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Biomedical subjects

F D Thomas

Publications and source records attributed to F D Thomas.

At least 37 records · Page 2Linked to original sources

Differences between caries levels in 5-year-old children from fluoridated Anglesey and non-fluoridated mainland Gwynedd in 1987.

Using standard epidemiological techniques, several indicators of dental health showed significantly lower levels of caries experience in 5-year-old children from fluoridated Anglesey compared with a similar group from non-fluoridated mainland Gwynedd. The mean dmft was 0.80 in Anglesey and 2.26 in mainland Gwynedd. The mainland Gwynedd children had suffered more toothache and experienced more dental extractions. This study showed that fluoridation of water supplies remains an effective and relevant public health measure, and illustrates the value of a parental questionnaire in epidemiological surveys of younger children.

Child, Preschool↗

Sustained pectin ingestion: effect on gastric emptying and glucose tolerance in non-insulin-dependent diabetic patients.

The effects of sustained pectin ingestion on gastric emptying, glucose tolerance, and hormone responses were studied in 12 stable, non-insulin-dependent (type 2) diabetic patients. Patients were placed on a 2400 kcal, low-fiber (3 g) diet for 2 wk, followed by 4 wk of an isocaloric diet supplemented with 20 g apple pectin/d. Gastric-emptying half-time, plasma glucose, glucagon, and human pancreatic polypeptide levels were determined. Gastric-emptying half-time was prolonged 43% (p less than 0.025) by pectin supplementation and returned to normal 3 d after its discontinuation. Fiber supplementation decreased the incremental area under the glucose tolerance curve from 34.8 +/- 3.0 to 27.9 +/- 3.2 mmol/L (p less than 0.01) but did not affect hormonal responses to a meal. Sustained pectin ingestion slowed the gastric-emptying rate and improved glucose tolerance; however, a direct relationship could not be demonstrated between changes in gastric emptying and changes in the incremental area under the glucose curve (r = 0.22).

Adult↗

Evaluation of cyclosporine nephrotoxicity in rats with various renal radioactive agents.

The efficacy of different radiodiagnostic agents for demonstrating the decline in renal function from cyclosporine (CyA) nephrotoxicity was assessed in rats receiving a standard dose of the drug for 2 wk, compared with control rats. The agents included [99mTc]DTPA, [131I]hippuran, [111In]lysozyme, [99mTc]glucoheptonate (GHA), [99mTc]dimercaptosuccinate (DMS) and [111In]aminated dextran (amdex). A small dose of [99mTc]- or [111In]DTPA was administered simultaneously to normalize the results for variations in drug response from one animal to another. There were statistically significant differences in the detectability of the renal functional impairment by plasma clearance, early and 2-hr renal uptake among the different agents. However, none was clearly superior to DTPA. This conclusion is consistent with previous studies which showed a parallel decline in glomerular filtration rate (GFR) and effective renal plasma flow in acute CyA toxicity probably due primarily to vasoconstriction.

Animals↗

Comparison of different radioactive agents for the detection of renovascular hypertension with captopril in a rat model.

In Goldblatt hypertension in rats produced by implanting a silver clip on the left renal artery, captopril induces a greater difference in the 1-min uptake of diethylenetriaminepentaacetic acid (DTPA) between the two kidneys than in baseline uptakes, similar to the experiences in unilateral renovascular hypertension in man. The combination of captopril and furosemide induces an even greater difference in renal uptakes than with captopril alone in this rat model. In paired experiments, DTPA complexes were used as a standard to compare the differences in renal uptake between the two kidneys after captopril-furosemide with other existing and potential renal radiodiagnostic agents. No statistically significant difference was found between DTPA, glucoheptonate, dimercaptosuccinic acid, aminated dextran, or lysozyme. However, the differences in renal uptake were significantly less with hippuran than with DTPA. Furosemide and captopril caused delayed renal retention of hippuran after one minute. This response appeared to be due to non-specific volume depletion because it occurred in both clipped and unclipped kidneys.

Animals↗

Abnormal orthostatic changes in blood pressure and heart rate in subjects with intact sympathetic nervous function: evidence for excessive venous pooling.

The normal ranges of orthostatic changes in blood pressure and heart rate have been defined in 92 individuals aged 18 to 64 years. In 34 individuals whose symptoms (especially orthostatic light-headedness) suggested cerebral ischemia, but in whom none of the known causes of orthostatic hypotension could be identified, we have found one or more of five theoretically possible orthostatic circulatory derangements: systolic hypotension, diastolic hypotension, diastolic hypertension, excessive narrowing of the pulse pressure, and tachycardia after standing for at least 3 minutes. The orthostatic disorders of blood pressure and heart rate identified in the 34 patients were significantly reduced, almost always into the normal range, by external pressure of 45 to 50 mm Hg applied through an inflatable pressure suit. After labeling with sodium pertechnetate Tc 99m and reinjecting the erythrocytes contained in 3 to 6 ml blood, external gamma counting over a fixed site in the calf, both in the recumbent and in the standing posture, showed excessive gravitational pooling of blood in the legs of five patients with orthostatic diastolic hypertension, of four with orthostatic narrowing of the pulse pressure, and of 10 with orthostatic tachycardia alone. Plasma norepinephrine concentrations were usually normal in recumbency and elevated above normal limits during standing for 15 to 30 minutes in the 18 patients so observed. Red cell mass, plasma volume, and circulating blood volume were subnormal in more than half the seven patients in whom these measurements were made. We conclude that most of the patients with idiopathic sympathicotonic abnormalities of orthostatic blood pressure control have a venous pooling syndrome often aggravated by hypovolemia, the cause(s) of which remains to be determined.

Adolescent↗

Airflow patterns in a human nasal model.

Nasal airflow patterns were studied by using xenon 133 gas to image the course taken by air as it flowed through a plastic model of the human nasal cavity. The model was produced from the head of a human cadaver, and was anatomically correct. A needle catheter was used to infuse the radioactive xenon into a continuous flow of room air maintained through the model by a variable vacuum source connected to the nasopharynx. The radioactive gas was infused at one of five release sites in the nostril, and the distribution of the radioactivity was imaged in the sagittal plane with a scintillation camera. The data were organized to show the activity in six contiguous regions of the midnose. For each catheter, release site activity patterns were determined for three flow rates. The results of this experiment showed that both catheter position and flow rate had significant and reproducible effects on the distribution of radioactivity within the model.

Catheterization↗

Complications of continuous ambulatory peritoneal dialysis: diagnostic value of peritoneal scintigraphy.

Eighteen patients with complications secondary to continuous ambulatory peritoneal dialysis underwent peritoneal scintigraphy utilizing Technetium-99m sulfur colloid. Patients were divided into three groups. Group 1 patients (11) had dialysate leaks leading to abdominal-wall edema, genital edema, or exit-site drainage. Scintigrams were abnormal in nine patients in this group and frequently provided localizing information that aided in the management of leaks. Group 2 patients (five) had recurrent peritonitis. Two of these patients had abnormal scintigrams. In one instance, scintigraphy detected multiple abdominal-wall hernias that may have been responsible for recurrent peritonitis, which resolved following corrective surgery. Group 3 patients (two) had inadequate ultrafiltration but no clinical evidence of a dialysate leak. Scintigrams were negative in this group, eliminating consideration of an underlying structural defect in the peritoneum. Scintigraphic imaging is possible for several hours following instillation of labeled dialysate. This capability is important, since scintigrams that were initially negative frequently became positive after several hours of ambulation. Postdrainage images were also helpful in confirming extraperitoneal leakage. This study demonstrates that peritoneal scintigraphy is a useful diagnostic tool in the management of complications of continuous ambulatory peritoneal dialysis.

Adolescent↗

Furosemide augments the effects of captopril on nuclear studies in renovascular stenosis.

Captopril facilitates detection of unilateral renovascular hypertension by selectively reducing glomerular filtration rate in affected kidneys. To determine if volume depletion augments this response, we compared the effects of captopril, furosemide, and combined furosemide plus captopril on individual kidney computer-derived clearances of 99mTc-diethylenetriamine pentaacetic acid (DTPA) and [131I]o-iodohippurate in two-kidney, one clip Goldblatt hypertensive rats and normal controls. In clipped kidneys, captopril reduced DTPA clearance significantly from baseline (from 0.31 +/- 0.02 to 0.19 +/- 0.04 ml/min/100 g; p less than 0.02) whereas furosemide alone had no effect (0.28 +/- 0.03 ml/min/100 g). Combined furosemide plus captopril further reduced clipped kidney DTPA clearance to a level significantly less than captopril alone (0.10 +/- 0.02 ml/min/100 g; p less than 0.02). Clipped kidney o-iodohippurate clearance was not changed from baseline by any treatment. In contralateral unclipped and normal kidneys, DTPA clearance did not decline from baseline following either captopril or furosemide plus captopril treatment. Since the dose of captopril used (3 mg/kg by intraperitoneal injection) did not reduce systolic blood pressure of hypertensive rats significantly, these changes probably reflect intrarenal rather than systemic hemodynamic effects of converting enzyme inhibition and are consistent with the hypothesis that captopril interferes with glomerular filtration in stenotic kidneys by reducing efferent arteriolar vascular resistance. Prior volume depletion accentuates the effect of captopril on stenotic kidney glomerular filtration rate, providing improved functional discrimination of stenotic kidneys from contralateral unclipped and normal kidneys. These results indicate that furosemide-induced volume depletion may increase the diagnostic sensitivity of captopril-enhanced 99mTc-DTPA renography in the detection of unilateral renovascular hypertension.

Animals↗

Detection of diffuse glomerular lesions in rats: II. Comparison of indium-111 cationic small macromolecules with technetium-99m DTPA.

Dextrans with average molecular weights of 5,000, 10,000, and 17,500 and inulin were rendered cationic by amination with 2-bromoethylamine hydrobromide. After limited coupling with DTPA cyclic dianhydride, they were labeled with 111In. A good correlation was found between their early renal uptake quantitated by camera-computer techniques and their renal clearance from multiple plasma samples in rats with glomerular damage induced by puromycin aminonucleoside and controls. However, there was poor correlation between the early renal uptake of these agents and the clearance of simultaneously injected [99mTc]DTPA. The 2-hr organ distribution and urinary excretion of these agents were compared with the corresponding values of DTPA. The differences in clearance between rats with glomerular damage and controls were greater with aminated dextran (mol wt 5,000) than with DTPA, confirming previous work with infusions of nonradioactive charged dextrans and neutral inulin. The cationic dextrans appear to reflect the presence or absence of the normal anionic charge of the glomerular membrane as well as changes in filtration rate. Aminated inulin did not differentiate between controls and rats with glomerular disease any better than DTPA, probably because the number of amino groups conjugated was insufficient to produce the charge effect.

Animals↗

Detection of diffuse glomerular lesions in rats: I. Comparisons of conventional radioactive agents.

Conventional renal diagnostic agents, [131I]hippuran, [99mTc]glucoheptonate (GHA), and [99mTc] dimercaptosuccinate (DMS) were compared with [99mTc] or [111In] diethylenetriaminepentaacetic (DTPA) for the detection of glomerular damage in rats compared with controls. The glomerular lesions were induced by the i.v. injection of puromycin aminonucleoside (PA) 9 days before the radionuclide studies, a model of spontaneous "minimal change" glomerulonephritis in humans. Computer-generated early renal uptake of [99mTc]DTPA or GHA correlated with the glomerular filtration rate (GFR) quantitated by biexponential plasma clearance of DTPA administered by single i.v. injection. The early renal uptake of hippuran and DMS correlated poorly with GFR as assessed by DTPA clearance. However, the 2-hr renal retention of DMS correlated well with the DTPA clearance. None of the parameters measured with [131I]hippuran correlated well with DTPA clearance, probably because of decreased protein plasma binding of hippuran secondary to hypoproteinemia in this experimental model. It was concluded that none of these agents was superior to labeled DTPA for the detection of glomerular damage in this experimental model.

Animals↗

Evaluation of plasma clearance by synthesis of continuous infusion: principles and use.

There is a technique of engineering analysis which can be described as "impulse synthesis" which uses the observational data of a system's response to a single sharp blow in order to predict its response to a steady force. This same technique has been applied to the calculation of in situ drug levels and for calculating plasma clearance values. The purpose of this paper is to elucidate the principles of this calculation technique and to critically assess its application to plasma clearance studies. We begin by tracing the history of the measurement of renal clearance of plasma. We then proceed to exposit the relevant principles of the synthesis technique. Finally, we report the results of our application of this technique to the analysis of simulated data in a manner intended to be of use to clinicians who might wish to consider employing the technique.

Humans↗

Technetium-99m DADS complexes as renal function and imaging agents: II. Biological comparison with iodine-131 hippuran.

To find a 99mTc agent with a high renal extraction efficiency similar to [131]hippuran, 21 analogs of DADS were labeled and evaluated. Preliminary screening by serial gamma camera imaging in rabbits showed that most analogs had a higher liver uptake and/or slower renal clearance, than hippuran. Three agents (P-DADS, AP-DADS, and CAP-DADS), exhibiting a relatively rapid blood clearance and lower liver uptake in the rabbit, were studied in greater detail in comparison with hippuran and CO2-DADS-A, the best analog to date. In the rat, the plasma clearance of the four DADS analogs was slower than that of hippuran. In rats with tubular damage induced by cisplatin, the difference in renal retention at 1 hr compared to controls was much greater with hippuran than with the DADS compounds. In the dog, there was marked hepatic retention of the four DADS compounds. In volunteers, serial posterior images obtained with these [99mTc]DADS complexes showed significant hepatic as well as renal activity. The 1-hr plasma clearance and urinary excretion were much lower than with simultaneously injected hippuran. Although these 99mTc agents are satisfactory for imaging the kidneys, they closely mimic the biodistribution of hippuran only in the rabbit, and not in the rat, dog, or man.

Animals↗

Improved right ventricular function following late pulmonary valve replacement for residual pulmonary insufficiency or stenosis.

Residual severe pulmonary insufficiency or stenosis may result in significant myocardial dysfunction late after repair of tetralogy of Fallot. Although pulmonary valve replacement has been advocated for selected patients, objective improvement in right ventricular function has been difficult to demonstrate. We undertook pulmonary valve replacement in 11 patients to treat residual insufficiency (n = 8) or stenosis (n = 3) and evaluated them before and after operation by radionuclide ventriculography and M-mode echocardiography. Patients' age at the original repair was 6.6 +/- 0.6 years (range 2 to 8 years) and at subsequent valve replacement was 14.6 +/- 1.5 years (range 5 to 20 years). Indications for pulmonary valve replacement were conduit stenosis indicated by a gradient greater than or equal to 75 mm Hg (n = 3), symptoms (n = 2), progressive cardiomegaly (n = 3), and new onset of tricuspid insufficiency (n = 3). Prior to pulmonary valve replacement, right ventricular ejection fraction was 0.29 +/- 0.12 (range 0.12 to 0.48) and rose to 0.35 +/- 0.10 (range 0.19 to 0.48) at a mean of 10.5 +/- 2.3 months after operation (p less than 0.05). Improvement (defined as an increase in ejection fraction greater than 0.05) was noted in seven patients whereas four demonstrated no change. Left ventricular ejection fraction before operation (0.55 +/- 0.12) was unchanged after pulmonary valve replacement (0.54 +/- 0.06). M-mode echocardiography demonstrated significant reduction in right ventricular dilatation. Right ventricular/left ventricular end-diastolic dimension fell from 1.03 +/- 0.30 to 0.73 +/- 0.13 after operation (p less than 0.01). Cardiothoracic ratio fell from 0.59 +/- 0.02 to 0.55 +/- 0.02 at a mean of 12 months after pulmonary valve replacement (p less than 0.01). Subjective improvement in exercise tolerance was noted in all seven patients who showed an increase in right ventricular ejection fraction. Of the remaining four patients, two had no improvement, one felt symptomatically improved, and one was too young for evaluation. These data demonstrate objective improvement in right ventricular function following pulmonary valve replacement and confirm the usefulness of this procedure in patients with significant right ventricular dysfunction secondary to residual pulmonary insufficiency and stenosis.

Adolescent↗

Ventricular arrhythmias and biventricular dysfunction after repair of tetralogy of Fallot.

To test the hypothesis that subclinical levels of ventricular dysfunction contribute to the development of ventricular arrhythmias after repair of tetralogy of Fallot, 38 postoperative patients were studied by radionuclide ventriculography and M-mode echocardiography. Eighteen patients (group I) had Lown grade 2 or greater ventricular arrhythmias on ambulatory electrocardiography or treadmill exercise, or both; 20 patients (group II) had no documented ventricular arrhythmias. Radionuclide ventriculograms were performed using technetium -99m-labeled red cells; ejection fractions were derived by computer from multigated images, with normal values being 45% for the right ventricle and 55% for the left ventricle. From M-mode echocardiography, right and left ventricular end-diastolic dimensions were expressed as a ratio, the highest normal value being 0.45. By radionuclide ventriculography, right ventricular ejection fraction was lower for group I (28 +/- 3%) than for group II (31 +/- 2%), but the difference was not significant (p less than 0.10). Left ventricular ejection fraction was significantly lower for group I than for group II (45 +/- 5% versus 55 +/- 3%, p less than 0.05). The echocardiographic right and left ventricular diastolic dimension ratio was elevated in all patients except two in group II; it was significantly greater in group I than in group II (0.84 +/- 0.06 versus 0.63 +/- 0.04, p less than 0.005). This study provides evidence for right ventricular dilation by M-mode echocardiography and for biventricular dysfunction by radionuclide ventriculography in patients who have undergone repair of tetralogy of Fallot.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Ventilator-driven xenon ventilation studies.

A modification of a common commercial Xe-133 ventilation device is described for mechanically assisted ventilation imaging. The patient's standard ventilator serves as the power source controlling the ventilatory rate and volume during the xenon study, but the gases in the two systems are not intermixed. This avoids contamination of the ventilator with radioactive xenon. Supplemental oxygen and positive end-expiratory pressure (PEEP) are provided if needed. The system can be converted quickly for conventional studies with spontaneous respiration.

Humans↗