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G J Ensing

Publications and source records attributed to G J Ensing.

At least 37 records · Page 2Linked to original sources

Effect of dose and specific activity on tissue distribution of indium-111-pentetreotide in rats.

UNLABELLED: To increase the target-to-background ratio in receptor scintigraphy, we hypothesized that receptor scintigraphy is best performed using the lowest possible mass with the highest possible specific radioactivity of the radioligand. METHODS: Rats were injected with 2 or 10 micrograms of unlabeled octreotide or 2 or 10 micrograms of 111In-pentetreotide. Scintigraphic images were then obtained from 10 min before to 20 min after the 111In injection. RESULTS: In some instances, there was a significant increase in 111In uptake in somatostatin receptor-positive organs. In others, there was a significant decrease. Since no significant differences were found in background radioactivity in the percent dose uptake of 111In in receptor-negative organs, these data indicate that target-to-background ratios can be increased by the administration of nonradiolabeled peptides under select conditions. CONCLUSION: The uptake of 111In-pentetreotide in somatostatin receptor-positive organs results in a tissue-specific bell-shaped function of the injected mass of the radiopharmaceutical. This curve may also apply to somatostatin receptor-positive tumors, the visualization of which may be enhanced by optimizing the mass of 111In-pentetreotide.

Animals↗

A new 99mTc labelling method for leucocytes: in vitro and in vivo comparison with 99mTc-HMPAO.

A new method for the labelling of mixed leucocytes with 99mTc-tropolone was optimized and compared with a 99mTc-HMPAO leucocyte labelling procedure in vitro and in vivo. In the present study, leucocytes obtained from patients suffering from Crohn's disease, were isolated and labelled with 99mTc-HMPAO or labelled according the new 99mTc-tropolone procedure using 9.8 mM tropolone, 1 microM stannous chloride and 0.8 mM potassium borohydride (KBH4) at pH 5.5-6. Labelling efficiency with 99mTc-tropolone yielded 92 +/- 3%, which is higher compared to the 99mTc-HMPAO labelling procedure (64 +/- 13%) using 10(8) of leucocytes. In vitro stability and viability of both the tropolone and the HMPAO labelled cells was investigated. The viability test of the 99mTc-labelled leucocytes was performed in autologous plasma at 37 degrees C and compared with unlabelled leucocytes. After 18 hours of incubation a significant (P < 0.05) higher stability was observed for 99mTc-tropolone labelled leucocytes (84 +/- 5%) compared with that of 99mTc-HMPAO labelled leucocytes (73 +/- 5%). The viability of the 99mTc-labelled leucocytes observed for both labelling procedures was similar to unlabelled leucocytes. In vivo experiments were performed in mice. 99mTc-tropolone or 99mTc-HMPAO labelled murine mixed leucocytes were injected in mice, with a Staphylococcus aureus ATCC 25923 thigh infection. Analysis of scintigraphic images yielded a faster clearance of the 99mTc-tropolone labelled leucocytes. This was most likely due to a significant (P < 0.02) higher liver uptake at 4 hours after administration of the 99mTc-tropolone labelled leucocytes (19%) in comparison with 99mTc-HMPAO labelled cells (9%). Faster and significant (P < 0.02) higher accumulation of the 99mTc-tropolone labelled leucocytes was observed at the site of infection compared with 99mTc-HMPAO labelled leucocytes at all time-intervals after the administration of the 99mTc-labelled leucocytes. The new 99mTc-tropolone leucocyte labelling procedure, offers an attractive low-cost agent for research purposes.

Abscess↗

Optimized localization of bacterial infections with technetium-99m labelled human immunoglobulin after protein charge selection.

To improve the scintigraphic detection of bacterial infections a protein charge-purified fraction of polyclonal human immunoglobulin was applied as a radiopharmaceutical. This purification was achieved by attaching the immunoglobulin to an anion-exchanger column and by obtaining the column-bound fraction with buffer. The binding to bacteria in vitro and the target to non-target ratios of an experimental thigh infection with Staphylococcus aureus or Klebsiella pneumoniae in mice were evaluated to compare the purified and the unpurified immunoglobulin. The percentage of binding to all gram-positive and gram-negative bacteria used in this study was significantly (P < 0.03) higher for the purified than for the unpurified immunoglobulin. For the in vivo study, mice were infected in the thigh muscle with Staph. aureus or K. pneumoniae. After 18 h 0.1 mg of technetium-99m labelled polyclonal immunoglobulin or 99mTc-labelled protein charge-purified polyclonal human immunoglobulin was administered intravenously. At all time intervals the target (infected thighs) to non-target (non-infected thighs) ratios for both infections were significantly higher (P < 0.03) for protein charge-purified polyclonal immunoglobulin than for unpurified polyclonal human immunoglobulin. Already within 1 h the infected tissues could be detected by the purified immunoglobulin. It is concluded that 99mTc-labelled protein charge-purified immunoglobulin localizes both a gram-positive and a gram-negative thigh infection more intensely and faster than 99mTc-labelled unpurified immunoglobulin.

Animals↗

A human vascular disorder, supravalvular aortic stenosis, maps to chromosome 7.

The pathogenesis of vascular disease is unclear, but genetic factors play an important role. In this study we performed linkage analyses in two families with supravalvular aortic stenosis, an inherited vascular disorder that causes narrowing of major arteries and may lead to cardiac overload and failure. DNA markers on the long arm of chromosome 7 (D7S371, D7S395, D7S448, and ELN) were linked to supravalvular aortic stenosis in both families with a combined logarithm of likelihood for linkage (lod score) of 5.9 at the ELN locus. These findings indicate that a gene for supravalvular aortic stenosis is located in the same chromosomal subunit as elastin, which becomes a candidate for the disease gene.

Aortic Valve Stenosis↗

Improved detection of a staphylococcal infection by monomeric and protein A-purified polyclonal human immunoglobulin.

The present study was undertaken to compare the technetium-99m labelled non-specific polyclonal human immunoglobulin (Ig) with 99mTc-labelled monomeric human immunoglobulin (m-Ig), 99mTc-labelled, protein A-purified, human immunoglobulin (A-Ig) and 99mTc-labelled monomeric, protein A-purified, human immunoglobulin (mA-Ig) as tracer agents for the detection of a thigh infection with Staphylococcus aureus. In vitro the binding of the various tracer agents to bacteria at various intervals was determined. For the in vivo evaluation, mice were infected and received one of the various labelled proteins. Scintigrams were made 0.25, 1, 4 and 24 h later. All 99mTc-labelled Igs bound to bacteria in vitro: the percentages of binding for the m-Ig (from 1 h onwards) and A-Ig and mA-Ig (from 3 h onwards) were significantly higher than that for Ig. The in vivo target-to-non-target (T/NT) ratios were significantly higher from 4 h onwards for all purified Igs than for Ig. Protein A-purified Igs yielded higher T/NT ratios than m-Ig. Furthermore, the amount of activity in the liver was significantly lower 24 h after administration of m-Ig, A-Ig and mA-Ig than after administration of Ig. It is concluded that in this experimental infection 99mTc-labelled monomeric Ig localizes a staphylococcal thigh infection better and faster than 99mTc-labelled unpurified Ig. However, the accumulation obtained with protein A-purified Ig or protein A-purified monomeric Ig was the highest of all tracer agents tested.

Animals↗

Binding of 99mTc-labelled polyclonal human immunoglobulin to bacteria as a mechanism for scintigraphic detection of infection.

The aim of the present study was to determine whether 99mTc-labelled polyclonal human immunoglobulin (99mTc-HIG) binds to bacteria in vitro as well as in vivo. In vitro, the binding of 99mTc-HIG to various gram-positive and gram-negative bacteria was determined. In vivo, mice were infected with Staphylococcus aureus Cowan I (protein A rich) or S. aureus EMS (protein A deficient) in a thigh muscle and then 99mTc-HIG or 99mTc-labelled human serum albumin (99mTc-HSA) was administered; scintigrams were made 1, 4, and 18 h later. In vitro binding of 99mTc-HIG to bacteria was higher for gram-positive than for gram-negative forms. A positive correlation was found between the protein A content and the degree of binding to S. aureus. This was also found in vivo. The accumulation of 99mTc-HIG at the site of infection was significantly (P less than 0.01) higher than that of 99mTc-HSA, for both strains of S. aureus. It is concluded that vascular permeability cannot fully explain the accumulation of 99mTc-HIG at the site of infection and that binding of 99mTc-HIG to bacteria plays a role in this respect.

Animals↗

Detection of a local staphylococcal infection in mice with technetium-99m-labeled polyclonal human immunoglobulin.

The purpose of this study was to investigate both the ability of 99mTc-labeled polyclonal human immunoglobulin (HIG) to localize an infection and the modes of action involved in this process. Mice, infected with Staphylococcus aureus ATCC 25923 in a thigh muscle, received HIG intravenously. Scintigrams were made 1, 4, and 24 hr later; subsequently the mice were killed and the activity in several organs and thighs was determined. The radiopharmaceutical demonstrated a time-dependent accumulation at the site of infection. It was found that vascular permeability or Fc binding alone could not account for the mode of action of HIG. Neither the origin of Ig (human versus murine) nor the total amount of protein (0.01-1.0 mg Ig per mouse) affected the target-to-background (T/B) ratios. Ratios were not different for leukocytopenic animals. A correlation (p less than 0.001) was demonstrated between the number of bacteria at the site of infection and the T/B ratio. This was also found after antibiotic treatment (p less than 0.02).

Animals↗

Autosomal dominant supravalvular aortic stenosis: large three-generation family.

Supravalvular aortic stenosis (SVAS) can be inherited as an isolated autosomal dominant trait or can be a component manifestation of the Williams syndrome. Some consider the Williams syndrome to be due to more severe expression of the gene defect that causes isolated SVAS. We describe a family with isolated SVAS that is the largest thoroughly studied family with this disorder to our knowledge; no patients in this family had Williams syndrome. Five members of this family were reported by Lewis et al. (Dis Chest 55:372-379, 1969). We reevaluated this family and now include examinations of the parents, additional sibs and children of the original 5 patients. Twenty relatives had physical and echocardiographic examinations. In addition, information from outside sources was obtained on 7 relatives not personally evaluated. The SVAS showed marked variability of expression and was not associated with mental retardation or with the facial manifestations of Williams syndrome. We think that previous reports of Williams syndrome reputedly occurring within the same family as isolated autosomal dominant SVAS were inadequately documented. Based on our family and review of the literature, we suggest that isolated SVAS and Williams syndrome represent clinically distinct entities.

Adolescent↗

Caveats of balloon dilation of conduits and conduit valves.

The results and complications of percutaneous balloon dilation involving 10 patients with a stenotic right ventricle to pulmonary artery prosthetic conduit and 1 patient with an obstructed right atrium to left pulmonary artery Dacron graft (modified Fontan) are reported. For the 10 patients (14.5 +/- 5 years) with a right ventricle to pulmonary artery conduit, the mean (+/- SD) predilation conduit valve gradient was 57 +/- 22 mm Hg, right ventricular pressure 104 +/- 21 mm Hg and right ventricle to pulmonary artery gradient 75 +/- 23 mm Hg; 2 of the patients had additional pulmonary artery stenosis requiring dilation. In one patient, the balloon could not be advanced across the conduit valve. In 9 of 10 patients in whom dilation was successfully performed, the conduit valve gradient decreased by 59 +/- 13%, right ventricle to pulmonary artery gradient by 43 +/- 22% and right ventricular pressure by 31 +/- 11%. After dilation, right ventricular pressure was less than 65% of systemic pressure in seven patients, although no pressure was less than 40%. In 8 of the 11 patients, surgery was avoided or postponed. Complications included loss of a balloon fragment after rupture during the unsuccessful dilation of the right atrium to left pulmonary artery graft and circumferential balloon rupture requiring catheter retrieval of the distal portion of the balloon from the femoral vein after successful dilation of the right ventricle to pulmonary artery conduit. Conduit valve dilation by balloon can reduce but rarely eliminate conduit obstruction, and balloon rupture may occur and can result in fragment loss or embolization.

Adolescent↗

Spectrum of findings in a family with nonsyndromic autosomal dominant supravalvular aortic stenosis: a Doppler echocardiographic study.

Nonsyndromic familial supravalvular aortic stenosis is an autosomal dominant disorder. However, for many reported families, systematic study of all family members with echocardiographic or hemodynamic techniques has not been performed and degree of penetrance has not been assessed. The supravalvular stenosis in these family members usually is not associated with mental retardation or other characteristics of Williams syndrome. Although some believe that autosomal dominant supravalvular aortic stenosis is part of the spectrum of Williams syndrome, others believe that these are separate entities. Doppler echocardiograms were analyzed on 23 members of a 34 member family with several known to have supravalvular aortic stenosis; 20 studies were performed by the authors and 3 were done elsewhere and made available for review. No family member had mental retardation, characteristic facies or other findings of Williams syndrome. Three of the 34 had supravalvular aortic stenosis requiring surgery. Of 22 members examined echocardiographically who had not had prior surgical repair, 13 had supravalvular aortic stenosis. Echocardiographic findings ranged widely, from calcification of the ascending aorta in a 71 year old man with minimally increased flow velocity (1.7 m/s) to mild narrowing with mildly increased flow velocity in six members to significant narrowing with impressively increased flow velocity (2 to 4 m/s) in seven. In addition, four patients had mild narrowing of pulmonary artery branches and eight had peak pulmonary artery flow velocity above normal. This study demonstrates complete penetrance with extremely variable expression in this family with autosomal dominant supravalvular aortic stenosis and emphasizes the importance of using echocardiographic techniques in studying the family members who are suspected of having an inherited cardiovascular disease.

Adolescent↗

Cardiovascular response to exercise after the Mustard operation for simple and complex transposition of the great vessels.

After the Mustard operation, patients have reduced exercise tolerance, abnormal right and left ventricular responses to exercise and cardiac rhythm disturbances. The cardiovascular response to exercise was measured noninvasively in 19 patients from 4.5 to 20 years (mean 10.3) after operation. Mean work performed and maximal oxygen uptake for the group were substantially subnormal (42 +/- 23% and 59 +/- 18% [mean +/- 1 standard deviation] of the predicted values, respectively). Resting heart rate, blood pressure, systemic arterial blood oxygen saturation, cardiac index, stroke volume and systemic vascular resistance were not significantly different from control values. At maximal exercise, heart rate, systemic arterial blood oxygen saturation, cardiac index and stroke volume were significantly reduced in comparison with control values. After the Mustard operation, cardiovascular status at rest may be relatively normal, but during maximal exercise, marked abnormalities occur in nearly all indexes of cardiovascular function. Decreased cardiac output response to exercise is a result of decreased stroke volume response and, to a lesser extent, diminished heart rate. It is associated with abnormally increased total systemic vascular resistance.

Adolescent↗

Regional pulmonary perfusion estimated by high-speed volume scanning CT.

Three pigs with surgically created aortopulmonary shunts and two pigs who had sham operation were scanned in a fast computed tomography (CT) scanner, the dynamic spatial reconstructor (DSR). Each pig was scanned during injection of a bolus of roentgen contrast medium in the right atrium and during injection into the left ventricle. In addition to these DSR scans, radiolabeled, 15-micron-diameter microspheres were injected into the right atrium and into the left ventricle. The quantitative distribution of roentgen contrast agent was used to estimate regional pulmonary blood flow independently from the right and left circulations using analysis of the indicator dilution curves derived from the DSR images (Y). These values were compared to the regional values of pulmonary perfusion based on the microsphere distribution (X). The correspondence between the two methods (for all pigs together) was Y = 0.83X + 0.52 with r = 0.964. The less than unity slope is attributed to the partial collapse of the lung at the time of sectioning (for counting of tissue radioactivities). As regional air content of the lung also was measured from the DSR images, these data support the contention that regional ventilation and perfusion can be estimated from a fast CT scan of the thoracic contents during the passage of a bolus of contrast medium.

Animals↗

Development and application of a radioreceptor assay for scopolamine.

6 beta,7 beta-Epoxy-3a(1aH,5aH)-tropanyl-(S)-tropate (scopolamine) has proved to be a very effective drug in the prevention of motion sickness, however, the drug has a small therapeutic window, a low bioavailability and a short half-life. A transdermal drug delivery system (Scopoderm TTS) was developed to circumvent these problems as well as the variability in gastric absorption. In order to study the pharmacokinetics of the drug and its glucuronide, a highly sensitive radioreceptor assay with an absolute detection limit of 15 pg scopolamine was developed. In children undergoing minor surgery, a Scopoderm TTS patch of different sizes (according to the age of the children) was applied to the retro-auricular skin. Urine samples were collected and assayed for free and conjugated scopolamine. Furthermore possible anticholinergic effects on the pupil reaction, salivation, blood pressure and heart rate were monitored. The urine excretion of free and glucuronidated scopolamine showed large intra- and interindividual variations. However, in all age groups relatively high percentages of free scopolamine were found, namely 47.5% (3-6 years), 48.3% (7-12 years) and 36.0% (13-18 years) of the sum of free plus glucuronidated scopolamine. During the application of the patch, a prolonged plateau of scopolamine excretion could be found. Although in general the patches were well tolerated, both locally and systematically, moderate anticholinergic effects were observed in patients.

Adolescent↗

Left atrial mass 16 years after radiation therapy for mediastinal neuroblastoma.

Tumors involving the heart during childhood are rare. However, neuroblastoma, a common pediatric malignancy, has been described to involve the cardiovascular system in 3%-12% of patients dying with this tumor. Rarely is such involvement diagnosed ante mortem and never, to our knowledge, has a benign cardiac tumor been reported to present in childhood after successful eradication of neuroblastoma. We describe the identification and surgical resection of a nodular, hypertrophied, calcified, pedunculated left atrial mass in a 16-year-old boy who was complaining of exercise-associated presyncope and headaches 16 years after irradiation and chemotherapy for mediastinal neuroblastoma.

Adolescent↗

Dynamic three-dimensional anatomy of pulmonary arteries in pigs with aorto-to-pulmonary artery shunts.

Accurate quantitation of three-dimensional pulmonary arterial geometry is difficult in vivo by the usual clinical imaging techniques. We have used a fast, multislice, computed tomography (CT) scanner, the dynamic spatial reconstructor (DSR), to obtain such measurements. After one injection of contrast medium into the right atrium, all major pulmonary arteries were imaged in three dimensions at 60 per second intervals throughout several cardiac cycles. Computer-generated pseudothree-dimensional displays were generated to show the arteries from several views so that superposition of arteries could be avoided. Using this technique, we have quantitated pulmonary arterial geometry in five pigs, three of them with surgically created aortopulmonary shunt and two with sham shunts. Pulmonary arterial cross-sectional areas (CSA) along the length of the left and right pulmonary arteries as they course through the lower lobes of the lungs were measured at peak-systole and end-diastole. From these image data, the systolic to diastolic change in CSA was measured. The regression line relating the CSA at these two phases had slopes in the five pigs ranging from 0.41 to 0.85. The magnitude of this slope corresponded closely with pulmonary arterial pressure, which ranged from 20 to 92 mm Hg.

Animals↗