Thirty patients with clinically suspected infective endocarditis were scanned with Indium-111- or Tc-99m-HMPAO-labeled granulocytes. The scans were correlated with the clinical course, and in 20 cases with the results from histologic examination of the valves. In six cases the scintigraphic examination gave correct positive results, in three cases false negative, in one case a false positive, and in 20 cases correct negative results. If we limit the analysis to only the histologically proven cases, our data suggest a specificity of the method of 86 % and a sensitivity of about 67 %.

Thirty patients with clinically suspected infective endocarditis were scanned with Indium-111- or Tc-99m-HM-PAO-labeled granulocytes. The scans were correlated with the clinical course, and in 20 cases with the results from histologic examination of the valves. In six cases the scintigraphic examination gave correct positive results, in three cases false negative, in one case a false positive, and in 20 cases correct negative results. If we limit the analysis to only the histologically proven cases, our data suggest a specificity of the method of 86% and a sensitivity of about 67%.

A normal baseline TSH serum concentration is accepted as excluding thyroid dysfunction. The present study examined the usefulness of that concentration as a screening test for functional autonomy. 310 patients were retrospectively examined. They were all clinically euthyroid and had normal peripheral thyroid hormone concentrations. The positive predictive value for the confirmation of autonomy was 55.5%, the negative predictive value for the exclusion of autonomy 87.7%, using 0.5 mU/l as a lower limit. The probability for the presence of thyroid autonomy in patients with a TSH serum concentration below 0.3 mU/l was 72.5%.

The fecal excretion of 111In-oxine-labeled autologous granulocytes was determined in 58 patients with Crohn's disease. A representative analysis of the total amount of excreted cells requires a 4-day stool sampling at least in those patients suffering from Crohn's ileitis or ileocolitis. Various laboratory tests (Orosomucoid, alpha 1-antitrypsin, C-reactive protein, erythrocyte sedimentation rate, leukocytes, thrombocytes, albumin, Fe, alpha 1-globulin and alpha 2-globulin) and the van Hees index significantly correlated with this specific estimate of intestinal inflammation, indicating that it is of little importance which one is clinically used for the assessment of inflammatory activity in Crohn's disease.

Spontaneous migration of a radionuclide tracer from the vagina to the peritoneum may be visualized by scintigraphic imaging (hysterosalpingoscintigraphy, HSS). A prospective study was designed to evaluate diagnostic criteria for normal tubal passage of a control group (n = 7) and to establish the predictive value of the HSS technique in defining functional deficiency in anatomically patent tubes. In 56 patients with tubal and unexplained infertility, a comparison between the results of the tracer migration study and of contrast hysterosalpingography and laparoscopy was made. The overall correlation was 65%. Clearly discrepant results (i.e. an abnormal migration pattern in anatomically patent tubes) were recorded in 18% and were positively, yet not significantly associated with tubal adhesive disease and with a history of tubal microsurgery. Interpretation of scans was equivocal in another 18% of patients due to undetectable ascension of the tracer to the uterus. It is suggested that the radionuclide is moved forward by the same passive transport processes which are concerned with support of the migration of spermatozoa to the ovum, and that failure of tubal migration of the tracer may render patients eligible for in-vitro fertilization/embryo transfer treatment.

In the follow-up of five patients with histologic proven medullary thyroid carcinoma (MTC) and raised serum calcitonin and CEA levels the pentavalent Tc-99m-(V)-DMSA and the Tc-99m-MDP bone scan had the highest sensitivity in the localisation of metastases. Both methods are not tumor specific. A false positive Tc-99m-(V)-DMSA uptake in an old osteomyelitis of one vertebra could be demonstrated. The J-123-MIBG and In-111-F(ab2)' antibody scan did not allow to localise one of the above described metastases. In conclusion in the follow-up of patients with MTC and elevated tumor marker concentrations the Tc-99m-(V)-DMSA and the Tc-99m-MDP bone scan should be the second diagnostic procedures after sonography has been performed.

A prospective study was designed to evaluate the efficacy of radionuclide hysterosalpingoscintigraphy using 99mTc-labelled human serum albumin macroaggregates in 17 patients (34 tubes). In normal females the niacroaggregates migrate spontaneously through the female reproductive tract following application into the posterior vaginal fornix. They can be seen in the uterine fornix 20 min p. i. (range: 5-90 min) and as free pelvic activity 120 min p. i. (range 40-180 min). Free pelvic activity could also be demonstrated by culdocentesis. In infertile patients with failure of tubal patency images after 180 min offered no additional information. For the routine diagnosis camera images 5, 60 and 180 min p. i. are recommended. Using 5-10 MBq 99mTc the radiation exposure to the ovaries is about 1/9th of the exposure from a normal radiologic hysterosalpingogram. The reported data show results comparable with those of hysterosalpingography (HSG) in females with patent or with nonpermeable tubes, but in cases of high-pressure patency by HSG the results of scintigraphy are superior to those of HSG. Moreover, this method provides new insights into sperm motility under various physiological and pathological conditions.

The in vitro and in vivo behaviour of 99Tcm-HMPAO (hexamethylpropyleneamineoxime) (n = 12) and 111In-oxine (n = 11) labelled granulocytes, isolated by density-gradient centrifugation (Metrizamide/plasma gradients), was compared in patients with suspected inflammatory diseases. The in vitro elution of both labels and the viability of the labelled cells (99Tcm, 98.5%; 111In, 96.5%) was comparable but the labelling efficiency was different (99Tcm, 44±13%; 111In, 72.5±5.5%). In vivo, the lung (t1/2 max 7.7 min), liver and spleen perfusion patterns were nearly identical; the image quality for detail in 99Tcm scans was superior to 111In images. The blood disappearance curves of 99Tcm and 111In were comparable. In the small number of patients examined all infections could be diagnosed correctly, without false-positive or false-negative results. Disadvantageous is the renal excretion of 99Tcm complexes (3+ % over 20 h) with kidney and bladder activity from the beginning of the study. The-biliary excretion in half of the patients (n = 6) with unspecific positive small and large bowel visualization and the late intestinal excretion also render the diagnosis more difficult. The recommended best imaging times for abdominal and retroperitoneal inflammations are 30 min to 2 h after injection. Late scans in septic prosthetic joints have disproportionate long acquisition times. As a potential, cell labelling compound, 99Tcm-HMPAO has a promising future in comparison to 111In scans because of the good availability of 99Tcm, the image quality and the lower radiation exposure to the patient when lower activities for the early diagnosis of abdominal inflammatory diseases are reinjected.

Radiolabelled granulocytes in chronic inflammatory bowel diseases (CIBD) are able to diagnose the disease extent and assess the disease activity. It may be performed with 111In oxine- and 99Tcm hexamethylpropyleneamineoxime (HMPAO)-labelled cells. The granulocyte scan localizes inflamed bowel segments with an accuracy comparable with radiology and endoscopy including biopsy of the bowel (r = 0.95; P less than 0.001). The specificity of the scan for diseased segments is near 100%, the sensitivity 92%. A three-phase white blood cell scan (imaging: 0.5, 4, 20 h post injection) allows differentiation of diseased bowel segments from abscesses and fistulas. False positive results are possible in necrotic carcinomas. The 99Tcm HMPAO scan shows rapid renal and delayed biliary and intestinal excretion of tracer. In this way diagnostic problems arise in the small pelvis. Because of the intestinal and biliary excretion, early images should be obtained (0.5-2 h post injection). Later scans with 99Tcm HMPAO are of minor importance. The disease activity can very specifically be assessed by the determination of the percentage faecal 111In excretion (96 h faecal collection). Active and non-active diseases can be clearly differentiated. We found no correlation with the subjectively influenced Crohn's disease activity index (CDAI) (r = 0.25; P greater than 0.05), but good correlations with the Dutch Index (van Hees: r = 0.67), ESR (r = 0.69), serum albumin (r = -0.54) and orosomucoid (r = 0.65). The percentage faecal excretion correlates well with the histologically estimated leucocytic bowel infiltration. Because of the intestinal 99Tcm HMPAO excretion the determination of faecal excretion is pointless in 99Tcm studies.(ABSTRACT TRUNCATED AT 250 WORDS)

m In-granulocyte scans have shown to be a reliable tool in the diagnosis of the extent and the activity of chronic inflammatory bowel diseases and their frequent complications such as fistulas and abscesses (1, 2, 4, 5). Nevertheless, the method is, compared with sonography and endoscopy, not the procedure of choice in all follow-up examinations in the predominantly young patients, because of the radiation exposure. We recommend the l n In -granulocyte scan as a possible non-invasive procedure without necessary preparations of the bowel in the follow-up. For primary diagnosis the scan is recommended in all situations where endoscopy or double-contrast studies are impossible or even contraindicated, as in acute pancolitis with the risk of bowel perforation, in rectum or sigma stenosis where colonoscopy cannot be performed, and in suspected abscesses. The diagnosis of an abscess demands sudden therapeutic intervention. Another emergency is the diagnosis of a toxic megacolon where scintigraphic images have not yet been published.

The lipophilic 99Tcm hexamethylpropyleneamineoxime (HMPAO) complex can be used for labelling platelets as well as granulocytes. For the evaluation of optimal labelling parameters, platelets were isolated according to standard isolation procedures. The labelling efficiency (%) depends on incubation temperature (22 degrees C: 40%; 37 degrees C: 50%), incubation time (3 min: 20%; 25 min: 55%) and the incubation medium (plasma: 40%; saline: 50%). The 60 min 99Tcm elution from the platelets is around 8%. The platelet recovery, used as a quality parameter, is around 25 +/- 4% and is stable for at least 240 min. The high elution rate from the platelets leads to renal excretion of the label and so to significant kidney and bladder activity. Intestinal excretion of the label can also be frequently demonstrated. Fresh thrombotic lesions can usually be detected 4 h after reinjection of the labelled platelets, and in some patients as early as 1 h after reinjection of the platelets. In conclusion, 99Tcm HMPAO seems to be a promising platelet label for imaging thrombotic lesions but not for platelet-survival studies because of the short physical half-life of 99Tcm.

The in vitro and in vivo behaviour of 99Tcm-HMPAO (hexamethylpropyleneamineoxime) (n = 12) and 111In-oxine (n = 11) labelled granulocytes, isolated by density-gradient centrifugation (Metrizamide/plasma gradients), was compared in patients with suspected inflammatory diseases. The in vitro elution of both labels and the viability of the labelled cells (99Tcm, 98.5%; 111In, 96.5%) was comparable but the labelling efficiency was different (99Tcm, 44 +/- 13%; 111In, 72.5 +/- 5.5%). In vivo, the lung (t1/2 max: 7.7 min), liver and spleen perfusion patterns were nearly identical; the image quality for detail in 99Tcm scans was superior to 111In images. The blood disappearance curves of 99Tcm and 111In were comparable. In the small number of patients examined all infections could be diagnosed correctly, without false-positive or false-negative results. Disadvantageous is the renal excretion of 99Tcm complexes (3+% over 20 h) with kidney and bladder activity from the beginning of the study. The biliary excretion in half of the patients (n = 6) with unspecific positive small and large bowel visualization and the late intestinal excretion also render the diagnosis more difficult. The recommended best imaging times for abdominal and retroperitoneal inflammations are 30 min to 2 h after injection. Late scans in septic prosthetic joints have disproportionate long acquisition times. As a potential cell labelling compound, 99Tcm-HMPAO has a promising future in comparison to 111In scans because of the good availability of 99Tcm, the image quality and the lower radiation exposure to the patient when lower activities for the early diagnosis of abdominal inflammatory diseases are reinjected.

Thirty-three studies in 29 patients with suspected inflammatory heart diseases (natural endocarditis, N = 10; prosthetic valve endocarditis, N = 6; perimyocarditis, N = 17) were performed prospectively using 111In-oxin-labelled granulocytes with low red cell and platelet contamination after a Percoll/plasma or Metrizamide/plasma gradient centrifugation. In four out of 10 patients with suspected natural endocarditis, circumscribed activity could be seen over the heart. Once, an additional splenic infarction could be diagnosed. Three patients with surgically proven sterile valves had a true negative scan. In three out of six patients with prosthetic valve endocarditis a pathologic 111In activity could be seen in relation to the prosthesis. Three patients showed a negative scan after 3 weeks' antibiotic pretreatment. Six out of 17 patients with suspected perimyocarditis showed a significant positive leukocyte scan. In two of the six this was proven by biopsy; in four cases, only clinical diagnosis was made. 111In leukocyte imaging is able to diagnose highly acute inflammatory heart diseases non invasively. Because of the inadequacy of other diagnostic procedures, the scan may be of great clinical importance in prosthetic valve endocarditis. Natural endocarditis can be successfully diagnosed by other procedures, but in fever of unknown origin the scan also allows the diagnosis of acute inflammatory endocarditis.

Intestinal protein loss in chronic inflammatory bowel diseases may be easily determined by measurement of alpha-1-antitrypsin (alpha 1-AT) stool concentration and alpha 1-AT clearance. Both parameters were significantly raised in 36 and 34 patients respectively with chronic inflammatory bowel diseases, compared with eight patients with non-inflammatory bowel diseases, or 19 healthy volunteers. There was wide range of overlap between active and inactive inflammatory disease. Contrary to serum alpha 1-AT, faecal excretion and clearance of alpha 1-AT did not correlate with ESR, serum-albumin, orosomucoid, and two indices of disease activity. A comparison of alpha 1-AT faecal excretion and clearance with the faecal excretion of 111In labelled granulocytes in 27 patients with chronic inflammatory bowel diseases, showed no correlation between the intestinal protein loss and this highly specific marker of intestinal inflammation. Enteric protein loss expressed by faecal excretion and clearance of alpha 1-AT does not depend on mucosal inflammation only, but may be influenced by other factors.

Leucocyte elastase is a neutral proteinase which plays an important role in the pathogenesis of inflammatory disorders. Infiltration of bowel mucosa by neutrophil and eosinophilic granulocytes is a characteristic feature of chronic inflammatory bowel diseases. We studied plasma elastase in 44 patients suffering from Crohn's disease or ulcerative colitis. Plasma levels were significantly higher in these patients compared to 7 patients with non-inflammatory bowel diseases or 53 healthy controls. Elevated plasma levels were more often found in patients with active inflammation than in those with inactive disease. Elastase did neither correlate with leucocyte counts, serum albumin, ESR, alpha 1-proteinase inhibitor and orosomucoid nor with clinical indices or the faecal excretion of 111In-labelled granulocytes. In serial studies of 15 patients, elastase did not always run parallel to the disease activity. We conclude that plasma elastase does not reliably indicate the inflammatory activity in chronic inflammatory bowel diseases.