EM proves invaluable in the confirmation of chordoma in the sacral mass of a middle-aged man.

A case of a 47-year-old male with a sacral spine mass was investigated by histology, immunohistochemistry (IHC), and electron microscopy (EM). The light microscopy of the first core biopsy revealed scant cellularity with spindle and round cells with eosinophilic cytoplasm within a fibromyxoid background. Immunostaining with pancytokeratin, cytokeratin 19, and S100 was nonspecific. Another biopsy was attempted to obtain a more definitive diagnosis. Light microscopy of the second core had scant cellular material. However, the tissue was specifically requested for ultrastructural evaluation and revealed features diagnostic of chordoma. After definitive diagnosis, radical resection of the mass was performed. This case illustrates how EM was instrumental in the definitive diagnosis before radical resection in a case that was not clear by hematoxylin and eosin (H&E) and IHC alone.

Cytotoxic and antiprotozoal activity of flavonoids from Lonchocarpus spp.

A number of flavonoids isolated from Lonchocarpus spp. were evaluated for their antiprotozoal and cytotoxic activity. Flavone 6 and chalcone 7 were found to be the most active against Leishmania parasites and against cell cultures of Leukemia P388DI and adenocarcinoma prostate PC-3.

Brain tumors in the older person.

BACKGROUND: The incidence of brain tumors is increasing rapidly, particularly in the older population. Advances in molecular biology help to explain differences in biologic behavior and response to therapy of brain tumors in the elderly compared with younger patients. The number of elderly patients who desire and receive therapy for brain tumors and are included in clinical trials is increasing. METHODS: This article reviews the literature on the epidemiology, clinical aspects, and therapy of brain tumors, with emphasis on the older patient population. RESULTS: The increased incidence of brain tumors in the elderly is principally due to the increasing number of people who comprise the older population. Age and performance status are important independent prognostic indicators, together with tumor histology. Surgery, radiation therapy, and chemotherapy can benefit elderly patients with brain tumors with favorable histologies, tumor location, and good performance status. The response rates to available therapies are less favorable than in younger patients, and only a small number of elderly patients are enrolled in clinical studies addressing new treatment modalities. CONCLUSIONS: Brain tumors in the elderly have specific characteristics that determine their biologic behavior and response to therapy. There is a need for clinical studies designed for treatment of brain tumors in older patients, and requirements for rehabilitation and support systems for the elderly need to be addressed.

A sponge/dinoflagellate association in the haplosclerid sponge Haliclona sp.: cellular origin of cytotoxic alkaloids by percoll density gradient fractionation.

Light-microscopic and electron-microscopic studies of the tropical marine sponge Haliclona sp. (Order: Haplosclerida; Family: Haliclonidae) from Heron Island, Great Barrier Reef, have revealed that this sponge is characterized by the presence of dinoflagellates and by nematocysts. The dinoflagellates are 7-10 micrometer in size, intracellular, and contain a pyrenoid with a single stalk, whereas the single chloroplast is branched, curved, and lacks grana. Mitochondria are present, and the nucleus is oval and has distinct chromosomal structure. The dinoflagellates are morphologically similar to Symbiodinium microadriaticum, the common intracellular symbiont of corals, although more detailed biochemical and molecular studies are required to provide a precise taxonomic assignment. The major sponge cell types found in Haliclona sp. are spongocytes, choanocytes, and archaeocytes; groups of dinoflagellates are enclosed within large vacuoles in the archaeocytes. The occurrence of dinoflagellates in marine sponges has previously been thought to be restricted to a small group of sponges including the excavating hadromerid sponges; the dinoflagellates in these sponges are usually referred to as symbionts. The role of the dinoflagellates present in Haliclona sp. as a genuine symbiotic partner requires experimental investigation. The sponge grows on coral substrates, from which it may acquire the nematocysts, and shows features, such as mucus production, which are typical of some excavating sponges. The cytotoxic alkaloids, haliclonacyclamines A and B, associated with Haliclona sp. are shown by Percoll density gradient fractionation to be localized within the sponge cells rather than the dinoflagellates. The ability to synthesize bioactive compounds such as the haliclonacyclamines may help Haliclona sp. to preserve its remarkable ecological niche.

Cellular origin of chlorinated diketopiperazines in the dictyoceratid sponge Dysidea herbacea (Keller).

The tropical marine sponge Dysidea herbacea (Keller) contains the filamentous unicellular cyanobacterium Oscillatoria spongeliae (Schulze) Hauck as an endosymbiont, plus numerous bacteria, both intracellular and extracellular. Archaeocytes and choanocytes are the major sponge cell types present. Density gradient centrifugation of glutaraldehyde-fixed cells with Percoll as the support medium has been used to separate the cyanobacterial symbiont from the sponge cells on the basis of their differing densities. The protocol also has the advantage of separating broken from intact cells of O. spongeliae. The lighter cell preparations contain archaeocytes and choanocytes together with damaged cyanobacterial cells, whereas heavier cell preparations contain intact cyanobacterial cells, with less than 1% contamination by sponge cells. Gas chromatography/mass spectrometry analysis has revealed that the terpene spirodysin is concentrated in preparations containing archaeocytes and choanocytes, whereas nuclear magnetic resonance analysis of the symbiont cell preparations has shown that they usually contain the chlorinated diketopiperazines, dihydrodysamide C and didechlorodihydrodysamide C, which are the characteristic metabolites of the sponge/symbiont association. However, one symbiont preparation, partitioned by a second Percoll gradient, has been found to be devoid of chlorinated diketopiperazines. The capability to synthesize secondary metabolites may depend on the physiological state of the symbiont; alternatively, there may be two closely related cyanobacterial strains within the sponge tissue.

Indoor radon prediction from soil gas measurements.

This study of radon levels in southwest England investigates the correlation between indoor and soil gas radon concentrations and considers the influence of geology, meteorological variables, spatial and depth variations. This paper examines the value of soil gas measurements as an indicator of potential indoor radon concentrations and highlights a number of factors that need to be considered. Only a very weak correlation was obtained between the overall 222Rn concentration in soil gas and inside the home. However, for high soil gas concentrations a stronger correlation with the indoor level was observed. Typically, the soil gas concentration was between a factor of 10 and 1,000 times greater than that indoors. Levels as low as 10 kBq m(-3) in the soil could produce an indoor concentration above the UK action level of 200 Bq m(-3). The moisture content and the inhomogeneity of soil permeability were identified as chiefly responsible for any perturbation of a soil gas concentration associated with a particular geology. Alone, measured soil gas concentrations have only a limited use in the prediction of indoor 222Rn concentrations.

Combination of 6-thioguanine, procarbazine, lomustine, and hydroxyurea for patients with recurrent malignant gliomas.

OBJECTIVE: To determine the efficacy of the combination of 6-thioguanine, procarbazine, lomustine, and hydroxyurea for patients with recurrent malignant gliomas after failure of either previous radiotherapy alone or previous radiotherapy plus nitrosourea-based chemotherapy. METHODS: Seventy-seven patients with recurrent malignant gliomas were studied. 6-Thioguanine was administered for 4 days before lomustine, and procarbazine was administered for 1 day before and 2 days after lomustine to potentiate lomustine's antitumor effect. Hydroxyurea was initiated 1 day before lomustine and continued for a total of 3 days. RESULTS: Thirty patients with glioblastomas and 47 patients with anaplastic gliomas were eligible for evaluation. In the glioblastoma group, 2 of 30 patients had a partial response and 8 of 30 patients had stable disease. This group of patients who responded and had stable disease included 6 of 10 patients who had not undergone previous chemotherapy but only 4 of 20 who had undergone previous chemotherapy. The overall median time to disease progression for the glioblastoma group was 9 weeks. In the anaplastic glioma group, 11 of 47 patients had a partial response and 25 of 47 had stable disease, including 23 of 30 without previous chemotherapy and 13 of 17 who had undergone previous chemotherapy. The median time to disease progression for the whole anaplastic glioma group was 24 weeks; however, the time to disease progression was 50 weeks for responding patients who had not undergone previous chemotherapy and 25 weeks for those who had undergone previous chemotherapy. CONCLUSION: Our results indicate that chemotherapy with a combination of 6-thioguanine, procarbazine, lomustine, and hydroxyurea is active for patients with recurrent anaplastic gliomas and glioblastomas not previously treated with nitrosourea-based chemotherapy but is inactive for patients with glioblastomas previously treated with chemotherapy.

[Utilization potential of the CO2-laser in dermal changes]. / Einsatzmöglichkeiten des CO2-Lasers bei dermalen Veränderungen.

44 patients with various cutaneous lesions including 18 tattoos, 13 hypertrophic scars or keloids, 4 xanthelasmas, 4 capillary haemangiomas, and 5 other benign cutaneous lesions were treated by CO2-Laser. 28 of these patients were reexamined after a follow-up period of three to four years. Good results were achieved with the CO2-Laser in the treatment of tattoos, xanthelasmas, and haemangiomas. Satisfactory results were obtained in one patient with peri-ungual Koenen-tumors and in two patients with perianal condylomas. Keloids and plantar warts recurred after an initial improvement. The attempts to remove hypertrophic scars did not bring the desired results. In four cases a superficial local wound infection led to a delayed healing process together with an aesthetically unsatisfying final appearance. CO2-Laser treatment brings certain advantages in selected cases where traditional techniques of plastic surgery have a higher complication rate and are additionally a greater burden for the patient. Particularly larger tattoos, multiple xanthelasmas, and capillary haemangiomas are successfully removed with the CO2-Laser, despite the time consuming method for the attending physician.

Management of brain metastases from breast carcinoma.

Brain metastases occur clinically in about 10% of patients with stage IV breast cancer, in the setting of widespread extracranial metastases. Prognosis is poor and management is aimed at relieving acute symptoms and improving neurologic status, as well as controlling the metastatic disease. Therapies include surgery, radiotherapy, chemotherapy, and hormonal therapy, used alone or in combination. Performance status is the single most important factor determining treatment choice. In selected patients, surgery can improve survival and performance status. Radiotherapy is the palliative treatment of choice, providing rapid relief of symptoms, especially headache. Recent innovations include accelerated split courses of radiotherapy given in two or three daily fractions, use of radiosensitizers, brachytherapy, and radiosurgery. Systemic therapy remains controversial, but studies show that cytotoxic agents can be palliative against brain metastases if the primary tumor is sensitive to the drug or drugs used.

Radon in soil gas and its relationship with some major faults of SW England.

The south-west of England was designated by the National Radiological Protection Board (NRPB) as the first 'Radon Affected Area', as over 1% of the housing stock is estimated to have an indoor radon concentration in excess of the 200 Bq m(-3) Action Level. The situation is even worse for houses situated above uraniferous granite intrusions, where over 30% are thought to be above the Action Level.The aim of this study is to investigate the relationship between the level of radon in soil gas and the local geology. Particularly high radon levels were measured along major fault zones. This could be explained by: increased rate of migration of the radon due to the permeable fault, the presence of radium or radon-bearing ground water within the fault, or secondary uranium mineralisation. Seasonal variations are also considered.

Selective and non-selective lymphocytotoxicity in human melanoma: observation on the effect of long-term culture and fetal bovine serum on target-cell sensitivity to lymphocytes.

In vitro cell mediated cytotoxicity (CMC) assays have been conducted in a human melanoma system with a 3H-proline retention technique. Melanoma target cells from long-term cultures ("cell lines") are found to exhibit increased susceptibility for lymphocyte cytotoxicity in comparison to the same target cells from short-term culture. The higher sensitivity of the "cell line" derived target cells is seen with lymphocytes, irrespective of diagnosis of the donor. In parallel experiments with the target cells grown in medium supplemented with fetal calf serum (FCS) and AB+ human serum (from a normal male doner), the melanoma target cells grown with FCS do not show any enhanced cytotoxicity, suggesting no causal relationship of such enhanced sensitivity of "cell line"-derived target cells to "heterologous melanoma antigens" that might have been acquired by the target cells following the use of FCS in tissue culture. In controlled assays of in vitro CMC, lymphocytes from melanoma patients (14/44) exhibited selective cytotoxicity (destruction of only one target-cell type) against the melanoma target cells, whereas only 3/97 control lymphocytes (other malignancies and normal donors) showed such melanoma-selective cytotoxicity. This difference is statistically significant at p less than 0.001. Non-selective cytotoxicity (destruction of two or more unrelated target cell types) was seen with lymphocytes from 9/44 melanoma patients, 13/51 patients with other malignancies and 8/46 normal donors. No correlation of selective cytotoxicity could be established with donors' age, sex, stage of disease, therapy or history of blood transfusion. Such a correlation may emerge as our series becomes larger. Despite the lack of any correlation between selective cytotoxicity and disease status, our study reaffirms the existence of selective cytotoxicity by melanoma patients' lymphocytes against melanoma target cells.

Variables and specificity of in vitro lymphocyte-mediated cytotoxicity in human melanoma.

In vitro cell-mediated cytotoxicity (CMC) assays have been carried out in human melanoma system with blood effector lymphocytes on [3H]proline-labeled target cells in a 48-hr microcytotoxicity technique. Three lymphocyte purification procedures (Ficoll:Hypaque gradient, plasma gel sedimentation followed by nylon column incubation, and plasma gel sedimentation followed by separation with nylon powder and glass beads) are compared in parallel experiments for characteristic effector cell composition and cytotoxic potential against target cells of dissimilar histology. The cytotoxicity is defined by the loss of target cell 3H cpm as measured by residual target cell 3H cpm in individual microwell following incubation with lymphocytes. Target cell 3H cpm loss by test lymphocytes is compared with target cell 3H cpm loss by several age and sex matched control lymphocytes (from normal donors and unrelated cancer patients); further comparison between the various control lymphocytes is also made in each assay. As control for target cells, autologous fibroblasts and homologous tumor cells of dissimilar histology are always included in each assay. Specific cytotoxicity is defined as statistically significant and selective destruction of only melanoma cells by the test lymphocytes as compared to the control lymphocytes. Significant but nonselective destruction of 2 or more target cells of unrelated histology is regarded as nonspecific cytotoxicity, while no destruction of any target cells signifies no cytotoxicity. The Ficoll:Hypaque preparations consistently exhibit the highest nonlymphocytic cell contamination (8 to 16%); the nonlymphocytic cells are, almost exclusively, monocytes. They also produce relatively high percentage of thymus independent (B) cells (8 to 15%). The ultimate cell composition of the 2 plasma gel-nylon preparations is essentially identical. In either plasma gel-nylon preparations, the nonlymphocytic contamination is minimal (0 to 4%) and thymus-dependent (T) cell percentage is considerably higher (92 to 99%) with none or few B cells.