A meal conference format to teach ambulatory nutrition concepts. Third-year medical students participated in a program using a meal conference approach to teach ambulatory nutrition concepts called "Building Better Health Through Nutrition." The series of three interactive presentations was given during the required family medicine clerkship. A pretest and posttest were used to measure acquisition of nutrition knowledge. There was a statistically significant (P less than 0.05) average increase in posttest compared to pretest scores. Seventy percent of students rated the meal conference approach as "effective" or "very effective" and 76% stated that the series expanded their knowledge of nutrition's role in clinical medicine. We conclude that the meal conference format is an effective way to teach nutrition during the clinical years in medical school.


A multidisciplinary educational program to promote head and neck cancer screening. An educational program to promote screening through primary health care for the squamous cell cancers of the buccal cavity, pharynx, and larynx as developed and implemented, and its impact on screening was documented. Providers of care for high-risk patients at seven inner-city health care sites in Boston were identified and targeted for training. Of the 327 providers who were targeted for training from December 1986 through June 1989, 261 (80%) attended educational sessions. Screening exams were documented on an average of 14.7 patients per targeted provider through December 1989. The educational program was associated with a large increase in documented screening for these cancers, compared with baseline rates. Several adaptations in the program were required, including a demonstration of efficient screening to address the concerns of these providers about time constraints. Variations in the quantity and quality of documented screening among health care sites were noted.


Physician/patient communication: a model considering the interaction of physicians' therapeutic strategy and patients' coping style. During the last decade, several studies have demonstrated the importance of information-seeking versus information-avoiding coping styles of cancer patients receiving educational information from their physician. During the same period of time other studies have demonstrated important differences in the communicative style of oncologists providing educational information to their patients. However, the implications of the interaction of these two areas of research have not been systematically considered. We present here a hypothetical model concerning the implications of physicians with different communicative styles interacting with patients with different coping styles.


Teachers' attitudes to cancer education: a discussion in the light of a recent English survey. Various attempts have been made at encouraging cancer education in British schools, and while some have had limited success, there is still a reluctance amongst teachers to adopt this subject in the classroom. The study discussed in this paper was an attempt to ascertain the current status of cancer education in English secondary education. Over 1,200 English secondary (11-16 years olds) schools took part and the data were collected between February and June 1990. Although there is evidence to suggest an element of self-selection, results from this sample indicate a growing commitment and enthusiasm for cancer education, in comparison to previous, similar studies. Over half the teachers had taught about cancer and 68.8% rated it an important health education topic. However, cancer did rate lowest out of a variety of health issues. Several reasons for this are discussed and all appear to relate to teachers' negative attitudes toward cancer, apparently based on preconception and misinformation. These must be overcome if cancer education is to achieve its true potential in English schools.


Survey design and observations relating to cancer education funding. Cancer Education Survey II: cancer education in United States medical schools (conducted by The American Association for Cancer Education with the support of the American Cancer Society). A survey has been conducted of cancer education programs for medical students in United States medical schools by the American Association for Cancer Education with grant support from the Department of Detection and Treatment of the American Cancer Society (formerly the Professional Education Department). Two questionnaires were used, an Educational Resources Questionnaire (ERQ), which 126 of the 128 medical schools completed and returned, and a Faculty and Curriculum Questionnaire (FCQ), which was completed and returned by 1,035 faculty members who had been named as active in undergraduate medical student cancer education by respondents in each school who had been designated by the Dean's Office to complete the ERQ. Overall conclusions included: (1) increased coordination of cancer education activities is a major need in many schools; (2) there is widespread interest in the further development of cancer education objectives; (3) development of a national cancer education curriculum is needed; (4) there is interest in the development of improved instructional materials and methods; (5) development of evaluation methods is needed for cancer education programs; and (6) an ongoing funding process is needed to provide support for interdepartmental coordination of cancer education activities. Cancer prevention and detection topics were ranked above cancer treatment in plans for future curriculum emphasis. More detailed conclusions and recommendations are provided in this publication and three subsequent articles in this issue of the Journal of Cancer Education.


Instructional methods and the use of teaching resources in cancer education curricula. Cancer Education Survey II: cancer education in United States medical schools. The findings on cancer teaching methodology presented in this abstract come from an American Association for Cancer Education (AACE)/American Cancer Society-sponsored survey of American allopathic medical schools in 1989 and 1990 to determine how and how well cancer is presented in the medical school curriculum. Responses were received from 126 institutional and approximately 1,000 faculty respondents. Approximately one-third (368) of faculty respondents indicated the use of specific learning objectives; utilization does vary across disciplines. The lecture remains the dominant form of instructional method. Computers were reported as an instructional modality by only 16% of the faculty respondents. Prepared audiovisual instructional materials appeared to be widely utilized. Use varied from 86% for 35mm slides to 11% for video discs. Faculty favored the development of new teaching materials for ten topic areas ranging from approximately 40% for early detection and prevention to a low of approximately 25% for rehabilitation and continuing care. The survey identified an underutilization of existing outpatient facilities and tumor registries for cancer teaching purposes. The findings give rise to questions concerning the appropriateness of the match between specific instructional goals and the teaching methods employed. Eight recommendations designed to strengthen cancer training are made.


Enhancing the level of nutrition education at Tufts University's Medical and Dental Schools. The current medical and dental curricula at Tufts were evaluated to ascertain the breadth and depth of their nutrition programs. The program, which both schools plan to initiate, to enhance the level of nutrition education involves (1) development of nutrition units for the first and second year, (2) expansion of required nutrition courses in the second year, (3) diet lunches in the third year introducing the role of nutrition in the clinical setting, and (4) nutrition rounds in the fourth year. A combined medical-dental seminar will be presented each year. At the end of the five-year funding period, it is anticipated that a manual will be available to all medical and dental schools that includes (1) nutrition units, (2) methods of dietary assessment in medical-dental practices, (3) nutrition interaction for the prevention of chronic disease in medical-dental practices, and (4) nutrition support for chronic disease and cancer, and case studies on nutrition and disease. The success of this program will be evaluated on the basis of goals and a national nutritional literacy exam.


Dental student education in oncology: design and assessment of an undergraduate course. Five-year survival rates of oral cancer patients remain poor. To better prepare undergraduate dental students to recognize this problem and contribute to solutions, a 24-hour lecture course in oral oncology was instituted. A pre-course quiz, daily quizzes, a midterm and a final examination were administered to assess student knowledge. The course covered all aspects of oral cancer from epidemiology and etiology, through diagnosis, treatment, and rehabilitation. Student oncology knowledge was assessed by analyzing the test results of two consecutive third-year dental classes. Overall, students adequately meet the course objectives, but assessment of specific topics reveal some deficits in particular areas. Evaluation of student knowledge provides valuable information to instructors for improving course content and student achievement.


Defining and accomplishing clinically related objectives in an eight-hour oncology course for first-year medical students. Designing a clinically relevant cancer curriculum for freshmen attending medical schools with a traditional curriculum poses the following challenges: (1) there is limited curriculum time; (2) the subject matter is complex. The authors defined some of the responsibilities of the general physician in regard to cancer and six related objectives that first-year students could accomplish in an eight-hour multidisciplinary oncology course. A case-based, modified essay examination required students to demonstrate that they could begin to integrate principles of prevention, screening, diagnosis and staging, and treatment modalities. Ninety percent of the students accomplished the objectives. However, in working up the cancer case, 70% of the students did not mention the physical examination and 53% forgot multidisciplinary consultation. In a curriculum with limited objectives, first-year students can begin to deal efficiently with the complexities of cancer. Evaluation data revealed those objectives and related physician responsibilities requiring reinforcement in subsequent training.


The effect of breast clinic participation on the education of third-year medical students. Traditional methods of teaching concepts of breast disease to medical students have included didactic lectures, patient interviews and examinations in the hospital, and patient-directed rounds with housestaff and attendings. From 1980 to 1987, third-year students at the University of South Carolina School of Medicine participated in these educational experiences and were tested at the conclusion of the eight-week surgical core rotation, utilizing written and oral examinations. Beginning in July 1987, students began participating in a defined weekly Diagnostic Breast Clinic which included in-depth instruction in patient examination techniques, mammographic interpretation, and treatment planning. Results of oral and written examinations, specifically regarding knowledge of breast cancer, were compared between the early and later periods. Significantly improved performance was noted in students exposed to a defined breast clinic experience and strongly supports the integration of specific cancer clinic experiences in undergraduate medical education.


Cigarette smoking among young physicians and their approach to the smoking problem of their patients. We have undertaken a survey of 100 interns and 100 residents at University of Ankara Medical School to find out their smoking rates as well as their view of the smoking problem in Turkey and their approach to the patient who smokes. The smoking rate of interns and residents were comparable to those of the 146 nonmedical university students surveyed at the same time (31% and 37% versus 38%). Our results indicate that smoking residents have less confidence in their efficacy to influence the patients to quit smoking when compared to nonsmokers (34.2% versus 14.5%; p < 0.05). Likewise, they have a higher, though not significant, tendency not to counsel their patients than those who are not smoking. Therefore we conclude that a successful smoking cessation program in Turkey requires encouragement of the medical students and residents to quit smoking and better training of them with regard to smoking intervention methods in order to increase their confidence of efficacy.


Quality of life and patients with cancer: a comparative study of patient versus physician perceptions and its implications for cancer education. A group of 300 matched pairs of adult patients with cancer (PWC) and their physicians were interviewed concerning the effects of disease and treatment on the patients' quality of life (QL). Patients were asked to rate specific QL factors that concerned them personally, while physicians were asked to evaluate the QL concerns of a hypothetical patient population exhibiting characteristics and diagnoses similar to those of their matched patients. The results indicated that physicians failed to recognize age as a factor having a direct impact upon the QL of their patients. Specifically, physicians estimated that elderly PWC, rather than young PWC, experienced more problems in four out of five QL categories, while in actuality younger patients reported more difficulties in all five categories when compared to their older counterparts. These data suggest that physicians should become more sensitive to the individualized, personal nature of their patients' QL and the factors that may shape or modify it. Implications for cancer education suggest a focus upon determining specific PWC needs as opposed to teaching general QL problems. Students should also be taught not to assume that all PWC experience the same QL concerns; rather, students should be taught to develop a specific history seeking to determine these needs. Finally, educators and students should recognize that young PWC apparently have more difficulty with their disease and its therapy than older PWC.


The use of illustrations and narrative text style to improve readability of a health education brochure. Research suggests that much of the available health education literature requires a level of reading ability that makes it inaccessible to a large proportion of the population in greatest need of health information. The present study tested the value of illustrations and a narrative text style as means of improving the readability of a brochure designed to provide information on cervical cancer and condyloma. Two versions of the brochure were designed, one that had only text presented as simple sentences in bullet-type format (SMOG reading level score of 7.7), and a second version that had somewhat more difficult text formatted in a narrative style (SMOG grade level score of 8.4) together with drawings designed to complement the text. A randomized study design was used to test for comprehension, perceived ease of understanding, and overall rating of the two brochures. Women selected from one private and three public health primary-care clinics were randomly assigned to read one of the two brochures. The brochure with illustrations and narrative text was given a significantly higher overall rating than the one with bullet-type text and no illustrations, while no difference was found in perceived ease of reading. Among poor readers, comprehension was significantly greater for women who read the brochure with illustrations and narrative text, with no difference in comprehension of the two brochures for better readers. The results suggest that the use of aids such as illustrations and text style can make health education literature more accessible to high-risk populations, while remaining interesting enough to appeal to individuals at all levels of reading ability.


Understanding cultural differences through family assessment. While much has been documented with regard to the role of the family in managing the stress of a diagnosis of cancer, there has been a paucity of attention devoted to cultural differences, which are vital factors in the family's unique ability to cope. Health care professionals in large urban settings are often required to assess families that are unfamiliar to them. This paper focuses on the need to educate health care professionals in order that they can more clearly conceptualize the structure, function, and health-related needs of families from differing cultural backgrounds. Nine interviews with Greek, Chinese, and Italian immigrant families were analyzed retrospectively with regard to family perceptions of hospitalization and experiences surrounding coping and problem solving with respect to a diagnosis of cancer. Findings revealed that fear and loneliness were predominant emotions at the onset of hospitalization. Coping strategies and the management of stress frequency differed from the suggestions of health personnel. This paper concludes that the content of health education curricula needs to be broadened to include attention to cultural considerations.


An instrument for measuring cancer patients' preferences for support groups. The purpose of this study was to develop a valid and reliable instrument to assess cancer patients' preferences for all types of social support and organizational features of cancer support groups. The content of the instrument was the result of a detailed analysis of four resources: (1) literature relating to cancer support group interventions, (2) program materials from existing groups, (3) interviews with individuals who developed or directed groups, and (4) interviews with patients who have participated in cancer support groups. A jury of six experts was used to establish content validity of the instrument. The reliability of the instrument was examined by measuring a sample of 258 cancer patients. The reliability coefficients of the instrument were all above .80, except for two types of social support (instrumental and informational-educational), which were .72 and .78, respectively. It was concluded that the instrument produces valid and reliable measurements of cancer patients' preferences for cancer support groups.


Change in the oestrogen receptor status of breast cancer with age--comparison of two types of assay. The oestrogen receptor (ER) is considered to be an essential component of the mechanism of response of a breast tumour to endocrine therapy, but ER measurements have proved to have only modest predictive value. In the present study, we have examined ER status by both immunocytochemical assay (ER-ICA) on a fine needle aspirate and by radioligand-binding assay (DCC) on an excised portion of tumour. There was a correlation between the ER level detected by the two assays (Spearman's r = 0.77 for DCC versus ER-ICA staining intensity, r = 0.70 for DCC versus ER-ICA percentage of cells stained, P < 0.0001, n = 137 in each case). Each assay showed an increasing proportion of ER+ve results with increasing patient age. In the case of ER+ve tissues only, while ER concentration by DCC assay increased steadily with age (r = 0.39, P < 0.0001, n = 108), the ER-ICA assay revealed that, staining intensity increased with age (r = 0.26, P = 0.001, n = 149) but the percentage of cells stained did not (r = 0.08, P = NS, n = 149). It is concluded that increasing endocrine responsiveness with advancing age could reflect the increasing proportion of ER+ve tumours with increased levels of ER per cell (as indicated by staining intensity) rather than increasing proportion of ER+ve cells.


Active melanogenesis in non-S phase melanocytes in B16 melanomas in vivo investigated by double-tracer microautoradiography with 18F-fluorodopa and 3H-thymidine. 3,4-Dihydroxy-2-[18F]fluoro-L-phenylalanine (2-[18F]FDOPA) and [6-3H]thymidine ([3H]Thd) were simultaneously injected into mice transplanted with B16 melanomas of FM3A mammary carcinoma. Melanogenesis was differentiated from DNA synthesis in the mitotic cell cycle by monitoring grain distribution with double-tracer microautoradiography. The percentages of pigmented cells were inversely proportional to those of [3H]Thd-labelled cells, indicating that the greater the number of melanocytes, the smaller was the number of proliferating cells. The number of grains produced by 2-[18F]FDOPA in the [3H]Thd-unlabelled melanocytes was significantly higher (P < 0.001) than the numbers in the [3H]Thd-labelled melanocytes and in nonmelanocytes. The [3H]Thd-unlabelled non-melanocytes and FM3A cells showed the lowest accumulation of 2-[18F]DOPA, which may have resulted from the basic amino acid demand by malignant neoplasms via amino acid transport. The [3H]Thd-labelled cells, regardless of whether they were pigmented or not, had slightly more grains with 2-[18F]FDOPA than the [3H]Thd-unlabelled non-melanocytes (P < 0.05), which may have resulted from the enhanced amino acid requirement for proliferation. Melanogenesis appeared to be activated only in the non-S phase of the mitotic cycle in melanocytes.


Influence of tumour physico-chemical conditions on interleukin-2-stimulated lymphocyte proliferation. The proliferative response of murine lymphocytes to interleukin-2 (IL-2) was examined under physico-chemical conditions present in solid tumours, namely low oxygen and glucose concentrations and acidic pH. Lymphocytes were cultured for four days in 30 U ml-1 IL-2 to simulate serum IL-2 concentrations attainable with high-dose systemic IL-2 therapy. Lymphocyte proliferation was significantly (P < 0.05) reduced by low oxygen concentrations (both anoxia [0% O2] and hypoxia [10%, low glucose (6 mg dl-1), or acidic pH (6.7 or 6.4). Moderate glucose concentration (32 mg dl-1), or neutral pH (7.0) did not impair proliferation. This study indicates that impairment of lymphocyte proliferation by tumour physico-chemical conditions may be a factor in the relatively poor success rate of IL-2/LAK cell immunotherapy.


Malignant progression of a mouse fibrosarcoma by host cells reactive to a foreign body (gelatin sponge). The QR regressor tumour (QR-32), a fibrosarcoma which is unable to grow progressively in normal syngeneic C57BL/6 mice, was able to grow progressively in 13 out of 22 mice (59%) when it was subcutaneously coimplanted with gelatin sponge. We established four culture tumour lines from the resultant tumours (QRsP tumour lines). These QRsP tumour lines were able to grow progressively in mice even in the absence of gelatin sponge. The ability of QRsP tumour cells to colonise the lungs after intravenous injection and to produce high amounts of prostaglandin E2 (PGE2) during in vitro cell culture was much greater than that of parent QR-32 cells. These biological characteristics of QR-32 cells and QRsP tumour cells were found to be stable for at least 6 months when they were maintained in culture. We also observed that QR-32 cells were able to grow progressively in five out of 12 (42%) mice after coimplantation with plastic non-adherent peritoneal cells obtained from mice which had been intraperitoneally implanted with gelatin sponge. These host cells reactive to gelatin sponge increased the production of high amounts of PGE2 by QR-32 cells during 48 h coculture. Preliminary in vitro studies implicated the involvement of hydrogen peroxide and hydroxyl radical as some of the factors necessary to induce QR-32 cells to produce high amounts of PGE2 and to accelerate tumour progression.


Modulation of the proliferative response of breast cancer cells to growth factors by oestrogen. A number of growth factors have been implicated in the control of the proliferation of breast cancer cells and some have been reported to mediate the proliferative effects of oestradiol. MCF-7 cells were treated with growth factors in the presence and absence of oestradiol. Oestradiol increased the response of cells to the proliferative effects of epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha) and basic fibroblast growth factor (bFGF). Platelet derived growth factor (PDGF) and cathepsin D had no effect in the presence or absence of oestradiol while TGF-beta slightly reduced the stimulation by oestradiol. In the absence of oestradiol, there was little effect of combinations of growth factors although the effects of bFGF and IGF-I were additive. In the presence of oestradiol, the effects of bFGF and TGF-alpha were additive whereas bFGF acted as an IGF-I antagonist. Overall, bFGF had the greatest effect on cell proliferation although this was less marked than the previously described effect of the IGFs and insulin. The effects of oestradiol on the sensitivity of cells to the proliferative effects of bFGF did not appear to result from regulation of bFGF receptor expression.


p53 expression in Reed-Sternberg cells of Hodgkin's disease. Mutation of the p53 protein may represent the commonest genetic event in human malignancy. Abnormal p53 expression has been reported in a variety of carcinomas, sarcomas and lymphoid neoplasms; however there is little information in relation to Hodgkin's disease. The expression of the nuclear phosphoprotein was investigated in paraffin-embedded biopsies from fifty patients with Hodgkin's disease using a polyclonal antibody, CM-1 and in snap-frozen material with monoclonal antibodies, PAb 1801 and PAb 240. Specifically, immunoreactivity was localised to the Reed-Sternberg cells or mononuclear variants in both nodular sclerosing (86% cases) and mixed cellularity (57% cases) subtypes of Hodgkin's disease. However, no positive staining was found in our cases of nodular lymphocyte predominant type Hodgkin's disease. Serial biopsies following recurrence of disease demonstrated consistent results. It is suggested that overexpression of p53, probably mutant, may have a role in the tumorigenesis of Hodgkin's disease.


Induction of HSP70 is associated with vincristine resistance in heat-shocked 9L rat brain tumour cells. The most prominent cellular changes in heat-shock response are induction of HSPs synthesis and reorganisation of cytoskeleton. Vincristine was used as a tool to evaluate the integrity of microtubules in 9L rat brain tumour cells recovering from heat-shock treatment. Cells treated at 45 degrees C for 15 min and recovered under normal growing condition became resistant to vincristine-inflicted cytotoxicity and microtubule destruction. Among all HSPs, the level of HSP70 and the degree of vincristine resistance are best correlated. HSP70 and tubulin were found to be associated with each other as they were co-immunoprecipitated by either anti-HSP70 or anti-beta-tubulin monoclonal antibody. The current studies establish for the first time that HSP70 can complex with tubulin in cells and this association may stabilise the organisation of microtubules thus protect the heat-treated cells from vincristine damage. These findings are noteworthy in combining hyperthermia and chemotherapy in the management of malignant diseases.


Growth, morphology and chemosensitivity studies on postconfluent cells cultured in 'V'-bottomed microtiter plates. This study assessed the growth pattern, cellular organisation and chemosensitivity of established human tumour cell lines growing as postconfluent cultures in 'V'-bottomed, 96-well microtiter plates. Cross-sections of the colon (HT29, SW620, SW1116), ovarian (A2780) and head and neck (UM-SCC-22B) carcinoma microcultures allowed in situ evaluation of the cellular organisation in the wells. After 5 days of growth, every cell line had reached confluence, but each of them displayed a specific pattern of cell stacking which ranged from two to ten layers. Postconfluent HT29 cells displayed morphologic features suggestive of some degree of enterocytic differentiation. Growth and cytotoxicity could be studied reliably and reproducibly in this system with the sulforhodamine B protein assay. Against HT29 postconfluent cultures, the EC50's (drug concentrations producing absorbance readings 50% lower than those of non-treated wells) of 5-fluorouracil and of the ether lipid, hexadecylphosphocholine, were 1 mM and 50 microM respectively. The possibility to perform chemosensitivity tests using semiautomated microtiter plate technology supports further evaluation of this system as an alternative antitumour drug testing model.


No effect of dose, hepatic function, or nutritional status on 5-FU clearance following continuous (5-day), 5-FU infusion. One hundred and eighty seven patients (155 males, 32 females) with histologically proven and previously untreated head and neck cancer were entered in the study. A total of 222 cycles of therapy were analyzed (cisplatin 100 mg m-2 on day 1 and 5-day continuous intravenous infusion of 5-FU 550-1069 mg m-2 day-1, mean 875.5 mg m-2 day-1). Significant interpatient variability for various 5-FU pharmacokinetic parameters was observed including an almost ten-fold range in 5-FU clearance (5-FU Cl, ml min-1 m-2 = 791-7769, mean 2820.7). Log 5-FU Cl was not modified by 5-FU dose (r = -0.1034, P = 0.124, n = 222). Poor linear correlations between log 5-FU Cl and hepatic function tests were observed (respective r and P values for 222 cycles, log AST:0.0526, 0.4365; Log ALT: -0.1167, 0.0842; Log A1K. Phos.:0.154, 0.0214; Log GGT: 0.0652, 0.3436; Log LDH: -0.0984, 0.1563; Log bilirubin: 0.1278, 0.0601). The log 5-FU Cl was also poorly correlated with the serum concentration of various nutritional proteins (respective r and P values for 222 cycles, Albumin: 0.0110, 0.8714; prealbumin: -0.1067, 0.1129; transferrin: 0.0439, 0.5226). Laboratory data including indices of hepatic function and nutritional status cannot account for the interpatient variability in 5-FU disposition.


Intake of vegetables, fruits, beta-carotene, vitamin C and vitamin supplements and cancer incidence among the elderly: a prospective study. A cohort of 11,580 residents of a retirement community initially free from cancer were followed from 1981 to 1989. A total of 1,335 incident cancer cases were diagnosed during the period. Relative risks of cancer were calculated for baseline consumption of vegetables, fruits, beta-carotene, dietary vitamin C, and vitamin supplements. After adjustment for age and smoking, no evidence of a protective effect was found for any of the dietary variables in men. However, an inverse association was observed between vitamin C supplement use and bladder cancer risk. In women, reduced cancer risks of all sites combined and of the colon were noted for combined intake of all vegetables and fruits, fruit intake alone, and dietary vitamin C. Supplemental use of vitamins A and C showed a protective effect on colon cancer risk in women. There was some suggestion that beta-carotene intake and supplemental use of vitamin A, C, and E were associated with reduced risk of lung cancer in women, but none of these results were statistically significant. These inverse associations observed in women seem to warrant further investigation, although there was inconsistency in results between the sexes.


Contribution of 3H-thymidine labelling index and flow cytometric S-phase in predicting survival of patients with non-Hodgkin's lymphoma. The 3H-thymidine labelling index (3H-dT LI) of cell suspensions from fresh material and the flow cytometric S-phase (FCM-S) of nuclei recovered from paraffin blocks were determined on the same pathologic lymph node specimen for 190 non-Hodgkin's lymphomas (NHLs). FCM-S was defined by a planimetric method and by an optimization procedure. Poor correlation coefficients were observed among the three cell kinetic variables. All three cell kinetic variables were significant indicators of 8-year survival and median survival time. The life-regression procedure evidenced a significant relative contribution of 3H-dT LI and FCM-S, thus suggesting a different biologic meaning of the two cell kinetic variables. This finding was further supported by evidence that simultaneous use of 3H-dT LI and FCM-S can identify groups of patients with different survival better than when either modality is used alone. Multivariate analysis indicated that the risk groups as defined by cell kinetic variables are predictors of survival even in the presence of established factors such as histology and stage.


Sarcomas in north west England: III. Survival. Survival data on a population-based series of bone, soft tissue and visceral sarcomas diagnosed in the North West of England between 1982-84 and subjected to histopathological peer review are presented. Five-year crude survival for all cases was 34%. Survival in males and females did not differ significantly (P = 0.6, 5-year survival 32% vs 36%) but was markedly worse for patients diagnosed over the median age of 60 years, even when allowance was made for underlying mortality (P = 0.03, 34% vs 44%). Five-year survival rates for the major site groups were: bone 44%; soft tissues of head, neck and trunk 36%; soft tissues of extremities 35%; female genital tract 35%; retroperitoneum 15%; gastro-intestinal tract 13%. Analysis by the major histological types revealed the following survival rates: leiomyosarcoma--female genital tract 25%, gastro-intestinal tract 14%, non-visceral soft tissue 21%; malignant fibrous histiocytoma of soft tissue 29%; liposarcoma 52%; osteosarcoma of bone 46%; and chondrosarcoma of bone 50%.


The influence of aminoglutethimide and its analogue rogletimide on peripheral aromatisation in breast cancer. The influence of the prototype aromatase inhibitor Aminoglutethimide (AG) and its analogue Rogletimide (RG) on peripheral aromatisation were investigated in 13 postmenopausal women with advanced breast cancer. Seven patients received AG 1,000 mg daily plus Hydrocortisone (HC) cover and six received RG as dose escalation of 200 mg bd, 400 mg bd and 800 mg bd. In vivo aromatase inhibition was investigated using the double bolus injection technique with [4-14C] oestrone ([4-14C]E1) and [6,7-3H] androstenedione ([6,7-3H]4A) followed by a 96 h urine collection. The labelled urinary oestrogens were separated and purified by chromatography and HPLC. Plasma oestradiol (E2) was also measured. AG mean aromatase inhibition was 90.6% +/- 1.8 s.e.m. and E2 suppression 75.7% +/- 7.3 s.e.m. RG mean aromatase inhibition was 50.6% +/- 9.8 s.e.m. at 200 mg bd, 63.5% +/- 5.7 s.e.m. at 400 mg bd and 73.8% +/- 5.8 s.e.m. at 800 mg bd. E2 suppression was 30.7% +/- 9.5 s.e.m., 40.2% +/- 10.3 s.e.m. and 57.6% +/- 9.2 s.e.m. respectively. These results confirm the efficacy of AG as an aromatase inhibitor. RG produced dose dependent E2 suppression and aromatase inhibition, but even at the maximum tolerated dose of 800 mg bd had sub-optimal aromatase inhibition and oestradiol suppression compared with AG.


Lobular panniculitis after subcutaneous administration of interleukin-2 (IL-2), and its exacerbation during intravenous therapy with IL-2. Interleukin-2 (IL-2) is now registered for the treatment of renal cell carcinoma in a number of European countries. The subcutaneous (sc) route of administration is being used increasingly because of its better toxicity profile compared with higher dose intravenous (iv) protocols. We report here a patient who developed a lobular panniculitis at the site of sc IL-2 injection which prevents continuation of sc therapy. Subsequent administration of the same IL-2 dose by iv injection caused recurrence of the problem again necessitating discontinuation of IL-2 treatment.


Lung cancer and passive smoking: reconciling the biochemical and epidemiological approaches. The accurate determination of exposure to environmental tobacco smoke is notoriously difficult. There have been to date two approaches to determining this exposure in the study of association of passive smoking and lung cancer: the biochemical approach, using cotinine in the main as a marker, and the epidemiological approach. Typically results of the former have yielded much lower relative risk than the latter, and have tended to be ignored in favour of the latter, although there has been considerable debate as to the logical basis for this. We settle this question by showing that, using the epidemiologically based meta-analysis technique of Wald et al. (1986), and misclassification models in the EPA Draft Review (1990), one arrives using all current studies at a result which is virtually identical with the biochemically-based conclusions of Darby and Pike (1988) or Repace and Lowry (1990). The conduct of this meta-analysis itself raises a number of important methodological questions, including the validity of inclusion of studies, the use of estimates adjusted for covariates, and the statistical significance of estimates based on meta-analysis of the epidemiological data. The best estimate of relative risk from spousal smoking is shown to be approximately 1.05-1.10, based on either of these approaches; but it is suggested that considerable extra work is needed to establish whether this is significantly raised.


Significance of S-phase fraction and hormone receptor content in the management of young breast cancer patients. Tumours from 336 breast cancer patients under the age of 50 were analysed for hormone receptor content and by DNA flow cytometry. Sixty-six percent of the tumours were positive for estrogen receptors (ER), 60% were progesterone receptor (PR) positive and 42% showed DNA diploid profiles. DNA hypodiploid tumours were relatively frequent (7%), especially in patients aged 40 years or less (11%). S-phase fraction (SPF), with a mean of 10%, correlated significantly with receptor status, DNA ploidy, lymph node status, tumour size and age. With a median follow-up period of 34 months, the distant recurrence-free interval was independently predicted by lymph node status, tumour size, SPF and PR content. Amongst the 212 patients who had not received adjuvant systemic treatment, receptor status was, in addition to lymph node status and SPF, independently related to distant recurrence rate. A high SPF identified a subgroup with high recurrence rate, comprising approximately one third of the node-negative patients. Similarly, the one third of node-positive patients who had PR-positive tumours with a low S-phase fraction formed a subgroup with low recurrence rate. We conclude that hormone receptor assays and DNA flow cytometry should be useful tools in the management of breast cancer patients less than 50 years of age.


Interleukin-4 receptor and epidermal growth factor receptor expression in colorectal cancer. Interleukin-4 receptor (IL-4R) and Epidermal Growth Factor receptor (EGFR) were assessed as factors associated with adenoma-carcinoma progression in colorectal cancer and tumour invasion. A monoclonal antibody (MR6) was applied to detect IL-4R in: metaplastic polyps (five cases), adenomas (15 cases), and carcinomas (44 adenocarcinomas and one squamous cell). Positive labelling was obtained in all polyps, adenomas and in 40/45 carcinomas. Normal colonic mucosa of these patients, as well as macrophages and lymphocytes infiltrating the tumour stroma, were also positively labelled with MR6. Four out of five poorly differentiated adenocarcinomas did not show IL-4 receptor expression. No significant correlation was found with tumour size, lymph node stage and IL-4 receptor expression. On the above specimens a parallel detection of epidermal growth factor receptors (EGFR) by a monoclonal antibody (EGFR 1) was carried out. Expression of EGFR was found in 14/20 polyps and in 22/45 carcinomas. All but one of the EGFR positive malignant tumours showed coexpression of IL-4 receptor. Lymph node involvement by tumour cells was detected in 25 out of 45 patients. Eighteen of these 25 cases were positive with EGFR1.


Single agent high-dose cisplatin (200 mg m-2) treatment in ovarian carcinoma. Twenty patients with epithelial ovarian carcinoma were treated with high-dose cisplatin 200mg m-2. Patients were to receive three cycles at 21 day intervals. Treatment was stopped if severe myelosuppression or any neurotoxicity occurred. Overall, eight (40%) of patients responded with a complete response in five (25%). Four of 16 (25%) previously treated patients responded. The median duration of response was 44 weeks (range 6-130). In patients previously treated there was a significant association (P < 0.002) between response and a remission free interval of 52 weeks or more from primary chemotherapy. Toxicity was assessable in 18 patients. Alopecia and nausea/vomiting were common. Myelosuppression was recorded in nine patients delaying planned administration in eight of 35 cycles. Five patients developed anaemia and six thrombocytopenia. Neurotoxicity affected seven patients and varying degrees of tinnitus six patients. Neurotoxicity and myelosuppression were indications for cessation of treatment in 8 patients receiving less than three cycles. Analysis revealed no significant association between toxicity and prior cisplatin exposure, age or the amount of high-dose cisplatin administered. This series reveals that it is possible to achieve good response rates using high-dose cisplatin without encountering debilitating neurotoxicity.


Flavone acetic acid (FAA) with recombinant interleukin-2 (TIL-2) in advanced malignant melanoma. II: Induction of nitric oxide production. Plasma samples were collected from 20 patients undergoing phase I clinical trial with flavone-8-acetic acid (FAA; 4.8 g m-2 per dose) in combination with recombinant human interleukin-2 (rhIL-2; 6-18 i.u. m-2 per day) for the treatment of metastatic melanoma. Samples were analysed for nitrate content as an indication of the oxidation of L-arginine to nitric oxide. Pretreatment plasma nitrate levels (53 +/- 4 microM) were significantly above those of healthy volunteers (19 +/- 4 microM). The maximum plasma nitrate concentration obtained after treatment, 190 +/- 29 microM (range 49 to 655 microM), was comparable to that of mice treated with FAA. Most of the increases occurred 3-5 days after initiation of a 5 day infusion of rhIL-2, but three of the increases occurred within 2 days of a 1 h infusion of FAA alone. The maximum plasma nitrate concentrations of the three patients which underwent remission (two complete, one partial) following treatment (368 +/- 143 microM) were significantly higher (P < 0.05) than those of patients with progressive disease. Hypotension was the major dose-limiting side effect, and there was no relationship between the degree of hypotension and the rise in plasma nitrate. The results provide evidence that treatment of patients with FAA and rhIL-2 induce the synthesis of nitric oxide, a physiological mediator and potential cytotoxic agent.


Haemostatic changes and thromboembolic risk during tamoxifen therapy in normal women. Tamoxifen has been implicated as a risk factor for venous thrombosis in advanced breast cancer although the evidence for increased arterial or venous thrombosis with tamoxifen in early breast cancer is less clear. The effect of tamoxifen on haemostasis, and thereby possible thromboembolic risk, was investigated in normal women enrolled in a placebo controlled trial of tamoxifen as a chemopreventative agent for breast cancer. There was an initial reduction in fibrinogen levels in all women on tamoxifen over the first year of follow-up and a marginal reduction in antithrombin III and Protein S in postmenopausal women at 6 months. There were no changes in cross linked fibrinogen degradation products or Protein C for pre or post-menopausal women. There was no increase in the incidence of thromboembolic events on tamoxifen. This study demonstrates that tamoxifen has only marginal effects on factors involved in haemostasis reported to affect the incidence of arterial or venous thromboembolic disease. The follow-up time is relatively short (maximum 36 months) and careful long term follow-up is necessary to detect clinically significant morbidity.


The adenoma-carcinoma sequence in the colorectum--early appearance of a hierarchy of small intestinal mucin antigen (SIMA) epitopes and correlation with malignant potential. The colorectal adenoma-carcinoma sequence was examined in relation to the ectopic expression of the oncofoetal Small Intestinal Mucin Antigen (SIMA), to the development of morphologic changes in the adenoma and perineoplastic mucosa and to indices of malignant potential. Four anti-SIMA MAbs, which define a novel hierarchy of SIMA epitopes in the normal small intestine and adjacent to colorectal cancers, were used in a retrospective immunohistochemical study of Familial Adenomatous Polyposis (FAP, n = 183) and non-familial (n = 44) adenomas. Inappropriate expression of SIMA epitopes was first detected in mucosa adjacent to minute microadenomas larger than three glands, and with increase in size, in increasing amounts within adenomas themselves, but not with microadenomas smaller than three glands or regions of flat mucosa free of adenomas. SIMA epitope expressed in mucosa adjacent to adenomas preceded changes in perineoplastic morphology, which progressed with adenoma growth to resemble transitional mucosa (TM) adjacent to cancers. Thus, the onset of both SIMA expression and morphological changes in TM were consistent with reactive rather than pre-existing field change phenomena. The previously reported hierarchy of four SIMA epitopes (5C5, 3D4, 4D3, 6C5) was also consistently observed in the adenoma-carcinoma sequence, and applied to (i) the order of epitope detection, (ii) the number of positive adenomas and (iii) extent of staining; (iv) the height in the crypt and (v) distance from the adenoma to which epitopes were expressed in perineoplastic mucosa. These observations are consistent with a progression of changes in mucin composition with adenoma development. The percentage of positive adenomas and reactivity scores for each anti-SIMA MAb correlated with increasing adenoma size, degree of dysplasia and growth pattern. SIMA expression appears to predate the earliest reported oncogene and tumour suppressor gene changes, was persistent and increased throughout adenoma development. SIMA epitopes are thus markers of very early neoplastic change, whose expression correlates with malignant potential and may contribute to the accumulation of changes necessary for tumourigenesis.


Increased p53 protein content of colorectal tumours correlates with poor survival. Allelic losses on the short arm of chromosome 17 occur frequently in colorectal cancers. Despite the existence of other common molecular events such as loss of the long arms of chromosomes 18 and 5, it has been demonstrated that the former has the greatest prognostic significance. Of the various genes mapping to the commonly deleted sequence, the best candidate as a 'target' seems to be the p53 antioncogene. We applied our methods of detection of the p53 protein in a series of 78 colorectal cancers stored in a tumour bank from 1985 to 1989, for which the median follow-up was 42 months. Nuclear-attached p53 was quantified by flow cytometry and soluble p53 was assayed by ELISA. Both assays used a monoclonal antibody considered to be specific for a conformational epitope present only on the mutated protein. Fifty of the 78 tumours (64%) were found to present significant levels of p53 attached to the nucleus. A further two tumours contained high levels of p53 only in their soluble fraction. Thus, 52 out of 78 cancers (67%) were considered to be positive for p53. The p53 content correlated with 17p loss (P < 0.002), hyperdiploid DNA content (P < 0.001) and tumour site (P < 0.03), but not Dukes' stage (P = 0.15). p53 negative cases had a better overall survival than p53 positive ones (P < 0.03). When the 14 stage D tumours were excluded from the analysis, p53 was no longer significantly predictive of survival (P < 0.07), but remained predictive of recurrence (P < 0.02) and metastasis (P < 0.03). Multivariate analysis was not performed because of the small number of cases. Overall, disease-free and metastasis-free survival were compared to the positivity obtained either with pAb 421 and/or 1801 or pAb 240 since all three were used in the flow cytometric analysis, defining subsets of 421-, 1801+ and 421-, 1801-, 240+. The presence of nuclear protein presenting the mutation-specific epitope, recognised by pAb 240, was found to be the most discriminant. It must be noted that univariate survival analysis demonstrated that more than 80% of patients with p53-negative tumours were alive at 3 years vs less than 50% in the p53-positive group. A large prospective study should be conducted to define the exact prognostic significance of the p53 content of colorectal carcinomas.


Clinical pharmacokinetics of epirubicin: the importance of liver biochemistry tests. The influence of liver biochemistry tests on epirubicin pharmacokinetics has been investigated in 52 women with advanced breast cancer, 27 of whom had radiologically proven liver metastases. Patients received epirubicin 12.5-120 mg m-2 given as an i.v. bolus. Epirubicin levels were measured by HPLC following the first cycle of treatment. Epirubicin elimination, expressed as clearance (dose/AUC), in the 22 patients with normal AST and bilirubin was compared with that of 30 patients with a raised AST +/- raised bilirubin. Epirubicin clearance was significantly reduced in the patients with a raised AST, whether their serum bilirubin was normal (22 patients) or elevated (eight patients). In the 30 patients with a raised AST +/- raised bilirubin, epirubicin clearance correlated strongly with the level of AST (r = -0.72) but not with serum bilirubin, alkaline phosphatase, albumin or creatinine. Using a multiple regression analysis, AST was the only one of these biochemical variables predictive of epirubicin clearance (r2 = 0.47, P = 0.0006). We conclude that a raised serum AST is a more sensitive and reliable measure of abnormal epirubicin pharmacokinetics than increased bilirubin. These findings have implications for anthracycline treatment in patients with abnormal liver biochemistry.


Cholesterol metabolism during the growth of a rat ascites hepatoma (Yoshida AH-130). The metabolism of cholesterol has been investigated in tumour cells, ascitic fluid and blood serum during the growth of an ascites hepatoma (Yoshida AH-130) in the rat. High rates of cholesterol synthesis and elevated free and esterified cholesterol content were observed in tumour cells. During tumour growth, the host animals progressively developed marked changes in the level and distribution of serum cholesterol consisting in an increase of total cholesterol and of a marked reduction of HDL cholesterol (HDL2 subfraction in particular). In agreement with previous observations, these findings indicate that a consistent pattern of altered cholesterol homeostasis develops in relation to normal or neoplastic tissue growth. High synthetic rates and intracellular accumulation of cholesterol are observed in the proliferating cells. Moreover, blood serum cholesterol decreases in the HDL fraction while it increases in LDLs, suggesting that during proliferative processes cholesterol fluxes between tissues and serum lipoproteins are markedly perturbed.


Chemosensitivity testing of fresh human gastric cancer with highly purified tumour cells using the MTT assay. A major problem associated with the chemosensitivity testing of fresh human tumour cells using the MTT assay is the contamination of nonmalignant cells in the tumour tissues. Highly purified fresh human gastric cancer cells could be obtained from 43 solid tumours and eight malignant ascites for the MTT assay. The success rate of the MTT assay was 87.9% (51 of the 58 cases), and the purity of tumour cells was greater than 90% after separation on Ficoll-Hypaque and Percoll discontinuous gradients in primary, or metastatic lesions, and also ascites. Cisplatin, mitomycin, and doxorubicin were more potent drugs than etoposide and 5-FU against gastric cancer cells. The chemosensitivity in differentiated cancer was equivalent to that in non-differentiated cancer. Twenty of the 51 patients with gastric cancer had evaluable lesions, and they received chemotherapy according to the results of the MTT assay using highly purified tumour cells. A clinical response was obtained in 12 of these 20 patients (response rate: 60.0%; five with complete response, seven with partial response).


Treatment with a non-steroidal anti-inflammatory agent delays the growth of spontaneous pulmonary metastases of a mammary adenocarcinoma of non-detected immunogenicity. Previous reports showed that treatment with non-steroidal anti-inflammatory agents (NSAIA) can alter the growth profile of a variety of tumours. In this study, the effect of NSAIA treatment on the growth of the primary tumour and the appearance of spontaneous pulmonary metastases, was investigated. A mammary adenocarcinoma of non-detected immunogenicity, C7HI, was grafted subcutaneously in the lateral flank of Balb/c mice. Oral treatment with approximately 1 mg kg-1 day-1 piroxicam delayed both tumour growth and the growth of pulmonary metastases. Survival of mice bearing the primary tumour was significantly lengthened by anti-inflammatory treatment. Similarly, in separate experiments, after surgical removal of the primary tumour by day 34 after grafting, the group of mice treated orally with piroxicam also exhibited a higher survival rate than the control group. Upon surgical removal of the primary tumour 34 days after grafting, piroxicam treatment significantly decreased both the number and size of pulmonary metastases. The results of this study lends support to the hypothesis that inhibition or modulation of inflammation may delay tumour organisation and growth. It is suggested that piroxicam treatment may be an appropriate adjunct therapy to delay the appearance of pulmonary metastases and to increase life-expectancy in a host whose primary tumour has to be surgically removed.


The detection of specific gene rearrangements in non-Hodgkin's lymphoma using the polymerase chain reaction. Characteristic gene rearrangements are present in most non-Hodgkin's lymphomas (NHL). These are usually detected by Southern blotting techniques. In this study, the ability of the polymerase chain reaction (PCR) to detect the t(14;18) chromosomal translocation and immunoglobulin heavy chain (IgH) gene rearrangement was evaluated. DNA from 14 follicular and 42 diffuse B-cell lymphomas was examined using oligonucleotide primers specific for opposing sides of the IgH gene rearrangement on chromosome 14 (towards conserved VH and JH sequences) and opposing sides of the t(14;18) chromosomal translocation (towards the major breakpoint region of the bcl-2 gene on chromosome 18 and conserved JH sequence on chromosome 14). The t(14;18) translocation was detected in 57% of follicular lymphomas and 21% of diffuse B-cell lymphomas. Clonal IgH gene rearrangements using PCR were detected in 50% follicular and 52% of the diffuse lymphomas. Either or both of these rearrangements were detected in 93% follicular and in 59% of diffuse lymphomas. PCR is a rapid and easy technique that can detect the abnormal rearrangement of the bcl-2 gene and clonal IgH rearrangement, indicating the presence of lymphoma. This may be of benefit in monitoring response to therapy and in predicting prognosis in this disease.


Potent antitumour activity of (-)-(R)-2-aminomethylpyrrolidine (1,1-cyclobutanedicarboxylato)platinum(II) monohydrate (DWA2114R) against advanced L1210 leukaemia in mice. The time dependency of the antitumour activity of (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)platinum(II) monohydrate (DWA2114R) was examined in mice inoculated i.p. with 10(5) mouse L1210 leukaemia cells. The increase in life span was greater in mice treated with 72 mg kg-1 DWA2114R on the 6th day following tumour inoculation than in mice treated at earlier times. Such superior effects against advanced L1210 were also seen with cis-diammine (1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) but not seen with the parent compound, cis-diamminedichloroplatinum(II) (CDDP) or other antitumour agents devoid of platinum. After the injection of DWA2114R on day 6, most of the ascites tumour cells accumulated in the S and G2/M phases of the cell cycle and the total cell number markedly decreased from 10(8) to less than 10(6). On the other hand, only a temporary G1 arrest and a less than 50% reduction of the cell number were induced after a similar treatment on day 3. Interestingly, the superiority of DWA2114R for advanced L1210 was lost in athymic nude mice and mice depleted of T cells by anti-thymocyte antisera. In addition, mice cured of advanced L1210 specifically rejected re-inoculated L1210 cells. These results indicate that the superior antitumour activity against advanced L1210 is unique to DWA2114R among the agents tested (except for CBDCA) and is caused by both an increased drug susceptibility of tumour cells and a drug-induced antitumour effect mediated by T cells of the host mice.


O6-alkylguanine-DNA-alkyltransferase activity and nitrosourea sensitivity in human cancer cell lines. The DNA repair enzyme, O6-alkylguanine-DNA-alkyltransferase (ATase), is thought to be the principal mechanism controlling resistance to nitrosoureas and related alkylating agents. We compared the sensitivities of five human testis and five bladder tumour cell lines to two nitrosoureas (N-nitroso-N-methylurea (MNU) and mitozolomide) with cellular levels of ATase. Enzyme levels ranged from 3 to 206 fmol mg-1 protein (0.1 x 10(4) to 5.1 x 10(4) molecules/cell) in the testis lines and from 11 to 603 fmol mg-1 (0.4 x 10(4) to 9.1 x 10(4) molecules/cell) in the bladder lines. Based on IC50s in an MTT assay, the testis tumour cell lines were, on average, four times more sensitive to MNU and six times more sensitive to mitozolomide than the bladder cell lines. The cytotoxicities of MNU and mitozolomide were closely related (R = 0.9). In the testis cell lines ATase activity (molecules/cell) was related to IC50s for mitozolomide (R = 0.97) but not MNU (R = 0.78). In the bladder cell lines and overall, ATase activity correlated with cellular sensitivity to neither agent. Relatively high levels of resistance occurred in cells expressing low levels of ATase, and amongst cell lines expressing high levels of ATase, large differences in IC50s were observed. These results support the suggestion that resistance to nitrosoureas can be mediated by mechanisms other than ATase and that at relatively high levels of expression, ATase does not confer resistance in proportion to its activity.


The prognosis of primary and metastasising melanoma. An evaluation of the TNM classification in 2,495 patients. The prognostic value of the TNM classifications of the UICC dated 1978 and 1987, was investigated in a population of 2,495 patients who were followed up over the long term. In the case of primary melanoma, Breslow's tumour thickness proved to be the most powerful predictor of patient survival in multivariate analysis, while the significance of Clark's level ranged after that of both localisation of the primary tumour and the sex of the patient. The continuous proportional relationship between tumour thickness and risk of death makes it possible to regrade thickness groups. Grading cutoffs at 1, 2 and 4 millimetres, with no account being taken of depth of invasion, proved to be particularly favourable for a classification in accordance with prognostic criteria. In advanced stages of the disease, the outcome of locoregional and distant metastasis is significantly different; and furthermore in the case of locoregional metastasis, in-transit and satellite metastases exert a significantly better prognosis than regional lymph node involvement. Isolated juxtaregional lymph node metastases occurred primarily or during the course of the observation period in only 19 patients of our group, and, in comparison with visceral metastases, proved to have only an insignificantly better prognosis. For this reason, it would appear meaningful to assign them to a common stage. On the basis of these results, proposals are made for modifications of the TNM classification.


Anticipatory nausea and emesis, and psychological morbidity: assessment of prevalence among out-patients on mild to moderate chemotherapy regimens. The prevalence of nausea and emesis among a series of out-patients (n = 95) receiving mainly mild-to moderately-emetic cytotoxics, was assessed, along with levels of psychological morbidity. Particular focus was given to the rates of psychologically-based (anticipatory) nausea and emesis. Results indicated that 23% of patients experienced anticipatory nausea and the majority reported that this occurred before at least half of the previous treatment cycles. Both emetic challenge of chemotherapy regimen and younger age were linked to this anticipatory effect. The data clearly indicated that nausea and emesis, both post-treatment and in anticipation of treatment, carried a psychological cost with anxiety being highest in those experiencing anticipatory nausea and/or emesis. The role of anxiety in the aetiology of psychologically-based nausea and emesis was not evaluated and it is considered that a prospective study is needed to clarify the exact contribution of psychological factors in the incidence of both post-treatment and anticipatory side-effects.


The expression of 5T4 antigen in colorectal and gastric carcinoma. The expression of 5T4, an oncotrophoblast cell surface antigen was examined in 72 colorectal and 27 gastric carcinomas, with immunoperoxidase technique, on frozen sections. Highly significant association was found between 5T4 expression in the malignant cells and metastatic spread. The results suggest that the appearance of 5T4 molecules in cancer cells reflects a change which may contribute to the development of metastatic potential.


The influence of the host on the course of gastric carcinoma. Immunoglobulins (Ig) and some complement components (C) were quantified in sera from patients with gastric carcinoma before surgery and at regular intervals during a 5-year follow-up. The preoperative concentrations of C1-INH and C4 were higher (P < 0.0005 and P < 0.005) and IgG lower (P < 0.0005) in 50 patients with recurrence than in 46 5-year survivors. The prognostic significant of C1-INH was superior to that of the extent of disease (F-values 37.1 and 26.1). The preoperative immune data classified 76% of the patients correctly as to recurrence and no recurrence. Also, the preoperative C1-INH concentration had a highly significant effect on time to recurrence of cancer (P = 0.0007), adjusting for age and disease extent. After surgery the mean IgG concentrations were within normal range and without difference between the two groups. On the other hand, the concentrations of C1-INH and C4 in the individual patients in both groups remained the same from before to after surgery and throughout the observation period (P = 0.34). Apparently, the serum levels of C1-INH and C4 do not reflect the bearing of cancer. We therefore suggest that these variables represent an independent immune state that is appropriate to the host. A comparison of our variables with those of healthy individuals seems to support this idea. This immune state has a significant influence on whether a resected gastric cancer will recur, and also on how soon recurrence may be manifest.


Cancer potential in liver, lung, bladder and kidney due to ingested inorganic arsenic in drinking water. In order to compare risk of various internal organ cancers induced by ingested inorganic arsenic and to assess the differences in risk between males and females, cancer potency indices were calculated using mortality rates among residents in an endemic area of chronic arsenicism on the southwest coast of Taiwan, and the Armitage-Doll multistage model. Based on a total of 898,806 person-years as well as 202 liver cancer, 304 lung cancer, 202 bladder cancer and 64 kidney cancer deaths, a significant dose-response relationship was observed between arsenic level in drinking water and mortality of the cancers. The potency index of developing cancer of the liver, lung, bladder and kidney due to an intake of 10 micrograms kg day of arsenic was estimated as 4.3 x 10(-3), 1.2 x 10(-2), 1.2 x 10(-2), and 4.2 x 10(-3), respectively, for males; as well as 3.6 x 10(-3), 1.3 x 10(-2), 1.7 x 10(-2), and 4.8 x 10(-3), respectively, for females in the study area. The multiplicity of inorganic arsenic-induced carcinogenicity without showing any organotropism deserves further investigation.


Increased expression and mutation of p53 in choroidal melanoma. Using CM-1 antibody directed against the human p53 protein, high levels of mutant p53 protein expression were found in 12 out of 18 malignant choroidal melanomas. In contrast, we failed to observe elevated p53 expression, indicating the absence of p53 mutation in seven choroidal naevi, a potentially premalignant condition that can progress to form malignant melanoma. For two choroidal melanomas, we demonstrated that high levels of p53 protein were accompanied by exon 7 mutations. The mutations were found at codon 238, TGT-->TTT and codon 253, ACC-->AGC. These observations suggest that acquisition of abnormalities of the p53 gene may be an important step in the development of malignant melanoma.


Cancer mortality in African and Caribbean migrants to England and Wales. Cancer mortality during 1970-85 of immigrants from East and West Africa and the Caribbean to England and Wales is described. Overall cancer mortality was raised in West African males (RR 1.38, 95% CI 1.25-1.54), and non-significantly raised in West African females (RR 1.14, 0.96-1.37) compared to mortality in the England and Wales-born population. Much of the increased risk was due to very high rates of liver cancer in males (RR 31.6, 23.8-41.9), but rates were also raised for a wide range of other cancers in each sex. Only lung and brain cancer had significantly decreased mortality. In East Africans, overall cancer mortality was low in males (RR 0.63, 0.56-0.70), and in females (RR 0.80, 0.72-0.89). Mortality was significantly low for cancers of the stomach, pancreas and testis, and Hodgkin's disease in males, for cervical cancer in females, and for lung cancer and melanoma in both sexes. Cancer sites with significantly raised mortality included oropharyngeal cancer, leukaemia, and multiple myeloma in both sexes. In Caribbean immigrants overall cancer rates were significantly low in males (RR 0.71, 0.68-0.74) and in females (RR 0.76, 0.73-0.80). Mortality was significantly low for many cancers including colorectal, lung, testis and brain cancers. Mortality was significantly raised only for cancer of the prostate in males, of the placenta in females, and of the liver, non-Hodgkin's lymphoma and multiple myeloma in both sexes. Overall, mortality was high from prostatic cancer and liver cancer, and was low from brain cancer, in predominantly ethnic African immigrant groups. Both East and West African immigrants had raised rates of leukaemia. All of the migrant groups had high rates of multiple myeloma and low rates of testicular, ovarian and lung cancer. Genetic and environmental factors that may contribute to these patterns are discussed.


The epidemiology of AIDS-associated non-Hodgkin's lymphoma in the World Health Organization European Region. This paper describes the epidemiology of AIDS-associated non-Hodgkin's lymphoma (NHL) in the World Health Organization (WHO) European Region. Data, collected by the WHO Collaborating Centre on AIDS in Paris, France, were derived from the national AIDS surveillance systems of 21 countries. Among 53,042 cases reported as of the end of June 1991, 1,617 (3.0%) had NHL as the presenting clinical manifestation of AIDS. The proportion of cases presenting with NHL ranged from 1.1% in children infected perinatally to 3.9% among haemophiliacs. In comparison with intravenous drug users (IVDUs) (2.6% of whom had NHL), a moderate excess was found among homosexual or bisexual men (odds ratio - OR -:1.2, 95% confidence interval - CI -:1.0-1.3). Over time, the proportion of NHL was constant, but whereas among homosexual or bisexual men the frequency of NHL as AIDS-indicator disease significantly increased (9.7% per year), among IVDUs a significant downward trend emerged (17.1% per year). In respect to age, two peaks of NHL were seen at the age groups 10-19 (3.8%) and 50-59 (4.3%). The proportion of AIDS-associated NHL significantly increased with increasing age among homosexual and bisexual men and heterosexuals whereas it decreased among IVDUs. All these differences, however, have to be interpreted cautiously on account of the limitations of the reporting systems.


Breast self examination and survival from breast cancer. The survival of 616 women aged 15-59 with breast cancer, 226 of whom had been taught and practised breast self examination (BSE) prior to diagnosis and 390 of whom had not, is reported. Six year survival rates were 73.1% in the BSE taught group and 66.1% in other women (P = 0.07).


The influence of carbogen breathing on tumour tissue oxygenation in man evaluated by computerised p02 histography. Tumour tissue oxygenation has been measured in man during carbogen breathing (95% O2, 5% CO2) using a commercially available polarographic electrode system (Eppendorf p02 histograph). At least 200 tumour measurements in each of 17 patients with accessible tumours were taken before, and subsequently continuously after the commencement of carbogen breathing for periods of 10 to 30 min. In 12 out of 17 patients studied there was a significant increase in median tumour p02 during the first 10 min of carbogen breathing (range 9 to 1800%). There was an initial rapid increase in tumour p02 which was maintained until 8 to 12 min, but then decreased throughout the subsequent treatment period. Although there was a reduction in the proportion of point measurements < or = 10 mmHg in 11 out of 13 patients, during carbogen breathing, measured points of < or = 2.5 mmHg were only eliminated in three out of 11 tumours. The time course has implications for the planning of clinical trials utilising radiotherapy with carbogen breathing.


Lack of prognostic significance of DNA ploidy and S phase fraction in breast cancer. DNA Ploidy and S phase fraction (SPF) were measured in Stage I and II breast cancers from patients with at least 8 years of follow-up, to assess the prognostic significance of these data. Disaggregated sections of formalin-fixed, paraffin-embedded tumour were analysed by flow cytometry. SPF was calculated using a rectangular model of S phase, after subtraction of background debris using an exponential model. 64% of tumours were DNA aneuploid. The median SPF was 4.5% for DNA diploid, and 10.9% for DNA aneuploid tumours. There were small reductions in survival at 10 years for DNA aneuploid tumours, and for tumours with above median SPF, but these were not statistically significant. The relative hazard for DNA aneuploid tumours was 1.20 (95% CI 0.81-1.76), and for high SPF was 1.31 (95% CI 0.87-1.98). Neither factor was statistically correlated with survival in multivariate analysis. Technical and theoretical factors limit the accuracy and reproducibility of flow cytometric data, and may explain the lack of prognostic information given.


Glutathione S-transferase activity and isoenzyme composition in benign ovarian tumours, untreated malignant ovarian tumours, and malignant ovarian tumours after platinum/cyclophosphamide chemotherapy. Glutathione S-transferase (GST) isoenzyme composition, isoenzyme quantities and enzymatic activity were investigated in benign (n = 4) ovarian tumours and malignant ovarian tumours, before (n = 20) and after (n = 16) chemotherapy. Enzymatic activity of GST in cytosols was measured by determining 1-chloro-2,4-dinitrobenzene conjugation with glutathione, cytosolic GST subunits were determined by wide pore reversed phase HPLC, using a S-hexylglutathione-agarose affinity column, and isoelectric focussing. Both GST activity and GST pi amount were not related to histopathologic type, differentiation grade, or tumour volume index in untreated malignant tumours. GST isoenzyme patterns were identical in benign tumours and malignant tumours before and after platinum/cyclophosphamide chemotherapy, while GST pi was the predominant transferase. Mean GST activity and GST pi amount were decreased (P < 0.05) in malignant ovarian tumours after platinum/cyclophosphamide chemotherapy compared to untreated ovarian malignant tumours. No relation was found in untreated ovarian tumours between GST pi amount and response to platinum/cyclophosphamide chemotherapy. Thus, within the limitations of the current study no arguments were found for a role of GST in in vivo drug resistance of malignant ovarian tumours to platinum/cyclophosphamide chemotherapy.


Glutathione S-transferase activity and isoenzyme distribution in ovarian tumour biopsies taken before or after cytotoxic chemotherapy. A study involving the measurement of glutathione S-transferase activities and isoenzyme distributions in human ovarian tumours has been carried out. These tumours have been obtained either at initial debulking surgery, prior to cytotoxic chemotherapy, or at second look laparotomy following chemotherapy. The response rates of these two groups to chemotherapy differ markedly, with patients who have relapsed following initial chemotherapy showing a reduction in response rates to subsequent chemotherapy. Analysis of these data show no statistically significant differences between the glutathione S-transferase activity or isoenzyme distribution in these two groups of patients. Significant differences were observed in the glutathione-S-transferase activities (GST) between tumours and normal ovaries. GST activities in pre-chemotherapy tumours (n = 33, P = 0.01) and post-chemotherapy tumours (n = 20, P = 0.001) where significantly higher than the GST activity in normal ovaries (n = 15). One feature was the expression of the basic isoenzyme which is expressed more in normal ovaries than in tumours. No differences in these parameters were observed in normal peritoneal tissue taken from patients before or after chemotherapy. These data do not support the hypothesis that changes in glutathione S-transferase enzyme activity or isoenzyme expression are major determinants of response to chemotherapy in ovarian tumours.


The selection of cases for randomised trials: a registry survey of concurrent trial and non-trial patients. The British Stomach Cancer Group. A randomised trial of adjuvant chemotherapy vs placebo in operable stomach cancer recruited 249 patients from the West Midlands Region between 1976-1980. A Cancer Registry survey identified a further 1261 suitable concurrent cases. Trial patients were compared with the 960 non-trial cases from participating Districts. Only 493 (51%) non-trial cases passed all of the prospective trial selection criteria for entry. Stage and fitness caused the majority of exclusions and were also highly prognostic. A univariate analysis comparing eligible patients with the trial showed the two groups to be balanced for the significant independent prognostic factors of the trial. However, differences in patient age and the surgery performed indicate that recruitment may have been influenced by unknown selection factors. This survey highlights the difficulty of retrospective selection and confirms the need for randomised controls. Data available from specialist Registries may be used to help develop new protocols and to verify and extend trial results.


Competing risks determining event-free survival in early breast cancer. To evaluate the natural history of a disease and the effects of therapeutic interventions, it is important to determine which are the causes of treatment failure and to assess the extent to which each cause contributes to the total failure rate. The paper presents a new biostatistical technique to decompose the total event-free survival of a diseased population into cause-specific failure rates. The technique was based on a competing risk approach thereby avoiding biases related to assumptions of independence between different types of event. Such assumptions are inherent in the conventional Kaplan-Meier or actuarial methods. The competing risk method was used to analyse the pattern of failure among 2,850 pre- and postmenopausal patients with early-stage breast cancer and the results were compared to those obtained using conventional methods. The following events were analysed: loco-regional recurrence, distant metastasis, contralateral breast cancer, other new primary malignancies, and intercurrent deaths. The rate of new primary malignancies was found to be significantly higher in post- than in premenopausal patients (6% vs 3% at 10 years). In low-risk, node-negative postmenopausal patients the incidence of recurrences from breast cancer were found to be no greater than other types of events. This observation highlights the significance of the effect of different adjuvant therapies not only on the disease itself but also on the risk of second primary malignancies and other intercurrent diseases. In general, it was found that the conventional statistical methods tended to overestimate the event-specific rates. In conclusion, the method based on competing risks permits an unbiased analysis of all types of events determining the total event-free survival. It is thus useful for the description of the natural history of breast cancer as well as other diseases.


Monitoring blood flow to colorectal liver metastases using laser Doppler flowmetry: the effect of angiotensin II. Many colorectal liver metastases are hypovascular, and their low level of perfusion is associated with limited drug uptake and poor response rates with regional chemotherapy. We have previously shown that hepatic arterial vasoconstrictors may increase drug delivery to liver tumours, but the underlying haemodynamic changes have not been defined. Using intraoperative laser Doppler flowmetry (LDF) we have assessed the effect of intraarterial angiotensin II (AI) on tumour blood flow in ten patients with colorectal liver metastases. Measurements were performed during placement of infusion catheters for regional chemotherapy. Blood flow was recorded continuously with a Periflux PF3 perfusion monitor via a probe held on the tumour surface, following hepatic arterial infusion of 15 micrograms AII over 90 s. Six patients with isolated small metastases (< 5 cm in diameter) showed increases in flow, which reached a peak at 170-240 s from the start of AII infusion, and which were closely correlated with the corresponding increase in arterial pressure (r = 0.92, P = 0.009). Of the four patients with large confluent tumour deposits, two showed smaller transient increases in flow over the first 60 s of AII infusion and two had no measurable flow response. Increased blood flow following AII infusion may increase the exposure of tumour to therapeutic agents. This study suggests that both tumour size and the effect upon systemic arterial pressure may be important determinants of the blood flow response to AII. LDF may provide useful information about the potential of AII and other vasoconstrictors to enhance targeting precision.


Prognostic variables for the selection of patients with operable soft tissue sarcomas to be considered in adjuvant chemotherapy trials. From 1975 to 1988, 144 patients naive of treatment, with non-metastatic soft tissue sarcoma were treated at Fondation Bergonié by surgery, followed by radiotherapy and without chemotherapy. An analysis of prognostic variables was done on this population to determine patients for whom an adjuvant chemotherapy would be relevant. Prognostic variables in overall survival (OS), metastasis-free survival (MFS), disease-free and local free recurrence survivals were analysed by univariate and multivariate analysis. In multivariate analysis using Cox's model, only tumour depth and tumour grade were significant with the MFS end point, while tumour depth, tumour grade and tumour site were significant when considering OS. A predictive stratification for patients is proposed: a favourable prognostic group with grade 1 tumour or superficial, grade 2 tumour (5-year OS: 97.8%; 5-year MFS: 100%); an intermediate prognostic group with deep, grade 2 tumour or superficial, grade 3 tumour (5-year OS: 58.8%; 5-year MFS: 48.1%); and finally a poor prognostic group with deep, grade 3 tumour (5-year OS: 31.7%; 5-year MFS: 34.1%). Patients in the intermediate and poor prognostic groups who present a high metastatic risk are to be considered for adjuvant chemotherapy trials.


Value of epidermal growth factor receptor status compared with growth fraction and other factors for prognosis in early breast cancer. The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein whose expression is important in the regulation of breast cancer cell growth. The relationship between EGFR status (determined by an immunocytochemical assay) and various prognostic factors was investigated in 164 primary breast cancers. Overall 56% of tumours were EGFR-positive and the expression of EGFR was unrelated to axillary node status, tumour size and histological grade; and it was poorly associated with the tumour proliferative activity measured by Ki-67 immuno-cytochemistry. The relapse-free survival (RFS) probability at 3-years was significantly worse for patients with EGFR positive tumours (P = 0.003) and for those whose Ki-67 score was > 7.5% (P = 0.0027), as well as in patients with axillary node involvement (P = 0.01) and with poorly differentiated tumours (P = 0.04). Immunocytochemical determination of EGFR and cell kinetics gave superimposable prognostic information for predicting RFS with odds ratios of 3.51, when evaluated singly. In our series of patients EGFR, Ki-67 and node status retain their prognostic value concerning RFS in multivariate analysis. The 3-year probability of overall survival (OS) was significantly better in node-negative patients (P = 0.04) and was similar in EGFR-positive and negative patients. In conclusion, EGFR status appears to be a significant and independent indicator of recurrence in human breast cancer and the concomitant measurement of the tumour proliferative activity seems to improve the selection of patients with different risks of recurrence.


Comparison of plasma prolactin and CEA in monitoring patients with adenocarcinoma of colon and rectum. Plasma prolactin (PRL) and carcinoembryonic antigen (CEA) were measured by radioimmunoassay in 74 patients with adenocarcinoma of colon and rectum. The markers were correlated with disease stage, histological grade and progression/remission of disease. The circulating preoperative median PRL and CEA levels were significantly higher in colorectal cancer patients than in their respective controls. PRL was elevated in all Dukes stages and in all histological grades of the tumour whereas the rise in CEA was more pronounced in Dukes D. Out of 74 patients, 29% (21/74) developed recurrent disease and 31% (23/74) responded to the treatment. With regard to monitoring recurrence(s), the predictive value of PRL was 94% which was significantly greater than that of CEA which was only 62%. In patients who developed liver metastases PRL remained elevated whereas CEA showed more than 100-fold increase. Therefore, we feel that CEA is a better marker for monitoring patients who developed liver metastases. From our results, we suggest that PRL can be used as a better overall marker for detecting recurrence(s) in patients with colorectal adenocarcinoma.


Teaching sociology: sharing learning.

Teaching sociology: sharing learning. The ideas in this article arose from discussions between two nurse educators brought together from different professional backgrounds to teach on a new Project 2000 course. It is a frank and honest account of a partnership involving two teachers--a nurse and a sociologist. It is also an illustration of theory-in-use; of an attempt in the workplace to move away from the split between theories in sociology, nursing and education and their practical application. The authors discuss how they worked in partnership--planning, delivering and evaluating their contribution to the course's 18 month long common foundation programme.


Cardiology: improving nurses' resuscitation skills. Nurses have a crucial role to play in determining whether victims of cardiac arrest survive, but skills vary and, perhaps because of the onerous responsibility placed upon them, some nurses feel less than confident in using their abilities to the full. The author describes a resuscitation training course for staff in one hospital, designed to bolster confidence and to ensure all nurses are equally competent in giving assistance when cardiac arrest occurs.


Education: perceptions of supernumerary status. This, the first of three related articles, explores the attitudes of students, preceptors and lecturers to supernumerary status. While the contractual aspect of supernumerary status is understood by the three groups, there is confusion about the educational aspect. Next week, the reality of supernumerary status from the experience of students will be examined, while the final article will look at the role of students, preceptors, sisters/charge nurses and lecturers in the implementation of supernumerary status.


The management of fractures of the hip.

The management of fractures of the hip. Proximal femoral fractures are a common reason for admission to orthopaedic units, and one which may become even more regular as the population ages. Despite this, newcomers to the orthopaedic arena, such as nursing students, may be confused when faced by different hip fractures and the treatments which may be offered. This article seeks to clarify some of these points by outlining the anatomy of the proximal femoral region, various common fractures, the treatments available to the surgeon and aspects of nursing care associated with the pre and post operative phases of the patient's care.


An independent stoma care service.

An independent stoma care service. This article describes the establishment of an independent stoma care service, and the problems the author encountered. Set up just over four years ago, it is one of the few independent stoma care services in the UK. It currently caters exclusively for patients in private hospitals in London and the South-East of England, and the author also holds a clinic in Harley Street. Over 300 patients benefit from the service.


Care of people with diabetes in hospital. Although most hospitals have protocols for the care of people with diabetes who are admitted as a result of their condition or other illness, deficiencies in the care offered are still regularly reported. This article explores reasons why the care of people with diabetes in hospital seems to be unsatisfactory, and proposes some solutions to the problems.


A milieu approach to dementia day care.

A milieu approach to dementia day care. Applying the principles of therapeutic milieu, in which individual needs can be recognised within those of a group, can help people with dementia to realise their potential. The implementation of a system of care based on such an approach in a day unit is described, focusing on the need to acknowledge the essential worth of attenders and providing adequate support for staff.


Education. The reality of supernumerary status. This is the second of three related articles looking at the reality of supernumerary status for undergraduate nursing students in Northern Ireland. The first (1) explored students, preceptors and lecturers' perceptions of the term 'supernumerary'. Next week, the role of students, charge nurses and preceptors will be examined in relation to its implementation. This article portrays the reality of supernumerary status from the students' perspective, using diaries and a questionnaire.


Ensuring compliance in enteral feeding.

Ensuring compliance in enteral feeding. Enteral feeding provides a lifeline for some patients, but is not without its own hazards and risks. The complications include blocking of tubes and gastrointestinal intolerance, and may inhibit and delay the patient's recovery from illness. This article discusses the difficulties, and offers some potential solutions to them.


Mental health: use and abuse of control and restraint. The recent report of the inquiry into complaints at Ashworth Hospital (1) recommended that control and restraint techniques, used to contain violent conduct, should be used as a last resort, 'and should be subject to careful scrutiny to determine system failures'. This article, which points out that nurses in many areas are victims of increased levels of violence, defines control and restraint techniques, who should use them and in which situations their use may be sanctioned. The author concludes that although preservation of the patient's rights and dignity is paramount, nurses who have undergone control and restraint training are more confident practitioners when they are confronted with violent situations. In a second article next month, Tarbuck will look at issues of ethics and the human rights of patients.


Education: implementation of supernumerary status. This series of three articles began with a discussion of perceptions of supernumerary status and was followed by an examination of the reality of the term as seen through the eyes of students, teaching and ward staff. The series concludes this week with an exploration of the context in which supernumerary status can best be implemented.


Current initiatives in open learning.

Current initiatives in open learning. This article considers the needs for open learning in pre- and post-registration nurse, midwife and health visitor education. Examples of institutions using open learning are provided and the English National Board's current initiatives in relation to open learning packages are detailed. The Board's future initiatives demonstrating its commitment to the support of open learning are also described.


Living aids: wheelchair evaluation and prescription. This article reviews the assessment procedure for patients who require a wheelchair. The author, a medical specialist in prosthetics and orthotics, describes the important physical and social factors which must be considered, and defines what equipment is available from the National Health Service and elsewhere.


Off-the-shelf audit: is it feasible?

Off-the-shelf audit: is it feasible? Increasing interest in audit in the health service has focused attention on the tools and methods used to achieve it. These can be extremely expensive, so a tendency to opt for off-the-shelf packages has developed. This article reviews how one such instrument, The Central Nottinghamshire Psychiatric Nursing Audit, has been used in two settings over the past three years, with particular emphasis on its cost-effectiveness.


The named nurse in perspective.

The named nurse in perspective. This is the first of three articles that concentrate on the implications of the named nurse initiative for nursing practice. The way the initiative has been put into practice in Sheffield Health Authority will be described next week, followed by Steve Wright's analysis of the value of wearing name badges. To set the scene, Royal College of Nursing General Secretary Christine Hancock takes a wider look at the concept of the named nurse and relates it to systems of organising nursing that are in general use.


A new development in radiology: TIPS.

A new development in radiology: TIPS. Interventional radiology has had a significant impact on patient care over the past 20 years, with the development of low-risk procedures. Nurses specialising in this field must maintain their knowledge of innovations to ensure that the nursing care of such patients remains appropriate. This article describes the indications for and procedural technique of transjugular intrahepatic portosystemic shunting (TIPS), a new initiative in interventional radiology. Although there are risks and side-effects, initial evidence of the method's efficacy suggests it has great potential in reducing morbidity and length of hospital stay.


The role of the support worker.

The role of the support worker. The major contribution which nurses make to patient care could be enhanced still further if nurses' professional skills were used to the full. Advances in medical technology, faster patient throughput, increasing numbers of very elderly people and higher consumer expectations have changed and extended the demands on nurses and nursing.


Distribution of interleukin 1 receptor antagonist protein (IRAP), interleukin 1 receptor, and interleukin 1 alpha in normal and psoriatic skin. Decreased expression of IRAP in psoriatic lesional epidermis. The distribution of interleukin 1 alpha (IL-1 alpha), type 1 interleukin 1 receptor (IL-1R), and the interleukin 1 receptor antagonist protein (IRAP), was investigated in biopsies of normal skin, and in uninvolved and lesional skin of patients with psoriasis, using specific monoclonal antibodies. We report the novel finding that IRAP is distributed throughout the living layers of the epidermis in normal skin, and is also associated with sebaceous glands and eccrine sweat glands. Our finding that the inhibitor protein IRAP is present in areas where the pro-inflammatory cytokine IL-1 alpha is distributed provides strong evidence in favour of a cytokine regulatory system in normal skin. We further document for the first time that IL-1R in normal skin is localized to the living layers of the epidermis, sebaceous and eccrine glands, as well as to a prominent network of dermal dendritic cells, and upper dermal blood vessels. There was a consistent reduction in the level of IRAP expression in lesional compared with uninvolved skin in biopsies from six out of seven psoriasis patients. Decreased IRAP expression in lesions of psoriasis indicates that alterations in the level of this inhibitor protein may be important in the pathogenesis of inflammatory skin conditions.


Intracellular expression of type VII collagen during wound healing in severe recessive dystrophic epidermolysis bullosa and normal human skin. The ability of keratinocytes to synthesize basement membrane components in vivo during wound healing in normal human skin and in severe recessive dystrophic epidermolysis bullosa (RDEB) was investigated. Indirect immunofluorescence using anti-type VII collagen (VIIc, recognizing the globular non-helical component of the molecule), anti-type IV collagen, anti-laminin and bullous pemphigoid antisera, was performed on biopsies of intact skin and of healing skin taken between 7 and 14 days after dermatome injury (upper to mid-dermal wounding) in eight patients with severe RDEB and in seven normal subjects. Baseline anti-type VIIc immunofluorescence showed completely absent staining of the epidermis, dermis and dermo-epidermal junction in severe RDEB samples, and bright linear dermo-epidermal junction fluorescence in normal human skin. In 5/5 normal human skin samples taken 9-12 days post-wounding, some type VIIc expression was noted within basal cells as well as in a continuous or interrupted linear distribution at the basement membrane zone. In all the severe RDEB biopsies sampled between days 10 and 13 (5/5), anti-VIIc fluorescence was also seen with varying intensity within basal and lowermost suprabasal cells, and in one day 14 sample at the dermo-epidermal junction. Low levels of intracellular type IVc were seen in both groups, but only in those samples taken 7-9 days after injury; later biopsies showed only continuous dermo-epidermal junction staining. Linear basement membrane zone labelling with laminin and bullous pemphigoid antisera was seen in all samples in both sets of subjects, even at day 7, but there was no detectable intracellular antisera staining.(ABSTRACT TRUNCATED AT 250 WORDS)


Epidermolysis bullosa in Northern Ireland. Cases of epidermolysis bullosa (EB) diagnosed in Northern Ireland during a 23-year period (1962-84) were identified from dermatology clinic files, paediatric hospital notes and cases known by general practitioners. A total of 48 confirmed new cases of EB were diagnosed during the screening period. This involved 31 families, with identification of 36 further cases. The distribution of incident EB subtypes was: simplex 31 (65%), junctional 1 (2%), dystrophic 12 (25%) and acquisita 4 (8%). The incidence rate of new cases of EB diagnosed per year is 1.4/million and prevalence of all forms estimated at 32/million. The prevalence of simplex, junctional and dystrophic forms is 28, 0.7 and 3/million, respectively.


Exposure to house dust mites in homes of people with atopic dermatitis. The median relative density of house dust mite populations was determined in mattresses in the homes of 23 people with atopic dermatitis (AD) who were mite-sensitive. It was significantly higher (total mites [dead and live] 174/0.1 g of dust: live mites 45.5/0.1 g) than in those of 23 healthy non-atopics (total mites 52/0.1 g; live mites 7.5/0.1 g; P < 0.05, < 0.01, respectively; Mann-Whitney U-test). There was no significant difference between mite population densities in mattresses in damp homes (n = 27; total mites 188/0.1 g; live mites 36/0.1 g) and those in homes with no damp (n = 19; total mites 116/0.1 g; live mites 26/0.1 g). These data demonstrate a clear association between AD and exposure to large numbers of mites, independent of the presence of domestic damp. People with AD were exposed to densities of > 500 mites/0.1 g of mattress dust five times more frequently than non-atopics, corresponding to a relative risk of 25.0, but were exposed to densities of < or = 50 mites/0.1 g five times less frequently. The overall relative risk for AD, with a cutoff of 50 mites (total)/0.1 g, was 8.1. There was an obvious positive correlation between magnitude of exposure and frequency of disease. It is hypothesized that the association between high densities of mites and AD is related to differences in lipid composition of the shed squames on which the mites feed: those of people with AD may be of greater nutritional value than those of non-atopics, thus enhancing mite population growth.