M. De Roo

Improvement of gastric emptying in diabetic gastroparesis by erythromycin. Preliminary studies

Erythromycin mimics the effect of the gastrointestinal polypeptide motilin on gastrointestinal motility, probably by binding to motilin receptors and acting as a motilin agonist. Erythromycin may thus have clinical application in patients with disturbances of gastroduodenal motility, such as diabetic gastroparesis. To examine this possibility, we studied the effect of erythromycin on gastric emptying in 10 patients with insulin-dependent diabetes mellitus and gastroparesis. We studied the emptying of liquids and solids simultaneously on separate days after the intravenous administration of erythromycin (200 mg) or placebo, using a double-isotope technique and a double-blind, crossover design. Erythromycin shortened the prolonged gastric-emptying times for both liquids and solids to normal. For example, 120 minutes after the ingestion of a solid meal, mean (+/- SE) retention was 63 +/- 9 percent with placebo and 4 +/- 1 percent with erythromycin, as compared with 9 +/- 3 percent in 10 healthy subjects. The corresponding values 120 minutes after the ingestion of a liquid meal were 32 +/- 4, 9 +/- 3, and 4 +/- 1 percent, respectively. Gastric emptying also improved, but to a lesser degree, in the 10 patients after four weeks of treatment with oral erythromycin (250 mg three times a day). These preliminary results suggest that erythromycin may have therapeutic value in patients with severe diabetic gastroparesis.

Histological alterations in chronically hypoperfused myocardium. Correlation with PET findings.

BackgroundIn patients with chronic coronary artery disease (CAD) and left ventricular dysfunction, flow/metabolic studies of the myocardium with positron emission tomography (PET) are able to distinguish viable but dysfunctional myocardium from irreversible ischemic injury and scar tissue. In this study, PET findings of blood flow and metabolism in chronically hypoperfused myocardium were correlated with histology. Methods and ResultsWe studied 33 patients suffering from CAD. In each patient, myocardial blood flow and metabolism were measured with PET 1 or 2 days before revascularization. During surgery, transmural biopsies were taken from the left ventricular anterior wall and planimetrically scored for the degree of myolysis (sarcomere loss). The amount of connective tissue was calculated using morphometric techniques. Contrast ventriculography demonstrated abnormal wall motion in 23 patients. Fourteen patients with a mismatch pattern (decreased flow with preserved metabolism) in the biopsy region after quantitative analysis of the PET data showed 11±6 vol% fibrosis and 25±13% cells with sarcomere loss. The space formerly occupied by sarcomeres was mainly replaced by glycogen and mitochondria. A significant wall motion improvement was noted 3 months after surgery. Nine patients showed a match pattern (concordant flow/metabolism defects). The biopsies revealed 35±25% fibrosis and 24±15% glycogen-storing cells. The biopsies of the 10 patients with normal anterior wall motion showed 8±4% fibrosis and 12±8% glycogen-accumulating cells. ConclusionsIt can be concluded that areas with impaired wall motion and a PET match pattern show extensive fibrosis. Regions with reduced flow and preserved FDG metabolism, however, contain predominantly viable cells. In these regions, significant recovery of wall motion is found after revascularization. Regions with normal wall motion contain predominantly viable cells. Cells with reduced contractile material and increased glycogen content are mainly found in areas with wall motion impairment but are also present in areas with normal wall motion and a severe stenosis of the coronary vessel.

Thyroid function in patients with hyperemesis gravidarum

An increased free thyroxine (T4) index was observed in 73% of 33 consecutive pregnancies complicated by severe hyperemesis gravidarum. The free triiodothyronine (T3) index was increased in only four of 11 hyperthyroxinemic patients. In five hyperthyroxinemic patients tested, no increase in serum thyrotropin was observed after the injection of thyrotropin-releasing hormone (THR). Goiter, exophthalmos, or previous history of hyperthyroidism was absent in all patients. The thyroxinemia returned to normal in one to several weeks, whether or not it was treated with antithyroid drugs. The thyroid function during the period of hyperemesis had no influence on the subsequent rate of abortion or duration of pregnancy. A lower birth weight, however, was observed in children born to hyperthyroxinemic mothers. Hyperemesis gravidarum should be included in the differential diagnosis of elevations in free T4 index during pregnancy and included in the differential diagnosis of hyperthyroidism.

A new thresholding method for volume determination by SPECT

The quantification of organ volumes from SPECT images suffers from two major problems: image segmentation and imperfect system transfer function. Image segmentation defines the borders of an organ and allows volume measurements by counting the voxels inside this contour in all slices containing parts of this organ. A review of the literature, showed that several investigators use a fixed threshold (FT) to determine the organ pixels. It is our aim to demonstrate that the threshold has to be adapted to every single case because its value is dependent upon several factors, such as size and contrast. Therefore a threshold selection algorithm, based on the gray level histogram (GLH), is evaluated. It is nearly impossible to calculate and eliminate errors induced by the complex system response function. A correction method based on linear regression is proposed. By minimizing the relative error (σ), a linear correlation (Y=AX+B) between the true volume (Y) and the measured volume (X) is established for three fixed thresholds (30%, 40%, 50%) and for the GLH method. The methods are evaluated on a series of nineteen phantoms with a volume range between 9.8 and 202.5 ml. The relative error is minimal for the GLH method. The whole procedure is semi-automated and virtually operator independent.

Measurement of skeletal flow with positron emission tomography and 18F-fluoride in femoral head osteonecrosis

Positron emission tomography (PET) with 18F-fluoride was utilized to determine the regional blood flow to the femoral head in early osteonecrosis. Five patients with a history of unilateral hip trauma and a normal contralateral side were selected. Skeletal flow and fluoride uptake in the abnormal and normal hips were compared directly, and the relation between bone blood flow and final outcome, i.e., surgical replacement or conservative treatment, was evaluated. In this pilot study, a flow ratio of at least 2 between the abnormal and normal femoral head was necessary to predict a successful outcome with a conservative regimen. A minimum flow of 0.04 ml/min/ ml was measured in one patient whose affected femoral head healed conservatively. Our preliminary study indicates that this type of highly technical investigation appears feasible in clinical practice and permits prediction of the outcome depending upon regional skeletal flow measurements in vivo.

Comparative evaluation of 99Tcm-Hynic-HSA and 99Tcm-MAG3-HSA as possible blood pool agents.

SummaryTwo strategies have been used to increase the 99Tcm binding strength of human serum albumin (HSA) and thus enhance its blood retention. In a first approach, HSA was derivatized with a varying number of hydrazino nicotinyl (Hynic) side-chains using N-hydroxysuccinimidyl hydrazino nicotinate. Labelling of this albumin derivative with 99Tcm resulted in labelling yields of 90–95%. On the other hand, a 99Tcm-MAG3-HSA conjugate was prepared using the preformed chelate approach. In this way, non-specific binding of 99Tcm to HSA could be excluded. The in vitro stability of both 99Tcm-HSA derivatives was evaluted by cysteine challenge experiments and revealed a much higher stability for 99Tcm-Hynic-HSA than for 99Tcm-MAG3-HSA. The biological behaviour of the preparations was evaluated in mice and a rabbit using 125I-HSA as an internal biological standard. The blood retention of 99Tcm-MAG3-HSA decreased more rapidly than that of 125I-HSA in both animal species, whereas 99Tcm-Hynic-HSA seemed to provide a quasi-perfect 99Tcm-labelled analogue for 125I-HSA and 99Tcm-red blood cells (99Tcm-RBCs). In addition, the blood retention of 99Tcm-Hynic-HSA appeared to be similar to that of 99Tcm-RBCs in a volunteer. These results clearly indicate the superiority of 99Tcm-Hynic-HSA over 99Tcm-MAG3-HSA as a possible blood pool agent.

Chronic osteomyelitis: diagnosis with technetium-99m-d, l-hexamethylpropylene amine oxime labelled leucocytes.

To evaluate the diagnostic value of technetium-99md,l-hexamethylpropylene amine oxime (HMPAO) labelled leucocytes in combination with a99mTc-methylene diphosphonate (MDP) bone scan in the detection of chronic osteomyelitis, we retrospectively reviewed 55 patients. Prior to the99mTc-d,I-HMPAO labelled leucocyte scan, all patients underwent a99mTc-MDP bone scan. The correct diagnosis was confirmed by long-term clinical follow-up (n=29) or by bacteriological cultures (n=26). We found an overall sensitivity of 94%, a specificity of 91% and an accuracy of 92% for99mTc-d,l-HMPAO labelled leucocyte scintigraphy in the diagnosis of chronic osteomyelitis. When the patients were divided into three groups according to the location of the infection, our study results showed a sensitivity and specificity for the central location (containing active bone marrow) of 94% and 100% respectively; for the peripheral location (hands and feet) both parameters were 100%, and for the middle location (all sites between the central and the peripheral location) the values were 92% and 81% respectively. Specificity and accuracy were significantly lower in the middle location than in the central and peripheral locations. The results of our study confirm that a99mTc-d,l-HMPAO labelled leucocyte scan in combination with an99mTc-MDP bone scan is a reliable way to diagnose chronic osteomyelitis, except for vertebral osteomyelitis.

Investigation of the labelling characteristics of 99mTc-mercaptoacetyltriglycine

S-Benzyl-, S-benzamidomethyl- and S-benzoylmercaptoacetyltriglycine were synthesized and compared in exchange labelling experiments for the preparation of 99mTc-MAG3. The rate of exchange from 99mTc-tartrate to 99mTc-MAG3 starting from the respective precursors was determined in different conditions. Labelling proceeded most rapidly starting from the S-benzoyl protected precursor but efficient labelling was also accomplished using the more stable S-benzamidomethyl- and S-benzylmercaptoacetyltriglycine. 99mTc-MAG3 was also prepared by direct labelling of unprotected mercaptoacetyltriglycine at alkaline pH. Radiochemical purity in these conditions is mainly dependent on the pH during labelling.

Diagnostic value of 99Tcm-d,1-HMPAO-labelled leukocyte scintigraphy in the detection of vascular graft infections

&NA; Prosthetic vascular graft infection is a relatively uncommon complication of peripheral vascular surgery. We retrospectively analysed technetium‐99m‐d,l‐hexamethylpropylene amine oxime (99Tcm‐d,l‐HMPAO) labelled leukocyte scans of 21 patients with a suspected vascular graft infection. Operative findings, bacteriological cultures, radiological findings or clinical follow‐up were used to confirm the diagnosis. We found eight true‐positive and six true‐negative cases. There were no false‐positive scintigraphic diagnoses. The false‐negative rate was 33% (n=7). Our results show a sensitivity of 53%, a specificity of 100% and an accuracy of 66%. The conclusion is that a negative 99Tcm‐d,l‐HMPAO‐labelled leukocyte scan is of limited value in ruling out a vascular graft infection. A combination of computed tomography (CT‐scan) and a99Tcm‐d,l‐HMPAO‐labelled leukocyte scan is probably the most efficient way of diagnosing a vascular graft infection.

Quantitative scintigraphy of the sacroiliac joints

The effects of age and laterality on sacroiliac (SI) to sacral indices and ratios were assessed in 62 patients. For the 14 controls, the left mean SI to sacral index was significantly higher than the right one. There was no correlation between age and SI to sacral ratio (= average of right and left index). The mean ratio in 36 patients with sacroiliitis and 12 patients with low back pain was not significantly different from that of the controls, with a clear overlap of indices between controls and sacroiliitis patients.