Functional neuroimaging and presenting psychiatric features in frontotemporal dementia

BACKGROUND: Frontotemporal dementia (FTD) is a behavioural syndrome caused by degeneration of the frontal and anterior temporal lobes. Behavioural disturbances include psychiatric features. Whether patients with FTD present with psychiatric features varies with the initial neuroanatomical variability of FTD. OBJECTIVE: To identify presenting psychiatric changes not part of diagnostic criteria of FTD and contrast them with the degree of hemispheric asymmetry and frontal and temporal hypoperfusion on single photon emission computed tomography (SPECT) imaging. METHODS: 74 patients who met consensus criteria for FTD were evaluated at a two year follow up. All had brain SPECT on initial presentation. Results of an FTD psychiatric checklist were contrasted with ratings of regional hypoperfusion. RESULTS: The regions of predominant hypoperfusion did not correlate with differences on FTD demographic variables but were associated with presenting psychiatric features. Dysthymia and anxiety were associated with right temporal hypoperfusion. "Moria" or frivolous behaviour also occurred with temporal lobe changes, especially on the right. The only significant frontal lobe feature was the presence of a peculiar physical bearing in association with right frontal hypoperfusion. CONCLUSIONS: Patients with FTD may present with psychiatric changes distinct from the behavioural diagnostic criteria for this disorder. Early temporal involvement is associated with frivolous behaviour and right temporal involvement is associated with emotional disturbances. In contrast, those with right frontal disease may present with alterations in non-verbal behaviour.     

Radiolabeled L-lysine for tumor imaging

RATIONALE AND OBJECTIVES: The aims of this study were to label the versatile amino acid l-lysine with (99m)Tc using 2,3-dimercapto-succinic acid (DMSA) as a chelator, and to assess its tumor imaging feasibility under in vivo and in vitro conditions, and finally to determine the subcellular biodistribution of this radiopharmaceutical. MATERIALS AND METHODS: DMSA-l-lysine was chemically synthesized and labeled with sodium pertechnetate. Nuclear magnetic resonance (NMR) and mass spectral analysis of DMSA-l-lysine were conducted. Radiochemical purity was determined by thin-layer chromatography (TLC) and paper chromatography. Cellular uptake, competition and subcellular localization studies were performed in rat breast cancer cells (13762). In vivo studies of planar imaging and biodistribution studies were performed on female Fischer 344 rats. Medical Internal Radiation Dose (MIRD) dosimetry estimates were calculated. RESULTS: Radiochemical purity (determined by radio-TLC and high-performance liquid chromatography) of these compounds was >95%. (99m)Tc-DMSA-l-lysine showed good uptake in in vitro cell culture assays and uptake was reduced in competition studies. (99m)Tc-DMSA-l-lysine accumulates in the nucleus as much as in the cytoplasm and it was also shown that accumulation of the (99m)Tc-DMSA-l-lysine in the nucleus increases as a function of a time. There was an increase in tumor-to-blood and tumor-to-muscle count density ratios. Tumor/background ratios were 5.75 at 1 hour and 6.87 at 2 hours. In vivo tissue distribution studies revealed that radiation dosimetry of blood-forming organs were within radiation dose limits. CONCLUSION: DMSA-l-lysine kits can be labeled with (99m)Tc easily and efficiently, with high radiochemical purity and cost-effectiveness. In vitro cellular uptake and scintigraphic imaging studies demonstrated the pharmacokinetic distribution and feasibility of using (99m)Tc-DMSA-l-lysine for tumor imaging.     

Inherited impairment of nuclear androgen uptake as a cause of familial androgen insensitivity

The endocrine and biochemical characteristics of four related 46,XY pseudohermaphrodite patients with the Reifenstein Syndrome are presented. All of them (6 and 9 years old, first generation, and 9 and 12 months old, second generation) exhibited ambiguity of external genitalia and a family pedigree characteristic of an X-linked pattern of inheritance. Serum basal levels of LH, FSH, testosterone (T), androstenedione and 5 alpha-dihydrotestosterone (DHT) were within normal limits. Administration of hCG induced a normal response in terms of serum T in three of the patients, with a concomitant increase in serum DHT. However, an abnormally elevated T: DHT ratio was found in two of these subjects on the day of maximal T response (T: DHT ratio, 24 and 27; normal range, 4-21). Genital skin-derived fibroblasts from all patients were studied for [3H]DHT uptake in a whole-cell monolayer assay. Three of the mutant strains exhibited values of [3H]DHT uptake at 37 degrees C within the lower limits of normality (39.4-47.05 fmol/mg protein/h; normal strains, 36-101 fmol/mg protein/h), whereas fibroblasts from the remaining patient presented a slightly decreased uptake (31.66 fmol/mg protein); when studied at 42 degrees C, all mutant strains behaved as the normal controls. The existence of a specific 4.6 S cytosol androgen receptor was clearly seen in the two mutant strains when analysed by sucrose gradient centrifugation. Nevertheless, in one of the mutant strains, a significantly low maximal nuclear [3H]DHT uptake was detected (173.6 fmol/mg DNA; control strain, 301.6 fmol/mg DNA). The overall data were interpreted as demonstrating the existence of an impaired uptake of the androgen-receptor complex at the nuclear levels as the cause of the incomplete phenotypic expression of androgen action in this family. In this setting, the presence of low peripheral 5 alpha-reductase activity may be considered as a secondary manifestation of the androgen insensitivity.