John Maier

Radiation Myelitis of the Dorsolumbar Spinal Cord

RADIATIONMYELITIS is a rather rare complication following therapeutic irradiation to neoplasms in which the spinal cord has been unavoidably included in the treatment portals. Since 1940 a total of 15 cases of myelitis involving the thoracolumbar spine has developed in association with the treatment of testicular tumors at Walter Reed General Hospital, Washington, D. C. The present paper is an analysis of these cases and will report on the relative risk of developing injury to the thoracolumbar spinal cord following such irradiation. Methods In the last twenty-eight years over 800 malignant germ-cell tumors of the testicle have been treated at Walter Reed General Hospital. Irradiation has been one of the primary modalities in treatment, principally to the lymphatic pathways draining the testicle following orchiectomy. This irradiation has been given prophylactically or therapeutically, either in conjunctionwith or without a retroperitoneallymphadenectomy. In most patients the fields included the inguinal ...

Raman Molecular Imaging: A Novel Spectroscopic Technique for Diagnosis of Bladder Cancer in Urine Specimens

BACKGROUND Raman molecular imaging (RMI) is an optical technology that combines the molecular chemical analysis of Raman spectroscopy with high-definition digital microscopic visualization. This approach permits visualization of the physical architecture and molecular environment of cells in the urine. The Raman spectrum of a cell is a complex product of its chemical bonds. OBJECTIVE In this work, we studied the possibility of using the Raman spectrum of epithelial cells in voided urine for diagnosing urothelial carcinoma (UC). DESIGN, SETTING, AND PARTICIPANTS Raman signals were obtained from UC tissue, then from UC touch preps obtained from surgical specimens and studied using the FALCON microscope (ChemImage, Pittsburgh, PA, USA), with a×100 collection objective and green laser illumination (532 nm). Then, urine samples were obtained from 340 patients, including 116 patients without UC, 92 patients with low-grade tumors, and 132 patients with high-grade tumors. Spectra were obtained from an average of five cells per slide. MEASUREMENTS Raman spectroscopy of cells from bladder cancer (BCa) tissues and patients. RESULTS AND LIMITATIONS The Raman spectra from UC tissue demonstrate a distinct peak at a 1584 cm(-1) wave shift not present in benign tissues. The height of this peak correlated with the tumors grade. The signal obtained from epithelial cells correctly diagnosed BCa with sensitivity of 92% (100% of the high-grade tumors), specificity of 91%, and a positive predictive value of 94% and a negative predictive value of 88%. The signal correctly assigned a tumors grade in 73.9% of the low-grade tumors and 98.5% of the high-grade tumors. RMI for diagnosis of BCa is limited by the need for specialized equipment and training of laboratory personnel. CONCLUSIONS RMI has the potential to become a powerful diagnostic tool that allows noninvasive, accurate diagnosis of UC.

Studying Bacterial Metabolic States Using Raman Spectroscopy

Natural metabolic variability expected during characteristic growth phases in batch cultures of Escherichia coli and Staphylococcus epidermidis were studied by Raman spectroscopy. Spectral changes induced by metabolic changes found in the growth phases (i.e., lag, exponential, stationary, and decay) were identified. Maximum intensity of bands assigned to DNA and RNA bases are seen at the beginning of the exponential phase, when cells are metabolically active, and minimum intensities are seen when cells are decaying. High agreement in spectral variation due to growth phases was seen for all the trials that were performed, four growth cycles for E. coli and two for S. epidermidis. Batch cultures were monitored by standard plate counts to identify all growth phases, including decay. Spectral data were analyzed by principal component analysis (PCA) and discriminant analysis to identify similarities and differences and to estimate a classification performance based on growth phases. For the species evaluated, spectra during decay are grouped closer to each other and separated from lag, exponential, and stationary cells. These results suggest that Raman spectroscopy can be used to study metabolic states in bacteria and in particular cell viability.

Raman Spectroscopic Discrimination of Cell Response to Chemical and Physical Inactivation

Raman spectroscopy was applied to study Escherichia coli and Staphylococcus epidermidis cells that were inactivated by different chemicals and stress conditions including starvation and high temperature. E. coli cells exposed to starvation conditions over several days lost viability at the same rate that spectral bands assigned to DNA and RNA bases decreased in intensity. Band intensities correlate with standard plate counts with R2 = 0.99 and R2 = 0.97, respectively. Principal components analysis and discriminant analysis multivariate statistical techniques were used to evaluate the spectral data collected. Significant changes were observed in the spectra of treated cells in comparison with their respective controls (samples without treatment). As a result, there was a significant differentiation between viable and non-viable cells (treated and non-treated cells) in the first and second principal component plots for all the treatments. Discriminant analysis was used along with PCA to estimate a classification rate based on viability status of the cells. Non-viable cells were differentiated from viable cells with classification rates that ranged between 60 and 90% for specific treatments (i.e., EDTA-treated cells versus control cells). The classification rate obtained considering all the treatments (non-viable cells) and controls (viable cells) at the same time for each of the species studied was 86%. The classification rate based on species differentiation when all the spectra (viable and non-viable) were used was 87%. These results suggest that Raman spectroscopy is a powerful tool that can be used to evaluate viability and to study metabolic changes in microorganisms. It is a robust method for bacterial identification even when high spectral variations are introduced.

Total Pulmonary Irradiation for Metastases from Testicular Carcinoma

Abstract Both lungs were entirely irradiated in 11 patients with pulmonary metastases from testicular carcinoma; in 6 of these chemotherapy alone had been unsuccessful. Actinomycin D was combined with the irradiation in 8 patients. Midplane doses up to 2,100 rads in three weeks were well tolerated. All evidence of pulmonary metastases disappeared in 6 patients; in 3 others, reduction in metastatic size was marked but brief. All 4 previously untreated patients who received irradiation and concomitant actinomycin D had complete responses; 2 remained free of pulmonary disease for prolonged periods and 1 is alive with no evidence of disease three years after irradiation.

Raman molecular imaging of tissue and cell samples using tunable multiconjugate filter

Raman spectroscopy is a powerful technique for rapid, non-invasive and reagentless analysis of materials, including biological cells and tissues. Raman Molecular Imaging combines high molecular information content Raman spectroscopy and digital full field imaging to enable the investigation of cells and tissues. We have conducted widefield imaging using a new class of birefringent liquid crystal tunable filter that provides high throughput over an extended wavelength range. This tool has been applied to investigate the linkage between reagentless spectral imaging in tissue and cells and standard reagent based approaches. In this report, we describe Raman imaging data on a clinical tissue sample and cultured cells. The results demonstrate the sensitivity of Raman Molecular Imaging and fluorescence spectral imaging to molecular differences in biological systems laying the foundation for the eventual use of this approach as a biological research and clinical diagnostic tool.