Serous effusion cytology in gynecologic malignant mixed müllerian tumors.

We reviewed 51 serous effusions (50 peritoneal/one pleural) from 38 patients with uterine (30 cases) and ovarian (eight cases) malignant mixed Müllerian tumors (MMMT). There were 16 patients (42%) with positive effusion cytology specimens; 13 cases (81%) were diagnosed as adenocarcinoma with three cases (19%) interpreted as having a sarcomatous component. Eight of 16 positive effusion specimens had cell block material available for immunoperoxidase (IP) study that included cytokeratin (AE1/3), vimentin, muscle specific actin (HHF) and S-100 protein to determine if unsuspected mesenchymal components were present in the cases originally diagnosed as carcinoma (six cases), or sarcomas (two cases). In the six cases originally interpreted as carcinoma, three were diagnosed as adenocarcinoma and three as poorly differentiated carcinoma. All three of the cases considered adenocarcinoma and two of those diagnosed as poorly differentiated carcinoma reacted only with AE1/3 and vimentin. The remaining case, considered a poorly differentiated carcinoma, stained only with vimentin. In the two cases having cell blocks interpreted as having a sarcomatous component, only vimentin was positive in one while AE1/3, vimentin, HHF, and S-100 were positive in the other. The case where all immunohistochemical stains were reactive contained both carcinomatous and sarcomatous components. In the three cases considered sarcomatous, the cytomorphologic features helpful in the recognition of a mesenchymal component included a dissociated smear pattern of pleomorphic round to oval cells and/or spindle cells. In retrospect, the IP stains did not alter any of the original diagnoses.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical and pharmacological properties of new tetrahydropyrimido-[2,1-f]-purines.

Following a research program on piperazinoalkyl-substituted tricyclic purines, a number of N-9-aryl(alkyl)-piperazinopropyl substituted tetrahydropyrimido-[2,1-f]-purines were synthesized and tested pharmacologically with respect to their influence on the central nervous system. Two of the new compounds induced hypothermia and decreased the spontaneous locomotor activity of mice.

Synthesis and pharmacological screening of novel 10-substituted diazepino-[2,1-f]-purines.

Two series of N10 substituted derivatives of 1,3-dimethyl-2,4,9-trioxo-1,3,6,7,8,10-hexahydro-1,3-diazepino+ ++-[2,1-f]- purine and 1,3-dimethyl-2,4-dioxo-1,3,6,7,8,9-hexahydro-10H-1,3-dizepino- [2,1-f]-purine were synthesized and tested for CNS activity. The most active in central nervous system tests were compounds [II] and [XIV].

Synthesis and preliminary pharmacological assessment of novel gamma-hydroxybutyric acid derivatives.

Synthesis and properties of new N-substituted amides of alpha-(1,1-ethylenedioxy)-ethyl-gamma-hydroxybutyric acid are described. The compounds were obtained by aminolysis of 3-(1,1-ethylenedioxy)-ethyltetra-hydrofuran-2-on with primary alkylarylamines. Preliminary pharmacological assessment revealed that the compounds exert weaker influence on the central nervous system than the reference gamma-hydroxybutyric acid. Three of the novel compounds offered some protection against pentetrazole-induced tonic seizures in mice.

Synthesis and preliminary pharmacological assessment of novel 9-substituted pyrimidino-[2,1-f]-purines.

Synthesis, chemical properties and results of preliminary pharmacological evaluation of several new 9-substituted pyrimidino-[2,1-f]-purines are described. The most interesting was 1,3-dimethyl-2,4,8-trioxo-9-[gamma-N1-(N4-C6H5)-piperazynopropy l]-1,3,6,7-tetrahydro-9H-pyrimidino-[2,1-f]-purine (compound 4a), which exerted strong sedative, hypothermizing and cataleptogenic action and possessed some anti-amphetamine and anti-apomorphine properties.

The influence of new 9-(omega-[4-(2-pyrimidinyl)-1-piperazinyl]alkyl) pyrimidino[2,1-f]purines on the central nervous system.

Synthesis and the results of preliminary pharmacological evaluation of four new 9-substituted pyrimidino[2,1-f]purines, containing pyrimidinyl-piperazine substituent are described. Some of these substances induced hypothermia, antagonism of amphetamine action and neurotoxic effects. All compounds had weaker activity on the central nervous system than previously studied compounds containing phenyl-piperazine substituent.

Veno-occlusive disease of the liver induced by low-dose cyclophosphamide.

A 2-yr-old child with idiopathic pulmonary hemosiderosis and autoimmune thrombocytopenia developed hepatic veno-occlusive disease after being treated with long-term, low-dose cyclophosphamide. The authors believe that the injury was induced by cyclophosphamide. Although transplant dosages of cyclophosphamide alone or in conjunction with other drugs have been shown to induce hepatic venocclusive disease, this is the first case of hepatic venocclusive disease associated with nontransplant dosages of cyclophosphamide. Histopathologically, the injury was characterized by occlusive lesions of intrahepatic veins, both the terminal hepatic venules and portal veins branches, together with necrosis (predominately involving Zones 3 and 2) and hemorrhages. An added risk factor could have been release of platelet-derived growth factor that in turn activated and promoted proliferation of fibroblasts and smooth muscle cells in the vessels. Previously reported cases of cyclophosphamide-related injury are reviewed.

Synthesis and preliminary pharmacological screening of some 8-substituted methylxanthines.

Methods of synthesis, chemical properties and results of preliminary pharmacological screening for 8-amino substituted derivatives of caffeine (1-3) and 7,8-disubstituted derivatives of 8-aminotheophylline (8-12) have been described. The compounds show weak sedative and antidepressive activity and some of them (2, 10, 12) also small antinociceptive effect.

Synthesis and preliminary pharmacological assessment of novel 9-alkylamino substituted pyrimidino-[2,1-f]-purines.

Two series of N9-alkylaminomethyl-, alkylpiperazino-, alkylpiperidino-substituted 1,3-dimethyl-(hexahydropyrimidino)- and (tetrahydropyrimidono)-[2,1-f]-purines were prepared and their physicochemical and pharmacological properties were described. The most active in central nervous system tests were the compounds with phenylpiperazinealkyl substituent i.e. 1,3-dimethyl-2,4-dioxo-9-[N1N4-(phenyl)-piperazinopropyl]-1, 3,6,7,8,9- hexahydropyrimidino-[2,1-f] purine 6a and its butyl and isobutyl homologs 9 and 12. The compounds depressed statistically significantly spontaneous locomotor and amphetamine activity and showed sedative, analgetic and hypothermizing properties.