Preparation and evaluation of 99mTc(V)-DMSA complex: Studies in medullary carcinoma of thyroid

Consequent to the promising results reported with ^99mTc(V)-DMSA for imaging certain types of soft tissue tumors, we have developed methods to prepare this radiopharmaceutical in three ways:-(i) from freshly prepared reagents, (ii) through the use of a two component kit and (iii) use of the standard renal DMSA kit by a modified recipe. The ^99mTc(V)-DMSA complex has been subjected to paper electrophoretic and chromatographic procedures and also biodistribution studies. The distinctly different behaviour of this new product compared to that of the well known renal DMSA complex has been clearly established. Scintiimaging in a preliminary clinical trial in patients with medullary carcinoma of the thyroid has been encouraging.     

(186/188)Re] rhenium-ethylene dicysteine (Re-Ec): preparation and evaluation for possible use in endovascular brachytherapy

188ReO(4)(-), (188)Re-MAG(3), and (188)Re-DTPA are currently under investigation as radiation sources in liquid-filled balloons for prevention of restenosis following coronary angioplasty. Because (99m)Tc-labeled ethylene dicysteine (EC) is a well-established agent for renal tubular function imaging, the use of [(188)Re] rhenium-labeled EC as a potential agent for prevention of restenosis after angioplasty is worth evaluation. In this article, the preparation and pharmacological behavior of [(188/186)Re]Re complex of EC are reported. The yield of the Re complex was optimized by varying the parameters of complexation. The complex prepared under the optimized conditions was found to be stable over a period of 7 days when stored at pH 2 and at 4 degrees C. The pharmacological behavior of [(188/186)Re]Re-EC confirms its similarity to (188)Re-MAG(3) and its superiority over (188)ReO(4)(-) for use in endovascular brachytherapy.     

Post-elution concentration of 99mTcO4- by a single anion exchanger column. I: Feasibility of extending the useful life of column chromatographic 99mTc generator.

99mTc eluate in 0.7/0.35 M acetic acid and in 1:1 v/v 0.7 M acetic acid: 0.025 M ammonium acetate (30-40 ml) was conveniently concentrated by passing through a small column of a readily available weak anion exchanger, DEAE cellulose, (200 mg, 6 x 8 mm) and subsequent elution with 3 ml normal saline, with greater than 90% recovery. The quality of pertechnetate thus obtained and its compatibility for preparing 99mTc compounds were satisfactory. This method was successfully applied to the alumina column chromatographic generator produced in-house and to a commercial 99Mo-99mTc generator after extensive clinical use. Potential for much higher concentration factors with compacted anion exchanger cartridges as well as applicability for 188W-188Re generator are discussed.     

A paper chromatographic technique for quantitative evaluation of hydrolysed and ionic components in Tl radiopharmaceuticals

A reported paper chromatographic technique has been extended to delineate the hydrolysed components in ²⁰¹Tl radiopharmaceuticals for the determination of radiochemical purity. Detailed radiochemical purity analysis of ²⁰¹TlCl has been demonstrated using mini paper chromatographic systems. The technique is also useful in evaluation of the radiochemical purity of ⁶⁷Ga and ¹¹¹In radiopharmaceuticals.     

Harnessing the Genetic Plasticity of Porcine Circovirus Type 2 to Target Suicidal Replication

Porcine circovirus type 2 (PCV2), the causative agent of a wasting disease in weanling piglets, has periodically evolved into several new subtypes since its discovery, indicating that the efficacy of current vaccines can be improved. Although a DNA virus, the mutation rates of PCV2 resemble RNA viruses. The hypothesis that recoding of selected serine and leucine codons in the PCV2b capsid gene could result in stop codons due to mutations occurring during viral replication and thus result in rapid attenuation was tested. Vaccination of weanling pigs with the suicidal vaccine constructs elicited strong virus-neutralizing antibody responses. Vaccination prevented lesions, body-weight loss, and viral replication on challenge with a heterologous PCV2d strain. The suicidal PCV2 vaccine construct was not detectable in the sera of vaccinated pigs at 14 days post-vaccination, indicating that the attenuated vaccine was very safe. Exposure of the modified virus to immune selection pressure with sub-neutralizing levels of antibodies resulted in 5 of the 22 target codons mutating to a stop signal. Thus, the described approach for the rapid attenuation of PCV2 was both effective and safe. It can be readily adapted to newly emerging viruses with high mutation rates to meet the current need for improved platforms for rapid-response vaccines.     

Dose Measurements in the Build-Up Region for the Photon Beams from Clinac-1800 Dual Energy Medical Linear Accelerator

AIM: Since the skin dose becomes the limiting factor while deciding the tumorcidal dose, the detailed analysis of dose distribution in the build-up region is necessary for high-energy photon beams. In this study the beam characteristics affecting the build-up and skin dose for 6- and 18-MV photons are analyzed. MATERIALS AND METHODS: Measurements were made with 6- and 18-MV photons using a PTW parallel-plate ionization chamber (B 23344-036) and a RDM-1F electrometer. Build-up ionization measurements were made with the chamber fitted into a 25 x 25 x 25 cm polystyrene phantom with a fixed SSD of 100 cm. The entrance and build-up dose measurements were made with a polycarbonate and a mesh type metallic shielding tray and a 45 degrees wedge. Exit dose measurements were carried out for the graphite patient supporting assembly table top, 1.0 cm thick piece of wood and the 1.0 cm thick patient supporting perspex base frame for head and neck treatments. RESULTS: It was observed that the dmax decreased slightly with field size as with other accelerators. For both photon energies the surface dose was observed to increase with increase in field size. It was also noticed that the dose in the build-up region increases slightly when the polycarbonate secondary blocking tray is introduced with the increase in surface dose. The data show that the tray perturbation factor (TPF) at surface decreases steadily with tray-surface distance for both photon beams for all field sizes. It was noted that the TPF was more when the polycarbonate tray was introduced at shorter tray-surface distances for both energies. At tray-surface distances above 60 cm the TPF almost remained close to unity for 6-MV photons for all field sizes, whereas the continuous decrease in TPF could be noted for 18-MV photon beams even after the TPF reached unity. CONCLUSION: The increase in surface dose with field size for both photon energies is due to the electron scattering from the intervening materials. The use of wedge filters absorbs low-energy scattered electrons significantly and hence, the relative surface dose (RSD) is always less than unity. The increase in dose enhancement percentage with graphite compared to perspex supporting assembly indicates that the electron backscatter is proportional to the atomic number of the medium.     

Safety of imatinib in chronic myeloid leukemia in blastic crisis presenting as cholestatic jaundice

Acute leukemia presenting as cholestatic jaundice is rare. It can occur due to granulocytic sarcoma compressing the bile ducts in case of acute myeloid leukemia. Rarely, diffuse infiltration of the liver sinusoids by the leukemic blasts can present as cholestatic jaundice. We report a case of chronic myeloid leukemia in lymphoid blast cell crisis presenting with severe cholestatic jaundice due to diffuse infiltration of the liver sinusoids with lymphoblasts. This patient tolerated imatinib well and, coinciding with the hematological response, there was marked reduction in the cholestasis due to blast clearance from the hepatic sinusoids. He was subsequently treated with combination chemotherapy and achieved morphological and cytogenetic remission.     

Outcomes after laparoscopic surgery in neonates with hypoplastic heart left heart syndrome

Background/Purpose

Laparoscopy has advanced the care of children for a variety of pediatric surgical diseases. However, complication rates for laparoscopic interventions in neonates with hypoplastic left heart syndrome (HLHS) have not been well described. The purpose of this study is to present the largest reported series of laparoscopic surgery performed in patients with HLHS.

Methods

We conducted a single-institution, retrospective chart review for all neonates with HLHS who underwent a laparoscopic procedure from September 2002 to March 2005. Data regarding patient characteristics, intraoperative monitoring, previous cardiac surgery, perioperative complications, and postoperative mortality were assessed.

Results

Twelve patients with HLHS underwent a total of 13 operations during the study period (8 combined Nissen fundoplication and gastrostomy tubes, 3 isolated gastrostomy tubes, 1 Ladd procedure, and 1 combined Nissen fundoplication and gastrocutaneous fistula closure). All cases were completed laparoscopically. Patients had undergone palliative cardiac surgery but were not completely corrected; therefore, they were cyanotic. Perioperative complications were observed in 6 patients (3 gastrostomy tube site infections, 1 small bowel obstruction, 1 postoperative sepsis, and 1 urinary tract infection). There was no mortality in this series.

Conclusions

From this experience, it appears that laparoscopy can be performed safely and with satisfactory outcomes in patients with HLHS. However, a multidisciplinary approach, including the availability of a skilled and experienced cardiac anesthesia team, is believed to be critical to optimize outcomes in these critically ill children.     

Oxidative stress in the development of liver cirrhosis: a comparison of two different experimental models

BACKGROUND/AIMS: Oxidative stress has been implicated in liver cirrhosis. Carbon tetrachloride and thioacetamide are the most widely used models to develop cirrhosis in rats and the present study compares oxidative stress in the liver induced by these compounds at different stages of cirrhosis development. METHODS: Twice-weekly intragastric or intraperitoneal administration of carbon tetrachloride or thioacetamide, respectively, produced liver cirrhosis after 3 months. Histology, serum markers and hepatic hydroxy proline content confirmed the cirrhosis. RESULTS: An increase in oxidative stress parameters was seen in mitochondria, peroxisomes and microsomes from the liver after carbon tetrachloride or thioacetamide treatment. Oxidative stress was more severe in carbon tetrachloride treated animals than thioacetamide. Mild oxidative stress was evident at 1 and 2 months of treatment and a significant increase was seen by 3 months of treatment with either compound. By this time, frank liver cirrhosis was also observed. CONCLUSIONS: These results suggest that evidence of oxygen free radicals is also found early in the development of fibrosis and cirrhosis in both models.