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Biomedical subjects

N Mehta

Publications and source records attributed to N Mehta.

At least 91 records · Page 5Linked to original sources

Prostaglandins as reducing agents: a model of adenylate cyclase activation?

It has been suggested that adenylate cyclase activation involves reduction of a disulfide linkage. Prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), prostaglandin I2 (PGI2) and prostaglandin F2 alpha (PGF2 alpha) were tested for their ability to act as reducing agents with either cytochrome c, or the disulfide 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB), the latter with a catalytic amount of ferric chloride. PGE1, PGE2, and PGI2 significantly reduced cytochrome c while PGF2 alpha did not. PGE1, PGE2 and PGI2 reduced DTNB while PGF2 alpha did not. The results are consistent with the postulate that prostaglandins which are effective in activating adenylate cyclase can act as reducing agents and might be involved in reductive activation of adenylate cyclase.

Adenylyl Cyclases↗

The dobutamine stress test as an alternative to exercise testing after acute myocardial infarction.

Three weeks after myocardial infarction in 50 patients the effect of the infusion of a graded dose of dobutamine was compared with that of symptom limited treadmill exercise testing. The following variables were measured: blood pressure, heart rate, ST segment changes, Doppler aortic blood flow, and cross sectional echocardiographic dimensions. The heart rate and double product increased more during exercise than during dobutamine infusion, while maximum acceleration in the ascending aorta increased more during dobutamine infusion than during exercise. Significant ST depression was recorded in 22 patients during exercise and in 24 during dobutamine infusion; the concordance between the two tests was 88%. In all cases in which ST segment depression occurred in both tests the site of ST depression was the same. Dobutamine stress testing is an alternative to exercise testing in patients after myocardial infarction.

Adult↗

Endogenous vasopressin affects postural control of blood pressure in man.

1. Six healthy volunteers received intravenous infusions of isotonic (0.9% NaCl) and hypertonic (3% NaCl) saline on separate days. There were no significant changes in blood pressure or forearm blood flow, despite an increase in plasma arginine vasopressin (AVP) during hypertonic saline. 2. Immediately and 10 min after passive tilting to 50 degrees, mean forearm blood flow fell by 17.1 and 14.3% compared with the values in the supine position during isotonic saline and by 40.3 and 43.3% during hypertonic saline. Forearm vascular resistance rose by 23.6 and 17.8% with isotonic saline and by 80.2 and 88.2% with hypertonic saline for the two readings in the tilted compared with the supine position. 3. Tilting was associated with a 14.9 and 12.1% rise in diastolic blood pressure immediately and 10 min after assuming this position during hypertonic saline, and a rise of 6.4% in mean arterial pressure. 4. The results from this study are similar to those obtained previously, when small amounts of AVP were infused. They provide further evidence that AVP may have a physiological role in the postural regulation of blood pressure.

Adult↗

Accurate detection of triple vessel disease in patients with exercise induced ST segment depression after infarction.

The severity of coronary artery disease is an important determinant of prognosis after acute myocardial infarction. The ability of a symptom limited exercise test to predict the presence of triple vessel disease was assessed in 221 patients three weeks after infarction. Coronary angiography was performed in patients with exercise induced ST segment depression. The presence of ST segment depression alone was poorly indicative of triple vessel disease; however, some specific features of ST segment changes on exercise were of predictive value. Downsloping ST segment configuration alone or horizontal ST segment depression associated with an early onset and a late recovery time after exercise correctly identified 30 (90%) of 33 patients with triple vessel disease whereas it incorrectly identified only 6 (15%) of 39 patients with single and double vessel disease. An abnormal blood pressure response was also predictive. In patients with ST segment depression after infarction triple vessel disease can be detected accurately by a combination of the electrocardiographic and haemodynamic variables attained on exercise.

Adrenergic beta-Antagonists↗

Selection of patients--critical aspects.

Proper selection of patients is the most critical aspect in designing clinical trials in migraine research. We establish specific research diagnostic criteria for the definition of migraine. Additional factors in patient selection, migraine frequency, duration, medications and previous treatments, are reviewed. Exclusion criteria and the mixed headache syndrome patient are discussed.

Clinical Trials as Topic↗

Ceruminoma revisited.

Ceruminoma is a catch-all term that has caused much confusion both in the literature and in clinical practice in regard to the specific histologic diagnosis and proper treatment for tumors arising from the ceruminous glands of the external ear canal. The term ceruminoma has been used in the past to refer to both benign and malignant lesions. To clarify the terminology and better determine appropriate treatment, two cases of benign adenoma of the ceruminous glands along with their histopathologic findings will be presented. The specific characterization of the individual types of ceruminous gland neoplasms, their clinical manifestations, histopathology, and recommended treatment will then be discussed. Finally, suggestions for the appropriate nomenclature for these rare tumors will be reviewed.

Adenoma↗

Usefulness of noninvasive Doppler measurement of ascending aortic blood velocity and acceleration in detecting impairment of the left ventricular functional response to exercise three weeks after acute myocardial infarction.

Left ventricular (LV) function was assessed by Doppler ultrasound measurement of ascending aortic blood velocity and maximal acceleration in 165 patients 3 to 4 weeks after acute myocardial infarction (AMI); all were undergoing routine 12-lead electrocardiogram exercise stress testing. Patients were grouped according to electrocardiographic stress test response; a positive response was defined as at least 1 mm of ST-segment depression in any lead. The Doppler velocity signal yielded 3 variables of interest: peak velocity, maximal acceleration (an index of inotropic state) and the systolic velocity integral (an index of stroke volume). All 3 Doppler ejection variables were significantly lower at peak exercise in patients with a positive electrocardiographic stress test response than in those with negative response, with maximal acceleration showing the most significance (p less than or equal to 0.001). Coronary angiography was performed in 63 of the 67 patients with positive responses, and patients were separated into 2 groups according to extent of coronary artery disease (CAD): 1- and 2-vessel or 3-vessel CAD. Peak velocity and maximal acceleration were significantly lower in patients with 3-vessel CAD than in those with 1- and 2-vessel CAD (p less than or equal to 0.01 and p less than or equal to 0.01). Discriminant analysis showed maximal acceleration and peak velocity values at peak exercise to be 65% predictive of 3-vessel CAD, onset time to ST-segment depression was 74% predictive and the combination of Doppler and electrocardiographic variables increased 3-vessel CAD predictive value to 80%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Impaired left ventricular function in acute myocardial infarction assessed by Doppler measurement of ascending aortic blood velocity and maximum acceleration.

The Doppler-derived ejection variables systolic velocity integral, maximum acceleration and heart rate were recorded in 92 patients with acute myocardial infarction (AMI) and 73 age-matched normal subjects. Systolic velocity integral was validated as an index of stroke volume against a thermodilution technique in acutely ill patients. Patients with AMI were separated into clinically defined Forrester subsets and into survivors and nonsurvivors of the acute infarction period. Systolic velocity integral correlates significantly with stroke volume determined by thermodilution (r = 0.07) in patients with aortic root areas within the normal range. Patients had a 37% lower maximum acceleration (p less than or equal to 0.001), a 48% lower systolic velocity integral (p less than or equal to 0.001) and a 13% higher heart rate than the age-matched normal subjects (p less than or equal to 0.01). Systolic velocity integral and maximum acceleration both showed a systematic significant decrease through the Forrester subsets (p less than or equal to 0.01, p less than or equal to 0.001, respectively), and were also significantly different between the survivor and nonsurvivor groups (p less than or equal to 0.05, p less than or equal to 0.01, respectively.) Thus, noninvasive measurement of ascending aortic blood velocity and acceleration allows rapid assessment of left ventricular function and provides indexes closely related to the patients' clinical status and subsequent risk of mortality, indicating the potential of the Doppler technique in the prognosis and subsequent management of patients with myocardial infarction.

Aorta, Thoracic↗

Application of the medical anti-shock trouser (MAST) increases cardiac output and tissue perfusion in simulated, mild hypovolaemia.

We have studied the haemodynamic effects of the application of the medical anti-shock trouser (MAST) in 10 healthy subjects in the semi-upright position in order to simulate mild hypovolaemia. Left ventricular end diastolic dimension (EDD) was measured by M-mode echocardiography and cardiac output (CO) by the Doppler ultrasound technique. Forearm blood flow (FBF) was measured by plethysmography and blood pressure (BP) by the standard cuff technique. Systematic increases in MAST pressure of up to 80 mm Hg were applied. EDD increased to a maximum of 9.3% (p less than or equal to 0.01) which was associated with a maximum increase in CO of 31.7% (p less than or equal to 0.05). FBF increased by a maximum of 54.2% (p less than or equal to 0.001) whilst BP increased by a maximum of 12% (p less than or equal to 0.001). These results demonstrate that the application of the MAST is an effective means of transferring blood to the central circulation by compression of the capacitance vessels resulting in significant increases in cardiac output and tissue perfusion. At high pressures there was evidence of compression of resistance vessels, which may be useful in reducing blood loss. The ease and rapidity with which his suit can be applied suggests that it may be useful in the short term treatment of hypovolaemia.

Adult↗

Haemodynamic effects of vasopressin in man are related to posture.

Ten healthy volunteers received intravenous infusions of arginine vasopressin (AVP) at 0.1 m-unit min-1 kg-1 and 5% D-glucose on separate days. AVP caused a small fall in forearm blood flow and small rises in mean arterial pressure and systemic vascular resistance. Cardiac output was unaffected. When subjects were tilted to 50 degrees the fall in forearm blood flow was much greater, mean fall being 44.8% with AVP compared with 18.2% with D-glucose. Cardiac output also fell significantly more with AVP, and diastolic pressure, mean arterial pressure and systemic vascular resistance rose significantly more on tilting during AVP infusion than with D-glucose. Six of the same volunteers were given sequential infusions of 'low dose' (0.0125 m-unit min-1 kg-1) and 'high dose' (0.3 m-unit min-1 kg-1) AVP on a third occasion. Tilting still produced a mean fall in forearm blood flow of 41.2% during low dose infusion, despite a mean plasma AVP level of only 1.9 pg/ml, which is well within the physiological range. When the AVP concentration was increased 24-fold to the high dose, forearm blood flow fell only a further 8.8%. The low dose infusion was also associated with a marked fall in cardiac output on tilting and a rise in systemic vascular resistance. We conclude that AVP has profound haemodynamic effects in man at physiological concentrations. Although these effects are modest in the supine position, they become marked on tilting, suggesting a possible role for AVP in the postural control of blood pressure.

Adult↗

Ventilation and cardiac output during the onset of exercise, and during voluntary hyperventilation, in humans.

Three normal subjects performed rest--exercise transitions on a cycle ergometer, from rest to unloaded pedalling (0 W), 50, 100 and 150 W. Each experiment was performed in triplicate, with randomized work load order, in two sessions. Ventilation was obtained breath-to-breath by integration of a pneumotachygraph signal, and cardiac output beat-to-beat by a new development of the Doppler technique. Results were bin-averaged in 4 s bins over the first 20 s, and compared to resting values. Both ventilation and cardiac output increased significantly in the first 2 s. This initial rise in ventilation was due entirely to an increase in rate, the subsequent rise mainly to increase in tidal volume. Cardiac output increased predominantly through change in rate with smaller increases in stroke volume. A striking feature was a tendency for ventilation and cardiac output responses to be biphasic with an initial rise followed by a slight fall at the 14 s mark, and a subsequent rise, at all work loads. Overall correlation between ventilation and cardiac output was therefore high (r = 0.92). Six normal subjects hyperventilated for 45 s voluntarily, (a) at rate 24/min and normal tidal volume; (b) at normal rate and tidal volume of 1.5 l; (c) at rate 24/min and tidal volume of 1.5 l. Cardiac output, averaged over 10-45 s, rose by 0.4, 0.5, and 1.0 l min-1 respectively, with falls in end-tidal PCO2 of 4, 6, and 8 mmHg. Six normal subjects hyperventilated for 60 s with rate 24/min and tidal volume of 1.4 l, and end-tidal PCO2 maintained at 38 +/-2 mm Hg. Cardiac output, averaged from 10-60 s, rose by 1.0 l min-1. With increased rate and tidal volume, whether isocapnic or hypocapnic, cardiac output responses showed an overshoot with a peak value at about 30 s. The hypothesis of 'cardiodynamic hyperpnoea' considers a possible effect of increasing cardiac output on ventilation. The effects of ventilation on cardiac output must also be considered. We propose an extended hypothesis involving stable positive feed-back.

Adult↗

Immediate ventilatory response to sudden changes in venous return in humans.

We changed venous return transiently by postural manoeuvres, and by lower body positive pressure, to see what happened simultaneously to ventilation. Cardiac output was measured by a Doppler technique. In seven subjects, after inflation of a pressure suit to 80 and 40 mmHg at 30 deg head-up tilt, both cardiac output and ventilation increased. Ventilation increased rapidly to a peak in the first 5 s, cardiac output more slowly to a steady state in about 20 s, at 80 mmHg inflation. After inflation to 80 mmHg in six subjects at 12.5 deg head-up and 30 deg head-down tilt, cardiac output did not change in the first, and fell in the second case. There were no significant changes in ventilation. On release of pressure there were transient increases in both cardiac output and ventilation, with ventilation lagging behind cardiac output, in contrast to (2) above. In five subjects, elevation of the legs at 30 deg head-up tilt caused a rise in both cardiac output and ventilation, but in two subjects neither occurred. In all seven subjects there was a transient increase in cardiac output and ventilation when the legs were lowered. Ventilation and cardiac output changes were approximately in phase. We were therefore unable to dissociate entirely increasing cardiac output from increasing ventilation. The relation between them was certainly not a simple proportional one.

Adult↗

Validation of a Doppler technique for beat-to-beat measurement of cardiac output.

We have measured aortic flow in the ascending aorta in man with a Bach-Simpson BVM 202 blood velocity meter, and aortic root diameter by M-mode echocardiography, and thus derived beat-to-beat cardiac output (Q). We tested the technique in 21 patients (53 comparisons) with various cardiovascular problems against a thermodilution method, and in four normal subjects at rest and two levels of exercise (50 and 100 W) against a nitrous oxide rebreathing method. We obtained excellent overall correlation in a range of 0.5-10 litres/min (r = 0.98, n = 77, sy,x = 0.48 litre/min), the formula for the least squares regression being: (Q Doppler) = 0.95 (Q Thermodilution/N2O) + 0.11 litre/min. The Doppler signal is sufficiently noise-free to obtain maximum acceleration of flow from the first derivative of velocity.

Adult↗

Ascending aortic blood velocity and acceleration using Doppler ultrasound in the assessment of left ventricular function.

We have used a 2.2 MHz continuous-wave Doppler blood velocity meter (Bach-Simpson BVM 202) to measure ascending aortic blood velocity and acceleration, and have obtained from the velocity signal a noninvasive measure of stroke volume and cardiac output by combining the Doppler technique with M-mode echocardiography. In two separate studies we have systematically altered the loading conditions of the heart with lower body pressure; and the inotropic state of the heart with dobutamine (5 micrograms . kg-1 . min-1), and documented the changes in mean velocity (MV), maximum acceleration (MA), stroke volume (SV), cardiac output (CO) and left ventricular end-diastolic dimension (EDD) (M-mode echocardiography). Application of lower body pressure to subjects in a 30 degrees head-up tilt position caused a systematic increase in preload, as shown by a 9% increase in EDD, which raised SV by a maximum of 33% (p less than or equal to 0.001) and CO by 32% (p less than or equal to 0.01), thus showing a classical Starling response; whilst there was relatively little increase in MA. Conversely, infusion of dobutamine, an inotropic agent, caused a 29.2% increase in MA (p less than or equal to 0.01) with minimal increase in SV. Thus, the ability to measure ascending aortic blood velocity allows noninvasive monitoring of changes in both inotropic state and Starling function, with considerable ease and rapidity.

Adolescent↗

Increased forearm vascular resistance after dopamine blockade.

The peripheral haemodynamic effects of a 40 mg intravenous injection of domperidone (a dopamine antagonist) have been studied in 10 normal subjects. In four subjects domperidone was infused directly into the brachial artery and the effects on forearm blood flow were measured. When administered systemically, domperidone significantly decreased forearm blood flow by 9% (P less than 0.01) and significantly increased calculated forearm vascular resistance by 11% (P less than 0.01). The drug produced no measurable changes in forearm blood flow at any dose when infused directly into the brachial artery. A further study was carried out into the effects of a systemic injection of domperidone on peripheral sympathetic tone. Reduction of sympathetic tone in the forearm was achieved by passively raising the legs of eight recumbent subjects. Before domperidone administration, passive leg elevation significantly increased forearm blood flow by 39% and decreased forearm vascular resistance by 13%. After drug administration the absolute values of vascular resistance increased and the changes between the supine and elevated position values when compared with those of the corresponding values prior to drug administration were significantly lower. These results suggest that the role of domperidone in increasing peripheral vascular tone is unlikely to be mediated by a direct local effect on peripheral resistance vessels. Any effect the drug may have is suggested to be mediated via a central control mechanism.

Adult↗