Three dimensional transrectal ultrasound imaging of the prostate: initial experience with an emerging technology

PURPOSE: A three-dimensional ultrasound system (3-D US) was evaluated for its clinical utility in transrectal prostate imaging, in comparison with the current standard 2-dimensional transrectal ultrasound (TRUS) imaging system. METHODS AND MATERIALS: The computer program developed in our laboratory was coupled with a commercially available ultrasound transducer. Geometric validation and volumetric assessment was performed with "stretched-string" wire models and solution-containing balloons respectively. Anatomic correlation of 3-D TRUS images was performed with cadaveric prostates. Intraprostatic lesion localization by 3D-TRUS was assessed clinically by 2 observers in 11 patients prior to radical prostatectomy and the data compared with those yielded by 2-D TRUS. RESULTS: Geometric assessment by 3D TRUS in comparison with the "between strings in the phantom" model (true dimensions) had an error of up to 1.2%. Volume measurement by 3-D TRUS had an error, compared to the true volume, of 0.9%. The correlation coefficient (r) was 0.99985 for the end-firing probe and 0.978 for side firing. The 3-D images provided accurate representation of the true anatomy in the sagittal, transverse and most uniquely, the coronal plane. Two observers achieved better diagnostic accuracies with intraprostatic abnormalities using 3-D instead of standard 2-D TRUS. The negative predictive value and the specificity were improved. CONCLUSION: 3-D TRUS appears to provided accurate representation of the true anatomy with geometric and volumetric validation. Areas of potential clinical application of 3-D TRUS include treatment monitoring with volume measurements and various intervention and therapeutic procedures for both benign and malignant prostatic disorders.     

Survival of patients with high grade glioma treated with intrathecal thiotriethylenephosphoramide for ependymal or leptomeningeal gliomatosis.

BACKGROUND: The diagnosis of leptomeningeal dissemination of malignant glioma (meningeal gliomatosis) is associated with poor survival. Intrathecal (IT) chemotherapeutic agents used to achieve tumor control and improve survival include methotrexate, cytosine arabinoside (ara-C), thiotriethylenephosphoramide (thio-TEPA), neocarzinostatin, and 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-1-nitros ourea hydrochloride (ACNU). Little information exists about survival following administration of IT chemotherapy. The authors report survival data from a series of patients with supratentorial anaplastic astrocytoma (AA) or glioblastoma multiforme (GBM) treated for ependymal or leptomeningeal gliomatosis with IT thio-TEPA. METHODS: The authors reviewed the records of 14 patients treated between 1991 and 1997 (GBM: n = 9; AA: n = 5). All patients were diagnosed with ependymal (n = 8) or leptomeningeal (n = 6) dissemination of tumor on the basis of clinical signs and symptoms, ependymal or leptomeningeal contrast enhancement on magnetic resonance imaging (MRI), and/or cerebrospinal fluid analysis. All 14 patients underwent placement of a ventricular reservoir system and subsequent instillation of IT thio-TEPA on a weekly basis for 6-12 weeks. Response to treatment was evaluated clinically and by MRI at intervals of 1-3 months and 3-6 months from the initiation of IT thio-TEPA. Data on survival from the time of diagnosis of dissemination was assessed. RESULTS: The median survival, from the time of diagnosis of ependymal or leptomeningeal dissemination, of patients who received IT thio-TEPA was 10 months (AA = 19 months; GBM = 10 months). Five of 14 patients had a radiographic response to treatment within 6 months. The median survival of patients with a radiographic response was 15.5 months, compared with 10 months for nonresponders. No significant neurotoxicity or myelopathy was observed. CONCLUSIONS: Early treatment with IT thio-TEPA may result in improved survival with minimal morbidity. Radiographic response may predict prolonged survival.     

Low prevalence of the APC I1307K sequence in Jewish and non-Jewish patients with inflammatory bowel disease.

A germline sequence alteration at codon 1307 of the APC gene (I1307K) has been reported in 6-7% of the Ashkenazi Jewish population in the United States. This alteration is believed to predispose the APC gene to a secondary mutation at the same locus, resulting in an increased risk of colorectal carcinoma. There is an increased risk of colorectal carcinoma in patients with inflammatory bowel disease (IBD), a relatively large proportion of whom are Ashkenazi Jews. We therefore sought to determine whether the I1307K sequence variant occurred in the germline DNA of IBD patients. To our surprise, we found this sequence in only two of 267 patients with IBD (0.7%), occurring in only 1.5% of Jewish IBD patients. The I1307K sequence variant was not found in 67 patients with esophageal cancer, 53 patients with gastric carcinoma (13 MSI-H and 44 MSI-negative), or ten patients with sporadic MSI-H colon cancer. These findings suggest that the I1307K sequence is relatively rare in the germline of Jewish as well as non-Jewish IBD patients. It does not appear to contribute to the increased colorectal cancer risk present in these patients.     

Thiazoloindans and thiazolobenzopyrans: a novel class of orally active central dopamine (partial) agonists

The 2-aminothiazole moiety has proven its value in medicinal chemistry as a stable and lipophilic bioisosteric replacement of a phenol group. This approach has provided dopamine (DA) agonists with good oral availability. To further explore its use in the development of DA agonists, we have combined the 2-aminothiazole moiety with 2-aminoindans and 3-aminobenzopyrans, which are known templates for DA agonists. In this study we have synthesized 6-amino-3-(N,N-di-n-propylamino)-3,4-dihydro-2H-thiazolo[5, 4-f]-[1]benzopyran (12) and 6-amino-2-(N, N-di-n-propylamino)thiazolo[4,5-f]indan (20) and several analogues (13, 17, and 21). The affinity of the thiazolobenzopyrans and thiazoloindans for DA receptors was evaluated, which revealed compound 20 to have high affinity for DA D(3) receptors. In addition, the compounds were screened for their potential to inhibit lipid peroxidation, to determine their radical scavenging properties. Compounds 12, 20, and 21 were subjected to further pharmacological evaluation in a functional assay to determine intrinsic activity. Compound 20 was also studied with microdialysis (to determine effects on DA turnover in striatum) and in unilaterally 6-OH-DA lesioned rats (to determine their potential as DA agonists). These studies selected compound 20 (GMC 1111) as particularly interesting. Compound 20 caused a rotation activation in unilaterally 6-OH-DA lesioned rats and an increase in DA turnover in rat striatum. This dual agonist/antagonist action is best accounted for by its partial agonism at striatal DA D(2) receptors. Interestingly, 20 displayed long-lasting activity and excellent oral availability in 6-OH-DA lesioned rats, making this compound potentially useful for the treatment of Parkinson's disease.     

The Association Between Toddlerhood Self-Control and Later Externalizing Problems

Lower self-control is a significant correlate or predictor of a wide range of adult outcomes, and this association may be due to more general tendencies toward childhood externalizing problems. The present study examined the association between toddlerhood self-control expressed within a “don’t” compliance task (at 14–36 months) and later externalizing problems (parent-reported externalizing problems from age 4 to 12 years, teacher-reported externalizing problems from age 7 to 12 years, and self-reported conduct disorder symptoms at age 17 years) in a longitudinal, genetically informative study. The slope of self-control, but not its intercept, predicted later teacher-reported, but not parent- or self-reported, externalizing problems. That is, increase in self-control during toddlerhood was associated with lower levels of later teacher-reported externalizing problems. The slope of self-control was no longer a significant predictor of teacher-reported externalizing problems after controlling for observed disregard for others, a robust predictor of externalizing problems. Thus, the hypothesis that self-control is the primary predictor of externalizing problems was not supported. Results from genetic analyses suggested that the covariance between the slope of self-control and teacher-reported externalizing problems is due to both genetic and shared environmental influences.     

Integrated microfluidic bioprocessor for single-cell gene expression analysis

An integrated microdevice is developed for the analysis of gene expression in single cells. The system captures a single cell, transcribes and amplifies the mRNA, and quantitatively analyzes the products of interest. The key components of the microdevice include integrated nanoliter metering pumps, a 200-nL RT-PCR reactor with a single-cell capture pad, and an affinity capture matrix for the purification and concentration of products that is coupled to a microfabricated capillary electrophoresis separation channel for product analysis. Efficient microchip integration of these processes enables the sensitive and quantitative examination of gene expression variation at the single-cell level. This microdevice is used to measure siRNA knockdown of the GAPDH gene in individual Jurkat cells. Single-cell measurements suggests the presence of 2 distinct populations of cells with moderate (≈50%) or complete (≈0%) silencing. This stochastic variation in gene expression and silencing within single cells is masked by conventional bulk measurements.     

A novel CLCN1 mutation (G1652A) causing a mild phenotype of thomsen disease

We investigated a 62‐year‐old man who had mild clinical features of myotonia congenita. He was found to have a novel heterozygous G‐to‐A nucleotide substitution at position 1652 in exon 15 of the CLCN1 gene. Clinicogenetic studies performed on his family revealed that his asymptomatic son also shared the mutation. We conclude that a novel chloride channel mutation (G1652A) has caused a mild form of autosomal‐dominant myotonia congenita (Thomsen disease) in this family. Muscle Nerve, 2010