Pulmonary angiography in a non-teaching hospital over a 12-year period.

OBJECTIVE: To report the safety of pulmonary angiography in a non-teaching hospital and discuss the place of this investigation in the diagnosis of pulmonary embolism. DESIGN AND SETTING: A retrospective review of all patients undergoing pulmonary angiography over a 12-year period, November 1979 to October 1991, at Dandenong Hospital, Melbourne. A protocol was established whereby each procedure was performed with the assistance of staff and equipment from the intensive care unit to provide haemodynamic monitoring and measurement of pulmonary artery pressures. PATIENTS: During the review period 114 patients underwent pulmonary angiography, most (108) for suspected pulmonary embolism. RESULTS: One hundred and fifteen pulmonary angiograms were performed, and no deaths related to the procedure occurred. Complications included perforation of the right atrium in three patients, with no sequelae. Cardiac arrhythmias were common but self-limiting. CONCLUSION: In our series, pulmonary angiography was a safe procedure if undertaken with the appropriate monitoring measures. A protocol which includes the participation of the intensive care unit has proved helpful. In addition, it was found that clinical symptoms and signs were unreliable and in 24 patients who also had ventilation-perfusion (V/Q) scans, only seven scans were accurate. A review of the literature indicates that V/Q scans lack specificity and that pulmonary angiography may be performed safely. The latter investigation should be more frequently performed.     

Hemoglobin production in human bone marrow cultures is inhibited by lyophilized coagulation factor concentrates

Transfusion of blood products may be followed by viral hepatitis and aplastic anemia despite improved techniques for prevention. In view of the need for intensive therapy of hemophilia with blood products, the authors investigated the capacity of these concentrates to influence cultures of human bone marrow cells. Factor VIII concentrates contained a heat-stable dialyzable substance(s) that drastically impaired 59Fe incorporation in normal human bone marrow. Factor IX concentrates had less and cryoprecipitate had no such inhibitory activity. These studies may offer information regarding the effects of various blood products on bone marrow function.     

Does Systolic Blood Pressure Response to Lifestyle Intervention Indicate Metabolic Risk and Health‐Related Quality‐of‐Life Improvement Over 1 Year?

The purpose of this study was to determine whether responders (minimum 4‐mm Hg reduction of systolic blood pressure [BP]) at 24 weeks) to a 52‐week lifestyle intervention had greater changes in metabolic risk factors and health‐related quality of life than nonresponders. Participants (N=126; age, 57.4 [9.1] years) had waist circumference (WC), resting BP, glycated hemoglobin, lipids, and fitness assessed at baseline and at 12, 24, and 52 months. The 36‐item short‐form survey was administered to assess HRQOL. At baseline, responders had higher mental health scores (P=.04) and systolic and diastolic BPs (P<.001) than nonresponders. Across 52 weeks, responders also had greater improvements in diastolic BP (P<.001), WC (P=.01), and maximal oxygen uptake (P=.04) compared with nonresponders. Participants with clinically important changes in systolic BP at 24 weeks had greater metabolic improvements across 52 weeks, compared with those without clinically important systolic BP changes.     

The determinants of change in patella cartilage volume in osteoarthritic knees

OBJECTIVE: The rate of change in patella articular cartilage and factors influencing it, in subjects with osteoarthritis (OA), is unknown. We performed a cohort study to determine this. METHODS: One hundred ten subjects with OA had baseline skyline and lateral radiographs and magnetic resonance imaging (MRI) on their knee. They were followed 2 years later with a repeat MRI of the same knee. Patella and tibial cartilage volume was measured at baseline and followup. Risk factors assessed at baseline were tested for their association with change in patella cartilage volume over time. RESULTS: The annual percentage loss of patella cartilage was 4.5 +/- 4.3%. Sex, body mass index (BMI), and pain score at baseline were associated with an increase in cartilage loss. The rate of patella cartilage loss was greater in women than men, 5.3% versus 3.5% (p < 0.03), independent of age, BMI, and pain score. No association was seen between change in patellar cartilage volume and change in either medial or lateral tibial cartilage volume (r = 0.02, p = 0.86 and r = 0.08, p = 0.43, respectively). CONCLUSION: In OA, patella cartilage volume is lost at 4.5 +/- 4.3% per year. The main factors affecting this are sex, BMI, and baseline pain score. The poor correlation between patella cartilage loss and cartilage loss in the tibial compartment suggests that the pathogenetic mechanisms for OA in the patellofemoral and tibiofemoral joint may differ. Further work will be required to determine whether the rate of patella cartilage loss in OA is steady or phasic, and to determine which factors can be modified to reduce cartilage loss.     

Human cardiosphere-derived cells from patients with chronic ischaemic heart disease can be routinely expanded from atrial but not epicardial ventricular biopsies

To investigate the effects of age and disease on endogenous cardiac progenitor cells, we obtained right atrial and left ventricular epicardial biopsies from patients (n?=?22) with chronic ischaemic heart disease and measured doubling time and surface marker expression in explant- and cardiosphere-derived cells (EDCs, CDCs). EDCs could be expanded from all atrial biopsy samples, but sufficient cells for cardiosphere culture were obtained from only 8 of 22 ventricular biopsies. EDCs from both atrium and ventricle contained a higher proportion of c-kit+ cells than CDCs, which contained few such cells. There was wide variation in expression of CD90 (atrial CDCs 5-92?% CD90+; ventricular CDCs 11-89?% CD90+), with atrial CDCs cultured from diabetic patients (n?=?4) containing 1.6-fold more CD90+ cells than those from non-diabetic patients (n?=?18). No effect of age or other co-morbidities was detected. Thus, CDCs from atrial biopsies may vary in their therapeutic potential.     

Novel antiangiogenic therapies in ovarian cancer

Epithelial ovarian cancer is the leading cause of death in the developed world for women with gynecologic carcinomas. Despite the effectiveness of platinum salts and taxanes as primary treatments, approximately 80% of women will recur and for them prognosis with available treatments is poor. Of the novel mechanisms under active investigation, there is ample evidence to indicate that angiogenesis is important to the development, progression and poor prognosis of ovarian cancer. Novel treatments are therefore required. A number of agents are undergoing evaluation, including vascular disrupting agents, angiogenesis inhibitors, tyrosine kinase inhibitors and agents targeting the folate receptor. At present, Phase III data are only available for the VEGF-targeted monoclonal antibody, bevacizumab, and that has demonstrated a progression-free survival benefit when used in combination with first-line paclitaxel/carboplatin and continued as maintenance therapy. The strategy of inhibiting angiogenesis in ovarian cancer remains promising. However, other agents in development may point to other important targets in ovarian cancer.     

Comparison of patella cartilage volume and radiography in the assessment of longitudinal joint change at the patellofemoral joint

OBJECTIVE: To compare radiological assessment of the patellofemoral (PF) joint and cartilage volume as measured by magnetic resonance imaging (MRI) in a longitudinal study. METHODS: One hundred and two subjects with osteoarthritis (OA) had baseline and followup skyline and lateral radiographs and MRI of the same knee. Duration of followup was 1.94 +/- 0.23 years. Mid-patella joint space and narrowest joint space were measured on lateral PF radiographs. Minimum joint space in the lateral and medial facets was measured on skyline radiographs. Rate of progression of PF joint OA was measured quantitatively at each site. Patella cartilage volume was measured from the MRI. The rate of change in each radiographic measure was compared to the rate of change in patella cartilage volume. RESULTS: The average loss of patella cartilage was 133 +/- 143 microm(3)/yr (4.4%). The loss of joint space over the same period on lateral radiographs was 0.7 +/- 2.6 mm at the narrowest joint space and 0.2 +/- 3.8 mm at the mid-patella joint space. On the skyline radiographs, the loss of joint space at the medial facet was 0.4 +/- 3.9 mm and 0.2 +/- 3.4 mm at the lateral facet. Only change in narrowest joint space on the lateral PF radiographs correlated with change in patella cartilage volume (R = 0.22, p = 0.03). CONCLUSION: Our data suggest that narrowest joint space measured on lateral PF radiographs correlates best with loss of patella cartilage. Further work will be needed to determine how different radiological measures of the PF joint relate to the disease process in OA.     

Increased expression of the G gamma and A gamma globin genes associated with a mutation in the A gamma enhancer

We have previously described a unique type of delta beta-thalassemia in a Chinese family characterized by increased expression of the G gamma and A gamma fetal globin genes in the absence of a large deletion in the beta-globlin gene cluster. Our earlier study of the beta-globin gene on this delta beta-thalassemia chromosome showed a promoter mutation in the TATA box. In this report, we describe the results of our study of the fetal globin domain of this delta beta-thalassemia chromosome. We have cloned a 13-kb DNA fragment that includes the G gamma and the A gamma genes and the 3' A gamma enhancer element of this delta beta-thalassemia chromosome. DNA sequence analysis of the G gamma and A gamma-globin genes including their promoters did not show any mutations, but analysis of the putative enhancer element downstream from the A gamma-globin gene showed a C to T substitution 2,401 nucleotides downstream from the A gamma cap site. We performed DNA linkage analysis to determine if this mutation is unique to this chromosome or represents a common polymorphism. Our linkage analysis showed that this mutation is not a common polymorphism and that it is also not an intrinsic part of the haplotype of the chromosome on which it was found. We also studied the interaction of nuclear proteins from erythroid and nonerythroid cells with the DNA sequences surrounding this mutation. We have shown by in vitro DNase I footprinting that this mutation falls within a region that is occupied by a novel DNA-binding protein that binds to this site in nuclear extracts from erythroid, but not nonerythroid cells. The binding of this nuclear protein to DNA appears to be dependent on GATA-1 binding to an adjacent GATA-1 site. We have also developed a new functional assay to compare the activity of the normal and mutant A gamma enhancer elements in erythroid cells. Analysis of the activity of the mutant enhancer shows that the mutation completely eliminates all enhancer activity in this assay. These findings suggest that this mutation of the A gamma enhancer on a chromosome that carries a partially inactivated beta-globin gene may be responsible for the increased expression of both gamma-globin genes seen in this condition.     

Supplementary vitamin E does not affect the loss of cartilage volume in knee osteoarthritis: a 2 year double blind randomized placebo controlled study

OBJECTIVE: To determine whether vitamin E affects change in cartilage volume in patients with knee osteoarthritis (OA). METHODS: In a double blind, placebo controlled trial, 136 patients with knee OA (American College of Rheumatology clinical and radiographic criteria) were randomized to receive vitamin E (500 IU) or placebo for 2 years. Tibial cartilage volume was measured by magnetic resonance imaging at the beginning and end of the study. RESULTS: Baseline characteristics were similar in the 2 groups (67 vitamin E, 69 placebo); there were more women in the vitamin E group, 42 (63%) vs 33 (48%) in the placebo group. One hundred seventeen subjects (59 vitamin E, 58 placebo) completed the study. Loss of medial and lateral tibial cartilage was similar in subjects treated with vitamin E and placebo (mean +/- SD: medial 157 +/- 209 vs 187 +/- 220 micro m3 placebo, p = 0.51; lateral 186 +/- 258 vs 251 +/- 216 micro m3, p = 0.19). There were no significant differences between the vitamin E and placebo treated groups in improvement of symptoms from baseline. Dietary levels of antioxidants (vitamin C, beta carotene, retinol equivalents) had no effect on cartilage volume loss. CONCLUSION: Vitamin E does not appear to have a beneficial effect in the management of knee OA: it does not affect cartilage volume loss or symptoms.