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Biomedical subjects

J C Roos

Publications and source records attributed to J C Roos.

At least 73 records · Page 4Linked to original sources
PubMed1992

Kinetics and dosimetry of iodine-131-labelled antibody fragments after local administration in patients with rectal cancer.

In 11 patients with rectal cancer, a mixture of F(ab')2 fragments of anti-carcinoembryonic antigen and anti-CA 19.9 labelled with a diagnostic dose of iodine-131 (3-10 MBq) was administered submucosally around the tumour. In this study, the local kinetics in and the dose to the rectal wall, the whole body kinetics and the effective dose equivalent are presented. The early disappearance of the activity from the injection spot was characterized by a T1/2 of 21 h. Initially, about 50% of the plasma activity was due to free 131I. After 4 h, the plasma activity was almost completely protein bound (86%). Maximum plasma activity was observed after the 2nd day. From 72 h p.i., the plasma activity decreased with a T1/2 of 53 h. In the first 24 h, 14% of the injected dose was excreted in the urine and within 4 days about half of the administered activity. The absorbed radiation dose to the rectal wall was estimated to be 0.2 Gy/MBq, presuming a 20 cm3 distribution volume. The dose to the bone marrow was 0.2 mGy/MBq or 0.4 mGy/MBq, assuming a homogeneous tracer distribution or equal blood and bone marrow activity concentrations, respectively. The effective dose equivalent is 1.9 mSv/MBq, mainly determined by the dose to the rectal wall and to a lesser extent by the dose to the remaining body. Postulating comparable kinetics, 123I- or 111In- or 99mTc-labelled fragments would result in 4-25-fold lower effective dose equivalents.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Prognostic value of thallium-201 exercise scintigraphy in low-risk patients after Q-wave myocardial infarction: comparison with exercise testing and catheterization.

In a prospective study of 100 consecutive patients discharged after a Q-wave myocardial infarction, the value of reversible ischemia on thallium-201 scintigraphy to assess the risk of cardiac events (death or reinfarction) during 4 years was compared with variables from exercise testing and cardiac catheterization. Patients with markedly impaired left ventricular function [ejection fraction (EF) < or = 0.30] were excluded. During follow-up there were 20 cardiac events (10 cardiac deaths and 10 reinfarctions). Thallium-201 scintigraphy was significantly better than all exercise test variables and better than an EF < 0.40, with good sensitivity and specificity (75 and 51%, respectively). Exercise-induced reversible ischemia on scintigraphy yielded the same information as the presence of multivessel disease. Exercise test variables were of limited value to assess prognosis. Thus, thallium-201 scintigraphy can be used as the only tool to predict future cardiac events in low-risk patients after a Q-wave myocardial infarction.

Adult↗
PubMed1991

Human IgM monoclonal antibody 16.88: pharmacokinetics and immunogenicity in colorectal cancer patients.

Twenty colorectal cancer patients were given an intravenous injection of human IgM monoclonal antibody (MAb) 16.88 (8 mg) conjugated to 131I for tumor localization. After a 2-week interval, a second injection with 200, 500, or 1000 mg of unlabeled antibody added was given to groups of five patients each. at the end of the 2-hour infusion, 66% of the radioactivity remained in the circulation. Blood clearance of the 131I-labeled MAb 16.88 was biphasic with a mean half-life (T1/2 alpha) of 12 hours and T1/2 beta of 45 hours. Clearance rate was 0.09 L/hour. More than 90% of the 131I in serum was protein bound, with an immunoreactive fraction of 80% in the first 48 hours. Size exclusion chromatography indicated no degradation products other than 131I in serum and urine. The urinary excretion rate of 131I increased to 1.5% of the dose per hour at 24 hours, with 50% of the dose excreted in 34 hours. The pharmacokinetic profile of 131I-labeled MAb 16.88 was neither influenced by the total protein dose of antibody administered nor affected by specific uptake in tumor tissue in individual patients, as determined on early immunoscintigrams. The larger antibody doses showed a slightly slower excretion of 131I. The assays applied to determine immunogenicity were enzyme-linked immunosorbent assay, radioimmunoassay, and the dot-blot assay. They had sensitivities ranging from 5 ng/mL to 0.5 micrograms/mL for goat or rabbit antihuman IgM. The assays did not reveal antihuman antibody responses.

Adult↗
PubMed1991

[The diagnostic value of immunoscintigraphy using the monoclonal antibody OV-TL3 in patients with ovarian carcinoma].

Immunoscintigraphy, using radiolabeled monoclonal antibodies directed against tumor associated antigens, is a relatively new method for the detection of tumour localizations. The diagnostic accuracy of immunoscintigraphy was compared with computer tomography, magnetic resonance imaging, ultrasound, physical examination, and the CA 125 serum assay in patients suspected of having primary or recurrent ovarian cancer. One mg of the murine monoclonal antibody OV-TL3 F(ab')2 was labeled with 4 mCi 111Indium and administered intravenously to 28 patients. No adverse reactions were noted. Twenty patients underwent extensive explorative laparotomy 3 to 8 (median 4 days) days after injection of the immunoconjugate, allowing a histopathological verification of the actual tumour status of each patient. The sensitivity of immunoscintigraphy for the detection of ovarian cancer was at least equal to that of the other diagnostic methods. However, with immunoscintigraphy more tumour localizations were identified.

Adult↗
PubMed1991

Tumour localisation with 131I-labelled human IgM monoclonal antibody 16.88 in advanced colorectal cancer patients.

Human IgM monoclonal antibody 16.88 recognised an intracellular antigen strongly expressed in colorectal cancer tissue in 51% of our patients. Tumour localisation was carried out with 185 MBq 131I-16.88 (8 mg) in 20 of these patients with advanced disease. In 16 patients (80%) immunoscintigraphy was positive in at least one organ site with disease. Of all sites, 55% could be visualized. In general, lesions less than 3 cm could not be detected. Sequential immunoscintigrams of liver metastases showed variable patterns. Initial "cold" lesions corresponded to liver metastases with poor blood supply as indicated by 99mTc-sulphur-colloid and 99mTc-HMPAO scintigraphy, respectively. The mean (S.D.) biological half-life (whole body clearance of radioactivity) was 37.6 (5.0) h. A second infusion of 131I-16.88 with the addition of high doses of unlabelled 16.88 could be done safely, but did not result in better visualisation of tumour lesions or affect radioactivity clearance from the body.

Adult↗
PubMed1991

Qualitative and quantitative kinetics of submucosally administered antibody fragments in patients with rectal carcinoma: the detection of lymph node metastasis in relation to local tracer diffusion.

Immunoscintigraphy after submucosal administration of a mixture of 131I-anti-CEA and 131I-anti-CA-19-9 around the tumor in patients with rectal carcinoma may improve pre-operative staging and may contribute to the selection of patients eligible for local treatment. However, visual discrimination of local lymph node metastasis appears unreliable, partly because of scatter from the injection site and substantial diffusion of the radiotracer into the interstitium. Analysis of the diffusion profile, however, may improve the sensitivity and accuracy of this immunoscintigraphic approach.

Aged↗
PubMed1990

The effect of fenoldopam on renal haemodynamics and natriuresis in chronic renal failure.

The effect of oral administration of fenoldopam, a dopamine-1 receptor agonist, on blood pressure, renal haemodynamics and natriuresis was studied in 12 patients with chronic renal insufficiency. In addition, the effect of administering a low intravenous dose of fenoldopam on top of the oral dose was compared with the effect of the same intravenous dose given immediately before oral fenoldopam. Oral administration of fenoldopam (50 mg t.i.d. for 3 +/- 1 days followed by 100 mg t.i.d. for 8 +/- 1 days) induced a significant fall in blood pressure (median MAP from 107 to 101 mm Hg). Compared to baseline values, body weight, effective renal plasma flow (ERPF), glomerular filtration rate (GFR) and fractional sodium excretion remained unchanged. Infusion of fenoldopam (0.05-0.1 micrograms/kg/min) on day 1 led to a significant fall in blood pressure (median mean arterial pressure from 107.0 to 98.5 mm Hg), and a significant rise in effective renal plasma flow (median ERPF from 132 to 146 ml/min/1.73 m2). Median fractional sodium excretion increased significantly from 2.1 to 3.3%. GFR, filtration fraction and plasma aldosterone concentration did not change. No relationship was found between the fenoldopam-induced changes in ERPF and natriuresis, nor between baseline GFR or ERPF and fenoldopam-induced urinary sodium loss. Infusion of fenoldopam while patients were on oral fenoldopam had no effect on blood pressure, ERPF or GFR. However, again natriuresis was induced, which did not differ significantly from the fenoldopam-induced natriuresis on day 1. We conclude that oral fenoldopam has a moderate blood pressure lowering effect in patients with chronic renal insufficiency, but exerts no effect on ERPF or GFR. Secondly, a fenoldopam-induced natriuresis does not appear to be related to changes in ERPF or aldosterone secretion.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1990

Human IgM monoclonal antibody 16.88: pharmacokinetics and distribution in mouse and man.

Human IgM monoclonal antibody (MAb) 16.88 recognizes an antigen strongly expressed by colon cancer tissue. We used 131I-labelled 16.88 for biodistribution and pharmacokinetic studies in nude mice bearing WiDr or NIH:OVCAR-3 xenografts. Serum half-life was 8 h. Maximum tumour uptake was between 1 and 8 h after administration and amounted to, respectively, 3% and 1% of the injected dose g-1 for WiDr and NIH:OVCAR-3 tumours. Half-lives in these tumours were approximately 24 h. Tumour to normal colon uptake ratios increased from 2.3 at 24 h to 17 at 5 days after injection. Simultaneously, pharmacokinetic studies were performed in patients with advanced colon cancer reactive with 16.88. They were injected with 5 mCi 131I-16.88 by intravenous infusion over 2 h. Serum half-life was 20 h with greater than 90% of the 131I bound to 16.88. Within 40 h 50% of the injected dose was excreted as free 131I in the urine. In one patient an accelerated clearance was found, possibly caused by pre-existing antibodies reacting with 16.88. None of the patients showed an immune response against 16.88 antibody. Immunoscintigraphy showed positive tumour localization in the majority of the patients, best visualized at later days. We conclude that 16.88 has tumour localization properties while its human origin accounts for the lack of immunogenicity.

Animals↗
PubMed1988

Functional pneumectomy by a saccular aneurysm of the aortic root.

This case report describes a patient with severe stenosis of the right pulmonary artery due to an expanding arteriosclerotic aneurysm of the ascending aorta. The clinical data and the lung perfusion ventilation scintigrams supported the diagnosis of pulmonary embolism, and initially the patient was treated accordingly.

Aortic Aneurysm↗
PubMed1988

99mTc-MAG3: dynamic studies in patients with renal disease.

Animal studies have suggested that 99mTc-mercapto-acetylglycyl-glycyl-glycine (99mTc-MAG3) might be suitable for the determination of the renal plasma flow (RPF) because of its high renal clearance. In this study 131I-orthoiodohippurate (131I-OIH) and 99mTc-MAG3 (labeling always greater than 95%) were administered simultaneously in 11 patients (creatinine clearance ranging from 14 to 130 ml/min per 1.73 m2) to measure effective RPF(ERPF) using the standard technique (UV/P). Glomerular filtration rate (GFR; clearance of 125I-thalamate, 125I-OT) was also measured. The mean ratio of 99mTc-MAG3 clearance to 131I-IOH clearance was 0.55 +/- 0.02 (SEM), P less than 0.01, n = 16, and was independent of GFR and ERPF. To study this difference in renal handling of the radiopharmaceuticals, renal extractions by the right kidney were determined in another six patients after a single shot of the agents. Renal extraction of 99mTc-MAG3 was 0.60 +/- 0.03 after 5 min, and 0.41 +/- 0.08 after 30 min. Renal extraction of 131I-OIH amounted to 0.86 +/- 0.04 and 0.77 +/- 0.03, respectively. Using renal extractions of 0.41 and 0.77, respectively, it appeared that calculated renal plasma flows measured simultaneously with 99mTc-MAG3 and 131I-OIH were similar. Protein binding 30 min after the priming dose was 66% for 99mTc-MAG3 and 47% for 123I-OIH. We conclude that in spite of a high renal clearance (ratio to 125I-OT clearance 2.69 +/- 0.27), 99mTc-MAG3 seems unsuitable for an accurate determination of the RPF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Pacing and the non-invasive evaluation of myocardial fatty acid metabolism by means of 17-123I-heptadecanoic acid scintigraphy.

The extent of myocardial non-esterified fatty acid (NEFA) oxidation depends among other things on exogeneous NEFA supply and energy demand. In 6 patients with a multi-programmable pacemaker scintigraphy with 17-123Iodo-heptadecanoic acid (17-123I-HDA) was performed to investigate NEFA metabolism at two levels: at a control level (basal heart rate 69 +/- 6) and at increased pace frequency (104 +/- 5). In both situations the derived time-activity curves, measured during a period of 75 min, were fitted with a monoexponential plus a constant curve: A(t) = A(0).exp (-t In2/T1/2) + C. The half-time value, the uptake measured as the peak activity and the relative size of the oxidation pool were determined. The median of the half-time value did not change: 24 min (range 19-31) in the control heart rate study and 22 min (19-27) during the increased pace frequency study. The median of the uptake increased significantly from 33 cpm/pixel/2 mCi/100 kg (23-34) to 40 cpm/pixel/2 mCi/100 kg (35-42; p less than 0.05 Wilcoxon). The median of the relative size of the oxidation pool increased from 57% (52-62) to 69% (63-71; p less than 0.05). We conclude that during pacing the augmented need for NEFA resulted in a demonstrable increase in uptake and oxidation of 17-123I-HDA. This result suggests that radioiodinated NEFA may be a valuable tool to quantify noninvasively the level of the myocardial NEFA metabolism in the human heart.

Fatty Acids↗
PubMed1987

The hot skull: malignant or feminine?

Diffusely increased uptake in the calvarium on bone scintigraphy (a hot skull) is often present in patients with bone metastases and metabolic diseases. Excluding these known facts the prevalence of the hot skull and its relation with malignancy and, more specifically, with breast carcinoma have been studied in 673 patients. In women, the hot skull is clearly related to malignancy and to a lesser extent to breast carcinoma. However, another remarkable feature of the hot skull is its predominance in women in general (compared to men) and, therefore, the data suggest that the hot skull can also represent a normal variant of the female skull. We conclude that the hot skull has no clinical value in screening protocols.

Bone and Bones↗
PubMed1986

Changes in blood pressure and body fluid volumes during diuretic therapy in patients with essential hypertension who receive enalapril.

We evaluated the effect of additional chlorthalidone therapy on blood pressure and body fluid volumes in 10 patients with essential hypertension who did not respond to chronic converting enzyme inhibition with enalapril. Values assessed after 3 days and 6 weeks of combined enalapril and chlorthalidone therapy were compared with initial values during enalapril monotherapy. After 3 days the mean arterial pressure (MAP), plasma volume (PV), blood volume (BV), and extracellular fluid volume (ECFV) decreased. There was a positive correlation between the percentage decreases in MAP and BV. After 6 weeks the MAP decreased further, but the decreases in PV, BV, and ECFV were less pronounced. At this time there was a positive correlation between the percentage decreases in MAP and ECFV. Our results support the hypothesis that contraction of the ECFV is an antihypertensive mechanism of diuretics. The antihypertensive effect of diuretics is enhanced during converting enzyme inhibition, while the body remains protected against volume deficits, possibly by the lower blood pressure itself.

Aged↗
PubMed1986

The importance of plasma protein for blood volume and blood pressure homeostasis.

To evaluate the influence of plasma protein concentration and colloid osmotic pressure (COP) on blood volume and blood pressure, we studied 40 patients with the nephrotic syndrome (plasma protein 41.1 +/- 5.3 g/liter, COP 10.9 +/- 2.2 mm Hg) and 43 patients with chronic renal failure (plasma protein 65.0 +/- 5.8 g/liter, COP 22.4 +/- 3.0 mm Hg) at overhydration, during gradual edema removal to normal hydration, and occasionally, to mild dehydration. The number of measure points was 113 in the nephrotic syndrome and 92 in renal failure. In both groups blood volume was normal at normal extracellular fluid volume (ECFV). Elevation of ECFV to 300% of normal in the nephrotic syndrome occurred with only a modest elevation of blood volume (NS). Elevation of ECFV to 200% of normal in the patients with renal failure was attended by a major elevation of blood volume (P less than 0.01). Reduction of ECFV to about 10% below normal was accompanied by parallel blood volume reduction in both groups. Blood pressure was comparable at normohydration, and increased to clearly hypertensive levels only in the renal failure group with increasing ECFV and blood volume (P less than 0.01). No major blood pressure difference was observed between normal and subnormal hydration, but hypotension was observed twice in the nephrotic group. Apparently, patients with severe hypoproteinemia due to the nephrotic syndrome are generally able to preserve their blood volume even when free of edema. However, their blood volume is not elevated in overhydration, in contrast to patients with renal failure who are normoproteinemic. This difference in regulation of extracellular fluid distribution is probably related to the hypoproteinemia, and its effect to reduce tissue-fluid protein.

Adolescent↗
PubMed1985

Transthoracic electrical impedance as an index of extracellular fluid volume in man.

Findings in 76 subjects without cardiac failure were analyzed to detect relationships between observed changes in transthoracic electrical impedance (TEI) and total body extracellular fluid volume (ECFV) during various manoeuvres and between absolute TEI and ECFV values. TEI was normalized to electrode distance (Z0/delta el) and ECFV to lean body mass (ECFV/LBM). A distinct relation was found between percent changes of TEI and ECFV (r = -0.76, p less than 0.0001) and between absolute Z0/delta el and ECFV/LBM values (r = -0.66, p less than 0.0001 for men; r = -0.61, p less than 0.0001 for women). It is concluded that in the same subject a change in TEI is possibly a sensitive index for a change in ECFV and that a single measurement of TEI, normalized to electrode distance, gives information about the state of hydration (ECFV) of patients without cardiac failure.

Adult↗
PubMed1985

Preservation of blood volume during edema removal in nephrotic subjects.

During the gradual removal of edema with diuretics in 21 edematous patients with the nephrotic syndrome (NS) we monitored blood volume. For comparison, nine healthy subjects were studied after equilibration on diets containing 20, 200, and 1138 mEq sodium. The initial extracellular fluid volume (ECFV) in the patients exceeded the final ECFV by 63.4 +/- 8.4%. In 10 patients with a very low plasma oncotic pressure (8.2 +/- 0.4 mm Hg, Group 1), the blood volume changed little. In Group 2 (plasma oncotic pressure 13.4 +/- 1.0 mm Hg), it was 11.0 +/- 2.5% higher at entry than after edema withdrawal. In the normal volunteers, the highest sodium intake raised the ECFV by 21.4 +/- 4.1%. The accompanying rise in blood volume, 11.2 +/- 3.0%, was larger than in the patients of Group 1 (2.4 +/- 1.9%, P less than 0.04), but not of Group 2 (8.1 +/- 1.9%, NS) at similar degrees of expansion. There was no difference in blood volume between the edema-free patients and the normal subjects at low-sodium diet. The course of blood pressure and creatinine clearance during edema removal gave no evidence that functional hypovolemia was induced, but the plasma renin activity was higher than in the normal subjects at similar degrees of expansion. We conclude that the blood volume to ECFV relationship curve is flattened in the presence of hypoalbuminemia. Thus, the increase in blood volume that normally follows ECFV expansion is less in patients with the NS, but a drop below normal upon removal of edema is absent also.

Adolescent↗
PubMed1985

Blood to interstitial fluid volume ratio in chronic hypokalaemic states.

The distribution of extracellular fluid over the intra- and extravascular spaces was determined in hypokalaemic and normokalaemic patients. In six patients with Bartter's syndrome, four with pseudo-Bartter's syndrome, and twenty with essential hypertension (EH) chronically treated with chlorthalidone, serum potassium (serum K+) and extracellular fluid volume (ECFV) were decreased, while plasma volume (PV) and blood volume (BV) were normal (see Table 1 for means, standard deviations, and levels of significance). Consequently, the ratio of BV to interstitial fluid volume (IFV) was increased. In ten patients with EH on long-term combined enalapril chlorthalidone therapy, eight EH patients on long-term spironolactone treatment, and twenty-three EH patients treated by short-term sodium restriction, PV, BV, and ECFV were decreased, but serum K+ and BV/IFV were normal. In six patients with primary hyperaldosteronism (PHA) serum K+ was decreased, while PV, BV, and BV/IFV were elevated. Significant negative correlations between sK and BV/IFV were found in the Bartter patients (r = -0.88) and the pooled data of all patients (r = -0.50). These findings suggest an association between chronic hypokalaemia and a fluid shift from the extra- into the intravascular space. The hypothesis that this phenomenon is due to a decreased venous resistance as a consequence of chronic hypokalaemia is discussed.

Bartter Syndrome↗