Purpose To investigate p53 and hepatoma-derived growth factor (HDGF) expression and their association with clinicopathological features of Ewing family tumour (EFT). Experimental design A total of 108 cases of EFT were retrospectively analysed. p53 and HDGF expression were detected using immunohistochemistry, and the relationships between p53 expression and HDGF expression and clinicopathological features of EFT were analysed. Kaplan–Meier curves were applied to estimate overall survival, log-rank test was used to assess prognostic relevance of p53 expression with overall survival and Cox regression model was performed to evaluate HRs. Results p53 expression and high HDGF expression was found in 17 (15.7%) and 55 (50.9%) patients, respectively. p53 expression was significantly associated with metastatic stage at initial diagnosis (p=0.007) and tumour venous/nerve invasion (p=0.023). A significant positive correlation was found between p53 expression and HDGF expression in EFT (p=0.022). p53 expression was an independent prognostic factor for overall survival of patients with EFT (p<0.001). Patients with p53-positive/high HDGF expression had a significantly shorter overall survival than those with p53-positive/low HDGF expression or p53-negative/high HDGF expression or p53-negative/low HDGF expression. We first constructed a novel molecular staging system by combining p53 expression and HDGF expression, which significantly improved prognostic stratification for patients with EFT. Conclusions p53 expression was an independent prognostic factor for patients with EFT. Combining p53 expression and HDGF expression significantly improved prognostic stratification for patients with EFT.,OBJECTIVESTo describe the changing workload of an HIV/AIDS counselling unit between 1987 and 1990. DESIGNRetrospective examination of data collected by the HIV/AIDS counselling unit between 1987-90 on the number of counselling sessions with patients, family members and staff. SETTINGAn HIV/AIDS counselling unit established in 1987 in a London teaching hospital. MAIN OUTCOME MEASURESNumber of new referrals to the HIV/AIDS counselling unit and the number of follow-up sessions. Number of counselling sessions with family members, hospital staff and people making telephone contact with the unit. RESULTSNew referrals to the HIV/AIDS counselling unit increased from 117 (1987-88) to 926 (1989-90). Follow-up appointments increased from 403 to 2016 in the same period. Telephone counselling sessions increased five-fold, and counselling sessions with family members nearly ten-fold over the three year period. Staff consultations doubled. CONCLUSIONThe increase in the HIV/AIDS counselling unit's workload may be partly attributable to the rising incidence of AIDS in the community, reflecting earlier patterns of HIV infection. In addition, new HIV/AIDS services were developed in the hospital between 1987 and 1990. These included the establishment of a same-day HIV test and result clinic; integrated management of patients with HIV/AIDS, with an emphasis on early intervention in HIV infection; specialist services for families, antenatal clinic attenders and others affected by HIV; and the appointment of a designated HIV/AIDS consultant. New approaches to counselling and training health care providers in counselling skills will assume increasing importance in meeting future demand for HIV/AIDS counselling.
THE pathogenesis of pulmonary hypertension is incompletely understood. The histologic features of the small pulmonary arteries of patients with this disease suggest that the coagulation system on the endothelial surface may be activated as either a primary or a secondary process. 1 2 3 4 5 6 Vasoconstriction is a variable feature of pulmonary hypertension; some patients, but not all, respond to vasodilator drugs with a substantial reduction in pulmonary vascular resistance and pressure. 7 8 9 10 Thromboxane A 2 is both a potent pulmonary vasoconstrictor and a procoagulant, whereas prostacyclin has opposing effects, and an imbalance between the release of these two mediators could be involved in the . . .
PRIMARY pulmonary hypertension is an uncommon disease that is progressive and incurable. 1 , 2 The recent National Institutes of Health (NIH) Registry on Primary Pulmonary Hypertension documented a median survival of 2.8 years after the diagnosis. 3 In the 1980s interest in the treatment of primary pulmonary hypertension focused on vasodilator drugs and anticoagulant therapy. 4 , 5 Although there are numerous descriptions of the short-term hemodynamic effects of many vasodilator drugs, reports documenting long-term effectiveness have been scarce. Anticoagulants have been recommended, but their long-term effectiveness also remains in question. 6 7 8 In 1987 Rich and Brundage conducted a preliminary study of the use of high doses . . .
Pulmonary hypertension, defined as a mean pulmonary-artery pressure above 20 mm Hg or a pulmonary-artery systolic pressure above 30 mm Hg, can arise in a variety of cardiopulmonary conditions that increase pulmonary blood flow, pulmonary vascular resistance, and left heart impedance to blood flow. The pathophysiologic processes underlying different forms of pulmonary hypertension have traditionally been explained in hemodynamic terms. Pulmonary hypertension occurs in patients with mitral stenosis, for example, because of an increase in left atrial pressure that leads to an increase in pulmonary venous pressure and, consequently, to an increase in pulmonary-artery pressure. Patients with pulmonary thromboembolism may . . .
Patients with pulmonary hypertension are at risk of developing fatal right heart failure after heart transplantation. To evaluate this risk potential, candidates for heart transplantation are screened by measuring rest right heart pressures and the response to nitroprusside. To test the validity of this approach, the influence of pretransplantation right heart catheterization data on outcome after transplantation was analyzed in 293 of 301 consecutive patients. Patients with a pulmonary vascular resistance >2.5 Wood units measured at baseline study had a 3-month mortality rate of 17.9% compared with 6.9% in patients with resistance ≤ 2.5 units (p 2.5 units at baseline study could be differentiated further according to their hemodynamic response to nitroprusside; those whose resistance could be reduced to ≤ 2.5 units with a stable systemic systolic pressure ≥ 85 mm Hg had a 3-month mortality rate of only 3.8%. In contrast, patients whose pulmonary vascular resistance could not be reduced to < 2.5 units, and those whose resistance could be reduced to ≤ 2.5 units but only at the expense of systemic hypotension (systolic pressure ≤ 85 mm Hg) had a 3-month mortality rate of 40.6% and 27.5%, respectively. Furthermore, all 10 patients who died of right heart failure belonged to the latter two groups. These findings confirm the value of right heart hemodynamic measurements and the response to nitroprusside in predicting early mortality after heart transplantation and, in particular, mortality due to right heart failure. Valid risk stratification based on the hemodynamic response to nitroprusside requires consideration of the concomitant change in systemic pressure.
To test the utility of electrocardiographically gated spin echo nuclear magnetic resonance (NMR) imaging in quantitating right and left ventricular volumes and function in patients with primary pulmonary hypertension, right and left ventricular end-diastolic and end-systolic volumes, stroke volumes and ejection fractions were determined in 11 patients with primary pulmonary hypertension and in 10 subjects with normal echocardiographic findings. Ventricular chamber volumes were computed by summing the ventricular chamber volumes of each NMR slice at enddiastole and end-systole. This technique was verified by comparison of results obtained by this method and with the water displacement volumes of eight water-filled latex balloons and ventricular casts of eight excised bovine hearts. In the patients with primary pulmonary hypertension, right ventricular volume indexes were 121 ± 45 ml/m at end-diastole and 70.1 ± 41.6 ml/m at end-systole; both values were significantly greater than values in the normal subjects (67.9 ± 13.4 and 27.9 ± 7.5 ml/m , respectively). Left ventricular end-diastolic volume index was significantly less in the patients (44.9 ± 9.7 ml/m ) than in the normal subjects (68.9 ± 13.1 ml/m ). There was no significant difference in left ventricular end-systolic volume between the two groups (24.4 ± 8.6 and 27.1 ± 7.8 ml/m , respectively). Right and left ventricular ejection fractions in the patients with primary pulmonary hypertension (0.43 ± 0.21 and 0.46 ± 0.15, respectively) were significantly less than values in normal subjects (0.59 ± 0.09 and 0.6 ± 0.11, respectively). The ratio of right to left ventricular stroke volume indexes was 0.97 ± 0.1 in the normal subjects, not significantly different from the expected value of 1. In the patients with primary pulmonary hypertension, this ratio was significantly greater (3.17 ± 2.3), in part reflecting the presence of tricuspid regurgitation in these patients. Intra- and interobserver errors in the computation of ventricular volumes were low but were greater in patients with primary pulmonary hypertension. Nuclear magnetic resonance imaging provides a means of ventricular volume determination in the normal and failing ventricle.
Objective—To examine the effects of pulmonary hypertension on left ventricular diastolic function and to relate the findings to possible mechanisms of interdependence between the right and left sides of the heart in ventricular disease.Design—A retrospective and prospective analysis of echocardiographic and Doppler studies.Setting—A tertiary referral centre for both cardiac and pulmonary disease.Patients—29 patients with pulmonary hypertension (12 primary pulmonary hypertension, 10 pulmonary fibrosis, five atrial septal defect (ASD), and two scleroderma) were compared with a control group of 10 patients with an enlarged right ventricle but normal pulmonary artery pressure (six ASD, one after ASD closure, one ASD and pulmonary valvotomy, one tricuspid valve endocarditis and repair, and one pulmonary fibrosis). None had clinical or echocardiographic evidence of intrinsic left ventricular disease.Main Outcome measures—M mode echocardiographic measurements were made of septal thickness, and left and right ventricular internal cavity dimensions. Doppler derived right ventricular to right atrial pressure drop, and time intervals were measured, as were isovolumic relaxation time, and Doppler left ventricular filling characteristics.Results—The peak right ventricular to right atrial pressure gradient was (mean (SD)) 60 (16) mm Hg in pulmonary hypertensive patients, and 18 (5) mm Hg in controls. The time intervals P2 to the end of the tricuspid regurgitation, and P2 to the start of tricuspid flow were both prolonged in patients with pulmonary hypertension compared with controls (115 (60) and 120 (40) ν 40 (15) and 45 (10) ms, p values <0·001). Pulmonary hypertensive patients commonly had a dominant A wave on the transmitral Doppler (23/29); however, all the controls had a dominant E wave. Isovolumic relaxation time of the left ventricle was prolonged in pulmonary hypertensive patients compared with controls, measured as both A2 to mitral valve opening (80 (25) ν 50 (15) ms) and as A2 to the start of mitral flow (105 (30) ν 60 (15) ms, p values <0·001). The delay from mitral valve opening to the start of transmitral flow was longer in patients with pulmonary hypertension (30 (15) ms) compared with controls (10 (10) ms, p < 0·001). At the time of mitral opening there was a right ventricular to right atrial gradient of 12 (10) mm Hg in pulmonary hypertensive patients, but this was negligible in controls (0·4 (0·3) mm Hg, p < 0·001).Conclusions—Prolonged decline of right ventricular tension, the direct result of severe pulmonary hypertension, may appear as prolonged tricuspid regurgitation. It persists until after mitral valve opening on the left side of the heart, where events during isovolumic relaxation are disorganised, and subsequent filling is impaired. These effects are likely to be mediated through the interventricular septum, and this right-left ventricular asynchrony may represent a hitherto unrecognised mode of ventricular interaction.