Routine hysteroscopy for patients with a high risk of uterine malignancy

Seventy patients with abnormal vaginal bleeding were examined with a Storz hysteroscope. The examination took an average of only 5 min. Sixty patients had the examination under general anaesthesia, five under paracervical block and five had no form of anaesthesia. All tolerated the procedure well. There were no complications directly related to the hysteroscopic examination. There was complete correlation between the histology of the endometrium obtained at subsequent curettage and the hysteroscopic findings.     

Conjunctival granuloma caused by surgical talc.

Talc from surgical gloves has been known to be a cause of granulomas within the surgical cavity. We report a case in which recurrent conjuntival inflammation was found to be caused by talc.     

Adrenergic and purinergic neurotransmission in arterial resistance vessels of the cat intestinal circulation

The contribution of adrenoceptors and purine receptors in mediating neurogenic vasoconstriction was investigated in the autoperfused intestinal circulation of anaesthetised cats treated with atropine and propranolol. Prazosin (0.5 mg/kg) and yohimbine (1.5 mg/kg) reduced but did not abolish the vasoconstrictor responses to stimulation of the efferent sympathetic nerves. The inhibitory actions of the two antagonists were additive but even after alpha 1- and alpha 2-adrenoceptor blockade nerve stimulation still elicited a residual, frequency-related vasoconstriction. The initial, rapid, phase of this response was completely abolished after desensitisation of P2x-purinoceptors with a high dose (1.5 mg i.a.) of alpha,beta-methylene ATP. In the absence of alpha-adrenoceptor antagonists, alpha,beta-methylene ATP reduced neurogenic vasoconstriction particularly at low frequency (1 Hz) nerve stimulation, but also caused a short-lasting decrease in noradrenaline and methoxamine responses which indicates that the drug may have some non-specific effects on arterial smooth muscle. The results suggest that neurotransmission in arterial resistance vessels of the cat intestinal circulation is predominantly under adrenergic control mediated by postsynaptic alpha 1- and alpha 2-adrenoceptors, with a possible purine involvement in the initial rapid response of the blood vessels, particularly to low frequency nerve stimulation.     

Different mechanisms of decreased drug accumulation in doxorubicin and mitoxantrone resistant variants of the MCF7 human breast cancer cell line.

We selected two drug resistant variants of the MCF7 human breast cancer cell line by chronic in vitro exposure to doxorubicin (MCF7/D40 cell line) and mitoxantrone (MCF7/Mitox cell line), respectively. The cell lines are similar in growth characteristics including doubling time, DNA synthetic phase and cell size. Resistance to mitoxantrone conferred only partial resistance to doxorubicin; whereas resistance selected for doxorubicin appeared to confer complete resistance to mitoxantrone. Both agents selected for cross resistance to the Vinca alkaloids. MCF7/D40 cells display a classic-multi-drug resistance phenotype with expression of P-glycoprotein, decreased drug accumulation relative to the parental line and reversal of drug accumulation and drug resistance by verapamil. MCF7/Mitox cells likewise display resistance to multiple drugs, but in contrast to MCF7/D40 cells do not express P-glycoprotein by immunoblot or RNA blot analysis. Net drug accumulation in MCF7/Mitox cells was decreased relative to the parental cells but there was no selective modulation of drug accumulation or in vitro drug resistance by the addition of verapamil. Efflux of mitoxantrone was enhanced in both the MCF7/D40 and MCF7/Mitox cell lines relative to the MCF7/S cell line. We conclude that the two drug resistant cell lines have different mechanisms of decreased drug accumulation.     

Plasma lyso-phosphatidylcholine concentration is decreased in cancer patients with weight loss and activated inflammatory status

Background  

It has been observed that ras-transformed cell lines in culture have a higher phosphatidylcholine (PC) biosynthesis rate as well as higher PC-degradation rate (increased PC-turnover) than normal cells. In correspondence to these findings, the concentrations of the PC-degradation product lyso-phosphatidylcholine (LPC) in cancer patients were found to be decreased. Our objective was the systematic investigation of the relationship between LPC and inflammatory and nutritional parameters in cancer patients. Therefore, plasma LPC concentrations were assessed in 59 cancer patients and related to nutritional and inflammatory parameters. To determine LPC in blood plasma we developed and validated a HPTLC method.     

Physiologically based pharmacokinetic modeling of the pregnant rat: a multiroute exposure model for trichloroethylene and its metabolite, trichloroacetic acid

A physiologically based pharmacokinetic (PB-PK) model was developed to describe trichloroethylene (TCE) kinetics in the pregnant rat exposed to TCE by inhalation, by bolus gavage, or by oral ingestion in drinking water. The kinetics of trichloroacetic acid (TCA), an oxidative metabolite of TCE, were described by a classical one-compartment pharmacokinetic model. Among the required model parameters for TCE, partition coefficients (PCs) and kinetic constants for oxidation were determined by vial equilibration and gas uptake methods, respectively. The fat:blood PC was 33.9; the blood:air PC was 13.2; and the fetal tissue:fetal blood PC was 0.51. TCE was readily metabolized with high substrate affinity. In naive and pregnant female rats the maximum velocities of oxidative metabolism were 10.98 +/- 0.155 and 9.18 +/- 0.078 mg/kg/hr, while the estimated Michaelis constant for the two groups of rats was very low, 0.25 mg/liter. The first-order rate constant for oral absorption of TCE from water was 5.4 +/- 0.42/hr-1 in naive rats. With TCA, the volume of distribution (0.618 liter/kg) and the plasma elimination rate constant (0.045 +/- 0.0024/hour) were estimated both from intravenous dosing studies with TCA and from an inhalation study with TCE. By comparison of the two routes of administration, the stoichiometric yield of TCA from TCE was estimated to be 0.12 in pregnant rats. To develop a data base for testing the fidelity of the PB-PK model, inhalation and bolus gavage exposures were conducted from Day 3 to Day 21 of pregnancy and a drinking water exposure from Day 3 to Day 22 of pregnancy. Inhalation exposures with TCE vapor were 4 hr/day at 618 ppm. The TCE concentration in drinking water was 350 micrograms/ml and the gavaged rats received single daily doses of 2.3 mg TCE/kg. Time varying physiological parameters for compartment volumes and blood flows during pregnancy were obtained from the published literature. Using the kinetic parameters determined by experimentation, TCE concentrations in maternal and fetal blood and TCA concentrations in maternal and fetal plasma were predicted from the PB-PK model by computer simulation and compared favorably with limited data obtained at restricted time points during pregnancy for all three routes of exposure. On the basis of the PB-PK model, fetal exposure to TCE, as area-under-the-curve, ranged from 67 to 76% of maternal exposure. For TCA the fetal exposure was 63 to 64% of the maternal exposure. The fetus is clearly at risk both to parent TCE and its TCA metabolite.(ABSTRACT TRUNCATED AT 400 WORDS)     

Moderate drinking in ex-alcoholics: recent studies

The literature on the occurrence of moderate drinking in ex-alcoholics that has been published since the Rand report in 1976 is reviewed. Although differences in diagnosis, definitions of moderate drinking and length of follow-up make strict comparisons of the studies difficult, the majority of studies seem to indicate that the earlier reports of the frequency of such moderate drinking may be overly optimistic. Depending on the definition of moderate drinking that is used, the longer the interval required for alcoholics to sustain moderate, problem-free drinking, the less likely is such an outcome. Among treated alcoholics, the percentage probably ranges from about 2 to 12%; the percentage may be higher among alcoholics identified in community population samples. Thus far, the only factor common to alcoholics who are able to achieve moderate drinking is their being mild cases (i.e., having fewer lifetime alcohol-related problems than other alcoholics). Factors pertinent in assessing discrepancies between the various studies are discussed.