Striatal dopamine D2 receptor binding of risperidone in schizophrenic patients as assessed by 123I-iodobenzamide SPECT: a comparative study with olanzapine.

The aim of this investigation was to compare the degree of striatal dopamine-(D2) receptor blockade by two atypical antipsychotic drugs, risperidone and olanzapine. The percentage of D2 receptor occupancy during treatment was calculated by comparing the results of 123I-iodobenzamide SPECT with those from healthy control subjects. Twenty inpatients suffering from schizophrenia or schizoaffective psychosis according to DSM IV/ICD-10 criteria were treated with clinically recommended doses of risperidone and compared with 13 inpatients treated with up to 20 mg olanzapine. Neuroleptic dose and D2 receptor blockade correlated strongly for both risperidone (Pearson r = -0.86, p = 0.0001) and olanzapine (Pearson r = -0.77, p = 0.002). There was no significant difference between the D2 receptor occupancy of the two substances when given in the clinically recommended dose range (unpaired t-test, t = -0.112, p = 0.911).

Clinical impact of differential renal function to indicate and assess pyeloplasty and the significance of coexisting vesicoureteral reflux.

PURPOSE: In patients with ureteropelvic junction obstruction (JPJO) who are conservatively treated, 5% to 10% of them show a deterioration of renal function without recovery after delayed pyeloplasty. Should surgery be indicated based on observed deterioration of differential renal function (DRF)? Can we expect improvement of the DRF after pyeloplasty? What other influencing parameters may affect DRF? MATERIALS AND METHODS: In this study, the authors examined 85 ureterorenal junctions that had undergone the Anderson-Hynes technique for surgical correction of UPJO. Based on the values obtained from the preoperative DRF (Tc-99m mercaptoacetyltriglycine), the cases were separated into three categories: group I had poor DRF (less than 11% of total renal function [TRF]), group II had moderate DRF (11% to 33% of TRF), and group III had adequate DRF (more than 33% of TRF). Twelve months after surgery, renal function was reassessed. The results were correlated with age at surgery, symptoms, coexisting vesicoureteral reflux, and drainage. RESULTS: Seven ureterorenal junctions (8%) comprised group I, 15 (18%) comprised group II, and 63 (74%) comprised group III. After UPJO repair, 13% showed marked improvement in DRF, 86% remained stable, and 1% exhibited diminished function. In 50% of the renal cases with preoperative DRF less than 33%, postoperative improvement was seen. In follow-up renal scans, 30 cases (35%) revealed nonobstructive drainage, whereas the remaining 53 junctions (62%) showed moderate delayed drainage. Both the moderate delayed group (57%) and the nonobstructive group (50%) showed similar DRF improvement. Sixty-six percent of the patients with impaired DRF improved after pyeloplasty performed within the first 3 months of life, compared with 42.8% of patients in whom surgery was performed after 5 years of age. Vesicoureteral reflux was evident in 27.2% of the patients with preoperative impaired DRF compared with 11% with normal DRF. Forty-five percent of the patients with impaired DRF and no improvement after surgery had coexisting vesicoureteral reflux, compared with 9% of those with postoperative improvement. CONCLUSIONS: Sustained renal impairment after pyeloplasty is likely as a result of preexisting renal dysplasia with vesicoureteral reflux. Moderate delayed drainage after surgery does not affect DRF. Surgery for UPJO should be indicated independent of a DRF follow-up (except very low DRF) or the age at the time of diagnosis.

[Calculation of the partial function of the kidney with DMSA in pediatrics: is the evaluation of the geometric mean necessary?]. / Partialfunktionsberechnung der Nieren mit DMSA in der Pädiatrie: Ist für die Bestimmung das geometrische Mittel notwendig?

UNLABELLED: For assessment of differential renal function (PF) by means of static renal scintigraphy with Tc-99m-dimercaptosuccinic acid (DMSA) the calculation of the geometric mean of counts from the anterior and posterior view is recommended. AIM: Of this retrospective study was to find out, if the anterior view is necessary to receive an accurate differential renal function by calculating the geometric mean compared to calculating PF using the counts of the posterior view only. METHODS: 164 DMSA-scans of 151 children (86 f, 65 m) aged 16 d to 16 a (4.7 +/- 3.9 a) were reviewed. The scans were performed using a dual head gamma camera (Picker Prism 2000 XP, low energy ultra high resolution collimator, matrix 256 x 256, 300 kcts/view, Zoom: 1.6-2.0). Background corrected values from both kidneys anterior and posterior were obtained. Using region of interest technique PF was calculated using the counts of the dorsal view and compared with the calculated geometric mean [SQR(Ctsdors x Ctsventr)]. RESULTS: The differential function of the right kidney was significantly less when compared to the calculation of the geometric mean (p < 0.01). The mean difference between the PFgeom and the PFdors was 1.5 +/- 1.4%. A difference > or = 5% (5.0-9.5%) was obtained in only 6/164 scans (3.7%). Three of 6 patients presented with an underestimated PFdors due to dystopic kidneys on the left side in 2 patients and on the right side in one patient. The other 3 patients with a difference > 5% did not show any renal abnormality. CONCLUSION: The calculation of the PF from the posterior view only will give an underestimated value of the right kidney compared to the calculation of the geometric mean. This effect is not relevant for the calculation of the differential renal function in orthotopic kidneys, so that in these cases the anterior view is not necessary. However, geometric mean calculation to obtain reliable values for differential renal function should be applied in cases with an obvious anatomical abnormality.

[Prognostic value of hepatobiliary functional scintigraphy in diagnosis and after-care of biliary atresia]. / Prognostische Wertigkeit der hepatobiliären Funktionsszintigraphie in Diagnostik und Nachsorge der Gallengangsatresie.

AIM: To investigate the prognostic relevance of hepatobiliary scintigraphy (HBS) in newborns suffering from biliary atresia (BA) for establishing the primary diagnosis and in the postoperative follow-up after portoenterostomy (Kasai). METHODS: Twenty newborns with direct hyperbilirubinemia and 6 children after operative treatment of BA (Kasai) underwent HBS with Tc-99m-DEIDA. In patients without intestinal drainage, hepatocellular extraction was estimated visually and calculated semiquantitatively by means of liver/heart-ratio 5 min p.i. RESULTS: 10/20 patients with hyperbilirubinemia did not display biliary drainage; 6 had BA, 3 intrahepatic hypoplasia, and one showed a bile plug syndrome. 4/6 with BA but none of the 4 children with diagnoses other than BA presented with a good extraction. All of the 4 children with BA, who had either pre- or postoperatively a bad extraction, needed liver transplantation due to liver failure. Both of the two newborns with BA and favourable outcome after Kasai had a good extraction in the preoperative HBS and demonstrated good intestinal drainage in the postoperative scan. CONCLUSION: HBS rules out BA with high accuracy by demonstrating drainage of bile into the intestine. In newborns without drainage a good extraction favours the diagnosis of BA. In newborns with BA a bad extraction seems to indicate a poor postoperative prognosis after Kasai operation. HBS might therefore help to select those children who will not benefit from portoenterostomy. Postoperatively, HBS can easily and quickly confirm the successful hepatobiliary anastomosis by demonstrating biliary drainage into the intestine.

D2 receptor occupancy under recommended and high doses of olanzapine: an iodine-123-iodobenzamide SPECT study.

The aim of this study was to compare the degree of striatal dopamine D2 receptor availability in patients treated with recommended (5-20 mg, mean dose 11.9 +/- 6.3 mg daily) and higher doses (25-40 mg, mean 32.1 +/- 5.6 mg daily) of the novel antipsychotic drug olanzapine by means of [123I] IBZM Single photon emission computed tomography (SPECT). The results were compared to those of a group of 10 untreated, healthy, age- and sex-matched controls. The degree of dopamine D2 receptor occupancy in the patient group was correlated with the presence of extrapyramidal symptoms (EPS). A total of 20 patients who met the DSM III R criteria for schizophrenia or schizoaffective disorder received a clinically effective antipsychotic monotherapy with olanzapine. The mean daily dose of olanzapine ranged from 0.05-0.6 mg/kg body weight. The dopamine D2 receptor binding was reduced in all patients treated with olanzapine. Specific IBZM binding expressed as the [STR-BKG]/BKG ratio ranged from 0.13-0.61 (healthy controls 0.95). The D2 receptor availability revealed an exponential dose-response relationship (r = - 0.85, p < 0.001). The frequency of EPS induced by olanzapine was considerably lower. Only one patient, treated with 40 mg olanzapine, suffered from severe EPS symptoms and had to be given biperiden. There were no significant differences in the presence of EPS symptoms between patients with recommended doses and those with higher doses of olanzapine.

[Magnetic resonance imaging of benign and premalignant tumors in childhood]. / Kernspintomographische Diagnostik benigner und prämaligner abdomineller Tumoren im Kindesalter.

PURPOSE: To evaluate the potential of MRI in determining benign and premalignant abdominal tumors in childhood. METHODS: MR images of 93 children with 69 malignant and 24 benign abdominal tumors were analyzed retrospectively without and with knowledge of clinical findings. Based on the final diagnosis, MR findings were surveyed with regard to the correct differential diagnosis and to the differentiation between benign and malignant masses. RESULTS: Analysis of MRI alone revealed relatively low sensitivity of 67% for diagnosis of a benign tumor. The main reason was unspecific morphologic criteria leading to the false-negative diagnosis of a malignant tumor. Together with clinical and laboratory findings, sensitivity could be increased to 92%. The main criterion for differentiation of malignant tumors turned to be out the origin of tumor. Benign tumors could be best differentiated by their internal structure. CONCLUSION: When considering clinical findings in pediatric abdominal tumors, MRI represents a valuable modality for differential diagnosis.

In vivo effects of olanzapine on striatal dopamine D(2)/D(3) receptor binding in schizophrenic patients: an iodine-123 iodobenzamide single-photon emission tomography study.

Olanzapine is a new atypical antipsychotic agent that belongs to the same chemical class as clozapine. The pharmacological efficacy of olanzapine (in contrast to that of risperidone) has been shown to be comparable to that of clozapine, but olanzapine has the advantage of producing a less pronounced bone marrow depressing effect than clozapine. The specific aims of this study were (a) to assess dopamine D(2)/D(3) receptor availability in patients treated with olanzapine by means of iodine-123 iodobenzamide [(123)I]IBZM single-photon emission tomography (SPET), (b) to compare the results with findings of [(123)I]IBZM SPET in patients under treatment with risperidone and (c) to correlate the results with the occurrence of extrapyramidal side-effects (EPMS). Brain SPET scans were performed in 20 schizophrenic patients (DSM III R) at 2 h after i.v. administration of 185 MBq [(123)I]IBZM. Images were acquired using a triple-head gamma camera (Picker Prism 3000 XP). For semiquantitative evaluation of D(2)/D(3) receptor binding, transverse slices corrected for attenuation were used to calculate specific uptake values [STR-BKG]/BKG (STR=striatum; BKG=background). The mean daily dose of olanzapine ranged from 0.05 to 0.6 mg/kg body weight. The dopamine D(2)/D(3) receptor binding was reduced in all patients treated with olanzapine. Specific IBZM binding [STR-BKG]/BKG ranged from 0.13 to 0.61 (normal controls >0.95). The decreased D(2)/D(3) receptor availability revealed an exponential dose-response relationship (r=-0.85, P<0.001). The slope of the curve was similar to that of risperidone and considerably higher than that of clozapine as compared with the results of a previously published study. EPMS were observed in only one patient, presenting with the lowest D(2)/D(3) availability. The frequency of EPMS induced by olanzapine (5%) was considerably lower than the frequency under risperidone treatment (40%). Our findings suggest an exponential relationship between the daily dose of olanzapine striatal and decreased D(2)/D(3) striatal binding availability. The results are consistent with the findings of in vitro experiments reporting a higher D(2)/D(3) receptor affinity and a similar 5HT(2) receptor affinity of olanzapine as compared with clozapine. Thus, the decreased tendency to induce EPMS at therapeutic doses is not due to the limited occupancy of striatal D(2)/D(3) receptors in vivo. Patients are protected from EPMS by other intrinsic effects of the drug, i.e. the combination of both D(2)/D(3) and 5HT(2) receptor antagonism.

[Diagnosis of sentinel lymph node in malignant melanoma: preoperative lymphoscintigraphy and intraoperative gamma probe guidance]. / Diagnostik des "Sentinel Lymph Node" bei malignem Melanom: präoperative Lymphszintigraphie und intraoperative Sondenmessung.

AIM: The sentinel lymph node (SLN) has shown to reflect the histologic features of the remainder of the lymphatic basin in patients with melanoma and is of considerable prognostic relevance. Aim of the study was to localize the SLN pre and intraoperatively by means of lymphoscintigraphy and gamma probe guidance. METHODS: 38 patients with histologically proven malignant melanoma (tumor thickness > 0.75 mm) were preoperatively examined by injecting 40 MBq 99mTc-Nanocoll intradermally around the lesion. The first lymph node identified was marked on the skin. Immediately after scintigraphy patients were referred to the operation room and intraoperatively mapped using a handheld gamma probe. Activity of the SLN and of the adjacent nodes was measured ex vivo. After excision of the SLN, the lymphatic basin was re-checked for radioactivity and activity of the SLN and of the adjacent nodes was re-measured after removal. RESULTS: The hottest reading was found in all patients in vivo and ex vivo in the preoperatively marked lymph node. Morphologically (macroscopically, ultrasound, CT) all nodes were unsuspicious. Histologically, in 8 patients metastatic involvement of the lymph node was found which led to a wide exploration of the lymphatic basin with consecutive lymph node excision in 7 patients. CONCLUSION: The findings suggest that combined preoperative lymphoscintigraphy and intraoperative mapping with a gamma probe is a powerful approach for exact localization of the SLN. Diagnostic detection of the SLN may have considerable impact for patient management, since extended lymph node dissection may be confined to patients presenting with positive SLN.

Bone scintigraphy in non-neoplastic diseases in children.

Since the introduction of 99mTc labeled polyphosphates bone scintigraphy has become a widely accepted method for the evaluation of non-neoplastic bone diseases in children. High quality images require the child's immobilisation and a correct positioning as well as an optimized technical equipment. Two or three phase scintigraphy is the routinely procedure but additional techniques like pinhole images or SPECT can be very helpful for special indications and localisations. Due to the age and sex dependent differences of bone metabolism in the developing skeleton the interpretation of the bone scan in children is more difficult than in adults and requires more experience. Infections, trauma and aseptic necrosis are the most important non-neoplastic diseases requiring bone scintigraphy. Bone scan has a high sensitivity in the early detection of pathological bone metabolism indicating bone disease; other investigations, which are describing morphological changes like X-ray are less sensitive especially at the beginning of the disease. Negative bone scan rools out significant bone disorders with a high certainty. Follow-up studies can give additional informations about the response to therapeutical regimes and about the prognosis. To improve the specificity of a bone scan a combined interpretation of scintigraphy and X-ray is recommended.

A new strategy for characterizing proteinuria and haematuria from a single pattern of defined proteins in urine.

Prerenal, glomerular, tubulointerstitial and postrenal proteinurias and haematurias are usually differentiated by a number of non-invasive and invasive diagnostic procedures. We have applied a new analytical strategy based on the observation that different urine protein patterns are excreted in normal, prerenal, renal and postrenal proteinurias and haematurias. When analysed by turbidimetric procedures urine albumin, IgG, alpha 1-microglobulin and alpha 2-macroglobulin can be used as marker proteins to characterize the degree of glomerular permeability, tubular protein reabsorption and postrenal bleeding respectively. Primary glomerulopathies (selective and non-selective) and tubulointerstitial nephropathies can be differentiated by plotting the excretion rates of IgG or alpha 1-microglobulin against that of albumin. Postrenal contaminations are detected by quantitative turbidimetric assay of the high molecular weight proteins, alpha 2-macroglobulin and IgG. In postrenal bleeding, with albumin concentrations above 100 mg/l, the relative excretion rates of these proteins were proportional to their plasma concentrations. In glomerular haematurias, however, the ratios to albumin were much lower. The optimal discriminating ratio was found to be 2.0 x 10(-2) for alpha 2-macroglobulin/albumin and 2 x 10(-1) for IgG/albumin. Tubulointerstitial involvement in haematuria is characterized by elevated alpha 1-microglobulin excretion rates, with alpha 2-macroglobulin/albumin ratios below 2.0 x 10(-2) and IgG/albumin ratios above 2 x 10(-1). The reported procedure allows the exclusion and differentiation of clinically relevant proteinurias and haematurias in a single urine specimen.