Observations of carbon monoxide in comet Hale-Bopp.

The recently discovered comet Hale-Bopp (C/1995 01) sports a bright dust coma even though it is still far from the sun (presently 6 astronomical units). This feature has attracted considerable interest in the public and scientific arenas. The comet is headed toward perihelion at 0.92 astronomical unit in April 1997 and is widely expected to then become a spectacular naked-eye comet. With millimeter-wave observations, carbon monoxide (CO) has been identified as the driver for the early activity observed in Hale-Bopp.

Discovery of a new jupiter satellite.

During detailed analysis of Voyager 2 pictures of the Jupiter ring, a starlike object was identified in the plane of the ring. The same object was subsequently found on a higher-resolution frame and proved to be a satellite of Jupiter. This satellite has a circular orbit whose radius is 1.8 Jupiter radii, a period of 7 hours and 8 minutes, and a diameter of less than 40 kilometers. It is located at the outer edge of the Jupiter ring.

Measurements of 12C/13C, 14N/15N, and 32S/34S ratios in comet Hale-Bopp (C/1995 O1).

The 12C/13C, 14N/15N, and 32S/34S isotope ratios in comet Hale-Bopp (C/1995 O1) were determined through observations taken with the James Clerk Maxwell Telescope. Measurements of rare isotopes in HCN and CS revealed isotope ratios of H12CN/H13CN = 111 +/- 12, HC14N/HC15N = 323 +/- 46, and C32S/C34S = 27 +/- 3. Within the measurement uncertainties, the isotopic ratios are consistent with solar system values. The cometary volatiles thus have an origin in the solar system and show no evidence for an interstellar component.

A determination of the HDO/H2O ratio in comet C/1995 O1 (Hale-Bopp).

Deuterated water (HDO) was detected in comet C/1995 O1 (Hale-Bopp) with the use of the James Clerk Maxwell Telescope on Mauna Kea, Hawaii. The inferred D/H ratio in Hale-Bopp's water is (3.3 +/- 0.8) x 10(-4). This result is consistent with in situ measurements of comet P/Halley and the value found in C/1996 B2 (Hyakutake). This D/H ratio, higher than that in terrestrial water and more than 10 times the value for protosolar H2, implies that comets cannot be the only source for the oceans on Earth.

Deuterium in comet C/1995 O1 (Hale-Bopp): detection of DCN.

Deuterated hydrogen cyanide (DCN) was detected in a comet, C/1995 O1 (Hale-Bopp), with the use of the James Clerk Maxwell Telescope on Mauna Kea, Hawaii. The inferred deuterium/hydrogen (D/H) ratio in hydrogen cyanide (HCN) is (D/H)HCN = (2.3 +/- 0.4) x 10(-3). This ratio is higher than the D/H ratio found in cometary water and supports the interstellar origin of cometary ices. The observed values of D/H in water and HCN imply a kinetic temperature >/=30 +/- 10 K in the fragment of interstellar cloud that formed the solar system.

Doppler echocardiographic appearance of cusp tears in tissue valve prosthesis.

Characteristic Doppler echocardiographic abnormalities were noted in five patients with a failing tissue prosthesis shown to have severe regurgitation and no evidence of obstruction. The audio signal was musical in quality and the regurgitant flow pattern was bidirectional and striated. There were 4 to 6 striations in the mitral and 18 in the aortic regurgitant jets per 100 cm/s length of signal. Pulsed Doppler ultrasound localized the jet to the valve in all cases although angiography failed to localize it in one of four cases. At surgery each valve had a tear in or partial disintegration of one cusp whereas the other two cusps were intact, mobile and of normal thickness. The Doppler appearance is thought to be caused by fluttering of the disrupted cusp leading to the shedding of families of vortices in both a retrograde and an orthograde direction. It is suggested that this is likely to be a useful sign for the diagnosis of cusp tears.

Restoration of normal reflex responses to orthostatic stress during felodipine therapy in congestive heart failure.

The mechanisms underlying the abnormal responses to orthostatic stress in congestive heart failure are ill defined and little is known about the effects of specific therapy. In the present study intravascular pressures and plasma noradrenaline levels were measured in nine patients with heart failure subjected to 45 degrees and 90 degrees upright tilt. Studies were repeated during 4 weeks of vasodilator therapy with felodipine and again after felodipine withdrawal. Before the introduction of vasodilator therapy, tilt did not activate orthostatic reflexes despite significant reductions in left ventricular filling pressure and cardiac output. Thus, plasma noradrenaline, heart rate and systemic vascular resistance were unaffected and blood pressure fell. Felodipine resulted in a rapid and sustained improvement in left ventricular function but restoration of orthostatic reflexes was delayed and could be detected only after 48 h therapy. At this time, and during the subsequent 4 weeks, tilt-induced reductions in ventricular filling and cardiac output produced a normal rise in plasma noradrenaline and heart rate. A postural drop in blood pressure, however, was not averted because the direct action of felodipine on vascular smooth muscle prevented adrenergically-mediated increments in systemic vascular resistance. Felodipine withdrawal led to a prompt deterioration in left ventricular function. Orthostatic reflexes, however, were still intact 48 h later when tilt elicited a completely normal pattern of responses. These observations confirm that the abnormal responses to orthostatic stress in congestive heart failure are due principally to impairment of autonomic control mechanisms and are not related to the absence of venous pooling. Importantly the autonomic dysfunction is reversible with felodipine therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Endocrine and cardiac paracrine actions of insulin-like growth factor-I (IGF-I) during thyroid dysfunction in the rat: is IGF-I implicated in the mechanism of heart weight/body weight change during abnormal thyroid function?

Thyroid hormones are essential for the normal growth and development of many tissues. In the rat, hypothyroidism is associated with growth impairment, and hyperthyroidism with the development of a hypercatabolic state and skeletal muscle wasting but, paradoxically, cardiac hypertrophy. The mechanism by which thyroid hormone produces cardiac hypertrophy and myosin isoenzyme changes remains unclear. The role of IGF-I, an anabolic hormone with both paracrine and endocrine actions, in producing cardiac hypertrophy was investigated during this study in hyperthyroid, hypothyroid and control rats. A treated hypothyroid group was also included in order to assess the effect of acute normalization of thyroid function. Body weight was significantly lower in the hyperthyroid (mean +/- S.E.M.; 535.5 +/- 24.9 g, P < 0.05), hypothyroid (245.3 +/- 9.8 g, P < 0.001) and treated hypothyroid (265.3 +/- 9.8 g, P < 0.001) animals when compared with controls (618.5 +/- 28.6 g). Heart weight/body weight ratios were, however, significantly increased in the hyperthyroid (2.74 +/- 0.11 x 10(-3), P < 0.01) and treated hypothyroid (2.87 +/- 0.07 x 10(-3), P < 0.001) animals when compared with controls (2.26 +/- 0.03 x 10(-3). Serum IGF-I concentrations were similar in the control and hyperthyroid rats (0.91 +/- 0.07 vs 0.78 +/- 0.04 U/ml, P = 0.26), but bioactivity was reduced by 70% in hyperthyroid serum, suggesting a circulating inhibitor of IGF. Serum IGF-I levels (0.12 +/- 0.03 U/ml, P < 0.001) and bioactivity (0.12 +/- 0.04 U/ml, P < 0.001) were significantly lower in the hypothyroid group. Liver IGF-I mRNA levels were not statistically different in the control and hyperthyroid animals, but were significantly reduced in the hypothyroid animals (P < 0.05 vs control). Heart IGF-I mRNA levels were similar in the control and hypothyroid rats, but were significantly increased in the hyperthyroid and treated hypothyroid animals (increased by 32% in hyperthyroidism, P < 0.05; increased by 57% in treated hypothyroidism, P < 0.01). Cardiac IGF-I was significantly elevated in hyperthyroidism (0.16 +/- 0.01 U/mg heart tissue, P < 0.01), was low in hypothyroidism (0.08 +/- 0.01 U/mg, P < 0.01) and was normalized in the treated hypothyroid group (0.11 +/- 0.01 U/mg vs control, 0.13 +/- 0.01 U/mg). Low body mass during both hypothyroidism and hyperthyroidism is therefore associated with reduced systemic IGF bioactivity. In hypothyroidism there is a primary defect in the endocrine function of IGF-I, while in hyperthyroidism serum IGF bioactivity is reduced in the presence of normal endocrine production of this anabolic hormone.(ABSTRACT TRUNCATED AT 400 WORDS)

Association of antibodies to heat-shock protein-65 with percutaneous transluminal coronary angioplasty and subsequent restenosis.

Heat-shock protein (HSP)-65 of mycobacterial origin has been implicated in the mediation of atherosclerosis by immune mechanisms. Any role of HSP-65 in mediating restenosis is however not clear. We determined the anti-HSP-65 antibodies in 28 patients, 25 male and 3 female, aged 35 to 78 years, with coronary artery disease (CAD) and undergoing percutaneous transluminal coronary angioplasty (PTCA). Of the 28 patients, 12 suffered restenosis five to seven months later. The serum levels of antibody were measured at baseline, immediately after PTCA, before discharge from the hospital, and at 6 weeks, 3 and 6 months after the performance of PTCA. The antibody levels were expressed in OD U/log titre, as explained in the text, and termed estimated OD or EOD. The control group consisted of 29 healthy volunteers, 16 male and 13 female, aged 24 to 59 years. The mean EOD of the patients at baseline was higher than that of the controls (0.60 +/- 0.12, SD; 95% CI 0.56-0.64 compared with 0.53 +/- 0.13; 0.48-0.58; p < 0.01). There were no correlation between age and EOD of patients, controls or both taken together, ruling out the influence of age on the EOD changes in the given age range. The mean antibody levels of the patients with CAD were similar whether or not they suffered subsequent restenosis (0.61 +/- 0.15; 0.53-0.69 in the patency group, and 0.60 +/- 0.10; 0.54-.066 in the restenosis group). However, the patients who did not develop restenosis had a drop in their antibody levels immediately after PTCA (0.51 +/- 0.14; 0.48-0.55; 2-tailed p = 0.029), and at discharge from the hospital (0.52 +/- 0.15; 0.44-0.60; p = 0.036) as compared with the baseline. This decrease of antibodies was not observed in the restenosis group. Furthermore, the anti-HSP-65 antibody levels remained slightly low throughout the 6-month follow-up in the patients with patent coronaries as compared with patients who restenosed, but the decrease was statistically not significant at 5% level at any stage. Besides the anti-HSP-65 antibodies, the levels of anticardiolipin (ACL) antibody were also measured in all the patients. The levels of the ACL antibody were found to be within the normal range before and at all stages after PTCA, ruling out the PTCA-associated change in the anti-HSP-65 antibody as a non-specific occurrence. Thus, a drop in the level of antibody against HSP-65 after PTCA seemed to be associated with a favourable outcome, and may serve as a useful prognostic marker of coronary angioplasty.

Decrease in factor VII coagulant activity during percutaneous transluminal coronary angioplasty by heparin-mediated lipolytic action.

Levels of factor VII coagulant activity (FVII:C) and two-chain factor VIIa antigen (FVIIa:Ag) were measured in ten patients before and up to 6 h after receiving a bolus of heparin during percutaneous transluminal coronary angioplasty (PTCA). A significant and sustained post-heparin fall in the level of FVII:C was observed (approximately 30%) without any change in the level of FVIIa:Ag. The level of tissue factor antigen within the circulation remained unchanged. The observed decrease in FVII:C coincided with a significant decrease in triglyceride levels presumably due to lipoprotein and hepatic lipase released by the heparin. These findings appear to demonstrate a lipid (triglyceride) dependence of FVII:C. Thus, heparin may act indirectly as antithrombotic agent by limiting a lipid-dependent activation of the extrinsic pathway of coagulation.

The potential thrombogenic action of a nonionic radiographic contrast medium used during coronary angiography is offset by heparin during coronary angioplasty.

Iohexol sodium, a nonionic radiographic contrast medium, used in invasive imaging techniques has been shown to be potentially thrombogenic. In the present study, the effect of iohexol sodium on haemostatic factors was evaluated in 20 patients, 16 male and 4 female, 10 undergoing coronary angiography and another 10 undergoing coronary angioplasty. All the patients had angiographically-assessed coronary artery disease. The patients undergoing coronary angioplasty received a significantly larger quantity of the dye as compared with the patients undergoing coronary angiography. The former group of patients also received a bolus of 20,000 units of standard heparin in addition. The levels of thrombin-antithrombin-III complex (TAT), prothrombin fragments 1 and 2 (F1F2), D-dimer and the functional activity of tissue factor pathway inhibitor (TFPI) were assayed. While the baseline and 30-min post-dye levels of TAT and F1F2 were comparable in patients undergoing coronary angioplasty, the 30 min levels were significantly elevated in patients undergoing coronary angiography. The post-dye levels of TFPI activity were significantly increased in the former group due to the heparin-induced release of TFPI. It is concluded that the thrombogenic potential of iohexol sodium was overcome by heparin used routinely during coronary angioplasty.

Electrophysiologic, hemodynamic and metabolic effects of intravenous bepridil hydrochloride.

Bepridil, a fast and slow channel blocking drug, was administered intravenously over 5 minutes in a dose of 3 mg/kg body weight to 19 patients. Ten patients received intravenous bepridil during electrophysiologic study, performed for the investigation of known or suspected cardiac arrhythmias. Sinus cycle length increase from 764 +/- 56 to 886 +/- 62 ms (p less than 0.002). AH interval increased from 101 +/- 6.9 to 137 +/- 11.9 ms (p less than 0.01). HV and QRS durations were not significantly affected. QTc interval increased from 395 +/- 13 to 423 +/- 13 ms (p less than 0.001). Atrial effective refractory period increased from 211 +/- 8 to 242 +/- 8.7 ms (p less than 0.005), and atrioventricular nodal effective refractory period increased from 299 +/- 26 to 366 +/- 30 ms (p less than 0.02). Right ventricular effective refractory period increased from 233 +/- 9.3 to 259 +/- 8.1 ms (p less than 0.001). In an additional 9 patients with coronary artery disease, a hemodynamic and metabolic study was performed. A transient mean decrease dP/dt max from 1,646 +/- 164 to 1,506 +/- 238 mm Hg/s (p less than 0.05) and a mean increase of 2.6 mm Hg (p less than 0.05) in left ventricular end-diastolic pressure were observed. Both values had returned to control levels 15 minutes after drug infusion. Blood pressure, cardiac output, coronary sinus blood flow and myocardial lactate extraction ratio did not change significantly. This profile of powerful electrophysiologic and minor hemodynamic changes indicates a potentially useful role for bepridil in the acute management of supraventricular arrhythmias and, possibly, ventricular arrhythmias.

Drug treatment of primary pulmonary hypertension.

Primary pulmonary hypertension is a rare but difficult-to-manage condition. Adequate clinical trials of agents used in its treatment have not been performed. A variety of drugs have been reported to provide benefit in patients with primary pulmonary hypertension, including beta-adrenoceptor agonists, alpha-adrenoceptor antagonists, and vasodilators such as isosorbide dinitrate, diazoxide, hydralazine, angiotensin converting enzyme inhibitors, prostaglandins and calcium antagonists. Calcium antagonists appear to offer the most promise, although treatment failures have occurred with them as well as with all other drugs used in this condition. In the absence of a specific treatment for primary pulmonary hypertension, several of the agents listed above should be tried before accepting therapeutic failure. Invasive investigation is necessary to adequately monitor the acute response to therapy. Whether combination therapy with 2 or more drugs might improve the response to treatment is an area worthy of further research.

Studies with felodipine in congestive heart failure.

Felodipine is a new calcium antagonist with a high degree of vascular selectivity. Its potential role in the treatment of congestive heart failure was examined in short and long term oral studies. Short term felodipine 5 to 15 mg in 11 patients increased (p less than 0.001) cardiac index (from 2.1 +/- 0.1 to 3.3 +/- 0.2 L/min/m2), and reduced systemic resistance (from 26 +/- 2 to 12 +/- 2 units) and left ventricular end-diastolic pressure (from 26 +/- 2 to 13 +/- 2mm Hg) without affecting heart rate. Left ventricular max dp/dt did not change, but max dp/dt/p increased from 19 +/- 1 to 24 +/- 1 sec-1 (p less than 0.001). Left ventricular unloading was reflected by a shift in the end-systolic pressure-dimension relationship downwards and to the left. Myocardial oxygen supply to demand ratio improved significantly; coronary flow increased from 141 +/- 11 to 176 +/- 15 ml/min and myocardial oxygen consumption fell from 18 +/- 2 to 14 +/- 1 ml/min (p less than 0.05). Long term therapy with felodipine 30 mg daily in 10 patients improved treadmill exercise tolerance after 4 weeks by 24% (p less than 0.001). Stroke index at submaximal exercise increased from 37 +/- 3 to 47 +/- 2 ml/beat/m2 (p less than 0.001). Pulmonary capillary wedge pressure fell significantly (22 +/- 5 to 10 +/- 3mm Hg), as did arteriovenous oxygen difference (12.7 +/- 0.9 to 9.7 +/- 0.6 vols/100ml). Importantly, these beneficial effects with felodipine were sustained during 4 weeks' therapy without evidence of tachyphylaxis. These data indicate that the selective vasodilator properties of felodipine may extend the clinical application of calcium antagonists to include the management of heart failure.

Evaluation of myocardial, hepatic, and renal perfusion in a variety of clinical conditions using an intravenous ultrasound contrast agent (Optison) and second harmonic imaging.

OBJECTIVE: To assess the potential of intravenous Optison, a second generation ultrasound contrast agent, and various ultrasound imaging modes to determine myocardial, kidney, and liver perfusion in normal subjects and patients with left ventricular dysfunction or chronic pulmonary disease together with renal or hepatic dysfunction. METHODS: Five normal subjects and 20 patients underwent grey scale echocardiographic imaging of myocardium, kidney, and liver during 505 intravenous injections of Optison. Images were assessed qualitatively by two independent observers and quantitatively using video densitometry to determine the peak contrast enhancement effect. RESULTS: Qualitative analysis showed that intermittent harmonic imaging was superior to either conventional fundamental or continuous harmonic imaging for all organs. Quantitative analysis showed that the peak change in echocardiographic intensity v baseline during continuous harmonic imaging was 11 units for myocardium (p < 0.03), 7 units for kidney (NS), and 14 units for liver (p < 0.05). During intermittent harmonic imaging the peak change was significantly greater, being 33 units for myocardium (p < 0.0001), 24 units for kidney (p < 0.0002), and 16 units for liver (p < 0.001). CONCLUSIONS: Organ tissue perfusion can be demonstrated following intravenous injection of Optison, particularly when used in combination with intermittent harmonic imaging techniques. This contrast agent is effective in a variety of clinical conditions.

Randomised trial of elective stenting after successful percutaneous transluminal coronary angioplasty of occluded coronary arteries.

BACKGROUND: The value of angioplasty in occluded coronary arteries is limited by a restenosis/reocclusion rate of 50-70%. In patients with subtotal occlusion, stent implantation has been shown to reduce clinical and angiographic restenosis. Retrospective observational studies have suggested that stenting could reduce restenosis in total occlusions. The value of sustained coronary patency on global and regional left ventricular function in this clinical setting has not been defined clearly. OBJECTIVES: To assess the medium term effect of elective intracoronary stent deployment after successful percutaneous transluminal coronary angioplasty (PTCA) of an occluded coronary artery. METHODS: Sixty patients with a total coronary occlusion successfully treated by PTCA were randomised to receive an intracoronary stent or no stent. Patients underwent clinical and angiographic follow up at six months. RESULTS: Thirty patients received a stent (group A) and 30 were treated by angioplasty alone (group B), all with initial success. One patient in group B required repeat angioplasty with stenting at 24 hours and one patient died after 10 days. Angiographic follow up was available for 57 patients. This showed a significantly reduced reocclusion rate in group A compared with group B (7% v 29%, p < 0.01) and a tendency to a reduced restenosis rate (22% v 40%, p = 0.105) in patients with no reocclusion. Left ventricular function, both global and regional, improved in group A. Only the regional left ventricular function in the area supplied by the target coronary artery improved in group B. Recurrence of symptoms and clinical events such as repeat angioplasty, coronary artery bypass grafting, death or myocardial infarction tended to be reduced in group A (4 (13%) v 9 (30%)). CONCLUSIONS: Intracoronary stent insertion is effective in reducing the rate of reocclusion and shows a trend towards reduced restenosis after opening of a total coronary occlusion by balloon angioplasty. Sustained patency of the target coronary artery is associated with improvement in global and regional left ventricular function.

Transesophageal echocardiography in the detection and surgical management of a papillary fibroelastoma of the mitral valve causing partial mitral valve obstruction.

Primary mitral valve tumors are rare. We describe the transesophageal appearances of a papillary fibroelastoma (Lambl's giant excrescence) of the anterior mitral valve leaflet causing partial mitral valve obstruction. Transesophageal echocardiography proved particularly useful in identifying the limited attachment of the tumor to the anterior mitral valve leaflet and excluding its attachment to the interatrial septum. These features helped to exclude the possibility of the tumor being a left atrial myxoma, the primary differential diagnosis of the lesion. Transesophageal echocardiography enabled the planned surgical option to be mitral valve repair and also allowed intraoperative monitoring to assess the results of the surgical repair.

Aortoatrial fistulae diagnosed by transthoracic and transesophageal echocardiography: advantages of the transesophageal approach.

Aortoatrial fistulae are uncommon, providing a difficult diagnostic challenge both in the clinical diagnosis and in the choice of an imaging modality that fully delineates the abnormal anatomy and flow patterns. This report describes four cases of aortoatrial fistula resulting from three different underlying causes. The fistula communicated with the right atrium in three cases and the left atrium in one. We also describe the diagnostic information obtained during both transthoracic and transesophageal echocardiography and stress that full detail of the abnormal anatomy and shunting could be obtained only with the transesophageal approach, with its improved image quality of the aortic root. No extra information, other than the coronary anatomy, was obtained during aortography in the two patients who underwent cardiac catheterization. Transesophageal echocardiography should, therefore, be the investigation of choice in patients in whom there is a suspicion of aortoatrial shunting after clinical examination and routine transthoracic studies, and it may avoid the need for invasive investigation in these potentially hemodynamically unstable patients.

The value of transthoracic echocardiography during percutaneous balloon mitral valvuloplasty.

Percutaneous balloon mitral valvuloplasty is a standard alternative to surgery in a selected group of patients with symptomatic dominant rheumatic mitral stenosis. With careful transthoracic and transesophageal echocardiographic selection of patients, there is a low complication and high success rate. Echocardiography has also been established as extremely useful in the long-term follow-up of patients. We present four cases that highlight our view that transthoracic echocardiography should be performed during the procedure, after each balloon inflation, and before and after the intervention. In our experience transthoracic echocardiography during balloon mitral valvuloplasty is invaluable in assessing commissural separation, increasing mitral valve area, new mitral regurgitation, and occasional unexpected anatomic sequelae of balloon inflation.

Left atrial spontaneous echo contrast assessed by TEE in patients with either native mitral valve disease or mitral valve replacement.

The incidence of spontaneous echo contrast in the left atrium, the factors with which it is associated, and its clinical significance were studied in 128 patients with native mitral valve disease or mitral valve replacement. All patients underwent both transesophageal and transthoracic echocardiography. Spontaneous echo contrast was visualized in 42 patients (33%) during transesophageal and in none during transthoracic echocardiography. Patients with spontaneous echo contrast had a significantly larger left atrial diameter (6.1 [1.1] cm vs 4.9 [0.9] cm, p < 0.001) and a greater incidence of both atrial fibrillation (54% vs 4%, p < 0.001) and left atrial thrombi (60% vs 28%, p < 0.01) compared with patients without spontaneous echo contrast. Multivariant analysis confirmed that these factors were independently associated with spontaneous echo contrast (left atrial size, p < 0.001; atrial fibrillation, p < 0.001; left atrial thrombus, p < 0.01). Patients with pure mitral regurgitation did not have any spontaneous echo contrast and anticoagulation did not influence its incidence. Spontaneous echo contrast was the only factor that was associated with a previous history of systemic embolization (history of systemic emboli in 28.6% of patients with spontaneous echo contrast vs 13.9% without spontaneous echo contrast, p < 0.05). In conclusion, spontaneous echo contrast is a common finding in the left atrium of patients with mitral valve disease or mitral valve replacement and represents a marker of increased thromboembolic risk in these patients.