Measurement of in vitro cellular pharmacokinetics of 5-fluorouracil in human and rat cancer cell lines and rat hepatocytes using a flow-through system

Summary A flow-throught system was used to study the cellular pharmacokinetics of 5-fluorouracil (5-FU) in four human cell lines (squamous-cell carcinoma HEp-2, colon carcinoma WiDr, hepatoma Hep G2, and breast carcinoma MCF-7) as well as in the rat hepatoma H35 cell line and in freshly isolated rat hepatocytes. The system made it possible to restrict the decrease in the concentration of 5-FU in the medium, to keep the volume in which the metabolites accumulated relatively small, and to study the dynamics of a response during and after a change in the composition of the eluent. Clearance of 5-FU from the eluent was achieved predominantly (>95%) by its catabolism to dihydrofluorouracil in the tumor cell lines and to 2-fluoro--alanine in the hepatocytes. Not only rat hepatocytes but also HEp-2 cells showed relatively high clearance values. A concentration-dependent 5-FU elimination was observed, indicating saturation of 5-FU elimination according to Michaelis-Menten kinetics (K_m 14–22 M). The maximal velocity (V_max) values ranged from 0.025 to 0.13 nmol 5-FU/10⁶ cells per minute. For HEp-2 cells, high-concentration pulse injections of 5-FU, thymine, uridine, or uracil immediately led to a reduction in 5-FU conversion, followed by recovery within 5 min. The flow-through system proved to be adequate for the study of the non-linear pharmacokinetics of 5-FU in different intact cells and for the comparison of various manipulations of these pharmacokinetics.Abbreviations 5-FU 5-fluorouracil - FUR 5-fluorouridine - F-DHU dihydrofluorouracil - F--ala 2-fluoro--alanine - F-UPA -fluoroureidopropionic acid - HEPES 4-(2-hydroethyl)-1-piperazine-ethane sulfonic acid - MEM modified minimal essential medium - HBSS Hanks' balanced salt solution - HPLC high-performance liquid chromatography Supported by grant IKA 87-16 from the Netherlands Cancer Foundation. One author (G. J. P.) is the recipient of a senior research fellowship from the Royal Netherlands Academy of Arts and Sciences (KNAW)     

Psychisch Kranke: Gesehen aus zwei verschiedenen Perspektiven Ein methodischer Beitrag zur Einstellungsforschung in der Psychiatrie

Zusammenfassung Anhand von Daten aus zwei Bevölkerungsumfragen zur Einstellung gegenüber psychisch Kranken wird untersucht, welchen Einfluss die Variation der Perspektive-die des Befragten selbst versus die der anderen-auf das Befragungsergebnis hat. Wie erwartet fällt das Urteil über psychisch Kranke positiver aus, wenn nach der eigenen Meinung gefragt wird, als wenn man das Urteil der anderen einschätzen lässt. Der Unterschied zwischen beiden Frageformulierungen nimmt mit dem Grad der Schulbildung zu und erreicht bei Personen mit Abitur ein substantiell bedeutsames Ausmass. Darüber hinaus sind die Antworten eindeutiger und pointierter, wenn nach der persönlichen Meinung gefragt wird.

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Summary The impact of the change in perspective (i.e. the personal opinion of those questioned versus what they perceive the others' opinion toward the mentally ill to be) on the results of the questionnaire is examined based on data from two population surveys measuring attitudes towards the mentally ill. As expected, the respondents' attitudes towards the mentally ill are more positive if they are asked to give their own opinion. The impact that the variation of the two formulations of these questions has on the respondents increases with their level of education and reaches a substantial amount among those with Abitur. Furthermore, the answers are clearer and more definite if those questioned are asked for their personal opinion.

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Résumé L'impact d'un changement de perspective (opinion personnelle comparée à l'opinion générale telle qu'elle est personnellement perçue) est examiné dans le cadre de deux études de population mesurant l'attitude envers les malades psychiques. Comme on pouvait s'y attendre, l'attitude des répondants est beaucoup plus positive lorsqu'il s'agit de leur opinion personnelle. La divergence entre l'opinion personnelle et la perception de l'opinion générale augmente au fur et à mesure que le niveau d'éducation s'accroît. Les réponses sont d'autre part bien plus clairement formulées lorsque les personnes experiment leur opinion personnelle.

     

Sexual assault tracking study: who gets lost to follow-up?

OBJECTIVES: To determine whether loss to follow-up can be predicted in patients who present to an emergency sexual assault assessment service and to generate hypotheses regarding the prediction of loss to follow-up on the basis of patient characteristics, assault characteristics and the services provided. DESIGN: Prospective, exploratory study. SETTING: Emergency department functioning as a regional sexual assault centre in a tertiary care hospital. PATIENTS: All 294 women over the age of 16 years who presented to the emergency department with a complaint of sexual assault and consented to be followed up. INTERVENTIONS: Telephone interviews at 24 to 48 hours and 1 month after presentation; face-to-face interviews after 1 week, 3 months and 6 months. MAIN OUTCOME MEASURES: Follow-up status (tracked versus lost to follow-up), State-Trait Anxiety Inventory (STAI-Y), Beck Depression Scale (Beck) and Rape Trauma Symptom Rating Scale (RTSRS). RESULTS: At 24 to 48 hours 136 (46%) of the patients could not be reached. Only 61 (21%) were still tracked at 6 months. Loss to follow-up at 1 month accurately predicted loss to follow-up at 6 months in 209 (98%) of 214 patients. For tracked patients the STAI-Y and Beck scores improved over 6 months. These scores at 1 week did not predict follow-up status at 6 months, but the numbers were small. Subjects with a higher RTSRS score at 24 to 48 hours were most likely to remain tracked throughout the 6 months. CONCLUSIONS: Decisions regarding how vigorously to track patients with a complaint of sexual assault can tentatively be based on the characteristics of the victim and of the assault. We hypothesize that the characteristics predicting loss to follow-up include denial and avoidance behaviour, lack of a telephone number or forwarding address, history of a psychiatric condition, a disability (e.g., deafness), characterization as a "street person," a high degree of violence or injury in the assault, and threat by the assailant. Although a predictive model requires further data, crisis intervention services in an emergency department are essential, given the large number of patients lost to follow-up.     

Laser angioplasty in peripheral arterial disease

Laser angioplasty was performed in 66 patients with total occlusion of the ilio-femoral artery. The system used consisted of a pulsed dye laser operating at 480 nm, 50 mJ pulse^–1, 2s pulse^–1 and 5 Hz. The treatment laser was coupled into a 200m optical fibre wrapped around a coil for improved flexibility and radiopacity. The treatment laser was connected with a diagnostic laser consisting of a continuous wave helium-cadmium laser operating at 325 nm, 50 ms and 3 mW for tissue detection using fluorescence spectroscopy. The primary success rate was 82%, the complication rate was 15% without any clinical sequelae and the 18 month follow-up patency rate was 64%. Due to the narrow pilot channel created by laser angioplasty, in each case a complementary balloon angioplasty was required to restore the arterial lumen. The success rate did not depend upon the length of occlusion but was rather related to the extent of calcification. Laser angioplasty guided by spectroscopy is effective and safe in patients with totally occluded peripheral arteries in whom mechanical devices failed to cross the obstruction.     

Continuous electrical stimulation as a helpful adjunct during intraoperative facial nerve monitoring

Routine intraoperative monitoring of facial function has been used since 1985. An adaptor has been developed for continuous stimulation (SACS) to be used with the new WR-S8, Monitor/Stimulation The SACS allows the microsurgical instruments and air drills to be electrified and to function as probe tips during surgical dissection. The new WR-S8 Monitor/Stimulator has an ultrasensitive strain gauge that detects facial movement before it is palpable. The remote probe allows an assistant to adjust the current easily. The routine use of facial nerve monitoring with SACS has decreased surgical time, has helped prevent iatrogenic injuries, and has improved our ability to save the facial nerve during otologic and neuro-otologic surgery.     

Mutagenicity of diisopropylamine dichloroacetate, the "active constituent" of vitamin B15 (pangamic acid)

Diisopropylamine dichloroacetate, the active component of many formulations of pangamic acid (trade-named "vitamin B15"), and diisopropylamine, a component of diisopropylamine dichloroacetate, both demonstrate mutagenicity in the Ames Salmonella/mammalian microsome mutagenicity test. Ninety percent of such agents prove carcinogenic, and this long-term possibility must be considered in any proposed use of pangamic acid containing diisopropylamine or diisopropylamine dichloroacetate.     

Tissue distribution and macromolecular interactions of 14[C-ring] melphalan in the rat

Summary The kinetics of uptake and elimination, covalent binding, and macromolecular interactions of ¹⁴[C-ring] melphalan was studied after a single oral dose (20 mg/kg, 0.1 mCi/kg) in normal rats. Peak radioactivity level in tissues was observed at 2–4 h after administration. Uptake of label in most tissues was rapid, with a t_1/2 of less than 1 h. Elimination was biphasic. Tissues of the gastrointestinal tract showed the most rapid rates of elimination, with t_1/2 of 13, 24, 18, and 19 h for stomach, duodenum, and small and large intestines, respectively. Bone marrow also showed a fast rate of elimination of radioactivity, with a t_1/2 of 30 h. Tissues with the slowest rates of elimination were skin, eye, spleen, pancreas, and lung, with t_1/2 of 333, 241, 149, 122, and 109 h, respectively. Covalent binding studies showed that melphalan, or its metabolites, bound irreversibly to all tissue macromolecular fractions. The percentage of covalently bound radioactivity increased with time in all tissues except kidney and eye, reaching up to 70%–80% of the total radioactivity remaining at 72 h. Elimination of covalently bound radioactivity was slower in the DNA fractions of the tissues of the gastrointestinal tract and heart compared with the elimination rate from lipid, protein, or RNA fractions. Slow elimination rates of ¹⁴[C-ring] melphalan equivalents from the protein fraction were observed in the skin, eye, and brain. Accumulation, rather than elimination, of radioactivity in this fraction was most prominent in the pancreas. In the bone marrow accumulation of radioactivity was observed in the lipid fraction.Abbreviations used in this paper are L-Pam Melphalan, l-phenylalanine mustard 4-bis (2-chloroethyl) amino-1-phenylalanine - l-DOH 4-bis (2-hydroxyethyl) amino-1-phenylalanine - l-MOH 4-2 hydroxyethyl 2 chloroethyl amino-1-phenylalanine - HPLC high-pressure liquid chromatography - TCA trichloroacetic acid - AUC area under the curve - GIT gastrointestinal tract     

Comparison of pesticide and particulate recoveries with the vacuum and dislodgeable surface pesticide residue techniques

The dislodgeable and vacuum surface residue techniques were compared for the quantity of pesticide residue and quantity and quality of particulate matter removed from Valencia orange leaves. Data trends for dislodgeable and vacuum parathion and paraoxon residues were correlated at r0.95 for both emulsifiable concentrate and wettable powder formulations.The amount of pesticide residue and particulate matter obtained was dislodgeable > glass fiber filter > 5.0 filter > 0.8 filter. The flow rate of the filter was correlated with the amount of residue removed.The quality of particulate matter as judged by size analyses was equal The dislodgeable technique removed about five times more particulate material and about eleven times more pesticide residue compared to the vacuum technique.Florida Agricultural Experiment Stations Journal Series No. 745.     

CLINICO-PATHOLOGIC CONFERENCE: 12-YEAR-OLD GIRL WITH FATIGUE, ANEMIA, WEIGHT LOSS, ABDOMINAL DISTENTION, AND OCCASIONAL NAUSEA AND VOMITING

A clinicopathologic case is presented. The patient was a 12-year-old white girl with a history of fatigue and dizziness, occasional nausea and vomiting, and anemia, who showed abdominal distention, especially in the epigastrium. An epigastric mass was palpable. Gastroscopy was done, and surgery followed. Pertinent laboratory findings are presented, and clinical discussion follows. The pathology is then presented and discussed.     

Kahnbeinfrakturen – Diagnostik, Klassifikation und Therapie

Herbert's classification of scaphoid fractures provides the underlying rationale for treatment according to the fracture type. A CT bone scan in the long axis of the scaphoid is the best means of differentiating between stable and unstable fractures. This is difficult from conventional X-rays due to the particular three-dimensional anatomy of the scaphoid. To avoid long-term plaster immobilization and to diminish the risk of a nonunion, unstable fractures of type B should be fixed operatively. With headless screws such as the Herbert screw, which are now available in a cannulated shape, the majority of scaphoid fractures of type B1 and B2 can be stabilized using minimally invasive procedures. Severely displaced fractures require the classical open palmar approach. Proximal pole fractures (B3) are best managed from the dorsal approach, using the Mini-Herbert screw. Stable fractures of type A2 can be treated conservatively in a below-elbow cast or, alternatively, stabilized percutaneously, which allows early mobilization.