Biomedical subjects

S Nordqvist

Publications and source records attributed to S Nordqvist.

14 recordsLinked to original sources

PubMed1982

Combination chemotherapy of the epipodophyllotoxin derivatives, teniposide and etoposide. A pharmacodynamic rationale?

Previous studies in vitro on the influence of extracellular protein binding of Teniposide (VM26) and Etoposide (VP16-213) on subsequent cellular uptake by experimental murine tumor cells [Cancer Res 38:2549 (1978); Drug Metab Rev 8:119 (1978)] suggested that a timed-sequential combination of VM26 and VP16-213 may increase the bioavailability of VP16-213. This was studied clinically in six cancer patients with ascites (five ovarian, one rectal) whereby VM26 (20 mg/m2) was given i.p. 2 h prior to VP16-213 (100 mg/m2; i.p.) In some patients, this regimen was administered i.v. The i.v. regimen was found to be more toxic (myelosuppression, nausea, vomiting) than i.p. regimen at same doses of drugs. Several patients remained stable to disease during 1-2 courses of therapy (3 weeks per course), one patient had partial remission, and has been stable in her disease for more than 4 months. In two patients, plasma and ascites fluid was analyzed for VP16-213 and VM26 by a new reverse-phase high performance liquid chromatography method. Both VM26 and VP16-213 could be eluted isocratically (28% v/v acetonitrile in water) from a c18 column with retention times of 6.6 and 13.3 min, respectively. Subsequent pharmacokinetic analysis of one patient suggests that protein binding displacement of VP16-213 in plasma and perhaps ascites fluid increased the pharmacokinetic volume of distribution (28 l) and reduced the elimination half-life (12 h). The data suggests that VP16-213 is distributed more widely in the body and is represented by a single compartment pharmacokinetic model. Analysis of VM26 in ascites and plasma suggests that the so-called "deep pharmacokinetic compartment" represents ascites equivalent space and that the plasma concentration represents VM26 as free and protein-bound drug in kinetic distinguishable compartments. Determinants of drug action are potentially composed of a multiplicity of physiological, biochemical, and other factors. The potential for manipulating the pharmacodynamic properties of drugs to achieve greater therapeutic potential needs further study.

Adult↗

PubMed1979

Tumor-bound immunoglobulin in human gynecologic cancers.

By the use of immunofluorescence techniques, immunoglobulin of the IgG class was consistently found in touch preparations and in frozen sections of squamous cell carcinomas of the uterine cervix (both keratinizing and nonkeratinizing) and in an adenosquamous cell carcinoma of the cervix, an adenocarcinoma of the cervix, a mixed mesodermal-uterine tumor, and a uterine adenocarcinoma metastasized to the ovaries. Trace amountsof IgM were found in 1 squamous cell carcinoma and in 1 adenocarcinoma of the cervix. Except for 1 tumor specimen consisting primarily of infiltrating lymphocytes that stained positive for human IgG, IgM, IgA, and C3, the tumors were consistently negative for IgA and C3. Specimens made from normal cervical tissue were uniformly negative for all immunoglobulins and complement. Positive staining for human IgG could be eliminated by incubation of the tumor preparations with unconjugated goat antihuman IgG before the preparations were stained with fluorescein isothiocyanate-conjugated goat antihuman IgG. Attempts to elute the tumor-bound IgG with glycine-HCl buffer (pH 2.2) were most successful with the use of unfixed tissue, although the positive staining for IgG could not be entirely eliminated. The elution effects of the low-pH buffer on tissue fixed over 2 hours in 10% Formalin were minimal.

Adenocarcinoma↗

PubMed1977

A procedure for dissociating Ayre scrape samples.

The dissociation of cervical cell suspensions after various chemical and enzymatic treatments was monitored by using the Centrifugal Cytology rotor to produce glutaraldehyde-fixed dispersions on conventional microscope slides and subsequent Pap staining. A special program was written in RPG II to record and analyze the results of the dissociation experiments in terms of white blood cells and the true cervical cells ("other cells"), and the degree of dissociation and recovery of both classes of cells. Since accurate differential counts on the untreated Ayre scrapes were difficult, the samples were syringed gently to break up the large or adventitious clumps. Cumulated results from control preparations indicate that the white blood cells and "other cells" are composed respectively of 92 and 63% single cells. The cells were further dissociated by: dissolving the cervical mucin sequentially with dithiothreitol and iodoacetic acid; depolymerizing the nucleohistone gel with ribonuclease; solubilizing the desmosomes with EDTA; removing the remaining cellular agglutinins with Varidase; and finally mechanical dispersion by hypertonic shock. The optimum procedure for dissociation involves the use of ribonuclease, dithiothreitol, iodoacetic acid EDTA, Varidase and sucrose shock. The white blood cells are now monodisperse and 81% of the "other cells" are found as single cells. If nuclear separation by two diameters is considered sufficient 98% of the "other cells" are single. The slide preparations are now sufficiently good that a scanning system is feasible.

Autoanalysis↗

PubMed1977

Optimization of the binding of dissociated exfoliated cervico-vaginal cells to glass microscope slides.

In order to monitor the development of a cell dissociation technique, it was essential to utilize the Centrifugal Cytology rotor to produce glutaraldehyde-fixed even cellular dispersions. The Cytology rotor has been improved to insure rapid alignment with the centrifugal field during both acceleration and deceleration, and the fixative is now delivered to the surface of the slide. The dissociation of the cells results in a loss of their adhesion to glass slides. Three bonding agents were tested: (a) Poly-L-Lysine; (b) Mayer's albumin fixative; (c) positively charging the slides with a silicone coating. The results with 65% albumin-coated slides were clearly superior to the other two. The addition of a postfixation step of 95% ethanol/4% polyethylene glycol did not significantly affect the recovery of the cells, but did eliminate some unevenness in the Centrifugal Cytology preparations, flattened the cells and expedited the procedure.

Albumins↗

PubMed1973