The effects of antithyroid drugs on intercellular mediators

The antithyroid drugs methimazole and propylthiouracil have been shown to affect the function of monocytes and B and T lymphocytes in vitro. The aim of this study was to investigate the mechanism responsible for signalling between these various cell types. Propranolol, a drug known to have no effect on the immune system, was also included as a control against which the effects of the other drugs could be monitored. Peripheral blood lymphocytes from control subjects were stimulated with phytohemagglutinin in the presence or absence of antithyroid drugs. Propranolol was found significantly to inhibit beta 2 microglobulin production. In addition it was also found to be a very weak scavenger of free oxygen radicals. Methimazole significantly increased interleukin 2 levels (p less than 0.01), but had no significant effect on either gamma-interferon or beta 2 microglobulin production. Propylthiouracil also increased interleukin 2 levels (p less than 0.001) and significantly decreased beta 2 microglobulin production (p less than 0.01). Both drugs were found to be scavengers of free O2 radicals. It would appear that IL-2 is involved in intercellular signalling and this process may involve free radicals.     

Clinical evaluation of angiotensin II enhanced perfusion scintigraphy in metastatic liver disease

The hepatic perfusion index (HPI) may be of value in the diagnosis of liver micro-metastases. However, raised values of HPI also occur in some benign liver conditions (e.g. cirrhosis), thereby weakening the diagnostic power of this test. It has been suggested that infusion of the vaso-active agent angiotensin II might improve the predictive value of dynamic scintigraphy because it has been shown to alter liver perfusion in patients with metastatic liver disease. Basal HPI values were not significantly different in a group of patients with metastases (n = 10) and a group with cirrhosis (n = 9). A significant rise in HPI occurred in the metastatic group using angiotensin II enhancement (p less than 0.01, Wilcoxon test). In the cirrhotic group there was no significant increase in the HPI with angiotensin II enhancement. Within the groups, there was considerable variation in response, with eight of ten metastatic and five of nine cirrhotic patients showing a rise in HPI during an angiotensin II infusion. As a result, there was complete overlap in the angiotensin II enhanced HPI for the two groups. Angiotensin II enhancement of HPI is therefore unlikely to improve the diagnostic power of dynamic scintigraphy in individual patients with established hepatic disease.     

A comparison of 10 MHz ultrasound and 201-thallium/99m-technetium subtraction scanning in primary hyperparathyroidism.

Both high resolution (10 MHz) ultrasound and 201-thallium/99m-technetium subtraction scanning (Tl/Tc) were carried out preoperatively in 25 patients with primary hyperparathyroidism. Operative findings were the standard against which these two imaging methodologies were compared. Tl/Tc scanning showed a sensitivity of 42% and a specificity of 97%. By comparison, sensitivity of ultrasound was 38% and specificity 89%. Both techniques were positive together in nine instances and correctly localized the parathyroid adenoma in eight of these. In 44% of cases, however, both methods together failed to localize any abnormal parathyroid tissue. The ability of these modalities to localize abnormal parathyroid tissue correctly tended to vary with gland size. Where both ultrasound and Tl/Tc scans were negative, median gland size was smaller at 170 mg (range 50-2,500 mg), compared with where Tl/Tc scanning was correct (750 mg, 150-6,820 mg; P < 0.03), ultrasound was correct (960 mg, 100-6,820 mg; P < 0.03) and both techniques together were correct (980 mg, 600-6,820 mg; P = 0.002). These results suggest that neither Tl/Tc scanning or ultrasound has sufficient sensitivity or specificity to be used routinely in the preoperative evaluation of patients with primary hyperparathyroidism.     

Bone scan findings in hypervitaminosis D: case report

Bone scans in three patients showed generalized symmetrical increased uptake of radiopharmaceutical by the skeleton and absent or faint kidney images. It is thought that these appearances may be attributable to excess vitamin D, but other possible contributing factors, including the presence of renal osteodystrophy, are discussed.     

Doxorubicin increases the effectiveness of Apo2L/TRAIL for tumor growth inhibition of prostate cancer xenografts

Background  

Prostate cancer is a significant health problem among American men. Treatment strategies for androgen-independent cancer are currently not available. Tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) is a death receptor ligand that can induce apoptosis in a variety of cancer cell lines, including androgen-independent PC3 prostate carcinoma cells. In vitro, TRAIL-mediated apoptosis of prostate cancer cell lines can be enhanced by doxorubicin and correlates with the downregulation of the anti-apoptotic protein c-FLIP. This study evaluated the effects of doxorubicin on c-FLIP expression and tumor growth in combination with Apo2L/TRAIL in a xenograft model.     

Angiotensin II as a potential method of targeting cytotoxic-loaded microspheres in patients with colorectal liver metastases.

Regional chemotherapy is commonly used to treat patients with colorectal liver metastases. However, improvement in survival has still not been demonstrated. Cytotoxic loaded albumin microspheres for arterial administration have been described as a means of improving the the therapeutic index, but their distribution depends upon the prevailing pattern of arterial blood-flow at the time of injection. In this study, the ability of the vasoactive drug angiotensin II to target arterially injected microspheres to colorectal liver metastases is assessed in nine patients using scintigraphic planar and tomographic imaging. The median tumour: normal ratio in nine patients with colorectal liver metastases was 3.4:1 before the administration of angiotensin II. The corresponding ratio after administration of angiotensin II was 7.3:1. The median improvement factor was 1.8 (P less than 0.05). The data suggest that worthwhile tumour targeting can be achieved with angiotensin II in patients with colorectal liver metastases.     

Gastrin-releasing peptide in normal and neoplastic human lung: measurement and biochemical characterization

Levels of gastrin-releasing peptide (GRP) were determined by radioimmunoassay in human normal main and lobar bronchus and parenchymal lung tissue extracts. It was found that the level of GRP differed significantly between all 3 areas. The concentration of GRP was statistically higher in main bronchus (median 6.74 ng/g) compared to both lobar bronchus (median 4.79 ng/g) and parenchymal lung (median 1.73 ng/g), and also statistically higher in lobar bronchus compared to parenchymal lung. Chromatographically, GRP-immunoreactivity in both main and lobar bronchial extracts corresponded to GRP1-27 and GRP18-27, while in lung tissue only one major species was identified which corresponded in retention time to GRP18-27. No significant difference was detected when the levels of GRP in normal lobar bronchus and normal lung tissue were compared to the levels in lobar bronchus and lung taken from patients with lung carcinoma, at a site adjacent to the carcinoma. However, a significant difference was observed between the GRP content of normal main bronchus compared to main bronchus from patients with carcinoma. GRP was measured in 26/56 lung carcinomas examined. The levels ranged from 42,000 ng/g in a carcinoid tumour to 0.18 ng/g in a squamous-cell carcinoma, though only in 6 tumours were the levels outside the range determined for normal pulmonary tissue. Chromatography of selected tumour extracts of different histopathologies showed that there were differences in the GRP products present.