Reduced HLA-A,B,C expression in tumourigenic v-raf transfected human urothelial cells.

Tumourigenic (TGrIII) human urothelial cells grown in vitro have previously been demonstrated to have a markedly decreased expression of beta 2-microglobulin and HLA-A,B,C antigens as compared to non-tumourigenic (TGrII) human urothelial cell lines. Furthermore, during 'spontaneous' in vitro transformation of a non-tumourigenic (TGrII) human urothelial cell line Hu609 into a tumourigenic (TGrIII) subline Hu609T/LLH, changes in morphology and tumourigenicity have been demonstrated to be accompanied by a decreased HLA-A,B,C expression. After malignant transformation of the non-tumourigenic (TGrII) human urothelial cell line HCV29 by DNA transfection with the v-raf oncogene, four sublines could be isolated. In this study we have investigated these sublines for their expression of membrane bound HLA-A,B,C antigens and provide further evidence that an inverse relationship exists between tumourigenicity and monomorphic HLA-A,B,C expression. Treatment of the cells with recombinant human interferon alpha for 3 days increased the expression of HLA-A,B,C antigens by 50-150% indicating that at least some of the reduced HLA-A,B,C expression could be due to decreased synthesis of HLA-A,B,C antigens. All the transfected cell lines overexpress v-raf and c-myc.

Should the lungs be ventilated during cardiopulmonary bypass? Clinical, hemodynamic, and metabolic changes in patients undergoing elective coronary artery surgery.

No beneficial effects were achieved by ventilating the lungs of a group of 10 patients during total extracorporeal circulation for coronary artery bypass operation. Ventilation of nonperfused lungs, which was suggested to prevent postoperative atelectasis, may even have negative effects. Intrapulmonary shunting increased significantly (p less than 0.05), while the shunt fraction in the nonventilated lungs of another group of 10 patients remained unchanged. There were only minor differences between the two groups with respect to systemic and pulmonary hemodynamic changes.

Expression of polymorphic HLA-A,B epitopes in human urothelial cell lines.

Malignant human urothelial cell lines propagated in vitro have previously been demonstrated to express low amounts of monomorphic HLA-A,B,C as compared to premalignant urothelial cells. In this study the expression of polymorphic HLA-A,B epitopes in human urothelial cell lines have been investigated in greater detail. The expression of HLA-B locus coded epitopes in malignant TGrIII cells was demonstrated to be low or absent as compared to pre-malignant TGrII or slightly transformed TGrI cells, suggesting a mechanism by which malignant cells could escape from the host immune response. The extreme polymorphism of HLA-A,B,C antigens suggests that HLA typing could be used as a method to identify the origin of cell lines which is essential in the study of the process of malignant transformation in vitro, or when correlating in vitro data with clinical observations of the patient. Two urothelial cell lines classified as slightly transformed (TGrI) and two as pre-malignant (TGrII) could, according to their expression of polymorphic HLA-A,B epitopes, be identified as genuine independent cell lines. One TGrII cell line previously designated Hu1734 shared the same HLA-A,B phenotype as the genuine HCV29 (TGrII) cell line and is therefore suspected to be a subline of the latter. Out of 18 cell lines and sublines classified as TGrIII the fidelity of four (Hu1922 and three sublines of T24) was proved by their HLA-A,B phenotype. Mistaken identity either by contamination or false labelling of the cultures was suspected in samples of six TGrIII cell lines and sublines. In four of these the HLA-A,B type characteristic for the T24 cell line could be demonstrated, but in general HLA typing of TGrIII cell lines as a method to identify the origin of the individual cell lines failed, primarily due to the decreased expression of HLA-A,B,C antigens and the apparent selective loss of HLA-B locus coded antigens.

In vitro studies of human bladder cancer.

Explantation and cultivation in vitro of 55 human biopsies of histologically normal urothelial tissue, and 63 biopsies from transitional cell carcinomas (TCC) revealed a primary success rate of about 75% and a secondary success rate of about 50% with no significant differences, between normal and TCC derived cultures. While only half of the subcultured biopsies of normal origin were able to grow for more than 4 passages all TCC derived cultures were able to do so. Based on morphology, life span, invasive growth into co-cultured fragments of embryonic chick heart, and tumorigenicity in nude mice the following transformation grades (TGr) were defined: Normal (TGr 0), non-malignant with prolonged, but finite life span (TGr I), premalignant with infinite life span but without tumorigenic and invasive potential (TGr II), malignant with infinite life span and tumorigenic and invasive properties (TGr III). Differentiation between TGr I - TGr III was possible by several other parameters, including cytological characteristics, molecular and immunological surface structure, relative oncogene expression, pyruvate kinase isoenzymes, DNA Repair, and growth pattern. However, in addition to these common characteristics, the individual cell lines of the various categories of transformation showed differences that allowed the identification of well defined cell lines and sublines.

[How to improve use of emergency contraception by adolescents?]. / Comment améliorer l'utilisation de la contraception d'urgence par les adolescents?

OBJECTIVES: To give an overview of knowledge on emergency contraception (EC) and its utilization in the adolescent population, and to present the practical guidelines useful for EC prescription. METHODS: Review of the literature on EC and results of a survey on sexual behavior of 16-20-year-olds in Switzerland are used. RESULTS: Both estrogen-progestin and estrogen are used for EC. Condom breakage, lack of compliance in oral contraception and failure in contraceptive use are the main reasons for using EC. Sexually active adolescents are aware of CPC and 20% of girls have used it in Switzerland. However, insufficient information and low quality of services in emergency situation could be important barriers to the use of EC. DISCUSSION: and conclusion. Practical knowledge and information on EC must be disseminated among adolescents and both professional training and development of the quality of services have to provide better access to EC.

[Back pain, bone metastases and medullary compression]. / Rygsmerter, knoglemetastaser og medullaer kompression.

A case of lung cancer and metastatic spinal cord compression is presented. Despite progressive backpain during two weeks and total loss of walking ability, the patient regained the ability to walk one week after radiotherapy for the malignant spinal cord compression. Guidelines for recommended diagnostic approaches are given.

[Electronic rectal temperature measurement. A clinical trial]. / Rektal elektronisk temperaturmåling. En klinisk undersøgelse.

Rectal measurement of body temperature with an electronic device (Ivac) was compared to measurement with mercury thermometers in 157 adult patients on a medical ward. The electronic thermometers were less accurate, giving 3.6 times as many febrile patients. This was reduced to 1.6 after thermometer calibration. It is necessary to make regular calibrations of Ivac thermometers.

[Indicators of coronary risks--attitude, knowledge and behavior. An interview study among 917 men and women aged 25-44 years]. / Koronare risikoindikatorer--holdning, viden og adfaerd. En interviewundersøgelse blandt 917 maend og kvinder i alderen 25-44 år.

The purpose of this study was to clarify whether there was any agreement between knowledge about coronary risk factors, attitudes to individual prevention of coronary heart disease and preventive health behaviour. In particular the differences between males and females were examined. A total of 749 persons ranging in age between 25 and 44 (that is 82% of a random group of 917 persons) were interviewed in this cross sectional study. Physical inactivity, smoking and fat consumption were used as behaviour related risk factors. Generally, young adult Danes had a poor knowledge and poor health behaviour related to coronary heart disease in spite of their positive attitudes towards prevention. The study indicated that neither attitudes nor knowledge were correlated to preventive health behaviour. Women had better health behaviour patterns than men despite the same amount of knowledge and attitudes. In the above mentioned connexions, men showed positive correlation while no correlation existed for women.

Randomized, double-blind trial comparing the antiemetic effect of tropisetron plus metopimazine with tropisetron plus placebo in patients receiving multiple cycles of multiple-day cisplatin-based chemotherapy.

PURPOSE: To compare the antiemetic efficacy and tolerability of tropisetron plus metopimazine with tropisetron plus placebo during 4 cycles of multiple-day, cisplatin-based chemotherapy. MATERIALS AND METHODS: 82 chemotherapy-naive patients with germ cell cancer scheduled to 4 cycles of multiple-day cisplatin-based chemotherapy (20 or 40 mg/m(2)/day for 5 days) given every 3 weeks were included. A double-blind parallel trial design was used and patients randomized to tropisetron plus metopimazine or tropisetron plus placebo. Tropisetron was administered as a single 5 mg intravenous dose on days 1-5 and a single 5 mg oral dose on day 6, and metopimazine as 30 mg orally t.i.d. on day 1, and q.i.d on days 2-6. RESULTS: Patients were evaluable for efficacy during a total of 195 cycles. Small, but certain advantages were obtained with the combination. In cycle 1, complete protection from emetic episodes on day 1, days 1-5, days 6-9 and days 1-9 was achieved in 85.7%, 42.9%, 86.2% and 40.5% with tropisetron plus metopimazine and in 90.0%, 22.5%, 64.3% and 17.5% with tropisetron plus placebo, respectively. This difference achieved statistical significance in the overall period, days 1-9 (P = 0.029). During the entire period (days 1-9), significantly less nausea was seen in patients receiving tropisetron plus metopimazine (P = 0.027), whereas other nausea parameters did not reach statistical significance. The cumulative emetic protection rate after 4 cycles was 0.51 with tropisetron plus metopimazine and 0.25 with tropisetron plus placebo (P = 0.037). Side effects were generally few and mild with both treatments and no significant differences were seen. CONCLUSION: Tropisetron plus metopimazine is superior to tropisetron during 4 cycles of multiple-day cisplatin-based chemotherapy, but both treatments are ineffective in a number of patients. The effect of the combination seems comparable to that of ondansetron plus dexamethasone. Newer drugs such as the neurokinin(1) receptor antagonist, aprepitant, should be investigated to optimize antiemetic therapy in patients receiving multiple-day chemotherapy.

The influence of thoracic epidural analgesia on the circulation at rest and during physical exercise in man.

The effects of thoracic epidural analgesia (TEA) on the circulation at rest, during, and after physical exercise were investigated in 10 volunteers. At rest, TEA did not affect oxygen consumption (VO2) or cardiac output (Q), but heart rate (HR) was, increased by 7 beats/min, and stroke volume decreased correspondingly by 13 ml. Systolic arterial blood pressure was slightly reduced, but no other changes in systemic or pulmonary circulatory parameters were produced. TEA did not change VO2 during exercise, a 2.11/min reduction of Q being accompanied by a 4.2% increase of oxygen utilization coefficient. HR showed a relative reduction of about 10%. At moderate work loads during TEA, systemic arterial blood pressures were significantly lower than during control exercise. The resulting rate pressure product (RPP) was markedly reduced, while total peripheral resistance (TPR) remained unchanged. During recovery after the termination of exercise during TEA, VO2, Q, HR, RPP and TPR fell more rapidly towards values obtained at rest. From a clinical point of view the results support the safeness of TEA and also support its use in surgical patients with heart disease.

[Pain creates pain]. / Smerte føder smerte.

If pain is allowed to go on uninhibited it may become more intense and difficult to relieve. A continuous afferent input of signals from the injured tissue will gradually sensitize dorsal horn neurones of the spinal cord, making them more receptive for transmission of pain messages to the brain cortex. The pain signal should be stopped at the periphery. Preventive use of peripheral and spinal nerve blocks, including local anaesthetics, and administration of non-steroidal antiinflammatory drugs and opioids can reduce the effects leading to sensitization. The best treatment is--pre-emptive analgesia--administered before the pain is established. Pain that is not adequately treated may lead to persistent morphological changes in the central nervous system, resulting in chronic pain refractory to treatment.

[Morphine-antiemetics mixtures for continuous subcutaneous infusion in terminal cancer]. / Morfin-antiemetika-blandinger til kontinuerlig subkutan infusjon ved terminal cancer.

Simultaneous pain, nausea and vomiting are not uncommon in terminal suffering requiring treatment with various compounds of analgesics and antiemetics. At Baerum Hospital the pump reservoirs for continuous, subcutaneous drug delivery are routinely filled by the hospital pharmacist. We examined the physico-chemical stability of various concentrations of mixtures of morphine-metoclopramide and morphine-metoclopramide-haloperidol at 25 degrees C. We found good stability for at least seven days. Addition of haloperidol seems to reduce stability. Plain morphine-haloperidol solutions are unstable. Split products were not found in any of the mixtures. We also examined the osmolality of current clinical compounds, focusing on local irritant effect at the infusion site. All solutions except for one with a high concentration of haloperidol were found to be close to isoosmolarl.

Use of Haemonetics Cell Saver for autotransfusion in cardiovascular surgery.

The Haemonetics Cell Saver was evaluated as a tool for the refining of blood shed during cardiovascular surgery. After blood filtration the red cells are concentrated, washed and re-infused as red cells suspended in normal saline (CS blood) with haematocrit around 60%. Platelets and plasma with desired and undesired components are removed. In 50 patients undergoing elective but complicated cardiovascular surgery an average of 4.4 units CS blood were produced. In 3 Jehovah's Witnesses the method was used in combination with immediate preoperative prebleeding and dextran infusion. No blood products were given. The haematocrit was maintained at a safe level subsequent to retransfusion. Platelet counts were never critically low and extremely low total protein did not lead to peripheral or pulmonary oedemas or coagulation problems. In an in vitro study it was shown that extreme dilution of coagulation factors is well tolerated before the clotting time (ACT) is affected. The Cell Saver proved to be an effective, reliable and safe device for autotransfusion of salvaged blood during cardiovascular surgery.

Cardiovascular effects of epidural analgesia. I. Thoracic epidural analgesia. An experimental study in sheep of the effects on central circulation, regional perfusion and myocardial performance during normoxia, hypoxia and isoproterenol administration.

Some circulatory effects of thoracic epidural analgesia (TEA) were investigated in splenectomized, open-chest sheep during normoxia, hypoxia and isoproterenol administration. During normoxia, TEA caused comparatively marked reductions in systemic arterial blood pressure, total peripheral resistance and cardiac output. A fall in heart rate was not compensated for by any rise in stroke volume. Myocardial contractility (LV dd/dt/IP) was not affected by TEA. The proportion of cardiac output diverted to the blocked area was markedly increased. Compensatory vasoconstriction was not observed within the unblocked area in six out of nine animals. Myocardial blood flow showed a pronounced reduction in accordance with the calculated changes of heart work, so that myocardial oxygen extraction remained unchanged. Studies under hypoxia revealed that cardiac responses to hypoxia in the sheep are mediated chiefly by neurogenic factors. TEA abolished the hypoxia-induced rise in heart rate but did not affect the increase in pulmonary vascular resistance caused by hypoxia. The administration of isoproterenol during TEA increased systemic arterial blood pressure, but due to further fall in total peripheral resistance it was not fully normalized. Cardiac output and heart rate increased markedly. Myocardial oxygen consumption and blood flow increased but did not reach control levels.

The value of activated coagulation time in monitoring heparin therapy during extracorporeal circulation.

The anticoagulant effect of heparin was studied in 20 patients undergoing aortocoronary bypass surgery. The protamine dose necessary to reverse heparin after extracorporeal circulation (ECC) was assessed in ten patients from individual heparin dose-response curves (HDR group). The other ten patients received protamine according to a routine protocol (control group). The protamine administration was followed in both groups by injection of 3-5 g tranexamic acid (Cyklokapron). A wide range of sensitivity to heparin was shown by the patients. Although almost twice as much protamine was given to the control group as to the HDR group, the effect on heparin reversal was similar. The variability of protamine dose did not influence the post-bypass levels of fibrinogen, AT-III, activated coagulation time (ACT) or Cephotest, and fibrinolysis was not observed in either of the groups. During ECC there was poor correlation between ACT and plasma heparin levels, and the use of heparin dose-response curves was grossly misleading in regard to true heparin concentration. The postoperative bleeding was not related to the levels of heparin or coagulation parameters after heparin reversal. The concentrations of fibrinogen and AT-III showed variations dependent on the changes in haematocrit. A number of factors other than heparin that influence ACT are discussed.

[Is cancer pain therapy insufficient?]. / Underbehandles kreftsmerter?

Pain from cancer is said to be poorly relieved. To examine the relevance of this statement in our hospital we registered morphine consumption used for cancer pain relief from 1983 to 1990. The use of morphine increased 20-fold during this period, corresponding to a 12-fold increase per patient. A probable explanation of this development is that cancer pain now receives more attention and use of morphine has become more acceptable. New methods such as subcutaneous continuous morphine administration from portable pumps, and the introduction of slow-release morphine, have improved and simplified the treatment. Probably several Norwegian hospitals still lag behind in this respect. Consequently much pain remains unrelieved. We suggest that hospitals evaluate their pain relief programmes. If these are found inadequate, the service should be reinforced. This would probably lead to earlier rehabilitation and improved quality of life for the patient.

[Continuous drug infusion in terminal cancer]. / Kontinuerlig legemiddelinfusjon ved terminal cancer.

Today's technology provides portable pumps which facilitate continuous infusion of drugs to relieve suffering in terminal disease. Subcutaneous and epidural infusion is now frequently used in our hospital. The most common indications are gastrointestinal obstruction, impaired absorption of drugs, refractory side effects of oral medication or poor compliance because good pain relief is no longer possible orally. During the last days of life, this method may be the only possible approach to good comfort and relief from terminal agitation and anxiety. Of the patients referred to the advisory group for seriously ill and dying in 1990, 64% received subcutaneous infusions and 15% epidural infusions during the last days or weeks of life. Continuous infusion of drugs from portable pumps has become an almost indispensible method of treatment in an ordinary clinic.

Correlation between classification of human urothelial cell lines and HLA-A,B,C expression.

Quantitative changes in major histocompatibility class I antigen expression in tumour cells are believed to affect the host immune response against the tumour. In tumourigenic (TGrIII) human urothelial cell lines the apparent loss of polymorphic HLA-A,B epitopes has previously been demonstrated. In the present study, 3 non-tumourigenic (TGrII) and 6 tumourigenic (TGrIII) human urothelial cell lines have been investigated for their quantitative expression of monomorphic HLA-A,B,C and B2-microglobulin. Evidence is provided that an inverse correlation exists between tumourigenicity and HLA-A,B,C and B2-microglobulin expression. Furthermore, treatment of the cells with neuraminidase partly restored the expression of monomorphic HLA-A,B,C suggesting that at least some of the observed quantitative differences could be due to masking of the membrane bound HLA antigens by sialic acid-containing glycoconjugates.