Changes in myocardial echo amplitude during reversible ischaemia in humans.

OBJECTIVE--This study investigated the changes in regional myocardial ultrasonic backscatter, measured as myocardial echo amplitude, that occur during reversible myocardial ischaemia in humans. DESIGN--Left anterior descending coronary angioplasty was used to produce reversible myocardial ischaemia in human subjects. Regional myocardial echo amplitude was studied in the interventricular septum and left ventricular posterior free wall before, during, and after coronary occlusion with the angioplasty balloon. Wall motion analysis of the left ventricle was performed from simultaneous cross sectional echocardiographic imaging. Patients were studied prospectively. PATIENTS--Six patients (mean age 56 (SD 11), range 46 to 69 years) with single vessel, left anterior descending coronary artery stenoses, were investigated during elective coronary angioplasty. A total of 11 balloon inflations were studied. SETTING--All patient studies were performed at Harefield Hospital. Echo amplitude analysis was performed at the Royal Brompton Hospital. INTERVENTIONS--Angioplasty was performed by the usual procedure at Harefield Hospital for elective coronary angioplasty. All routine medication including beta blockers and calcium antagonists were continued. Inflation pressures were up to 12 atm (1212 kPa) and mean inflation time ranged from 30 to 120 (86 (31)) s. In four studies the first inflation was examined, in three the second, in two the third, and in one each the fourth and fifth inflations. Echo amplitude and cross sectional echo-cardiographic studies were recorded with a 3.5 MHz Advanced Technology Laboratories (ATL) (720A/8736 series) mechanical sector scanner and an ATL Mark III (860-1 series) echocardiograph system with 45 dB logarithmic grey scale compression. MAIN OUTCOME MEASURES--Regional echo amplitude was examined in four regions of the left ventricle--namely, the basal and mid-septum, and basal and mid-posterior wall. Consecutive end diastolic and end systolic frames were analysed and cyclic variation was determined as the difference between the level of echo amplitude at end diastole and at end systole. Measurements were made before balloon inflation, at peak inflation, and after balloon deflation. Regional wall motion and systolic wall thickening were analysed qualitatively. RESULTS--Before balloon inflation, cyclic variation in echo amplitude was noted in all regions (basal septum, 2.4 (SD 1.1) dB; mid-septum, 2.5 (1.1) dB; basal posterior wall, 3.3 (2.1) dB; mid-posterior wall, 3.9 (1.6) dB). During balloon inflation there was a significant fall in cyclic variation to 0.4 (0.9) dB (p < 0.0002) in the mid-septum. This was predominantly owing to an increase in end systolic echo amplitude from 5.4 (2.0) dB to 9.3 (1.9) dB (p < or = 0.01). This was associated with the development of severe hypokinesis or akinesis in the mid-septum. No significant changes in echo amplitude occurred in the three other regions examined. Changes were completely reversed after balloon deflation. CONCLUSIONS--These results suggest a causal relation between occlusion of the supplying coronary artery and blunting of myocardial echo amplitude cyclic variation. It is suggested that balloon occlusion produced myocardial ischaemia. The resultant impairment of myocardial contraction then caused a blunting of cyclic variation in echo amplitude. The results of this study provide further data about the ability of quantitative studies of ultrasonic backscatter to identify alterations in the myocardium during injury.     

Effect of endothelium mimicking self-assembled nanomatrices on cell adhesion and spreading of human endothelial cells and smooth muscle cells

The goal of this study is to develop unique native endothelium mimicking nanomatrices and evaluate their effects on adhesion and spreading of human umbilical vein endothelial cells (HUVECs) and aortic smooth muscle cells (AoSMCs). These nanomatrices were developed by self-assembly of peptide amphiphiles (PAs) through a solvent evaporation technique. Three PAs, one containing the Tyr-Ile-Gly-Ser-Arg (YIGSR) ligand, the second containing the Val-Ala-Pro-Gly (VAPG) ligand, and a third without cell adhesive ligands, were developed. Cell adhesion and spreading were evaluated by a PicoGreen-DNA assay and live/dead assay, respectively. Our results show that PA-YIGSR significantly enhances HUVEC adhesion (26,704 ± 2708), spreading (84 ± 8%), and proliferation (50 ± 2%) compared with that of other PAs. PA-VAPG and PA-YIGSR showed significantly greater AoSMC adhesion compared with that of PA-S. PA-VAPG also showed significantly greater spreading of AoSMCs (63 ± 11%) compared with that of other PAs. Also, all the PAs showed significantly reduced platelet adhesion compared with that of collagen I (control). These findings would facilitate the development of novel vascular grafts, heart valves, and cell-based therapies for cardiovascular diseases.From the Clinical EditorThe goal of this study was to develop unique native endothelium mimicking nanomatrices and evaluate their effects on adhesion and spreading of human umbilical vein endothelial cells (HUVECs) and aortic smooth muscle cells (AoSMCs). These nanomatrices were developed by self-assembly of peptide amphiphiles through a solvent evaporation technique. The findings are expected to facilitate the development of novel vascular grafts, heart valves, and cell based therapies for cardiovascular diseases.     

Effect of Synthetic Truncated Apolipoprotein C-I Peptide on Plasma Lipoprotein Cholesterol in Nonhuman Primates

The present studies were conducted to determinewhether a synthetic truncated apoC-I peptide thatinhibits CETP activity in baboons would raise plasmaHDL cholesterol levels in nonhuman primates with lowHDL levels. We used 2 cynomolgus monkeys and 3baboons fed a cholesterol- and fat-enriched diet. Incynomolgus monkeys, we injected synthetic truncatedapoC-I inhibitor peptide at a dose of 20mg/kgand, in baboons, at doses of 10, 15, and 20mg/kgat weekly intervals. Blood samples were collected 3times a week and VLDL + LDL and HDL cholesterolconcentrations were measured. In cynomolgus monkeys,administration of the inhibitor peptide caused arapid decrease in VLDL + LDL cholesterolconcentrations (30%–60%) and an increase in HDLcholesterol concentrations (10%–20%). VLDL + LDLcholesterol concentrations returned to baselinelevels in approximately 15days. In baboons,administration of the synthetic inhibitor peptidecaused a decrease in VLDL + LDL cholesterol (20%–60%)and an increase in HDL cholesterol (10%–20%). VLDL+ LDL cholesterol returned to baseline levels byday 21, whereas HDL cholesterol concentrationsremained elevated for up to 26days. ApoA-Iconcentrations increased, whereas apoE andtriglyceride concentrations decreased. Subcutaneousand intravenous administrations of the inhibitorpeptide had similar effects on LDL and HDLcholesterol concentrations. There was no change inbody weight, food consumption, or plasma IgGlevels of any baboon during the study. Thesestudies suggest that the truncated apoC-I peptide canbe used to raise HDL in humans.     

Effects of mTOR inhibitor–related proteinuria on progression of cardiac allograft vasculopathy and outcomes among heart transplant recipients

We have previously described the use of sirolimus (SRL) as primary immunosuppression following heart transplantation (HT). The advantages of this approach include attenuation of cardiac allograft vasculopathy (CAV), improvement in glomerular filtration rate (GFR), and reduced malignancy. However, in some patients SRL may cause significant proteinuria. We sought to investigate the prognostic value of proteinuria after conversion to SRL. CAV progression and adverse clinical events were studied. CAV progression was assessed by measuring the Δ change in plaque volume (PV) and plaque index (PI) per year using coronary intravascular ultrasound. Proteinuria was defined as Δ urine protein ≥300 mg/24 h at 1 year after conversion to SRL. Overall, 137 patients were analyzed (26% with proteinuria). Patients with proteinuria had significantly lower GFR (P = .005) but similar GFR during follow-up. Delta PV (P < .001) and Δ PI (P = .001) were significantly higher among patients with proteinuria after adjustment for baseline characteristics. Multivariate Cox regression analysis showed higher all-cause mortality (hazard ratio 3.8; P = .01) with proteinuria but similar risk of CAV-related events (P = .61). Our results indicate that proteinuria is a marker of baseline renal dysfunction, and that HT recipients who develop proteinuria after conversion to SRL have less attenuation of CAV progression and higher mortality risk.     

Physiologic Changes of the Anorectum After Pelvic Radiotherapy for the Treatment of Prostate and Bladder Cancer

INTRODUCTION: The effect of pelvic radiotherapy on anorectal function is not clearly documented and is investigated in this prospective study. METHODS: Thirty-one males (median age, 70 years) with carcinoma of the prostate (n = 28) and bladder (n = 3) completed proctitis/incontinence symptom score questionnaires and anorectal physiology studies before and six weeks after pelvic radiotherapy. At six months after completion of radiotherapy, 25 of these patients were studied again. The results were expressed as medians and ranges and compared by the Mann-Whitney U test (2-tailed). RESULTS: Six weeks and six months after treatment, respectively, the proctitis symptom scores (0 (0-4) vs. 2 (0-7) (P < 0.001) vs. 2 (0-5) (P < 0.001)) and the incontinence symptom scores (0 (0-5) vs. 4 (0-11) (P < 0.001) vs. 3 (0-14) (P < 0.001)) increased. Urgency, frequency of defecation, anorectal pain, incontinence to liquid stool and to flatus, and alteration in lifestyle were significant symptoms after treatment. The following measurements decreased: anal canal resting pressure (83 (35-137) vs. 79 (26-152) (P = NS) vs. 71 (29-97) (P < 0.01) cm H2O), the squeeze increment (152 (51-135) vs. 162 (63-321) (P = NS) vs. 108 (45-296) (P < 0.042) cm H2O), and the maximum tolerated rectal volume (245 (115-450) vs. 194 (112-344) (P < 0.05) vs. 200 (109-350) (P < 0.138) ml). The rectal electrosensory threshold increased (20 (5.4-44) vs. 22 (9-50.5) (P < 0.134) vs. 31.5 (13.6-76) (P < 0.001) mA). CONCLUSIONS: Anorectal symptoms at six weeks after pelvic radiotherapy are related to reduced rectal capacity and compounded at six months by diminished internal and external sphincter function and rectal mucosal sensitivity.     

Metabolic regulation of apoproteins of high-density lipoproteins by estrogen and progesterone in the baboon (Papio sp)

To determine the metabolic regulation of the apoproteins of high-density lipoproteins (HDL) by estrogen and progesterone, 12 ovariectomized and hysterectomized baboons were fed a high cholesterol, high fat diet and were divided into four groups. One of these groups was the untreated control and the remaining three groups were treated with estrogen, progesterone, or a combination of both. After 10 months of treatment, there were significant differences in HDL apolipoprotein (apo) A-I and apo A-II levels in these groups. The apo A-I level was highest in baboons treated with the combination therapy, followed by those treated with estrogen. Baboons treated with progesterone and those in the control group had similar levels of apo A-I. Baboons treated with both estrogen and progesterone and estrogen alone had significantly higher levels of apo A-I than those in the control or progesterone group. Baboons treated with hormones had higher apo A-II levels than controls, and those treated with the combination therapy had the highest level. Metabolic studies suggested that both estrogen and progesterone increased apo A-I and apo A-II production. Progesterone also increased the fractional catabolic rate of apo A-I, but not of apo A-II. On the other hand, estrogen did not affect the fractional catabolic rate of either apo A-I or apo A-II. Thus, increased apo A-I content of HDL in baboons treated with both estrogen and progesterone or estrogen alone appears to be due to increased apo A-I synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Trichoderma harzianum ThU and Its Metabolites Underscore Alteration in Essential Oils of Ocimum basilicum and Ocimum sanctum

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Ocimum, an important commercial aromatic crop, is well known for the industrially acclaimed essential oil. In...     

Limited value of the resting electrocardiogram in assessing patients with recent onset chest pain: lessons from a chest pain clinic.

OBJECTIVE--To evaluate a clinic set up specifically to assess patients with recent onset chest pain, particularly those presenting with a normal resting electrocardiogram. DESIGN--Retrospective review of case notes. SETTING--Cardiac department of a tertiary referral cardiothoracic centre. PATIENTS--250 consecutive patients with recent onset chest pain seen within 24 hours of general practitioner referral. OUTCOME MEASURES--Clinical diagnosis and management. RESULTS--40% of patients were seen within seven days of the onset of symptoms. Twenty seven per cent had non-cardiac symptoms and could be discharged while 60% were considered to have cardiac pain. Sixty six patients (26%) were admitted directly from the clinic and 48 of these underwent coronary angiography within three weeks. Seventy patients (28%) have so far undergone intervention (angioplasty or coronary artery surgery), 22 within one month of presentation. One hundred and nine patients (44%) presented with a normal resting electrocardiogram, 21 of whom were considered to have unstable angina. Forty one of these patients were investigated of whom 37 were found to have significant coronary disease and 26 have undergone intervention. CONCLUSIONS--This experience highlights the inadequacy of a routine electrocardiogram reporting service in patients with recent onset of chest pain. An alternative facility offering immediate and complete cardiac assessment produced patient benefit with early diagnosis and intervention. Investigation of these patients, however, accounted for 5% of cardiac catheterisation laboratory throughput; this was a significant additional and unscheduled workload.     

Peritoneal Tuberculosis: Laparoscopic Patterns and Its Diagnostic Accuracy

We report laparoscopic findings in 38 proven cases of peritoneal tuberculosis. The laparoscopic appearances can be classified into three types: thickened peritoneum with miliary yellowish white tubercles with or without adhesions (n = 25), only thickened peritoneum with or without adhesions (n = 8), and fibroadhesive pattern (n = 5). Biopsies were avoided from fibroadhesive lesions due to risk of complications. Visual diagnosis was accurate in 95% of patients. In comparison, in 27 (82%) of 33 patients, the examination enabled a histologic diagnosis to he made on the basis of typical granulomas. The combined use of guinea pig inoculation and culture isolated Mycobacterium tuberculosis in six (37.5%) of 16 patients. Mycobacteria were scarcely (3%) seen on histological sections. We conclude that, although target biopsy is an effective method of obtaining an early diagnosis of peritoneal tuberculosis, chemotherapy may be started on the basis of visual laparoscopic appearances alone.