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Biomedical subjects

A Donath

Publications and source records attributed to A Donath.

At least 37 records · Page 2Linked to original sources

Immunoscintigraphy with biosynthetically-labeled 75Se-antibodies--II. Comparison with antibodies labeled by radioiodination.

The biodistribution of 75Se and 125I were compared in nude mice bearing melanomas and injected simultaneously with biosynthetically-labeled 75Se-MoAbs and radioiodinated 125I-MoAbs from the same anti-melanoma hybridoma. The 75Se dose recovery in the tumor (day 10) was twice that for 125I, but the tumor to normal tissue ratios were identical. It is concluded that biosynthetically-labeled MoAbs survive better in vivo, while the tumor to normal tissue ratios are governed by the excretion rate of labeled MoAb catabolytic products.

Animals↗

131I-metaiodobenzylguanidine and 125I-iodoamphetamine. Parameters of lung endothelial cell function and pulmonary vascular area.

Radioiodinated metaiodobenzylguanidine (MIBG) has been shown to be extracted in the lung by an active, sodium-dependent, saturable transport system similar to that which extracts norepinephrine. Accordingly, first transit uptake of MIBG has been investigated as a method for in vivo evaluation of pulmonary biogenic amine metabolism. Issues that still must be resolved include the degree to which MIBG extraction is affected by simple loss of available vascular surface (in distinction to changes in amine metabolism). If MIBG lung extraction is altered by loss of pulmonary vascular surface alone, then a tracer must be found that can serve as a simultaneous monitor of vascular surface loss in order to allow normalization of the MIBG data. One tracer with such potential is radioiodinated iodoamphetamine (IMP). Accordingly, an experimental model of pulmonary vascular surface loss (lobar ligatures) was applied in an isolated-perfused lung model with simultaneous administration of MIBG and IMP. A linear relationship was found between MIBG extraction and percent lung surface loss by weight (n = 21, r = 0.75, P less than 0.05). Addition of IMP (1 or 10 microM) to media containing MIBG (1 microM) (n = 28) inhibited overall MIBG extraction, but decreases in MIBG uptake with vascular surface loss were otherwise parallel to those in experiments without IMP. IMP, however, did not adequately reflect vascular surface loss at the concentrations used in this study (extraction of IMP 1 microM = 31.2% +/- 12.9% in control vs 32.7% +/- 7.7% with greater than 50% lung surface loss, n = 18, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗

Calcium absorption from milk in lactase-deficient subjects.

Intestinal calcium absorption from milk containing lactose (+) and from another containing glucose (-) was studied in eight patients with normal lactase (NL) and seven lactase-deficient (LD) subjects to determine if lactase deficiency is implicated in Ca absorption. The results were compared with data obtained from Ca ingestion in a water solution. Ca absorption was measured by a double-isotope technique and the kinetic indices were obtained by a deconvolution method. With (-), Ca absorption was identical in NL and LD subjects and slightly higher than with water solution (15%, NS). With (+), Ca absorption in NL subjects was identical with that from water solution; in LD subjects it increased (23%, p less than 0.02). These data indicate that: Ca is absorbed equally well from milk as from water solution; (+) favors Ca absorption in LD subjects, which suggests that milk ingestion might be encouraged in LD subjects to avoid Ca deficiency; and (-) should be a valuable alternative for lactose-intolerant patients.

Animals↗

Effect of absorbable and nonabsorbable sugars on intestinal calcium absorption in humans.

The effects of glucose, galactose, and lactitol on intestinal calcium absorption and gastric emptying were studied in 9, 8, and 20 healthy subjects, respectively. Calcium absorption was measured by using a double-isotope technique and the kinetic parameters were obtained by a deconvolution method. The gastric emptying rate was determined with 99mTc-diethylenetriaminepentaacetic acid and was expressed as the half-time of the emptying curve. Each subject was studied under two conditions: (a) with calcium alone and (b) with calcium plus sugar. Glucose and galactose increased the calcium mean transit time and improved the total fractional calcium absorption by 30% (p less than 0.02). Lactitol decreased the mean rate of absorption (p less than 0.001) and reduced the total fractional calcium absorption by 15% (p less than 0.001). The gastric emptying rate did not appear to influence directly the kinetic parameters of calcium absorption. These results show that both glucose and galactose exert the same stimulatory effect as lactose on calcium absorption in subjects with normal lactase whereas lactitol mimics the effects of lactose in lactase-deficient patients. Thus the absorbability of sugars determines their effect on calcium absorption.

Adult↗

Lung uptake of 131I-metaiodobenzylguanidine in sheep. An in vivo measurement of pulmonary metabolic function.

Circulating biogenic amines are known to be cleared by the mammalian lung. Their lung uptake is considered as an indicator of pulmonary endothelial integrity. Unfortunately, their use as markers of pulmonary metabolic function in human pathology is precluded by their biological effects and by the type of radiolabeling (3H and 14C), making them harmful for repeat injections and unfit for scintigraphy. Metaiodobenzylguanidine (MIBG) is structurally related to the neuron blocking agent guanethidine, devoid of significant biological effects, and has been shown to be extracted by the same active sodium dependent, saturable transport as norepinephrine in perfused rat lungs in vitro. We studied the single pass lung extraction of 131I-MIBG in five awake and five anaesthetised sheep using the standard double indicator dilution technique with 99mTc-human serum albumin (HSA) as an intravascular reference tracer. Intravenous bolus injection of increasing doses of MIBG up to 400 nmol resulted in a significant (F ratio = 7.778, P less than 0.0001) dose dependent decrease of MIBG extraction in both awake and anaesthetised sheep, without significant differences of extraction values between the two groups. For the 10 sheep, the averaged percentage single pass pulmonary uptake of MIBG at the peak of the dilution curve decreased from 32% +/- 3% (mean +/- SE, n = 27 measurements) with 20 nmol to 18% +/- 2% (n = 32) with 400 nmol. Estimates of the apparent Michaelis-Menten constant (Km) averaged 2 +/- 1.2 microM (n = 7), whereas estimates of the apparent maximum velocity of removal (Vmax) was 1.1 +/- 0.5 mumol/min (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗

High density avalanche chamber (HIDAC) positron camera.

A prototype positron camera has been constructed consisting of two high density avalanche chamber (HIDAC) detectors operated in coincidence with a resolving time (2 tau) of 40 nsec. The detectors are multiwire chambers, with specially constructed lead converters added to improve the photon detection efficiency at 511 keV. The current HIDAC detectors have a singles efficiency of approximately 12%, a sensitive area of 31 X 31 cm and an intrinsic spatial resolution of less than 2 mm full width at half maximum (FWHM). During data acquisition, the detectors are rotated around the patient in order to collect a complete angular data set. A three-dimensional image of the positron distribution is reconstructed from a single scan by weighted backprojection of the data into a matrix of either 64 X 64 X 64 or 128 X 128 X 16 voxels. The camera point response function is deconvolved by frequency-space filtering. Corrections are made during backprojection both for photon attenuation and for spatial variations in point source sensitivity. The reconstructed image is further corrected for contributions from accidental and scattered coincidences and displayed as a sequence of two-dimensional transverse, sagittal, or coronal sections. In addition, three-dimensional display is available using shaded graphics techniques. The prototype camera is currently undergoing clinical evaluation.

Bone Neoplasms↗

Effects of bopindolol on renal function.

The effect of the long-acting beta-blocking agent bopindolol on renal function was assessed in 10 healthy normotensive volunteers and 10 hypertensive patients. The subjects received 1 mg bopindolol at 8 p.m. for 21 days. The following determinations were made at 8 a.m. on recumbent, fasting subjects before day 0 (D0) and 12 h after day 1 (D1) the first dose of bopindolol, and on the 21st day of treatment (D21): blood pressure (diastolic = DBP), glomerular filtration rate (GFR) and renal plasma flow (RPF) as reflected by the plasma disappearance of 51Cr-EDTA and 125I-hippuran, plasma concentrations and 2- and 24-h urinary excretion of electrolytes, creatinine, and proteins and osmolality of the urine. Plasma renin activity was assessed on standing subjects. Following bopindolol administration GFR, RPF, and filtration fraction remained stable, in spite of a fall of DBP from 80 +/- 7 to 76 +/- 4 and to 72 +/- 9 mm Hg in normotensives (p less than 0.05) and from 106 +/- 11-96 +/- 10 and to 91 +/- 8 mm Hg in hypertensives (p less than 0.05) on D1 and D21, respectively. The drops in DBP at D1 correlated weakly with the pretreatment renin levels (p = 0.074, p less than 0.05). All the other variables remained stable, including diuresis, free water clearance, and fractional sodium excretion. It is concluded that in contrast to many other anti-hypertensive drugs including several beta blockers, bopindolol does not reduce renal function during short- or medium-term treatment in normal volunteers or hypertensive patients.

Adolescent↗

Tomographic imaging of the human thyroid using 124I.

After receiving between 100 and 300 mu Ci of the positron-emitting radioisotope 124I (half-life, 4.2 days), 64 patients with a variety of thyroid disorders were imaged with a high resolution positron camera. A 3-dimensional image of the distribution of radioiodine uptake within the thyroid was obtained from a single 10- to 15-min scan. This image may be viewed as a sequence of 2-mm thick transverse, sagittal, or frontal sections or as a 3-dimensional shaded surface. The functional volume of the thyroid may be estimated by counting the volume elements (voxels) inside the thyroid surface. The precision of the estimate varied from 6-15%, depending on the size and clinical status of the thyroid. The volume estimation procedure was validated with phantoms and with the thyroids of patients who subsequently underwent partial thyroidectomy. This 3-dimensional imaging technique may be useful for diagnosis and management of thyroid diseases.

Adenoma↗

Renal biopsy in SLE irrespective of clinical findings: long-term follow-up.

We analyzed data from 56 patients with Systemic Lupus Erythematosus (SLE) in whom renal biopsies were done systematically. The data taken into account for the study were: the histologic glomerular lesions at diagnosis, serum creatinine value, degree of proteinuria and qualitative urine sediment analysis at the time of biopsy, patient age at diagnosis and the evolution of renal function until the time the study was made. Therapy was prescribed according to the glomerular histologic lesion. The mean follow-up period from the time of the first biopsy was 8.2 years. At the time of the study, only 3 patients (5.3%) were on dialysis, while the rest of the patients (94.7%) had a satisfactory renal function. Our results indicate that systematic renal biopsy in SLE patients can furnish valuable data concerning the renal status whether there are clinical signs of renal involvement or not. Treatment based on the histologic images alone may considerably improve renal survival in SLE.

Adolescent↗

[Multidisciplinary study of the prolonged treatment of involution osteoporosis using sodium fluoride with calcium, phosphate and vitamin D].

A multidisciplinary study on the prolonged treatment of involution osteoporosis with fluoride was performed on a homogeneous population of 31 women aged 51 to 75 years (mean 64 years). The selection criteria were the following: significant backache, vertebral compression fractures on X-rays, bone biopsy evidence of osteoporosis, and absence of other risk factors after a complete workup. The patients were treated for a period of 3 to 6 years (mean 4 years) with daily doses of 30 mg (10 mg 3 times) fluorides ion associated during the last 3 years with 500 mg calcium twice daily, 750 mg phosphate and 1000 units vitamin D daily. The study demonstrated a favourable effect of the treatment on the backache and that it was well tolerated in the majority of cases, the side effects being intermittent osteo-articular pains of the lower extremities due to the fluoride in 9 patients, and gastric intolerance to the phosphate in 7. X-ray follow-up showed slowing of the vertebral compressions after the first year of treatment, but no effect on fractures of the extremities. There was no evidence of alterations in parameters of mineral and bone metabolism, and in endocrine, hepatic, renal or hematological assays. Histomorphometric and biophysical examination of biopsies indicated that, although there was no significant increase in the quantity of mineralized bone under the treatment, there was a very significant improvement in the crystallinity of the mineral substance, thus enhancing the quality of the bone tissue and its resistance to pressure. This study is the first in which a catamnesis of the patients was undertaken, 28 of them having received a clinical and radiological examination 2 years after the end of therapy: a favourable evolution was observed in most of the cases, both in those patients treated for a period of 3 years and in those whose treatment had lasted for a longer period.

Aged↗

In vivo imaging of the human thyroid with a positron camera using 124I.

A high-density avalanche chamber (HIDAC) positron camera was used for tomographic imaging of the human thyroid in vivo. Images were made 7 and 24 h after the oral administration of the positron-emitting radionuclide, sodium iodide 124I (with activities varying between 0.3 and 1 mCi), to patients scheduled for either partial thyroidectomy or radioiodine treatment. The results of thyroid imaging performed on 38 patients and their clinical relevance are discussed; as an illustration, three typical cases are presented. In Graves' disease, it was found that, whereas standard 131I and 124I scintigrams showed a diffuse goitre, positron images indicated a marked heterogeneity of the activity distribution, with "cold" areas in 8 out of the 11 cases studied. In conventional scintigrams, multinodular goitre showed a non-uniform radioiodine distribution, while positron images revealed considerable regional differences of activity uptake, with hot and cold areas in all of the 13 cases studied. As a consequence of the high spatial resolution of the camera [2.5 mm full width at half maximum (FWHM)], the functional volume of the thyroid may be estimated from 2 mm-thick transverse tomographic sections to within about 13%. This estimate may be compared with the measured volume after partial thyroidectomy, and in a follow-up scan, a further estimate can be made of the residual thyroid tissue remaining within the patient's body. In the case of radioiodine treatment in Graves' disease and multinodular goitre, the appropriate therapeutic dose of 131I can calculated according to the functional volume of the thyroid estimated from 124I tomographic images.

Adult↗

Cobalt-57 bleomycin scanning for lung cancer detection: a prospective study in thoracic surgery.

Patients displaying an abnormal chest X-ray, in some cases, cause a difficult diagnostic problem. A differential diagnosis between benign and malignant lesions is important to determine the choice of treatment i.e. whether or not to perform a thoracotomy. In a prospective study, we have examined the role of 57Co-bleomycin scanning for prethoracotomy assessment of 60 patients with a high clinical probability of lung cancer. For these patients, a sensitivity of 89%, a specificity of 84% and an accuracy of 88% were found. However, as a consequence of the six false-negative scans (two in-situ carcinomas and four stage I carcinomas), bleomycin scanning cannot be regarded as adequate for obviating thoracotomy in patients with a high clinical probability of lung cancer but a negative scan. Nevertheless, the technique is useful for the assessment of tumour size and for the detection of hilar, mediastinal and extra-thoracic metastases, with consequences for TNM staging. It has been found that the tumour dimension correlates well with the actual anatomo-pathologic size determined after surgical examination (r2 = 0.65 and p less than 0.01). Therefore, with an accuracy around 90% for the diagnosis of lung cancer, 57Co-bleomycin scanning offers a major tool for use in clinical investigation.

Adenocarcinoma↗

Tomographic imaging of the human thyroid with a positron camera before and after partial thyroidectomy.

A high-density avalanche chamber positron camera was used for tomographic imaging of the human thyroid before and after partial thyroidectomy. Images were made between 6 and 24 h after oral administration of the positron-emitting radionuclide, Na-124I with activities varying between 0.1 and 0.3 mCi before the surgical intervention and with activities between 0.03 and 0.05 mCi following partial thyroidectomy. The results of thyroid imaging performed on 50 patients and their surgical relevance are discussed; as an illustration, one typical case is presented. As a consequence of the high spatial resolution of the camera (2.5 mm full width at half maximum), the functional volume of the thyroid may be estimated from the transaxial tomographic sections before and following partial thyroidectomy, correct to about 10%. The thyroid surface, defined by the contours from each transaxial section, may be displayed using three-dimensional shaded-graphics techniques. This new imaging technique makes possible a fully three-dimensional description of the thyroid in vivo and contributes significantly to the surgical follow-up.

Goiter, Nodular↗

Pharmacokinetics and metabolism of the anti-arrhythmic carocainide in man.

The pharmacokinetics and metabolism of the anti-arrhythmic drug carocainide have been investigated in six healthy adult volunteers following single 100 mg intravenous and oral doses. Carocainide was labelled with 14C in the benzofuran ring. After i.v. administration, plasma concentration/time decay of carocainide was triexponential. Mean plasma elimination half-life of the drug was 5.0 +/- 2.2 h (i.v.) and 5.4 +/- 1.1 h (p.o.). Carocainide was virtually completely absorbed after the oral dose. The drug was eliminated mostly as unchanged drug in urine by the two routes of administration. There was some evidence that carocainide underwent enterohepatic cycling. Binding of carocainide to plasma proteins was saturable although not in the concentration range found in vivo. The drug was bound almost entirely to the alpha 1-acid glycoprotein fraction, to one class of binding sites with a moderate affinity constant (5.5 X 10(-4) M-1). Metabolism of carocainide, a secondary elimination process, occurred by oxidative cleavage of the benzofuran ring and by N-oxidation of the pyrrolidine ring.

Administration, Oral↗

57Co-labelled bleomycin scintigraphy for the detection of lung cancer: a prospective study.

The sensitivity and specificity of scanning with 57Co-labelled bleomycin for the diagnosis of lung cancer were determined from a prospective study involving a large group of patients with an abnormal chest roentgenogram. A semi-quantitative analysis of the scintigram was obtained by defining an index in terms of the excess isotope uptake within the tumour. Malignant pulmonary lesions were found in 121/175 patients and 113 had a positive scan. Benign pulmonary disorders were found in 54 patients, 45 of whom had a negative scan. The sensitivity and specificity were therefore 93% and 83% respectively. Bayes' theorem was then used to determine the predictive value of this test, either positive or negative, when the prevalence of disease varied from 10 to 90%. A receiver operating characteristic curve permits the choice of an appropriate value of the tumour uptake index to minimize the false positive fraction without classifying too many true positives as false negatives.

Adenocarcinoma↗

SPECT study of the fluid distribution in the intra-abdominal space during intraperitoneal treatment of ovarian cancer.

Only limited progress has been achieved in the treatment of ovarian cancer, the most common fatal gynaecological malignancy. Peritoneal dialysis with drugs known to be effective in ovarian cancer and large intraperitoneal fluid volumes (Belly Bath) have been used. The two critical determinants for a successful intraperitoneal chemotherapy programme are: (1) complete accessibility of the drug to all tumour-bearing areas; and (2) drug penetration into the residual tumour masses. We show that the scintigraphic technique in tomographic mode after administration of MAA-99Tcm-containing dialysate is a valuable adjunct for evaluation of patients undergoing intraperitoneal chemotherapy.

Adenocarcinoma↗