Differential uptake of estramustine phosphate metabolites and its correlation with the levels of estramustine binding protein in prostate tumor tissue

Estracyt (EMP) has been used for the treatment of hormone refractory prostate cancer for many years. Recently, new data from combination studies have given rise to new interest in this old drug. Explanations for the synergy found in the clinic are many, but one major factor may be the previous indication that the drug accumulates in the prostate tumor. We have, therefore, examined the level of the four metabolites, estromustine (EoM), estramustine (EaM), estrone, and estradiol in the tumor and serum of 14 patients with T2 and T3 prostate cancer receiving a single i.v. dose of 600 mg of EMP, about 12 h before radical prostatectomy. Because it has been suggested that the uptake into the prostate tumor is due to binding to the estramustine binding protein (EMBP), we have in addition measured the level of EMBP in the prostate tumor tissue. The main serum and tissue metabolite in all patients was EoM followed by EaM, estrone, and estradiol. The levels for EoM ranged from 63.8-162.8 ng/ml in the serum and from 64.8-1209 ng/ml in the prostate tumor, resulting in a mean ratio for serum to tumor of 1:5. The levels for EaM ranged from 8.3-51.4 ng/ml in the serum and 73.9-563.4 ng/ml in the tumor, giving a mean ratio for serum to tumor of 1:13. The levels of EMBP were higher in T3 tumors than in T2 tumors, 54.1 and 40.7 ng/g tissue, respectively. A significant correlation was found between the levels of EaM (r = 0.60) and the levels of EMBP in the tumor. These data demonstrate that 12 h after a single i.v. dose of 600 mg of EMP the levels of the cytotoxic metabolites EoM and EaM are substantially higher in the tumor than in the serum of the same patient and that a correlation exists between the levels of EaM in the tumor and the levels of EMBP. Thus, this supports the hypothesis that the EMBP is responsible for the retention of EoM and EaM in the prostate tumor.     

Groundwater pollution in porous media by fluids immiscible with water

The principle of migration of fluids immiscible with water in porous rocks is demonstrated by means of mineral oil products and chlorohydrocarbons.     

Splenic imaging with 99mTc-labeled erythrocytes: a comparative study of cell-damaging methods

Several methods of damaging red blood cells (RBCs) for splenic imaging were compared to determine the optimum approach. The RBCs from donor animals were labeled with 99mTcO4- and damaged by heat, excess acid citrate dextrose (ACD), excess Sn(II) ion, or the sulfhydryl inhibitors N-ethylmaleimide (NEM) or p-hydroxymercuribenzoate (PMB). The organ distributions of undamaged and damaged RBCs were determined in rats, and splenic imaging studies were performed in rabbits. Splenic deposition and spleen-to-liver ratios with heat- or sulfhydryl-damaged 99mTc-RBCs were significantly greater (p less than 0.001) than the values obtained using ACD or Sn(II) ion. Heat-damaging produces good splenic localization of 99mTc-RBCs but requires rigidly controlled incubation conditions. NEM-damaging provides an excellent and predictable alternative approach.     

The role of upstream U3 sequences in the pathogenesis of simian immunodeficiency virus-induced AIDS in rhesus monkeys

The nef reading frame overlaps about 70% of the U3 region of the 3' long terminal repeat (LTR) in primate lentiviruses. We investigated the functional role of these overlapping U3 sequences by analyzing the properties of three mutant forms of the pathogenic SIVmac239 clone. In mutant UScon, 90 of 275 bp in the upstream sequences (US) of U3 were changed in a conservative fashion without changing the predicted nef coding sequence. In mutant USnon, 101 of 275 bp in this region were changed in a nonconservative fashion, again without changing the predicted nef coding sequence. In mutant delta US, 275 bp in this region were deleted. Full-size, immunoreactive nef protein was synthesized in cells infected with the UScon and USnon mutants. The USnon and delta US mutants replicated with similar kinetics and to similar extents as wild-type, parental SIVmac239 in primary rhesus monkey peripheral blood mononuclear cell (PBMC) cultures. The UScon mutant replicated with slightly delayed kinetics in rhesus monkey PBMC cultures. In the CEMx174 cell line, the delta US mutant replicated similarly to the wild type, but the UScon and USnon mutants replicated with significantly delayed kinetics. Analysis of LTR-driven chloramphenicol acetyltransferase (CAT) activity and the effects of 5-azacytidine on virus replication suggested that the growth defect of the point mutants in CEMx174 cells was due in whole or in part to the introduction of multiple CG methylation sites in proviral DNA. Rhesus monkeys were experimentally infected with the UScon and USnon mutants, and the characteristics of the infection were compared with those of the parental SIVmac239. Analysis of the levels of plasma antigenemia, virus load, and CD4+ cells in PBMC revealed no decreased virulence of the mutant viruses. Analysis of lymph node biopsies taken from animals that received mutant viruses revealed histologic changes and levels of virus expression indistinguishable from those of the wild type. Furthermore, the wild-type behavior of the mutant viruses in rhesus monkeys occurred without any specific reversional events through at least 20 weeks of infection. These results, and the recent results of Kirchhoff et al. (F. Kirchoff, H. W. Kestler III, and R. C. Desrosiers, J. Virol. 68:2031-2037, 1994), suggest that these upstream sequences in U3 are primarily or exclusively nef coding sequence.     

Effect of cyclosporine on immune responses in submaxillary lymph nodes of pituitary-grafted rats

This work was undertaken to analyze the interrelationships between prolactin and cyclosporine in affecting immune responsiveness in submaxillary lymph nodes. Male rats received an anterior pituitary graft within breast muscles on day 5, or under the kidney capsule, on day 30 or 60 of life. On day 70 (rats operated on day 5 or 30) or on day 100 (rats operated on day 60) animals were injected with Freund's complete adjuvant and cyclosporine (5 mg/kg for 5 days), and were killed 2 days after immunization. Natural killer (NK) activity in submaxillary lymph node decreased in neonatally pituitary-grafted rats and increased in rats grafted on day 30 or 60, as did lymph node cellularity. Lipopolysaccharide (LPS)- and concanavalin A (ConA)-induced proliferation diminished in lymph nodes of rats grafted on day 30 or 60, respectively. Cyclosporine treatment diminished lymph node cell number and NK activity and increased the proliferative response to ConA. Cyclosporine depressive effect on lymph node cellularity was counteracted by the presence of a pituitary graft, as were the inhibition of NK activity and the stimulatory effect on ConA-induced cell proliferation. In pituitary-grafted rats, cyclosporine decreased submaxillary lymph node LPS-induced proliferation. Cyclosporine decreased the high circulating prolactin levels found in pituitary-grafted rats. The results are compatible with age-dependent, inhibitory and promoting activities of hyperprolactinemia on immune responses in lymph nodes, affected in a complex antagonistic and synergistic way by cyclosporine immunosuppression.     

New technique for lesser saphenous vein harvesting

A new technique using the Thompson self-retaining retractor system (Thompson Surgical Instruments, Inc, Traverse City, MI) to harvest lesser saphenous veins is presented. This modification, used in 10 patients undergoing redo myocardial revascularization, provided a rapid, comfortable, and convenient method for harvesting lesser saphenous veins.     

Electron paramagnetic resonance studies of cobalt-substituted angiotensin I-converting enzyme

The traditional treatment of high-flow vascular malformations consists of selective embolization, surgical removal, or a combination of both. Recurrence of the lesion and bleeding control are still the main problems, and the result of treatment is sometimes disappointing. We suggest treatment of these lesions with surgical ligation of the distal major feeding arteries followed by intravascular injection of a sclerosing agent (3% tetradecyl sulfate), and surgical excision and reconstruction when indicated. We have found this to be an effective treatment regimen. We present 14 cases of high-flow vascular malformations of the head and neck area treated with this approach, of which 4 cases developed skin necrosis. Three of these 4 cases of skin necrosis were later treated with skin grafting and, in 1 case, an upper arm skin tube flap was used for nasal tip reconstruction. Three cases underwent delayed reconstruction using tissue expanders. From a symptomatic and aesthetic point of view, preliminary satisfactory results were obtained. We feel that this approach is a good option for treating difficult, high-flow vascular malformations.     

Teleradiology by two different concepts. Technical note

Two different teleradiology concepts are described. Their advantages, disadvantages and costs are discussed.