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Biomedical subjects

M C Miller

Publications and source records attributed to M C Miller.

At least 181 records · Page 10Linked to original sources
PubMedDate not supplied

Talisman or taboo: the controversy of the suicide-prevention contract.

The suicide-prevention contract is a widely used but overvalued clinical and risk-management technique. The scant information on this topic in the psychiatric and mental health literature is reviewed, along with the literature on collateral subjects including suicide prediction, medicolegal aspects of treating suicidal patients, the therapeutic alliance, and countertransference with suicidal patients. A group of 112 psychiatrists and psychologists was surveyed about their use of suicide-prevention contracts; the majority of them had never received any formal training on the topic. A combination of factors--the unpredictability of suicide, the many different antecedents to completed suicides, the complex psychological reactions of clinicians (including fear of litigation), the incongruity between clinical and legal usages of the contract concept, and the hazards that come of collapsing a complex treatment process into a few words--limit the applicability of suicide-prevention contracts. We reason that the use of these contracts is based upon subjective belief rather than on objective data or formal training. We recommend an alternative approach to suicide risk management rooted in the well-known and well-defined principles of informed consent.

Communication↗
PubMedDate not supplied

In vitro evaluation of combination chemotherapy against human tumor cells (Review).

Combination therapy with multiple drugs or with multiple modalities is common practice in the treatment of cancer. The purpose of using drugs in combinations is to increase the therapeutic efficacy, decrease toxicity toward the host and minimize or delay the development of drug resistance. Presently used clinical protocols for cancer combination therapy are mainly obtained empirically or from clinical trials. Accumulation of experience from clinical trials is invaluable but is a slow and expensive process. Also, due to heterogeneous patient populations exposed to different environments, human clinical data frequently cannot be used for quantitative synergy determinations. Therefore, in vitro quantitative drug combination studies with cultured tumor cells are becoming imperative either as prospective studies or as adjuvant assessment for combination therapy. In recent years, a variety of in vitro assays have been developed to examine cytotoxicity or biochemical effects of drugs on cultured tumor cells. These methods can, not only quickly predict the potential therapeutic effects of the combined agents, but also provide the information or clues to the possible mechanisms of drug interactions. In addition, with the better understanding of various antineoplastic drugs and the development of new technologies to characterize actions of the drugs, the in vitro study of combination therapy is no longer limited to the measurement of cytotoxic effects. Instead, many other studies, such as cell cycle analyses, detection of apoptosis and biochemical analyses of drug interactions have also become common methods for the in vitro evaluation of combination drug therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Retention is the goal: extinguish burnout with self-esteem enhancement.

This article presents dialogues and selected strategies intended to enhance self-esteem and lessen burnout. While the article focuses on the dialogues and the strategies, it is necessary to begin with a brief discussion of self-esteem and burnout to make the connection between the two clear. The existing relationship between self-esteem and burnout contributes to the current nursing shortage. Among the reasons contributing to the nursing shortage is the exodus of nurses who have experienced or are experiencing burnout. This article guides nurses through a series of dialogues and strategies that, when practiced, will enhance self-esteem and decrease burnout by increasing job satisfaction for nurses.

Burnout, Professional↗
PubMedDate not supplied

Antineoplastic activities and cytotoxicity of 1-acyl and 1,2-diacyl-1,2,4-triazolidine-3,5-diones in murine and human tissue culture cells.

1-Acyl- and 1,2-diacyl-1,2,4-triazolidine-3,5-diones were found to be potent cytotoxic agents in murine and human cancer cell lines, e.g. L1210, P388, Tmolt3, colon adenocarcinoma, Hela cells and glioma. In vivo activity was demonstrated at 8 mg/kg/day against Ehrlich ascites carcinoma growth. In L1210 cells, 1-acetyl-4-phenyl-1,2,4-triazolidine-3,5-dione, 41, reduced DNA synthesis significantly with moderate reduction in RNA synthesis. Enzyme sites in L1210 cells which were markedly affected were m- and r-RNA polymerase, PRPP amidotransferase, IMP dehydrogenase, dihydrofolate reductase, thymidine, TMP and TDP kinases. Kinetic studies suggest the inhibition of rate limiting enzymes in the purine pathway by 41 was responsible for its cytotoxicity. Acute toxicity studies in mice indicated 41 was safe for therapeutic use at 20, 50, and 100 mg/ky/day.

Acylation↗
PubMedDate not supplied

The cytotoxicity of 3'-aminocyanoborane-2', 3'-dideoxypyrimidines in murine and human tissue cultured cell lines.

3'-Aminocyanoborane-2', 3'-dideoxythymidine (VIIa) and 3'-aminocyanoborane-2', 3'-dideoxyuridine (VIIIb) were successfully synthesized. The thymidine derivative (VIIIa) was shown to be a potent cytotoxic agent in murine and selected human suspended and solid tumor cell lines. Compound VIIIa inhibited L-1210 leukemia DNA and RNA synthesis with the protein synthesis requiring a higher concentration of drug for inhibition within 60 min. The purine pathway appeared to be the major target of Compound VIIIa with inhibition of IMP dehydrogenase and dihydrofolate reductase activities. The compound affected metabolic enzyme activities in the pyrimidine pathway as well as the nucleoside kinase activities. The DNA molecule did not appear to be target of the 3'-aminocyanoborane-2', 3'-dideoxythymidine (VIIIa), in that there was no change in ct-DNA viscosity, thermal denaturation or absorption of nucleosides of DNA nor was there any L-1210 DNA strand scission or inhibition of L-1210 DNA topoisomerase II activity when compound VIIIa was incubated at 100 microM.

Animals↗
PubMedDate not supplied

The cytotoxic activity of 1-acyl- and 1,2-diacyl-4,4-diethyl-3,5-pyrazolidinediones.

The 1-acyl- and 1,2-diacyl-4,4-diethyl-3,5-pyrazolinediones proved to be cytotoxic against the growth of a number of cell lines, including murine and human leukemias. HeLa suspended carcinoma, colon adencarcinoma SW480, KB nasopharynx and glioma tumors. Selected compounds were also active in the human lung bronchogenic MB-9812, and osteosarcoma TE418 screens. These derivatives were active in vivo in the Ehrlich ascites carcinoma screen in CF-1 mice at 8 mg/kg/day I.P. The mode of action in Tmol3 leukemia cells showed that the compounds reduced de novo synthesis of purines and pyrimidines and inhibited dihydrofolate reductase and ribonucleoside reductase activities. The DNA molecule was not a target although limited DNA strand scission may be possible.

Adenocarcinoma↗
PubMedDate not supplied

Cytotoxicity of ribo-and arabinoside boron nucleosides in tissue culture cells.

Ribose and arabinoside boron nucleoside derivatives were shown to be potent cytotoxic agents in murine and human suspended and solid tumor cell lines. The arabinoside derivative inhibited DNA and RNA synthesis with the protein synthesis requiring a higher concentration of drug for inhibition within 60 min. The purine pathway appeared to be the major target of the arabinoside 1 with inhibition of PRPP amido transferase and IMP dehydrogenase activities. Blockage of this pathway afforded reductions of deoxyadenosine and deoxyguanosine nucleotide pools. The DNA template did not appear to be target of the arabinoside 1, in that there was no change in DNA viscosity, thermal denaturation or absorption of nucleosides of DNA. However, compound 1 when incubated with L-1210 cells for 24 hr. showed a slight shift of the DNA in the gradient and moderate inhibition of ct-DNA topoisomerase II was demonstrated by 1 in vitro.

Animals↗