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Biomedical subjects

R Doshi

Publications and source records attributed to R Doshi.

17 recordsLinked to original sources

Can signal intensity of the continuous wave Doppler regurgitant jet estimate severity of mitral regurgitation?

Visual estimates of the intensity of the continuous wave (CW) Doppler regurgitant jet signal have been used to estimate the severity of valvular regurgitation. Theoretically, the strength of the reflected Doppler signal is a function of the number of scatterers. To test this approach quantitatively, free jets were produced in 27 experiments using a power injector and cornstarch suspension varying in concentration from 1% to 3%. Flow volume was varied from 5 to 15 ml, and orifice diameter varied from 2.5 to 10 mm. Machine settings were kept constant. Also, 22 patients with mitral regurgitation (MR)--5 mild, 11 moderate, and 6 severe by angiography--were studied. Average signal intensity under the CW Doppler flow curve was calculated using a computer image processor. In MR patients, average regurgitant flow (RF) intensity was compared with average mitral forward flow (FF) signal intensity. (1) The intensity under the CW flow signal in the free jet experiments correlated well with injection volume (r greater than 0.98). (2) RF average signal intensity did not correlate with angiographic MR severity (r = 0.21), but the ratio of RF to FF average signal intensity did correlate with MR severity (r = 0.73). (3) The sensitivity and the specificity of an RF/FF ratio greater than 0.65 for angiographically severe mitral regurgitation were both 83%. (4) The sensitivity and specificity of an RF/FF ratio less than 0.50 for angiographic mild mitral regurgitation were both 80%. The ratio of regurgitant to forward mitral flow CW Doppler signal intensity appears to be an accurate and clinically applicable method for estimating the severity of mitral regurgitation.

Adult

Transcriptional regulation of left ventricular beta-adrenergic receptors during chronic hypoxia.

beta-Adrenergic receptor downregulation is the end result of cellular adaptation to prolonged agonist exposure. The factors mediating receptor downregulation include receptor phosphorylation, receptor movement from the plasma membrane to intracellular sites, and alterations in nascent receptor synthesis. We have previously demonstrated a downregulation of the left ventricular beta-receptor during chronic hypoxia in vivo. To determine the mechanism of this downregulation, we produced chronic hypoxia in seven newborn lambs by creating right ventricular outflow obstruction and an atrial septal defect. Oxygen saturation was reduced to 65-74% for 2 weeks. Six lambs served as normoxic controls. Sarcolemmal membrane and cytosolic fractions were prepared from left ventricular free wall samples. beta-Receptor density in each fraction was determined with the radioligand [125I]iodocyanopindolol. Steady-state levels of beta-receptor mRNA were determined by Northern blot analysis using a beta 1-adrenergic receptor cDNA probe. During chronic hypoxia, left ventricular membrane beta-adrenergic receptor density decreased by 55% (153 +/- 28 fmol/mg for hypoxic lambs versus 342 +/- 79 fmol/mg for control lambs, p < 0.05). There was no corresponding increase in beta-receptor density in the cytosolic fraction (23 +/- 3 fmol/mg for hypoxic lambs versus 33 +/- 9 fmol/mg for control lambs, p = NS), nor was there a significant change in the ratio of beta 1-receptor/beta 2-receptor subtypes as assessed by radioligand binding (beta 1 subtype, 84.1 +/- 10.1% for hypoxic lambs versus 93.2 +/- 8.8% for control lambs; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Venous occlusion secondary to subluxation of the shoulder--a case report.

This is the case report of an eighty-seven-year-old woman who was seen because of swelling of her left upper extremity and breast of one week's duration. She had a history of severe arthritis of the knees and had been wheelchair-bound for seven years. Venography showed compression of the cephalic vein and thrombosis of the distal basilic vein with extension into the axillary and subclavian veins. To the author's knowledge, this is the first case report of venous thrombosis in association with subluxation of the shoulder.

Aged

Doppler color flow "proximal isovelocity surface area" method for estimating volume flow rate: effects of orifice shape and machine factors.

Previously described Doppler color flow mapping methods for estimating the severity of valvular regurgitation have focused on the distal jet. In this study, a newer Doppler color flow technique, focusing on the flow proximal to an orifice, was used. This method identifies a proximal isovelocity surface area (PISA) by displaying an aliasing interface. Volume flow rate (cm3/s) can be calculated as PISA (cm2) x aliasing velocity (cm/s). For planar circular orifices, a hemi-elliptic model accurately approximated the shape of PISA. Clinically, however, orifice shapes may be noncircular. In vitro flow experiments (n = 226) using orifices of various shapes (ellipse, square, triangle, star, rectangle) were performed. Volume flow rate calculated using a hemi-elliptic model for PISA was accurate, with average percent differences from actual flow rate = +4.3% for a square, -4.2% for a triangle, -4.7% for a star, -4.5% for an ellipse and -2.8% for a rectangle. However, average percent differences for calculated volume flow rates using a hemispheric model for PISA shape ranged from -11.6% (square) to -34.8% (rectangle). In addition, to evaluate whether PISA is influenced by machine factors, in vitro studies (n = 83) were performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Flow Velocity

Regulation of atrial autonomic receptors in experimental cyanotic heart disease.

During chronic hypoxemia, left ventricular beta-adrenergic receptor density is decreased and a dissociation occurs between increased chronotropic and decreased inotropic responses to chronically elevated sympathetic tone. To determine whether this dissociation was related to alterations in autonomic receptor populations in the right atrium, we studied right atrial cholinergic and beta-adrenergic receptors in chronically hypoxemic newborn lambs and in normoxemic controls. Heart rate response was determined by infusing isoproterenol at 0.1 or 0.5 microgram.kg-1.min-1. Muscarinic receptors were quantified with [3H]quinuclidinyl benzilate and beta-adrenergic receptors with [125I]iodocyanopindolol. Competition with ICI 118,551 was used to determine beta 1- vs. beta 2-receptor subtypes. In the hypoxemic lambs, isoproterenol resulted in a lesser percentage increase in heart rate (hypoxemic, 46 +/- 6% vs. control, 89 +/- 17%, P less than 0.05); however, because baseline heart rate was higher in the hypoxemic lambs (213 +/- 7 vs. 177 +/- 12 beats/min, P less than 0.05), maximal heart rate responses were similar (310 +/- 7 vs. 326 +/- 6 beats/min, NS). There was no change in receptor density or affinity of either muscarinic or beta-adrenergic receptors and no change in the proportion of beta 1- vs. beta 2-receptor subtypes. Thus the dissociation between the chronotropic and inotropic responses to chronic hypoxemia may be in part secondary to a differential regulation of beta-adrenergic receptors between the left ventricle and the right atrium.

Animals

Differential regulation of right and left ventricular beta-adrenergic receptors in newborn lambs with experimental cyanotic heart disease.

To determine whether chronic hypoxemia secondary to an intracardiac right-to-left shunt alters regulation of the myocardial beta-adrenergic receptor/adenylate cyclase system, we produced chronic hypoxemia in nine newborn lambs by creating right ventricular outflow obstruction and an atrial septal defect. Oxygen saturation was reduced to 65-74% for 2 wk. Eight lambs served as normoxemic controls. beta-receptor density (Bmax) and ligand affinity (KD) were determined with the radio-ligand [125I]iodocyanopindolol and adenylate cyclase activity determined during stimulation with isoproterenol, sodium fluoride (NaF), and forskolin. During chronic hypoxemia, Bmax decreased 45% (hypoxemic, 180.6 +/- 31.5 vs. control, 330.5 +/- 60.1 fmol/mg) in the left ventricle (exposed to hypoxemia alone) but was unchanged in the right ventricle (exposed to hypoxemia and pressure overload). KD was not different from control in either ventricle. Left ventricular isoproterenol-stimulated adenylate cyclase activity was decreased by 39% (30.0 +/- 4.3% increase vs. 44.1 +/- 9.5% increase) whereas right ventricular adenylate cyclase activity was unchanged. Stimulation of adenylate cyclase with NaF or forskolin was not different from control in either ventricle. Circulating epinephrine was increased fourfold whereas circulating and myocardial norepinephrine were unchanged. These data demonstrate a down-regulation of the left ventricular beta-adrenergic receptor/adenylate cyclase system during chronic hypoxemia secondary to an intracardiac right-to-left shunt.

Adenylyl Cyclases

Mechanism of decreased insulinogenesis in manganese-deficient rats. Decreased insulin mRNA levels.

Manganese-deficient rats exhibited seven-fold lower preproinsulin mRNA levels compared to control, as detected by dot blot hybridization of both total and poly(A)+ RNA using a preproinsulin cDNA probe. No differences in the size of the insulin mRNA were observed. Thus, decreased mRNA levels may be a major contributing factor to the decreased insulinogenesis observed in manganese-deficient rats.

Animals

Evidence of glutamatergic denervation and possible abnormal metabolism in Alzheimer's disease.

Excitatory dicarboxylic amino acids previously have been ascribed several functions in the brain. Here their total concentration and proposed neurochemical markers of neurotransmitter function have been measured in brain from patients with Alzheimer's disease (AD) and controls. Specimens were obtained antemortem (biopsy) approximately 3 years after emergence of symptoms and promptly (less than 3 h) postmortem some 10 years after onset. Early in the disease a slight elevation in aspartic acid concentration of cerebral cortex was observed in the patients with AD. A reduction in glutamic acid concentration of a similar magnitude was found. It is argued that this, together with a decrease in CSF glutamine content and lack of change in the phosphate-activated brain glutaminase activity of tissue, reflects an early metabolic abnormality. Later in the disease evidence of glutamatergic neurone loss is provided by the finding that in many regions of the cerebral cortex the Na+-dependent uptake of D-[3H]aspartic acid was almost always lowest in AD subjects compared with control when assessed by a method designed to minimise artifacts and epiphenomena. Release of endogenous neurotransmitters from human brain tissue postmortem did not appear to have the characteristics of that from human tissue antemortem and rat brain.

Aged

Echovirus encephalitis and myositis in primary immunoglobulin deficiency.

Two children are described with primary hypogammaglobulinaemia and encephalitis associated with echovirus infection. One also developed a condition resembling dermatomyositis which improved after he was given infusions of plasma containing antibody to the echovirus. Although both died of their encephalitis, the course of the brain disease in one of them may have been prolonged by treatment with specific antibody. These cases, together with another briefly mentioned case in an adult with congenital hypogammaglobulinaemia and echovirus infection, indicate that these patients are particularly susceptible to echoviruses.

Agammaglobulinemia

Giant cell tumor of the sphenoid bone.

The clinical and histological features of two cases of giant cell tumor of the sphenoid bone are described. Both presented with similar symptoms and signs, comparable to previously described cases. The problems in histological differential diagnosis are discussed and radiotherapy as the treatment of choice is suggested.

Adolescent

Hypothalamic and myocardial lesions after subarachnoid haemorrhage.

The hypothalamus and myocardium of 12 patients who had died after a subarachnoid haemorrhage, and of six patients who had died from other intracranial pathology were examined. Only in the patients who had died from subarachnoid haemorrhage were histological lesions found in both the hypothalamus and myocardium. The possible significance of these findings is discussed with particular reference to the sympathetic nervous system.

Adult

Doppler color flow mapping of the proximal isovelocity surface area: a new method for measuring volume flow rate across a narrowed orifice.

This manuscript describes a new method, validated in in vitro models, for quantitating volume flow rate across an orifice with Doppler color flow mapping. Flow through a narrowed orifice is characterized by the convergence of radial streamlines proximal to the orifice. In this color Doppler method, one or more isovelocity surface areas (PISA), delineated by blue and red aliasing velocity interfaces, can be identified proximal to the narrowed orifice. Volume flow rate (in milliliters per second) can then be calculated as PISA (in square centimeters) multiplied by the isovelocity of the PISA (in centimeters per second). Doppler color flow mapping was performed in in vitro models of constant and pulsatile flow through an orifice in a wall. The first proximal isovelocity surface area, with an isovelocity corresponding to the aliasing velocity, that is, one half the Nyquist sampling limit, could be identified as a blue and red color interface proximal to the orifice. Over a range of circular orifice diameters from 3 mm to 16 mm and flow rates from 0.5 to 18.7 L/min, the proximal isovelocity surface area could be imaged in two planes. This PISA was best described by a hemielliptic mathematical model with two different radii measured from long-axis and short-axis views. In the constant flow model, volume flow rate calculated from the Doppler PISA correlated well with actual volume flow rate measured simultaneously with a cylinder and stopwatch (r = 0.98, p less than 0.001, standard error of the estimate [SEE] = 0.36 L/min). In the pulsatile flow model, with jet velocities ranging from 2.6 to 7.7 m/sec and flow volume ranging from 1.0 to 10.3 L/min, calculated volume flow rate also demonstrated an excellent correlation with actual volume flow rate (r = 0.99, p less than 0.001, SEE = 0.53 L/min). Findings from these in vitro models suggest that quantification of the proximal isovelocity surface area by Doppler color flow mapping appears to be a promising technique for estimating volume flow rate across a narrowed orifice. This new color Doppler flow method may have advantages over previous Doppler methods in estimating volume flow rate in various clinical situations, for example, valvular regurgitation and shunt lesions.

Blood Flow Velocity