Role of protein kinase C in the modulation of multidrug resistance: expression of the atypical gamma isoform of protein kinase C does not confer increased resistance to doxorubicin.

Cross-resistance to anticancer drugs, termed multidrug resistance (MDR), is functionally associated with the expression of a plasma membrane, energy-dependent, drug efflux pump termed P-glycoprotein (PGP), the product of the mdr1 gene. We have shown previously that MCF-7 breast carcinoma cells transfected with the human mdr1 gene (BC-19 cells) exhibit greater MDR when stably transfected with protein kinase C alpha (PKC alpha). We now demonstrate that transfection of BC-19 cells with the gamma isoform of PKC (BC-19/PKC gamma cells), which is not normally present in BC-19 cells, does not confer increased resistance to doxorubicin, despite a 19-fold increase in PKC activity. All of the increased PKC activity is accounted for by PKC gamma and it is rapidly down-regulated by phorbol dibutyrate, within 15 min of treatment. Endogenous PKC alpha and PKC epsilon activities are not affected by phorbol dibutyrate. The cytotoxicity of doxorubicin was similar in BC-19/neo or BC-19/PKC gamma cells after either 2-hr or continuous drug exposure, and co-treatment with phorbol dibutyrate increased resistance to doxorubicin 4-fold in both cell lines. Phosphorylation of PGP was similar in both cell lines and drug accumulation was not affected by overexpression of PKC gamma. These results demonstrate that transfection of PGP-expressing cells with an atypical isoform of PKC does not confer increased MDR, and they suggest that the regulation of PGP is phenotype specific with respect to the isoform of PKC.     

Review of chemosystematics: multivariate approaches to oral bacteria and yeasts.

There are several problems related to the classification and identification of bacterial and yeast species assigned to the genera Actinobacillus, Haemophilus, Pasteurella, Bacteroides, Prevotella, Porphyromonas, Campylobacter, Wolinella, Treponema, Candida, Torulopsis, and Saccharomyces, most of which belong to the resident oral microflora. The present review was written to demonstrate how multivariate analyses of data on cellular fatty acids, sugars, enzyme activities, and lysis kinetics during ethylenediaminetetraacetic acid (EDTA) and EDTA plus lysozyme treatment can be used to distinguish closely related species of these bacterial and yeast genera. With the exception of the Actinobacillus-Haemophilus-Pasteurella group, fatty acids were more discriminating than sugars. Enzymes from whole cells and outer membrane vesicles also contributed to taxonomic distinction. Apparently, chemosystematics, involving multivariate analyses, is a useful adjunct in oral microbial taxonomy.     

Surgical technique and approaches in orthotopic liver transplantation]

The first clinical experience with orthotopic transplantation of the liver was summarized. Within the period of from February 1990 to May 1991, 8 operations were performed, including one retransplantation of the liver. The peculiarities and variants of surgical technique, general principles of the performance of operation, methods for vascular and biliary reconstruction are presented. After the operation, 3 patients are alive, no surgical complications were observed.     

Review article: controversy in the therapy of gastro-oesophageal reflux disease—long-term proton pump inhibition or laparoscopic anti-reflux surgery?

The treatment of gastro-oesophageal reflux disease is controversial. Whilst medical treatment is successful in patients with mild to moderate disease, the threshold of severity above which an operation should be contemplated remains a matter for debate. Laparoscopic anti-reflux surgery may be lowering this threshold, as this form of therapy provides several advantages over its open counterpart, but it is not without risk, and few long-term results are available. This article reviews treatment options for reflux disease and examines the relative position of current medical and surgical therapies.     

Deliberate departures from good general practice: a study of motives among Dutch general practitioners.

BACKGROUND: When general practitioners (GPs) act contrary to their own standards of good practice, they usually cite patient demands as the main reason. However, up until now, studies have relied on doctors' recollections of departures from their own norms, which may be unreliable. AIM: To systematically explore GPs' motives for deliberate departures from their own conception of good practice. METHOD: Forty-nine GPs, over five days, registered to what extent they had deviated from their own norms, and recorded the motives underlying any deviation. RESULTS: Of the 6087 consultations registered, 10% contained some departure from 'good' general practice, the majority (75%) of which was perceived by the doctor concerned as 'slight'. Doctors underpinned their departures mostly by referring to the doctor-patient relationship: the wish to be nice was used, on average, in 42% of deviations, and the wish to prevent a conflict in 30%. The most important non-relational motive was clinical uncertainty, which doctors used in 11% of their cases. DISCUSSION: Contrary to common belief, GPs often comply with patient requests because they wish to, and not because they feel forced to. Whether or not this behaviour affects the quality of care is largely dependent on the model of 'good' general practice used.     

Patients' experience of epilepsy and health care

OBJECTIVE: The aim of this study was to assess the severity of epilepsy and its effect on patients lives, and to describe patients' use of and attitudes to health care. METHOD: A questionnaire was sent to 595 people with epilepsy identified from 14 general practices in north-west Bristol. All patients aged 16 years and over receiving anti-epileptic medication for their epilepsy were included in the study. Areas investigated included severity of epilepsy and its effect on quality of life, anti-epileptic medication and its perceived effect, health care utilization and preferences for health care. RESULTS: Seizure frequency was strongly associated with adverse effects of epilepsy. Attacks of epilepsy were experienced at least monthly by 20.4% (95% confidence intervals (Cl) 17.0-23.7%) of patients, 29.4% (25.4-33.4%) took more than one anti-epileptic drug, 56.1% (50.1-62.2%) reported drug side effects, 74.1% (70.3-77.8%) would prefer to receive all or most of their epilepsy care in a general practice setting, and 69.8% (63.5- 76.2%) would like contact with a primary care-based epilepsy specialist nurse. During the previous year 42.4% (35.9-48.8%) of patients had not seen a doctor about their epilepsy. Of patients who had attended the general practice only 13.4% (9.6-17.2%) had regular arrangements to see their GP about epilepsy. Patients receiving both primary and secondary care had the greatest needs and wants for improved care. CONCLUSIONS: Structured care, including regular appointments, co-ordination of primary and secondary care, and increased monitoring and discussion, may improve the quality of life of people with epilepsy, but requires evaluation.      

Effects of acute nicotine administration on the function of the human parotid gland

The effect of acute administration of nicotine on the secretory function of the human parotid gland was investigated in 4 male volunteers. After intravenous infusion of 20 micrograms nicotine/kg b.w. within 10 min in all subjects an increased salivary amylase activity and protein concentration was observed. This phenomenon is believed to be caused by a stimulation of parotid beta-adrenoceptors secondary to a nicotine-induced release of catecholamines from the adrenals.