Ictal single photon emission computed tomography in absence seizures: apparent implication of different neuronal mechanisms.

Absence seizures represent a complex group of epilepsy, characterized by lapse of consciousness with staring. Bilateral, synchronous, and symmetric bursts of 3-Hz spike-and-wave discharges are observed on the electroencephalogram, whereas interictal background activity is normal. This kind of epilepsy has to be differentiated from other generalized epilepsies such as juvenile absence epilepsy and juvenile myoclonic epilepsy. Moreover, absence seizures, together with generalized spike-and-wave discharges, may coexist with other types of epilepsy such as frontal lobe epilepsy, temporal lobe epilepsy, benign epilepsy with centrotemporal spikes, and childhood epilepsy with occipital paroxysms. We have carried out ictal single photon emission computed tomography (SPECT) in 10 patients with clinical evidence of absence seizures with the aim to better understand and to distinguish this kind of seizure as primarily or secondarily generalized to a specific area and to obtain more information on the neuronal mechanisms involved in the different types of seizures, usually not identifiable at the first appearance. During the long follow-up period (9 months to 14 years), 7 of the 10 examined patients underwent interictal SPECT when they became seizure free. Our data permitted, in two patients, the diagnosis of childhood absence seizures; in three patients, they suggested the possibility of later appearance of other seizure types, on the basis of focal hyperperfusion indicating a possible focal firing. In three of the examined patients, the diagnosis of idiopathic localization-related epilepsies mimicking childhood absence seizures could be performed. In the last two patients, the hypothesis of a coexistence of absences with partial and generalized seizures was considered. From our results, it can be presumed that ictal SPECT findings may contribute to the physiopathologic classification of the different types of epilepsies. Moreover, anticonvulsant treatment more appropriate to the different forms of seizures can be used.

Insulin resistance and insulin-like growth factors in children with intrauterine growth retardation. Is catch-up growth a risk factor?

AIMS: To investigate (a) the prevalence of insulin resistance in children with intrauterine growth retardation (IUGR); (b) whether catch-up growth is associated with a higher risk of insulin resistance; (c) the insulin-like growth factor (IGF) system status. METHODS: 49 children with IUGR aged 9.1 +/- 3.3 years underwent anthropometric measurements, and assessment of insulin resistance and IGF system parameters. A fasting glucose/insulin ratio (G/I) <6 was chosen as suggestive of insulin resistance. RESULTS: 11/49 (22%) children had a G/I <6. Postnatal growth closely correlated with birth size and actual body mass index (BMI). None of the insulin resistance parameters was related to linear growth and BMI. Liver function markers were significantly related to insulin sensitivity status. The IGF system status was normal and did not correlate with insulin resistance indicators. CONCLUSIONS: (a) Children with IUGR have a high prevalence of reduced insulin sensitivity; (b) postnatal catch-up growth is related to intrauterine growth and actual nutritional status; (c) insulin sensitivity status is not related to postnatal growth but to liver function; (d) IGF system is normal and not related to the insulin resistance parameters during childhood.

Growth and insulin-like growth factors (IGFs) in children with insulin-dependent diabetes mellitus at the onset of disease: evidence for normal growth, age dependency of the IGF system alterations, and presence of a small (approximately 18-kilodalton) IGF-binding protein-3 fragment in serum.

Data on growth of children with insulin-dependent diabetes mellitus (IDDM) before the onset of disease are conflicting, and although the insulin-like growth factor (IGF) system has almost invariably been found altered at diagnosis, most of previous studies are affected by the small number of patients investigated. We studied 60 IDDM children at the onset of disease, comparing their stature with target height, normal growth standards, and height of 102 sex- and age-matched controls. Furthermore, we assessed serum IGF-I, IGF-II, and IGF-binding protein-3 (IGFBP-3) levels and IGFBP-3 circulating forms. IDDM children were subdivided into 2 groups according to an age above (n = 26) or below (n = 34) 6 yr. The values of endocrine variables of diabetics older than 6 yr were compared with those of 34 age-matched controls. Although the height of diabetics was higher than growth reference values (mean height +/- SD, 0.64+/-1.4 z-score) and their target height (mean target height +/- SD, 0.1+/-0.84 z-score; P < 0.005), no significant difference in height was found between IDDM children and controls (mean height +/- SD, 0.64+/-0.95 z-score) even analyzing the 2 age groups separately. Overall, IDDM children showed reduced levels of IGF-I (mean +/- SD, -0.65+/-1.9 z-score) and normal levels of IGF-II (mean +/- SD, -0.05+/-1.2 z-score) and IGFBP-3 (mean +/- SD, -0.06+/-1.2 z-score). However, whereas patients younger than 6 yr showed normal values of IGF-I, IGF-II, and IGFBP-3, these peptides were significantly reduced in older subjects compared with either younger IDDM children or controls (P < 0.01). IGFBP-3 immunoblot analysis revealed the presence of an approximately 18-kDa fragment of IGFBP-3 in addition to the major approximately 29-kDa fragment and the intact form (approximately 42-39 kDa) in 46 of 60 IDDM patients, whereas the approximately 18-kDa band was absent in all 34 control sera. No relationship was found between the endocrine variables and stature at diagnosis. In conclusion, our results indicate that IDDM children at the onset of disease are not taller than healthy peers and have increased IGFBP-3 proteolytic activity. Finally, although the IGF system is normal in younger IDDM children, older patients have reduced IGF levels.

IGF-I and IGF-binding protein-1 are related to cortisol in human cord blood.

OBJECTIVE: To assess cortisol concentrations in cord blood and investigate their relationships with the IGF system. STUDY DESIGN: Fifteen newborns with birth weight appropriate for gestational age (AGA) and 30 children with intrauterine growth retardation (IUGR) were studied. Serum samples were collected from umbilical cord blood and cortisol, IGF-I and IGF-binding proteins (IGFBPs)-1 and -3 were measured. IUGR infants were followed up for 3 months with repeated measurements of weight, supine length and knee-heel length (by knemometry). RESULTS: IUGR newborns showed significantly greater concentrations of IGFBP-1 (P<0.0001) and lower concentrations of IGF-I (P< 0.0001) and IGFBP-3 (P< 0.0001) than did controls. In AGA children, cortisol correlated inversely with IGF-I (r=-0.75, P< 0.002) and directly with IGFBP-1 (r=0.52, P <0.05), whereas no correlation between cortisol and IGF system-related variables was observed in IUGR. Finally, in IUGR children an inverse correlation was found between length gain in the first trimester of life and cortisol concentrations at birth (r=-0.54, P < 0.005). CONCLUSIONS: Cortisol might be a physiological regulator of fetal growth, at least in the last part of pregnancy, by modulating IGF-I and IGFBP-1 release under conditions of fetal stress. In IUGR children, a rearrangement of this growth control mechanism seems to occur. The close inverse relationship of cortisol with linear growth, if confirmed by large-scale studies, suggests cord blood cortisol to be potentially predictive of early postnatal catch-up growth in IUGR infants.

A process for the recovery of strontium from the urine of patients injected with 89Sr.

89Sr is a beta emitter used for palliation of pain in patients with metastatic bone cancer. After each intravenous administration, up to 80% of the isotope is eliminated in the urine. A simple chemical process is described, which permits the recovery and purification of the 89Sr from the urine.

Renal cell carcinoma detection and systemic therapy with tumour-affine gallium-67 and with yttrium-90 citrate solutions.

BACKGROUND: There have been no major advances in the systemic detection of renal cell carcinoma (RCC) and its unpredictable metastases. Surgery, thus, remains the mainstay of the curative treatment for the localized disease. The propose of the present study has been to systemically detect and treat advanced RCC respectively with Ga-67 and Y-90 radiopharmaceuticals containing tumour-affine species. PATIENTS AND METHODS: Thirty-three RCC patients were imaged with Tc-99m-MDP and then with Ga-67 citrate solution in order to detect RCC and its metastases. Yttrium-90 citrate solution, containing the radionuclide species chromatographically and electrophoretically identical to those in RCC-affine Ga-67 solution, was administered i.v. for systemic therapy of advanced RCC. Total-body distribution of Y-90 was studied with a gamma-camera equipped with an ultra-high-sensitivity collimator. The efficacy of the therapy was studied by the clinical condition of the patient and by the total-body scintigraphic imaging with Tc-99m-MDP and with Ga-67 citrate solution. RESULTS: Ga-67 detects RCC bone metastases better than Tc-99m-MDP. Systemic therapy of RCC metastasized to bones, lung and brain was obtained with RCC-affine Y-90 citrate solution. CONCLUSIONS: Third group metal radionuclides, Ga-67 and Y-90, detect and treat advanced RCC.

Advanced prostate cancer diagnosis and therapy with gallium-67 and yttrium-90, respectively.

BACKGROUND: Androgen deprivation therapy remains so far the mainstay of advanced prostate cancer treatment. Although it improves the quality of life of the patient for some time, the disease progresses and soon it becomes hormonally unresponsive. The object of our research has been to find a systemic therapy for prostate cancer patients whose disease no longer responds to hormone therapy, radiation therapy, chemotherapy and immunotherapy. PATIENTS AND METHODS: Thirty-one advanced prostate cancer patients with intense bone metastasis pain, bed ridden, and with permanent urinary catheter were first examined with Ga-67 and then treated with Y-90 solutions which were chromatographically and electrophoretically analysed for the presence of both cationic and anionic species of the radionuclide. The quality of life and prostate specific antigen (PSA values) values were followed for testing the success of the therapy. RESULTS: Prostate cancer-affine Y-90 cured the advanced prostate cancer patients who regained their normal life. The uptake of the radionuclide in the primary cancer and its metastases responsible for the treatment has been confirmed by scintigraphy. CONCLUSIONS: Prostate cancer-affine Y-90 solution, containing stable cationic and anionic species of the radionuclide, is effective in the cure of advanced prostate cancer patients.

Gamma camera imaging of osseous metastatic lesions by strontium-89 bremsstrahlung.

The aim of this study was to optimise the parameters affecting the Bremsstrahlung scintigraphy of patients injected with strontium-89 chloride. The parameters considered were : (1) instrumental detection efficiency, and (2) tissue attenuation factor for 89Sr calibrated sources, which permit quantitative evaluation of the activity in a given bone lesion. Some typical examples of in vivo 89Sr imaging are presented to illustrate the clinical utility of the imaging procedure developed by us, which is implemented in our department for all patients treated with 89Sr chloride.

Neuronal migrational disorders in children with epilepsy: MRI, interictal SPECT and EEG comparisons.

Single-photon emission computed tomography (SPECT) is being increasingly used in the investigation of children with epilepsy and may provide insights into congenital malformations. We analyzed the interictal 99Tc-HMPAO-SPECT in a series of seven children with developmental disorders of the neocortex, each of them representing a prototype of cerebral dysgenesis, such as lissencephaly, pachygyria, opercular dysplasia, polymicrogyria, nodular heterotopia and band heterotopia. The patients studied were selected among 22 epileptic children with neuronal migrational disorders (NMDs). Interictal SPECT hypoperfusion was observed in the area homologous to MRI findings in all the examined children. In three patients low perfusion was also present in the opposite hemisphere, probably due to functional involvement or related to an underlying microdysgenesis, not revealed by structural imaging. EEG features were in agreement with low perfusion areas, both anatomically and functionally, in all children. In one patient hypoperfusion area differed from that revealed by MRI and EEG. Ictal SPECT has been considered a useful tool for accurately locating the epileptic focus. Nevertheless, interictal brain perfusion studies, together with proton magnetic resonance spectroscopy, may play an important role in detecting anatomic substrate in developmental disorders of the neocortex.

Is IGF binding protein-3 assessment helpful for the diagnosis of GH deficiency?

OBJECTIVE: The measurement of serum immunoreactive IGFBP-3 levels has been proposed as a screening test to identify children with growth hormone deficiency (GHD). We tested the sensitivity and specificity of the IGFBP-3 assessment in comparison with the measurement of IGF-I. DESIGN: We assessed the IGFBP-3 and IGF-I circulating levels in normal subjects and patients with GHD or idiopathic short stature (ISS). PATIENTS: Eighty-two normal subjects, 16 GHD, and 10 children with ISS were studied. Controls were divided into three age groups: group A, 1-4 years (n = 16); group B, 5-9 years (n = 35), and group C, 10-14 years (n = 31). MEASUREMENTS: All subjects underwent standard anthropometry. In short patients, GH secretory status was assessed by clonidine and arginine stimulation tests. IGFBP-3 and IGF-I circulating levels were measured by radioimmunoassay. RESULTS: IGFBP-3 and IGF-I levels were closely related (r = 0.51, P < 0.0001) and IGFBP-3 was less age dependent than IGF-I (r = 0.57, P < 0.02 vs r = 0.64, P = 0.0001). Sensitivity (true positive ratio) and specificity (true negative ratio) of IGFBP-3 measurement were 50 and 92% respectively, whereas sensitivity and specificity of IGF-I assessment were 75 and 90% respectively. Below the age of 5 years, sensitivity was 20% for IGFBP-3 and 40% for IGF-I; specificity was 94% for IGFBP-3 and 88% for IGF-I. CONCLUSIONS: IGFBP-3 measurement had poor sensitivity in detecting growth hormone deficient patients, offering no diagnostic advantage over IGF-I, even in the first years of life, although, due to the high specificity, the finding of subnormal levels of IGFBP-3 was strongly suggestive of growth hormone deficiency. The presence of low IGFBP-3 and IGF-I levels in a short child with normal GH response to provocative tests should prompt further investigations, such as the determination of spontaneous GH secretion or assessment of the GH binding proteins together with an IGF-I and/or IGFBP-3 generation test, in order to identify neurosecretory dysfunction or GH receptor deficiency. Finally, we believe that there is no definitive test for diagnosing or excluding growth hormone deficiency and detailed analysis of the results of endocrine tests, clinical findings and other laboratory and radiological information is necessary to maximize diagnostic accuracy.