Photodynamic diagnosis of ovarian cancer using hexaminolaevulinate: a preclinical study.

The unfailing detection of micrometastases during surgery of patients suffering from ovarian cancer is mandatory for the optimal management of this disease. Thus, the present study aimed at determining the feasibility of detecting micrometastases in an ovarian cancer model using the intraperitoneal administration of the photosensitiser precursor hexaminolaevulinate (HAL). For this purpose, HAL was applied intraperitoneally at different concentrations (4-12 mM) to immunocompetent Fischer 344 rats bearing a syngeneic epithelial ovarian carcinoma. The tumours were visualised laparoscopically using both white and blue light (D-light, Karl Storz, Tuttlingen, Germany), and the number of peritoneal micrometastases detected through HAL-induced photodiagnosis (PD) was compared to standard white light visualisation. Fluorescence spectra were recorded with an optical fibre-based spectrofluorometer and the fluorescence intensities were compared to the protoporphyrin IX (PpIX) fluorescence induced by 5-aminolevulinic acid under similar conditions. The number of metastases detected by the PD blue light mode was higher than when using standard white light abdominal inspection for all applied concentrations. Twice as many cancer lesions were detected by fluorescence than by white light inspection. The hexyl-ester derivative produced higher PpIX fluorescence than its parent substance aminolevulinic acid at the same concentration and application time. Fluorescence contrast between healthy and cancerous tissue was excellent for both compounds. To overcome poor diagnostic efficiency and to detect peritoneal ovarian carcinoma foci in the large surface area of the human peritoneal cavity, HAL fluorescence-based visualisation techniques may acquire importance in future and lead to a more correct staging of early ovarian cancer.

Wintering greater scaup as biomonitors of metal contamination in federal wildlife refuges in the Long Island region.

Tissues of greater scaup (Aythya marila mariloides) and components of their habitat (sediment, plankton, macroalgae, and invertebrates) were collected for heavy metal analysis in the winter of 1996-97 from US Department of the Interior wildlife refuges in the Long Island region. Geographic and temporal relationships between the concentration of nine metals in tissue and in habitat components were examined. In greater scaup tissues and habitat components, concentrations of As and Se were highest in Branford, Connecticut; Pb values were greatest in Oyster Bay, New York; and Hg concentrations were largest in Sandy Hook, New Jersey. Over the course of the winter, the concentration of Hg in liver increased, and concentrations of Cd, Cr, Cu, Hg, Pb, Se, and Zn in kidney decreased. Based on several criteria derived from geographic and temporal trends, metals were ranked using the apparent biomonitoring efficacy of greater scaup (As = Cr > Cu = Pb = Zn = Hg > Se = Cd > Ni). Although the seasonal migration and daily mobility of greater scaup are drawbacks to using this species as a sentinel for metal pollution, it was possible to demonstrate a relationship between geographic and temporal patterns of metals in habitat and greater scaup tissue. However, most metal concentrations in tissue were below thresholds known to adversely affect health of waterfowl.

[Allo-transfusion saving measures in maxillofacial surgery]. / Fremdblutsparende Massnahmen in der Kiefer-und Gesichtschirurgie.

In terms of a prospective clinical study between June 1994 and May 1996, in 204 patients undergoing maxillo-facial surgeries with a expected blood loss of more than 500 ml a protocol of bloodsaving measures was followed. By means of an additional retrospective study, the consumption of homologous blood and the amount of bloodsaving measures between June 1990 and May 1994 was evaluated. Bloodsaving measures were consisting from acute normovolemic hemodilution, controlled moderate hypotension, cell saving, preoperative autologous blood donation, and administration of rh-erythropoetine. The methoda were applied isolated as well as in combination. Special concerns were given to a stable intraoperative homeostasis and to the acceptance of a low hematocrit perioperatively. Aim of the study was to investigate if, following the protocol, even in major maxillofacial procedures homologous blood transfusions almost completely can be avoided. Out of the 204 patients in the prospective study, only 30 received homologous blood. For the period June 94 to May 96, the reduction of the number of patients receiving homologous blood in relation to the period June 90 to May 94 was 83%. The results indicate that in the years 94 to 96 twice as much patients received bloodsaving measures. These led to a reduction of homologous blood consumption for 427 units in 1990 to 56 units 1996 (p < 0.001). If three measures, i.e. normovolemic hemodilution, cell saving, and hypotension were combined, the need of blood transfusion was at the minimum level. The effective reduction of homologous blood transfusion by consequent application of bloodsaving measures can with these data obviously be demonstrated.

Optimal timing of repeated rh-erythropoietin administration improves its effectiveness in stimulating erythropoiesis in healthy volunteers.

We studied the effect of recombinant human erythropoietin (rhEPO) on erythropoiesis when given at different time intervals to healthy adults. 15 volunteers were randomly selected to receive rhEPO (2 x 300 U/kg) and parenteral iron (2 x 200mg) either within a 24 h or 72 h interval. Controls received parenteral iron only. Maximum EPO levels were found 24 h after the first intravenous injection (day 1) with a mean value of 364 and 390 U/l for the rhEPO-treated groups. When second rhEPO administration was after 72 h (group III), volunteers showed significantly higher absolute reticulocyte counts and a higher percentage of young RNA-rich reticulocytes (HFR ratio) over several days compared to those who received rhEPO within a 24 h interval (group II). Both rhEPO-treated groups showed an increase in the mean reticulocyte cell volume. Reticulocyte haemoglobin concentration was inversely correlated with the increasing cell size with a nadir on day 8. Reticulocyte haemoglobin content showed a significant decrease in group II after day 5. Serum ferritin levels showed an inverse pattern to the rate of erythropoiesis. After an initial rise, the serum ferritin decrease was most pronounced in group III. Contrary to previous reports with oral iron supplementation, functional iron deficiency was not seen during rhEPO stimulation, due to parenteral iron administration. Our data suggest that the time has interval between repeated administrations of rhEPO has an important influence on its pharmacodynamics. rhEPO given within an interval of 72 h was more effective in stimulating erythropoiesis than administration within 24 h interval for the same total dose.

Recombinant human erythropoietin and parenteral iron in the treatment of pregnancy anemia: a pilot study.

Our aim was to correct severe iron deficiency anemia during pregnancy by using a combination therapy of recombinant human erythropoietin and parenteral iron. Eleven anemic pregnant women were treated once weekly until a hemoglobin value of 11.0 g/dl was reached. Red blood cell production was monitored by reticulocyte flow cytometry and hemoglobin increase. Iron status was assessed by serum ferritin values and transferrin saturation values. 8/11 patients showed an immediate response, noted by a continuous increase of reticulocytes, high fluorescent reticulocyte ratio and hemoglobin levels. Three patients who had lower serum ferritin values, low transferrin saturation and a lower reticulocyte count before treatment showed little response. The combination of rhEPO and parenteral iron is effective in stimulating erythropoiesis and in treating certain pregnancy anemias. This therapy could be an alternative for patients refusing blood transfusions or who are resistant to iron alone. Poor response to the treatment can be due to insufficient iron supplementation during therapy with rhEPO or due to factors that inhibit erythropoiesis during pregnancy, such as undetected infections.