The role of nuclear medicine in oncology

Nuclear Medicine offers screening methods for oncology such as bone and bone marrow scintigraphy. During the last two decades, special procedures have gained widespread application. This paper is centered around the “tumor-specific” radiopharmaceuticals. In patients with thyroid cancer, I-131 still plays a significant role. Ga-67 still has its indications in lymphoma, while in other diseases Tl-201 cloride is now the agent of choice. Especially in thyroid cancer, Tl-201 has proved to be a reliable tumor imaging radiopharmaceutical. More recently, Tc-99m MIBI was introduced for tumor imaging. Tc-99m HMPAO may also be used for tumor scintigraphy, especially in brain lesions. In addition, I-123 IMP has successfully been used for imaging malignant melanoma. Another promising field of tumor diagnosis is receptor imaging. In neuroblastoma and malignant pheochromocytoma, I-131/123 mIBG is the radiopharmaceutical of choice and may be considered as a receptor imaging agent also. First clinical results with In-111 octreotide show potentials as somatostatine-receptor radiopharmaceutical in insulinoma, islet cell carcinoma, medullary and lung cancer, while I-123 estradiol needs some improvement until it may be recommended as diagnostic tool in breast cancer. Since 1978, radiolabeled poly- or monoclonal tumor antibodies and their fragments have gained widespread application. Especially the Tc-99m 225.28S melanoma antibody, I-131 or Tc-99m CEA and In-111/I-131 labeled OC-125 antibodies have proven to be of clinical significance in melanoma, colorectal and ovarian cancer.     

A laboratory study of cyromazine on Aedes aegypti and Culex quinquefasciatus and its activity on selected predators of mosquito larvae

In a laboratory study, the insect growth regulator, cyromazine, exerted a high level of biological activity on Aedes aegypti and Culex quinquefasciatus treated in the 4th larval instar. At 1.5 and 1.0 ppm this IGR produced 97 and 99% inhibition of emergence in adult Ae. aegypti, respectively. In Cx. quinquefasciatus, there was 99% inhibition at 1 ppm and complete inhibition at 1.5 ppm. The overall pupal mortality was higher than larval or adult stages of both species. This material induced different types of morphogenetic abnormalities in pupae and adults of the 2 species similar to those induced by other IGRs. However, most abnormalities were observed in the pupal stage. Adverse effects were not detected on the 4 mosquito predator species during the acute or posttreatment tests.     

Chemotherapy in patients with resectable liver metastases from colorectal cancer

New chemotherapy drugs and, more recently, targeted therapies have significantly improved the outcome of patients with resected stage III colon cancer (adjuvant chemotherapy) and patients with unresectable metastases (palliative therapy). These advances raise several questions about the place of chemotherapy after and before surgery in patients with resectable liver metastases. To date, only a combined intra-arterial plus systemic fluoropyrimidine-based chemotherapy regimen has clearly demonstrated a relapse-free survival benefit. Yet, this approach is restricted to specialized centers, mainly because of technical difficulties and locoregional toxicities. The role of systemic use of oxaliplatin- and irinotecan-based regimens is currently under investigation. Planned trials will assess the role of anti-angiogenic and anti-epidermal growth factor receptor agents. We review the main trials performed in patients with resectable metastases, and discuss their potent impact on clinical practice.     

Electrophysiologic target localization in posteroventral pallidotomy

Summary The current interest in stereotactic posteroventral pallidotomy (PVP) for treating Parkinson's disease and the variability of published results have raised questions regarding techniques for target localization. In our technique the probe is guided to the optimum target at the most ventral pallidum and ansa lenticularis by macroelectrode stimulation of the internal capsule and optic tract from within the globus pallidus, with the thresholds providing a relative measure of the electrode proximity to these structures. We have characterized these localizing macroelectrode stimulation parameters in 57 posteroventral pallidotomies with consistent anatomic lesion placement, excellent outcome, and no complications.Using a 1.8 × 2.0 mm radiofrequency electrode for macroelectrode stimulation (RFG-3C, Radionics Inc.), minimum voltages (thresholds) to activate motor (at a frequency of 2 Hz) or visual (at a frequency of 100 Hz) responses as well as impedance measurements were obtained at the final target (Tf) and at distances proximal to Tf along the electrode trajectory. The visual and motor threshold voltages at Tf via our standard approach angles (50 ° above base plane, 20 ° from the sagittal plane), had a range of 1.0 to 1.5 V, and 2.0 to 3.5 V respectively. We also found that as the probe approaches Tf there is a significant decrease in voltage thresholds for motor (P<.0001) and visual (P<.0001) responses in an individual patient indicating that the probe is converging on these structures. Increases in impedance between Tf, 2–3 mm, and 4–5 mm proximal to Tf were also statistically significant (P<.0001). Microelectrode recording of electrophysiological neuronal activity at various points along the trajectory towards the target showed distinct firing patters providing identification of the globus pallidus externus and internus, ansa lenticularis, and optic tract.Macroelectrode electrophysiological stimulation within the target volume, inducing threshold responses in the internal capsule and optic tract, provides for accurate localization of the most effective PVP target in the ansa lenticularis. In unresponsive patients, the utilization of microelectrode recording for the identification of the pallidal borders and the optic tract improves safety.     

Effects of endurance exercise on the morphology of mouse neuromuscular junctions during ageing

Summary It has been suggested that age changes in the morphology of the neuromuscular junction (NMJ) may reflect altered physical activity levels rather than the unique effects of ageing. Additionally, previous studies have indicated that the structure of the NMJ may be modulated with exercise. To investigate these questions, quantitative morphometry was determined on soleus and extensor digitorum longus (EDL) nerve terminals stained with zinc iodide-osmium from C57BL/6NNia mice under control and endurance exercised conditions at 12, 18 and 24 months of age.As previously observed, the area, perimeter, extent length and branch number of nerve terminals increased with age in both soleus and EDL. The changes were similar between the muscle types, although the changes were more pronounced in the phasic EDL. In 12-month-old animals, 2 months of endurance exercise resulted in significantly larger nerve terminals in both soleus and EDL, suggesting a functional adaptation. Exercised 18- and 24-month-old nerve terminals were smaller than corresponding controls, which indicated that exercise minimized or prevented further age-related nerve terminal elaboration. At all ages the exercised nerve terminals comprised a more homogeneous population than corresponding controls, which indicates that uniform physical activity can modulate NMJ morphometry. The magnitude of the changes suggests that subtle alterations in normal cage activity with advancing age do not have a significant effect on the morphology of nerve terminals. However, the morphology of the NMJ does change significantly in response to physical exercise training.     

Establishment and characterization of a new human Burkitt's lymphoma cell line (WSU-BL)

A new human cell line, WSU-BL, was established from a malignant ascitic fluid occurring in a patient with Burkitt's lymphoma. The established line grows in a single-cell suspension with a doubling time of 19 hours and expresses L3 morphologic features by the French-American-British classification. Immunologic study revealed that WSU-BL cells express IgM-lambda both in the cytoplasm and on the surface and react with monoclonal antibodies to B-cell antigens (B1, B4, BL3, BL4, HLA-DR, and common acute lymphoblastic leukemia antigen [CALLA]). These cells are negative for T-cell and myeloid/monocyte antigens as well as Epstein-Barr virus nuclear antigen (EBNA). These results suggest that WSU-BL corresponds to an intermediate stage of B-cell differentiation. Both fresh tumor and WSU-BL cells had a hyperdiploid karyotype carrying the 8;14 chromosome translocation. Molecular studies showed that WSU-BL has a rearrangement of c-myc proto-oncogene and expresses c-myc RNA. Phorbol ester 12-0-tetradecanoylphorbol-13-acetate (TPA) and interferon-gamma (IFN-gamma) were able to induce several phenotypic changes on WSU-BL cells. Two-dimensional gel electrophoresis of total cellular protein showed that either TPA or IFN-gamma induced both the synthesis or loss of several proteins. Analysis of the protein patterns indicated that some proteins were uniquely responsive to either TPA or IFN-gamma and others were common to both. This cell line should be valuable for future studies of cell proliferation, differentiation, and oncogenesis concerning this neoplasm.     

Concomitant administration of cyclosporine and ketoconazole in idiopathic nephrotic syndrome.

BACKGROUND: The deliberate use of ketoconazole to reduce the need for cyclosporine (CsA) is not new, but it is particularly relevant because of the high cost of CsA. Many studies have documented this benefit in renal and cardiac transplants, but this co-administration has not been reported in patients with nephrotic syndrome. METHODS: This retrospective study included 207 nephrotic patients who were steroid resistant, dependent or frequent relapsers and received CsA therapy. Among these patients 153 received daily ketoconazole therapy in a dose of 50 mg with concomitant decrease of one-third of the CsA dose while 54 patients received CsA alone. The majority of our cases were children (179 were below 18 years) and male to female ratio was 1.7:1. RESULTS: The great majority of the study population received the drugs for 1-2 years. Patients who received CsA and ketoconazole were comparable with those who received CsA alone regarding age, sex, duration of renal disease, renal pathology, severity of nephrotic syndrome, renal function, hepatic function and steroid response. Co-administration of ketoconazole significantly reduced mean doses of CsA by 37% after 1 month and 47% at 1 year with overall net cost savings of 37%. Hepatic functions remained within the normal range in both groups. Additionally, co-administration of ketoconazole significantly improved the response to CsA therapy, successful steroid withdrawal and decreased the frequency of renal impairment. CONCLUSIONS: Co-administration of keto with CsA in idiopathic nephrotic patients significantly reduces CsA costs and may improve its response.     

Oesophageal pemphigus vulgaris

Symptomatic involvement of the oesophageal mucosa by pemphigus vulgaris is rare. We describe 1 patient who was treated with oral steroids during a blistering phase, when epigastric pain developed. Endoscopy revealed multiple ulcerations all over the oesophagus, but gastroduodenal mucosa was normal. The symptoms disappeared following cimetidine for gastro-oesophageal reflux and increase of steroid dosage. When painful symptoms appear from the upper digestive tract during corticosteroid treatment of pemphigus, the possibility of acantholytic involvement of oesophageal mucosa must be kept in mind. Its implication for the dosage of steroids is opposite that in steroid-induced peptic ulcers. Carefully performed upper gastrointestinal tract endoscopy is helpful in these patients.