference'. RESULTS: Six hundred and twenty-three CTC examinations on 207 patients with GCT were included. Intrathoracic metastases were identified in 1% of seminoma patients compared with 20% of non-seminoma (NSGCT) patients. CTC was more accurate than CXR in the detection of intrathoracic metastases at 0.97, 0.96-0.98 (95% CI) compared with 0.91, 0.89-0.93. The agreement between imaging techniques and the standard of reference (determined by Kappa statistic) was respectively 0.96 for CTC and 0.65 for CXR. In GCT patients undergoing re-assessment with both CXR and CTC, CXR never detected unknown intrathoracic metastatic disease. Abdominopelvic lymphadenopathy was associated with intrathoracic metastases (P < 0.001), however re-assessment CTC did identify intrathoracic metastases in 27 cases without concurrent abdominopelvic disease. CXR was negative in 19 of these. CONCLUSION: Routine interval CXRs are unnecessary in NSGCT patients undergoing regular re-assessment CTC due to the low additional yield and limited effect on management. Re-assessment should still include CTC. In low risk, pure seminoma patients (abdominal CT and marker negative) re-assessment CTC can be safely avoided. Baseline CTC is advocated with CXR alone for re-assessment.

Complete pre-operative imaging assessment of abdominal aortic aneurysm with spiral CT angiography.

PURPOSE: A prospective evaluation of spiral CT angiography (SCTA) as the sole pre-operative imaging modality for abdominal aortic aneurysm repair. MATERIALS AND METHODS: Spiral CT angiography was compared with conventional transfemoral angiography in 30 patients and results correlated with surgical findings in 22 patients. The following features were assessed: renal artery number and disease; upper and lower aneurysm extent; aneurysm size; perianeurysmal inflammation; iliac artery disease; radiation dose; and contrast usage. RESULTS: Spiral CT angiography agreed with conventional angiography in all cases of severe stenosis or occlusion of renal arteries and had 90% agreement overall for renal artery disease. Two of nine accessory renal arteries seen at conventional angiography were missed. For showing aneurysm extent SCTA was 100% sensitive, and performed better than conventional angiography. Aneurysm size was better shown with SCTA. In iliac disease SCTA, as performed in this study, was poor for mild-moderate disease, but detected four of six severely stenosed/occluded iliac arteries seen at conventional angiography. Prospective sensitivity for perianeurysmal inflammation was 33%. Radiation dose for SCTA was approximately twice and contrast dose approximately three times that for conventional angiography. CONCLUSION: Spiral CT angiography can provide all the necessary imaging information to plan aneurysm repair in the non-claudicant.

The role of computed tomographic examination of the pelvis in the management of testicular germ cell tumours.

AIM: To clarify the role of pelvic CT in the imaging of patients with germ cell testicular tumours (GCTT). PATIENTS AND METHODS: A retrospective analysis was undertaken of all CT examinations performed on patients with GCTT at a regional oncological centre over a 3-year-period. Patient notes were reviewed and data on histology, tumour marker levels, therapy and clinical course obtained. The review interpretation was combined with the original radiological report and clinical data to arrive at a consensus result. RESULTS: Four hundred and forty-three examinations on 167 patients were included. One hundred and nineteen examinations (27%) demonstrated abdominal and/or pelvic lymph node enlargement. Nodal metastasis was entirely or predominantly ipsilateral in 73/77 examinations from left-sided primary tumours (95%) and 35/42 examinations from right-sided tumours (83%). Pelvic nodal enlargement was identified in 37 examinations from 16 patients. Thirteen of these sixteen patients possessed an identifiable risk factor for pelvic nodal metastasis; the remaining three had unequivocal nodal metastases in the abdomen. Combined abdominopelvic CT increased the effective dose equivalent (EDE) by 2.6 mSv (74%) compared with abdominal examination alone. Three hundred pelvic CT examinations were performed on 117 patients without risk factors for pelvic nodal metastasis. For this cohort the radiation burden from pelvic CT was 0.78 manSv, giving a risk of induction of a single fatal cancer of 3.9%. CONCLUSION: We advocate pelvic CT only at the time of staging, except in patients with a risk factor for pelvic nodal metastasis. Any unequivocal abdominal lymph node enlargement should be regarded as a risk factor. Implementation of this policy would safely reduce pelvic CT examinations in patients with testicular tumours by nearly 50%, with a consequent reduction in patient radiation exposures and a resource saving.

Pulmonary nodules: effect on detection of spiral CT pitch.

PURPOSE: To compare spiral computed tomography (CT) performed at increased pitch with spiral CT performed at standard pitch in the detection of pulmonary nodules. MATERIALS AND METHODS: Spiral CT scanning of the thorax was performed with a pitch of 1.0 in 109 patients with pulmonary nodules due to metastases. The patients were also randomly assigned to undergo further scanning with a pitch of 1.2 (n = 34), 1.5 (n = 37), 2.0 (n = 38) at the same scanning session. The scan pairs were analysed for number, size, and distribution of nodules. RESULTS: A bias toward undercounting was noted on scans with a pitch of 1.5 and 2.0; however, this was not statistically significant. Correlation coefficients were r = .982, r = .977, and r = .989 for scans of pitch 1.2, 1.5, and 2.0, respectively. Disease in one patient would have been prospectively understaged from findings on a scan of pitch 2.0 because of poor conspicuity of a small solitary nodule. CONCLUSION: Findings from scans with increased pitch generally agree well with those from scans with standard pitch; however, there is a greater risk of understaging of disease in patients with solitary nodules as pitch increases. Pitch should be limited to no greater than 1.5 for initial staging of pulmonary metastatic disease.

Extracellular osmotic pressure modulates sodium-calcium exchange in isolated guinea-pig ventricular myocytes.

1. The sensitivity of the cardiac Na(+)-Ca2+ exchange current to changes in osmotic pressure was investigated in guinea-pig ventricular myocytes, using the whole-cell patch-clamp technique. 2. A hyposmotic challenge applied by removal of sucrose from the standard bathing solution reduced exchanger current, measured as the Ni(2+)-sensitive component of whole-cell transsarcolemmal current. These changes were fully reversible. 3. No response of whole-cell current to hyposmosis was observed when Ca2+ was removed from the bathing solution by chelation with 1 mM EGTA. 4. Inclusion of 25 microM exchanger inhibitory peptide (XIP) in the pipette solution caused a marked reduction in the Ni(2+)-sensitive component of membrane current, but the percentage change in Ni(2+)-sensitive membrane slope conductance evoked by hyposmosis was the same as when XIP was omitted from the pipette solution. 5. Exposure of cells to hyperosmotic solutions produced variable responses. In a majority of cells, solutions 30% hyperosmotic compared with control evoked a persistent increase in exchanger current, whereas for solutions 50% hyperosmotic, a larger but transient increase in current was observed. 6. Over a wide range of osmolalities (50-130% of isosmotic) the changes in Ni(2+)-sensitive membrane slope conductance were linearly related to the changes in extracellular osmotic pressure. 7. We propose that one consequence of exposing ventricular myocytes to anisosmotic solutions is modulation of Na(+)-Ca2+ exchange current.

Fine mapping of the Darier's disease locus on chromosome 12q.

Darier's disease (DD) is an autosomal dominant genodermatosis characterized by epidermal acantholysis and dyskeratosis. We have performed genetic linkage studies in 10 families with DD (34 affected) by analyzing 14 polymorphic microsatellite markers. Our results confirm recent reports mapping the DD gene to chromosome 12q23-q24.1. Haplotype analysis of recombinant chromosomes in our families, along with previously reported data, narrow the location of the DD gene to a 5 cM interval flanked by the loci D12S354 and D12S84/D12S105. This localization allowed exclusion of two known genes, PLA2A and PAH, as candidate loci for DD. Three other gene loci (PPP1C, PMCH, PMCA1), mapping in 12q21-q24, remain potential candidates.

Comparison of spiral-acquisition computed tomography and conventional computed tomography in the assessment of pulmonary metastatic disease.

In a prospective study, spiral-acquisition computed tomography (SACT) of the thorax was evaluated in 104 patients with extrathoracic malignancy and suspected pulmonary metastases, and was directly compared with conventional computed tomography (CCT) in 23 patients. The following parameters were assessed: lesion detectability; the effect on lesion detectability of reconstruction of scans at 5 mm and 10 mm slice increments; breathing artefact and slice misregistration. The radiation dose of the two techniques was measured using thermoluminescent dosimeters placed within an anthropomorphic chest phantom, and the visibility of simulated metastases inserted into the phantom was also compared using CCT, standard SACT and SACT with pitch greater than 1.0. Where metastases were present, SACT scans showed significantly better lesion detectability than CCT scans (p < 0.001). Image reconstruction of SACT data at 5 mm increments conferred no significant advantage in lesion detectability over 10 mm increment reconstructions. Compared with CCT, SACT scans showed reduced breathing artefact, and a complete absence of slice misregistration (p < 0.01). Phantom measurements of radiation dose and resolution were similar for both techniques. Increasing the pitch of the spiral in SACT caused only a small decrease in phantom resolution, but with the advantage of a reduction in the radiation dose. Spiral-acquisition CT is superior to conventional CT for the assessment of pulmonary metastatic disease.

High resolution computed tomography of the lungs in patients with rheumatoid arthritis and interstitial lung disease.

We performed high resolution computed tomography (HRCT) on the lungs of 20 patients with RA and clinical and radiological evidence of interstitial lung disease (ILD). A case control group of patients with RA but without evidence of ILD were similarly studied and all patients underwent detailed pulmonary function testing. Clinical findings, drug therapy, smoking status, the presence/absence of SS and disease activity were also assessed. HRCT showed a range of abnormalities among patients thought to have ILD. Interstitial fibrosis was confirmed in 16 but was frequently associated with emphysema. Ground glass opacification was present in seven, while basal honey-combing was also evident in seven patients. Both these features were present in two patients with ILD. Bronchiectasis was identified in six patients and was the predominant finding in two patients previously thought to have ILD. Among the control patients, HRCT was normal in only five. Clinically unsuspected ILD was present in four patients, while a further four had bronchiectasis. Pleural disease was identified in seven controls. Pulmonary function tests were generally poor predictors of HRCT findings, although a reduced residual volume (RV) [> 1 S.D.] was 83% specific for the presence of ILD and a raised RV [> 1 S.D.] was 64% specific for emphysema. Smoking did not correlate with the presence of either ILD or emphysema and there were no correlations between disease activity and HRCT findings. RA patients with evidence of ILD have abnormalities on HRCT which cannot be confidently predicted on any other non-invasive test.(ABSTRACT TRUNCATED AT 250 WORDS)

Fat-suppression magnetic resonance imaging in the preoperative localization of parathyroid adenomas.

Prospective localization of parathyroid adenomas was attempted in 16 patients with hyperparathyroidism prior to surgery. All patients had magnetic resonance imaging (MRI) using T1-weighted spin-echo (SE) sequences and a fat-suppression sequence, the short-tau inversion recovery (STIR) sequence. Correlation with the results of surgery yielded an overall sensitivity of 71% and a specificity of 94%. Performance was good in patients with previous surgery and with ectopic tumours. We believe that fat-suppression MRI is a valuable technique in the preoperative localization of parathyroid adenomas in patients with hyperparathyroidism.

MR pelvimetry--a practical alternative.

Pelvimetry remains a useful technique as part of the assessment of the term breech pregnancy where vaginal delivery is planned. MR pelvimetry is accurate, well tolerated and shows soft-tissue structures as well as bone. It avoids the potentially carcinogenic effects of ionising radiation and is thought to be completely safe for mother and fetus. A technique of MR pelvimetry is described which uses gradient-echo sequences. This quick, practical method makes minimal inroads into valuable scanning time, and may therefore be considered a potentially cost-effective alternative to conventional pelvimetry.

MR and CT in the assessment of Poland syndrome.

Seven cases of Poland syndrome were investigated with CT and/or MR to assess the extent of the muscle abnormalities of the shoulder girdle. In all cases the absence of the sternocostal head of the pectoralis major was clearly shown, as were any associated abnormalities of the pectoralis minor, serratus anterior, and latissimus dorsi. The latissimus dorsi muscle has an important role in reconstructive surgery and can be difficult to assess clinically. Cross-sectional imaging with CT or MR will give useful information in patients with Poland syndrome requesting anterior axillary reconstruction and breast mound formation.

Computed tomography in the preoperative assessment of Poland's syndrome.

Four cases of Poland's syndrome were investigated with thoracic computed tomography (CT) to determine the precise extent of the upper limb girdle abnormalities. CT confirmed in all cases the absence of the sternocostal head of pectoralis major and clearly showed associated abnormalities of pectoralis minor, serratus anterior and latissimus dorsi as well as bony structures. In view of the importance of latissimus dorsi in reconstructive surgery, we believe that a limited thoracic CT scan provides useful information in patients with Poland's syndrome requesting anterior axillary reconstruction and breast mound formation.