Pavlos Vassilakos

A double-blind study on a patient with tardive dyskinesia treated with pallidal deep brain stimulation

Background –  Tardive dyskinesia (TD) is a neurological disorder typically induced by long‐term exposure to neuroleptics. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) may represent a therapeutic alternative for TD, which is often resistant to conservative treatment.

Novel application of IGF‐I and IGFBP‐3 generation tests in the diagnosis of growth hormone axis disturbances in children with β‐thalassaemia

Children with β‐thalassaemia major (β‐thal) frequently have growth retardation in the presence of low serum IGF‐I and a normal GH response to pharmacological stimulation suggesting that they have GH insensitivity (GHIS). This study was carried out to study the cause of their growth retardation.

Increased cortisol concentrations in the cord blood of newborns whose mothers smoked during pregnancy.

Abstract Aim: To investigate the effect of tobacco smoke on cord blood cortisol concentrations. Methods: Cortisol concentrations were measured in cord blood from 211 term newborns of smoking and 211 term newborns of nonsmoking mothers; 48 and 36 newborns were delivered by cesarean section, respectively. In 16 cases, in addition to cord blood, maternal venous blood was obtained at delivery. Results: The median cord blood cortisol concentration in neonates of the smoking and the nonsmoking mothers was 23 and 13 μg/dL, respectively (P<0.0001). Cortisol concentrations were greater in the newborns whose mothers smoked, when compared to corresponding controls, whether they were delivered vaginally or by cesarean section. In the newborns delivered by cesarean section, there was a positive correlation between number of cigarettes smoked/day and cortisol concentrations, as well as a negative correlation between cortisol concentrations and neonatal length. There was no significant correlation between cortisol concentrations and birth weight or head circumference. Cortisol concentrations in the cord blood of neonates whose mothers were smokers and nonsmokers were by 29% and 45% lower from those measured in their mothers, respectively. Conclusions: Although a causal relationship between maternal smoking and high cortisol concentrations in cord blood was not established, the findings are in accordance with previous reports indicating elevated stress-hormones in newborns whose mothers smoked during pregnancy.

Cord blood α-fetoprotein concentrations in term newborns of smoking mothers

Abstract To investigate the toxic effect of tobacco smoke on the fetus, we measured in cord blood the concentrations of α-fetoprotein (AFP), the principal serum protein in early ontogenic development, and erythropoietin (EPO), as an index of chronic fetal hypoxia. A total of 103 consecutively enrolled term newborns of smoking mothers and 103 term infants of nonsmoking parents were studied. The mean ± SD AFP concentrations in the newborns of the mothers who smoked 1–50, 5–50, and 10–50 cigarettes/day were 86.4 ± 88.9, 96.3 ± 91.9 and 118.7 ± 103.7 ng/ml, respectively. The difference of all three groups from the control neonates (57.7 ± 37.2) was significant. The EPO concentrations in the newborns of the mothers who smoked 1–50 (53.9 ± 64.6 mU/ml) and 5–50 (56.3 ± 68.5) cigarettes/day were significantly greater than in the control neonates (29.5 ± 16.1). In the newborns of the smoking mothers there was a significant positive correlation between AFP concentrations and number of cigarettes smoked per day, and a negative correlation between AFP and birth weight or length. There was no correlation between AFP and EPO concentrations, as well as between EPO and birth weight, length or number of cigarettes smoked per day. Conclusion The absence of a correlation between erythropoietin and birth weight or length and the negative correlations between α-fetoprotein and these anthropometric parameters suggest that the intra-uterine growth retardation caused by maternal smoking is not due to tissue hypoxia, but that both growth retardation and elevated α-fetoprotein result from the direct or indirect toxic effect of a factor(s) present in tobacco smoke.

Increased Serum CA-15.3 Levels in Patients with Megaloblastic Anemia due to Vitamin B12 Deficiency

Objectives: To estimate the usefulness of serum tumor markers’ monitoring, as predictors of gastric cancer in patients with pernicious anemia. Patients and Methods: We investigated serum levels of carcinoembryonic antigen (CEA), α-fetal protein, cancer antigen (CA)-19.9, CA-125 and CA-15.3 in 50 patients with pernicious anemia and in 24 healthy controls, matched for age and sex. In 38 patients, the evaluation was repeated 1–6 months after the correction of cobalamin deficiency. Results: All patients and controls had normal serum CEA and α-FP, and the levels of these markers as well as those of CA-125 and CA-19.9 did not differ between the two groups. All 50 patients, but only 2 controls exhibited increased serum CA-15.3, and the difference between the two groups was very significant (129.4 ± 84.9 vs. 19.8 ± 7.3 IU/ml, p < 0.001), while no difference between males and females was found. A thorough clinical examination of all patients, and mammographic study in 18 females did not reveal any finding suspicious of breast cancer. CA-15.3 levels were positively correlated with serum lactate dehydrogenase, and negatively with B12 and hemoglobin, but they were substantially decreased after the correction of anemia, in all 38 patients tested, and in 33 of them they were restored to normal. After a median follow-up of 34 months, one patient developed a colon cancer, but none showed any sign suspicious of breast cancer. Conclusions: Serum CA-15.3 shows an aberrant increase in untreated patients with pernicious anemia, which is reversed after the correction of the anemia. The possible origin seems unrelated to mammary tissue, and may be released by the apoptosing bone marrow megaloblastic erythroblasts.

Fuzzy Cognitive Map based decision support system for thyroid diagnosis management

Knowledge-based systems are the most common type of artificial intelligence in medicine systems in routine clinical use. They contain medical knowledge, usually about a very specifically defined task, and are able to reason with data from individual patients to come up with reasoned conclusions. Although there are many variations, the knowledge within an expert system is typically represented in the form of a set of rules. Fuzzy cognitive map (FCM) is a knowledge based modeling methodology based on exploiting knowledge and experience from experts. It can handle uncertainty and can be constructed basely by expertspsila knowledge.

Dopamine transporter SPECT/CT and perfusion brain SPECT imaging in idiopathic basal ganglia calcinosis.

A case of idiopathic basal ganglia calcification in a 56-year-old woman with parkinsonism and cognitive impairment is described. The nigrostriatal dopaminergic pathway and regional cerebral blood flow were evaluated using dopamine transporter (DAT) brain single photon emission tomography combined with a low-dose x-ray computerized tomography transmission (hybrid SPECT/CT) and Tc-99m HMPAO brain perfusion SPECT study, respectively. DAT SPECT/CT imaging revealed a reduction in DAT binding in both striatum regions coinciding with bilateral calcifications in the basal ganglia. Brain perfusion scan showed hypoperfusion in basal ganglia regions, posterior parietal cortex bilaterally, left frontopolar and dorsolateral prefrontal cortex, and left temporal lobe. These findings correlated well with the clinical condition of the patient. Mineralization may play a critical role in the pathogenesis of neuronal degeneration. Cortical perfusion changes in patients may better explain the patients altered cognitive and motor functions.

Regional cerebral blood flow changes induced by deep brain stimulation in secondary dystonia

PurposeThe purpose of the present study is to investigate the effect of deep brain stimulation (DBS) on regional cerebral blood flow (rCBF) in cases of secondary dystonia as well as to correlate the rCBF changes with clinical outcomes.MethodsSix patients with medically intractable secondary dystonia who underwent DBS surgery were included in this study. Burke–Fahn–Mardsen Dystonia Rating Scale (BFMDRS) was used for the assessment of dystonia, before and after surgery. Single photon emission computed tomography (SPECT) of the brain was performed postoperatively in the two stimulation states (ON-DBS and OFF-DBS) and the changes of rCBF in the three following brain regions of interest (ROIs): primary motor cortex, premotor and supplementary motor cortex, and prefrontal cortex were evaluated.ResultsTwo patients exhibited excellent response to DBS, two patients got moderate benefit after the procedure, and in two patients, no clinical improvement was achieved. A mean improvement of 49.1% (0–90.7%) in BFMDRS total scores was found postoperatively. Brain SPECT data analysis revealed an overall decrease in rCBF in the investigated ROIs, during the ON-DBS state. Clinical improvement was significantly correlated with the observed decrease in rCBF in the presence of DBS.ConclusionsWhen conservative treatment fails to relieve severely disabled patients suffering from secondary dystonia, DBS may be a promising therapeutic alternative. Moreover, this study indicates a putative role of brain SPECT imaging as a postoperative indicator of clinical responsiveness to DBS.

Increased CA-15.3 levels in the serum of patients with homozygous β-thalassaemia and sickle cell/β-thalassaemia

Damle, R.N., Wasil, T., Fais, F., Ghiotto, F., Valetto, A., Allen, S.L., Buchbinder, A., Budman, D., Dittmar, K., Kolitz, J., Lichtman, S.M., Schulman, P., Vinciguerra, V.P., Rai, K.R., Ferrarini, M. & Chiorazzi, N. (1999) Ig V gene mutation status and CD38 expression as novel prognostic indicators in chronic lymphocytic leukemia. Blood, 94, 1840–1847. Hamblin, T.J., Davis, Z., Gardiner, A., Oscier, D.G. & Stevenson, F.K. (1999) Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood, 94, 1848– 1854. Keating, M.J., Chiorazzi, N., Messmer, B., Damle, R.N., Allen, S.L., Rai, K.R., Ferrarini, M. & Kipps, T.J. (2003) Biology and treatment of chronic lymphocytic leukemia. Hematology 2003 (American Society of Hematology Education Program Book), 153–175. Manshouri, T., Do, K.A., Wang, X., Giles, F.J., O’Brien, S.M., Saffer, H., Thomas, D., Jilani, I., Kantarjian, H.M., Keating, M.J. & Albitar, M. (2003) Circulating CD20 is detectable in the plasma of patients with chronic lymphocytic leukemia and is of prognostic significance. Blood, 101, 2507–2513. Rogers, A., Joe, Y., Dey, A., Jilani, I., Giles, F., Estey, E., Freireich, E., Keating, M., Kantarjian, H. & Albitar, M. (2004) Relative increase in leukemia-specific DNA in peripheral blood plasma from patients with acute myeloid leukemia and myelodysplasia. Blood, 103, 2799– 2801.

Technetium-99m depreotide imaging by single photon emission tomography/low resolution computed tomography in malignant lymphomas: comparison with gallium-67 citrate

ObjectivePrevious studies have demonstrated the feasibility of targeting lymphoma lesions with somatostatin receptor binding agents, mainly with In-111-pentetreotide. In the present work another somatostatin analog, Tc-99m depreotide, is investigated.MethodsOne-hundred and six patients, 47 with Hodgkin’s (HL) and 59 with various types of non-Hodgkin’s lymphoma (NHL), were imaged with both Tc-99m depreotide and Ga-67 citrate. Planar whole-body and single photon emission tomography/low resolution computerized tomography (SPECT/CT) images were obtained. A total of 142 examinations were undertaken at different phases of the disease. Depreotide and gallium findings were compared visually and semi-quantitatively, with reference to the results of conventional work-up and the patients’ follow-up data.ResultsIn most HL, intermediate- and low-grade B-cell, as well as in T-cell NHL, depreotide depicted more lesions than Ga-67 and/or exhibited higher tumor uptake. The opposite was true in aggressive B-cell NHL. However, there were notable exceptions in all lymphoma subtypes. During initial staging, 93.3% of affected lymph nodes above the diaphragm, 100% of inguinal nodes and all cases with splenic infiltration were detected by depreotide. On the basis of depreotide findings, 32% of patients with early-stage HL were upstaged. However, advanced HL and NHL cases were frequently downstaged, due to low sensitivity for abdominal lymph node (22.7%), liver (45.5%) and bone marrow involvement (36.4%). Post-therapy, depreotide detected 94.7% of cases with refractory disease or recurrence. Its overall specificity was moderate (57.1%). Rebound thymic hyperplasia, various inflammatory processes and sites of unspecific uptake were the commonest causes of false positive findings. The combination of depreotide and gallium enhanced sensitivity (100%), while various false positive results of either agent could be avoided.ConclusionExcept perhaps for early-stage HL, Tc-99m depreotide as a stand-alone imaging modality has limited value for the initial staging of lymphomas. Post-therapy, however, depreotide scintigraphy seems useful in the evaluation of certain anatomic areas, particularly in non-aggressive lymphoma types. The combination with Ga-67 potentially enhances sensitivity and specificity. If fluorodeoxyglucose positron emission tomography is not available or in case of certain indolent lymphoma types, Tc-99m depreotide may have a role as an adjunct to conventional imaging procedures.