[Thyroid regulation pathways and its effect on human luteal function]. There are interferences between function of the thyroid gland and the ovary. Thus, thyroid disorders may influence the ovarian cycle. Up to now interferences in three main areas are described: the secretion of GnRH, i.e. FSH and, above all, LH, the peripheral metabolism of steroids (androgens, estrogens, and SHBG), and metabolism of prolactin. By employing human luteal cells, we were able to demonstrate that there is also a direct impact of thyroid regulation on luteal function: TSH, but not TRH or T3 or T4, possesses a luteotropic activity and reaches one fifth of the biological activity of hCG. This kind or direct influence may play an important role in the pathophysiology in patients with hypothyroidism.


[Computer-assisted patient management. Individual electronic data processing-assisted documentation in gynecology]. EDP-supported documentation of patients has become increasingly important over the last several years. Seven autonomous wards of the gynecological department of the Hospital Rudolfstiftung were equipped with a clinical documentation system. The integration of this new system into the infrastructure of the KIS (Krankenhausinformationssystem) was accomplished with the help of the MD-ADV. We also implemented one of the best-known statistical analyzing systems, SAS, so that we have simple possibilities for statistical calculation and graphical plots.


[Local prevention of infection with metronidazole before vaginal hysterectomy--comparative effect compared with systemic prevention?]. A prospective clinical trial was designed to examine the influence of a local intravaginal application of metronidazole on postoperative infectious morbidity in 114 women undergoing vaginal hysterectomy. On the evening before vaginal hysterectomy, 51 patients received a vaginal suppository of metronidazole (500 mg). These patients were compared with a group of 63 patients who were given a single-shot prophylaxis with 1,500 mg cefuroxime intravenously. With regard to febrile morbidity, urinary tract infection and pelvic infection there was no significant difference in the two treatment groups. There was no statistically significant difference in the postoperative duration of hospital stay and additional antibiotic therapy between the two groups either. We did not see serious infections in our examination. Our results suggest that a local single-dose application of metronidazole in vaginal hysterectomy might have the same efficacy on postoperative infectious morbidity than a systemic antibiotic prophylaxis and that it can reduce antibiotic costs.


Biological gestational age and its calendar assessment with ultrasound. Part 2: Biological-calendar scales for prediction of birth-date. Evaluation of enzymatic and sonographic assessments has been done in terms of relativity of gestational length. The principle of relativity means that it is not the calendar time but the biological one that qualifies the results of both the diagnostic procedures and treatments. The described biological-calendar scale comprises and links both the enzymatic and ultrasonographic data. The shifting of the end of the biological scale to the end of the calendar scale enables the appropriate evaluation of both the child's maturation for labor, as well as the pregnancy duration from the last menstrual period until the end of normal births range. It is why almost all ultrasound scales heretofore useful only for 50% of deliveries (as usually encompassing range of 40 weeks) have to be lengthened.


[Image of the uterus in Greek-Roman antiquity and its representation]. The author describes the common ideas of the human uterus in Etruscan and early Roman Italy known from anatomical ex-votos and gems, most of them found in the regions of Etruria and Latium. In contrast, a medical or scientific concept of the human uterus can be found in various manuscript copies from ancient writers, especially in those derived from the Coan school of medicine, from ancient Greek philosophers and in those derived from Soranus of Ephesus, the best-known teaching authority on obstetrics in Roman medicine. Miscellaneous concepts were characteristic of drawings in later manuscript copies of the early middle ages.


Health promotion and disease prevention for the older adult: an overview of the current recommendations and a practical application. This report provides a description of the components of health promotion and disease prevention services for the older adult. The aspects to be included, the current available organizational and governmental recommendations, and a discussion of the criteria on which these recommendations were based are presented. A practical, easy-to-use worksheet will enable NPs to incorporate relevant health promotion and prevention activities into each client visit. This approach insures that the range of comprehensive services will be offered.


Managing relapse as a positive opportunity for change. During the process of lifestyle changes, there is a high incidence of relapse during the first three months. There are frequently negative feelings experienced by both the nurse practitioner and the client. This paper presents information concerning relapses, conceptualizing relapse as a positive experience, and strategies to support clients who encounter relapse in their efforts to maintain positive health habits.


Assessment of domestic violence by nurse practitioners. Domestic violence has reached epidemic proportions in American society. In the normal course of supplying medical care to women and children, NPs will encounter victims of physical, sexual, and psychological violence. It is imperative that NPs know how to assess for victimization and safety and that they provide patients with needed information about community services.


Assessing depression in primary care.

Assessing depression in primary care. NPs often see patients as they enter the health care system and are frequently confronted with overt and covert manifestations of depression. Early identification and treatment leads to the reduction of some symptoms and referral for treatment of others, thus promoting health and wellness while interrupting the development of additional symptoms.


The nurse practitioner as healer: a process of interactive simultaneity. Interactive simultaneity draws on the human-living-health model of nurse theorist Rosemarie Parse and the author's research on the healing activity of arctic and subarctic medicine women to enhance contemporary clinical practice in a variety of situations.


Spontaneous remission of cancer: an example of health promotion. Spontaneous remission provides an example of health promotion: that of the body/mind/spirit maximizing its potential and showing, not only the disappearance or lessening of pathology, but also the healing capabilities of the individual. This brief overview of a grounded theory research study summarizes nine healees' experiences with a diagnosis of cancer and their subsequent remissions.


Predictive value of microalbuminuria in patients with insulin-dependent diabetes of long duration. To investigate the predictive value of microalbuminuria (albumin excretion rate 30-300 mg/24 h) as a risk factor for overt diabetic nephropathy in patients with longstanding insulin dependent diabetes. 10 year follow up of patients with normoalbuminuria (albumin excretion rate < 30 mg/24 h), microalbuminuria (30-300 mg/24 h), and macroalbuminuria (> 300 mg/24 h) based on two out of three timed overnight urine samples. Outpatient clinic of Helsinki University Hospital. 72 consecutive patients who had had insulin dependent diabetes for over 15 years. Urinary albumin excretion rate, mortality, and prevalence of diabetic complications after 10 years. 56 patients were re-examined at 10 year follow up, 10 had died, five were lost to follow up, and one was excluded because of non-diabetic kidney disease. At initial screening 22 patients had macroalbuminuria, 18 had microalbuminuria, and 26 had normal albumin excretion. Only five (28%, 95% confidence interval 10% to 54%) of the microalbuminuric patients developed macroalbuminuria during the 10 year follow up and none developed end stage renal failure. Two (8%, 1% to 25%) normoalbuminuric patients developed macroalbuminuria and four (15%, 4% to 35%) became microalbuminuric. Seven (32%, 14% to 55%) of the macroalbuminuric patients developed end stage renal failure and six (27%, 11% to 50%) died of cardiovascular complications. Microalbuminuria is not a good predictor of progression to overt nephropathy in patients with longstanding insulin dependent diabetes.


Use of oral contraceptives by adolescents and its consequences in Finland 1981-91. To study use of oral contraceptives among Finnish teenagers during 1981-91 and how abortions, childbirths, sexually transmitted diseases, and cardiovascular diseases changed during this period. Biannual cross sectional surveys with mailed questionnaires from 1981 onwards and analysis of national statistics. Finland. A nationwide sample of 14, 16, and 18 year olds. Sample size varied from 1249 to 3887 and response rate from 85% to 94%. Proportion taking oral contraceptive, fertility and abortion rates, hospital discharge rates, rates of sexually transmitted diseases. The proportion of teenagers taking oral contraceptives increased steadily. In 1991 the percentages among 14, 16, and 18 year olds were 2%, 18%, and 41% compared with 0.2%, 7% and 22% in 1981. Most users had a steady partner (80% of 16 year olds and 85% of 18 year olds). By 1989 rates of abortion had fallen from 12/1000 to 9.3/1000 in 16 year olds and from 25/1000 to 19.2/1000 in 18 year olds; fertility rates had fallen from 4.5/1000 to 2.3/1000 and from 23.5/1000 to 15.3/1000 respectively. Rates in 14 year olds fell only slightly. Gonorrhoea infection fell and HIV infection remained rare. Rates of hospital discharge after thromboembolic venous disease rose slightly. The increased use of oral contraceptives is the most likely explanation for decreasing abortion and fertility rates among teenagers. Increased reliance on the condom because of the threat of AIDS may increase unwanted pregnancies.


Is diabetes mellitus related to undernutrition in rural Tanzania? To investigate the relation between undernutrition and diabetes. Survey of glucose tolerance in rural Tanzania. Eight villages in three widely separated regions of Tanzania. 8581 people aged 15 and above: 3705 men and 4876 women. Oral glucose tolerance, body mass index, height, and low haemoglobin and cholesterol concentrations. In the eight villages 42.7-56.9% of all men and 30.0-45.2% of all women had a body mass index below 20 kg/m2; the lowest quintile was 18.2 kg/m2 in men and 18.6 kg/m2 in women. The prevalence of diabetes did not change significantly from the lowest to the highest fifths of body mass index in men (lowest 1.6% (95% confidence interval 0.8% to 2.9%) v highest 1.3% (0.7% to 2.5%)) or women (1.1% (0.6% to 2.1%) v 0.5% (0.2% to 1.2%)). In men and in women prevalence of impaired glucose tolerance was greater in the lowest fifths of height (8.2% (6.3% to 10.6%), and 11.1% (9.2% to 13.3%)) respectively and body mass index (9.6% (7.5% to 12.1%), and 8.4% (6.7% to 10.5%)) than in the highest fifths (impaired glucose tolerance 4.7% (3.4% to 6.5%); and 5.1% (3.9% to 6.7%); body mass index 5.1% (3.7% to 7.0%), and 7.7% (6.2% to 9.6%). Rates of diabetes were not significantly associated with low body mass index or height, but overall rates were much lower than those in well nourished Western populations. Increased impaired glucose tolerance in the most malnourished people may reflect the larger glucose load per kilogram weight. The role of undernutrition in the aetiology of diabetes must be questioned.


Decision to treat mild hypertension after assessment by ambulatory monitoring and World Health Organisation recommendations. To determine if one ambulatory blood pressure recording over 12 hours could detect those patients with mild hypertension who needed treatment according to the World Health Organisation-International Society of Hypertension (ISH) guidelines based on the causal measurement of diastolic blood pressure at successive visits to a clinic. Comparison of decision to treat based on one ambulatory measurement over 12 hours and standard blood pressure measurements over six months in the same patients. Outpatient hypertension clinic. 130 men and women with diastolic blood pressure of 90-104 mm Hg at second visit to clinic. Blood pressure measurements over six months. Measurement from ambulatory monitoring. Decision to treat. Of the 130 patients included, 108 were followed up over the six months. Treatment was started according to WHO-ISH criteria in 44 (13 at the third visit, 13 at the fourth, 18 at the fifth). According to the selected criteria for ambulatory blood pressure monitoring 41 patients would have been treated. Both methods agreed that the same 27 patients required treatment and the same 50 did not, but they did not agree in 31 patients. When calculated at the optimal diastolic blood pressure threshold determined by a receiver operating characteristic curve, the sensitivity, specificity, and positive predictive value of ambulatory blood pressure monitoring were 71% (95% confidence interval 57% to 84%), 82% (72% to 92%), and 66% (51% to 81%), respectively. If the WHO-ISH criteria are accepted as the standard for deciding to treat patients with mild hypertension the predictive value of one ambulatory blood pressure recording over 12 hours is too low to detect with confidence those patients who need treatment when managed according to these criteria.


Electronic communication between providers of primary and secondary care. To study the effects of the introduction of electronic data interchange between primary and secondary care providers on speed of communication, efficiency of data handling, and satisfaction of general practitioners with communication. Comparison of traditional paper based communication for laboratory reports and admission-discharge reports between hospital and general practitioners and electronic data interchange. Twenty-seven general practitioners whose offices were equipped with a practice information system and two general hospitals. Paper based communication was evaluated by questionnaire responses from and interviews with care providers; electronic communication was evaluated by measuring time intervals between generation and delivery of messages and by assessing doctors' satisfaction with electronic data interchange by questionnaire. Via paper mail admission-discharge reports took a median of 2-4 days, and laboratory reports 2 days, to reach general practitioners. With electronic data interchange almost all admission-discharge reports were available to general practitioners within one hour of generation. When samples were analysed on the day of collection (as was the case for 174/542 samples in one hospital and 443/854 in the other) the laboratory reports were also available to the general practitioner the same day via electronic data interchange. Fifteen general practitioners (of the 24 who returned the questionnaire) reported that the use of electronic admission-discharge reports provided more accurate and complete information about the care delivered to their patients. Ten general practitioners reported that electronic laboratory reports lessened the work of processing the data. Electronic communication between primary and secondary care providers is a feasible option for improving communication.


Quality of life measures in health care. I: Applications and issues in assessment. Many clinicians remain unsure of the relevance of measuring quality of life to their clinical practice. In health economics quality of life measures have become the standard means of assessing the results of health care interventions and, more controversially, the means of prioritising funding; but they have many other applications. This article--the first of three on measuring quality of life--reviews the instruments available and their application in screening programmes, audit, health care research, and clinical trials. Using the appropriate instrument is essential if outcome measures are to be valid and clinically meaningful.


London after Tomlinson. Clinical research. Sir Bernard Tomlinson's report focuses on London's health services, but his proposals have major implications for the future of clinical research--not just in London but in the United Kingdom as a whole. They must be seen in the context of a widely perceived decline in British research and development which also threatens clinical research. This article examines the implications of Tomlinson's proposals and related strategies and recommends the construction of a research market for the patient costs of clinical research to complement the NHS market for patient services introduced in 1991. These arrangements would help sustain the clinical research base and guarantee excellence.


For public or profession?--The new GMC performance procedures. The upheaval in the General Medical Council two decades ago came from doctors not the consumers the council was set up to protect. Since then there have been repeated calls for doctors to improve their self regulation by amending the disciplinary procedures. Private member's bills have failed and the GMC has now proposed performance procedures to deal with doctors who exhibit a "pattern of poor performance." After months of wide consultation in and outside the medical profession the GMC will decide next week whether to endorse the procedures, which unlike the conduct hearings will be inquiries by peers. Professor Margaret Stacey suggests that the procedures lack clarity, smacking of that "trust me" principle whose subtext is "but I'm not telling you what I'm up to."


Effect of using protocols on medical care: randomised trial of three methods of taking an antenatal history. To compare the effectiveness of three methods of taking an antenatal history on the quality of obstetric care. Randomised controlled trial. Antenatal clinic of St James's University Hospital, Leeds. 2424 women attending the hospital for the first (booking) visit. Histories were taken by midwives using an unstructured paper questionnaire, a structured paper questionnaire (incorporating a checklist), or an interactive computerised questionnaire (incorporating 101 clinical reminders). The number of clinical responses to factors arising from the antenatal booking history according to method of taking the history. Actions were categorised as medical and surgical, obstetric, personal, current symptoms and treatment, related to maternal age, and related to two common actions (cervical smear testing and dental hygiene) and were weighted for clinical importance by 10 obstetricians. Overall the unstructured questionnaire generated 1063 actions, the structured questionnaire 1146, and the computerised questionnaire 1122. The clinical importance of these actions was lowest for the unstructured questionnaire (overall total value score 1987 v 2182 and 2110 for the structured and computerised questionnaires respectively). The structured questionnaire was better than the computerised questionnaire in the medical and surgical (total value score 191 v 184), obstetric (275 v 241), and personal (430 v 360) categories but inferior in the current symptoms category (179 v 191). Structured questionnaires (computerised or paper) provide more and better information, and their use improves clinical response to risk factors. Computerised systems offer no further advantage in antenatal clinics.


Audit of compliance with antenatal protocols. To assess the implementation of action protocols dictated by antenatal risk factors noted at the initial (booking) antenatal visit. Retrospective study of 2000 women delivered between 1 March 1990 and 29 March 1991. Maternity department of a district general hospital supporting a multiethnic population in inner London. Comparison of clinical actions performed against those dictated by the department's protocols. Analysis according to clinical importance, gestation at booking, maternal age, parity, birth order, ethnic origin, and certainty of gestational age. Interobserver agreement between the two auditors was good (kappa statistic for risk factors detected, 0.78; for actions generated, 0.80). Of the 15,658 actions dictated by department protocols, 3673 (23.5%) were actually performed by the clinicians. The 63 combinations of risk factors and actions believed by consultants to be of particular clinical importance had an action rate of 28.3% compared with 18.6% for those considered less important (p < 0.001). Mothers who first visited the hospital antenatal clinic at or before 24 weeks' gestation had 25.2% of relevant protocols fulfilled (p < 0.001). Compliance was significantly improved in women aged 36 or over (32.4%), black women (24.9%), and cases of uncertain gestation (24.5%). Parity and birth order were not associated with an altered action rate. Ethnic origin deemed as "other" (than white, black, Asian, or oriental) or "unknown" was associated with poor compliance (19.3%). Compliance to a set of agreed protocols was poor even though a computer system was available and a protocol manual had been distributed. Protocols were more likely to be implemented in women who booked early and in some groups of women deemed at high risk including older mothers, black women, and those denoted as having uncertain gestational age.


Policy for controlling pain after surgery: effect of sequential changes in management. To observe the effects of introducing an acute pain service to the general surgical wards of a large teaching hospital. A study in seven stages: (1) an audit of current hospital practice succeeded by the sequential introduction to the general surgical wards of (2) pain assessment charts; (3) an algorithm to allow more frequent use of intramuscular analgesia; (4) increased use of local anaesthetic techniques of wound infiltration and nerve blocks; (5) an information sheet for patients about postoperative pain; (6) the introduction of patient controlled analgesia; (7) a repeat audit of hospital practice. Data were collected on each patient 24 hours after operation. University Hospital of Wales, which has both district general and tertiary referral functions. 2035 patients over nine months from all surgical specialties (excluding cardiac) at the hospital. General surgical operations were studied in detail and separated into major, intermediate, and minor for data collection. A change in the median visual analogue pain scores 24 hours after surgery for pain during relaxation, pain on movement, and pain on deep inspiration at each stage of the study. There was a reduction in median visual analogue scores during the study. The median (95% confidence interval) scores for pain during relaxation decreased from 45 (34 to 53) in stage 1 to 16 (10 to 20) in stage 7 for major surgical procedures. Pain on movement decreased from 78 (66 to 80) to 46 (38 to 48), and pain on deep inspiration decreased from 64 (48 to 78) to 36 (31 to 38). The reductions in median scores for intermediate and minor operative procedures showed similar patterns. The introduction of an acute pain service to the general surgical wards led to considerable improvement in the level of postoperative pain as assessed by visual analogue scores. Simple techniques of regular pain assessment and the more frequent use of intramuscular analgesia as a result of using an algorithm were particularly effective.


White coat hyperglycaemia: disparity between diabetes clinic and home blood glucose concentrations. To identify patients with discrepantly high clinic blood glucose concentrations compared with self reported values and to assess whether such patients have errors in self monitoring technique. To determine whether, in patients with good technique, the discrepancy is a transient phenomenon related to clinic attendance. Prospective study of diabetes clinic patients recruited over six months. Outpatient diabetes clinic of a teaching hospital. 34 consecutive patients with non-insulin dependent diabetes who had had at least two consecutive clinic blood glucose concentrations more than 5 mmol/l higher than the mean self reported concentration. Assessment of monitoring technique; presence of cognitive or physical impairment; serum fructosamine concentration; home and clinic blood glucose concentrations. 15 of 34 patients had errors in monitoring technique, 12 of whom had cognitive or physical impairment. In the remaining 19, the mean (SD) blood glucose concentrations of capillary and venous samples taken at home (10.2 (0.6) and 12.2 (1.1) mmol/l respectively) were significantly lower than in those taken at the clinic (16.8 (1.6) mmol/l, p < 0.0002). The fructosamine concentration was significantly higher in patients with monitoring errors than those without (2.4 (0.4) v 1.8 (0.4) mmol/l, p < 0.0001). "White coat" hyperglycaemia was detected in about half the patients but errors in technique accounted for the rest of the discrepancies. Patients' ability should be assessed before teaching self monitoring and the technique checked regularly.


Reforming the Department of Health's research and development policy: from the devil to the deep blue sea? Research into health and social services in Britain is largely funded by the Department of Health. Regional NHS research and development has recently been reformed and a new report now proposes replacement of the 13 research units funded by the department with three or four large multidisciplinary centres. Evidence to support such a step is lacking, and many criticisms of the existing units arise from poor departmental planning rather than deficiencies of the units themselves. Large units may make research less responsive to the department's needs, and it is essential that the proposed new structure is thoroughly evaluated before it is introduced.


Secondary care beyond Tomlinson: an opportunity to be seized or squandered? The Tomlinson report's emphasis on primary care and its essentially quantitative analysis of hospital care in London leaves little space for a picture of how secondary care for Londoners should look. In this article Fiona Moss and Martin McNicol argue that most outpatient work does not need to be done in hospitals. With proper organisation and better premises a genuinely specialist consultative service can be provided in primary health care centres, with benefit to patients and communication between primary and secondary care doctors. Hospitals would then house those outpatient services that needed major investigative facilities and much reduced inpatient capacity. It may no longer be necessary for each acute unit to offer a full range of services. Such a pattern of secondary care will have implications for the organisation of accident and emergency services and for postgraduate training. Above all Moss and McNicol argue that Tomlinson's recommendations demand that general practitioners and specialists should re-examine the services hospitals provide and agree on the best settings for different sorts of health care and the most appropriate skills to provide it.


Computer-assisted interpretation of visual fields in glaucoma. Visual field abnormality is an important diagnostic sign in glaucoma. Therefore, the presence or absence of visual field loss most often strongly influences diagnostic and therapeutic decisions in glaucoma management. Interpretation of visual field results is often difficult, however. Physiological variability of perimetric sensitivity values contributes to these difficulties. It has been our aim to develop improved computer-assisted methods for the recognition of early glaucomatous field loss. Our approach has therefore been to design techniques that are highly sensitive to small but significant departures from normality. We have investigated normal physiological variability in perimetric results and combined the obtained knowledge with pathophysiological models which are sensitive to the spatial patterns of field loss commonly seen in glaucoma. Thus, we have devised probability scores in order to take the complex physiological variability into account, and developed a hemifield analysis and an arcuate cluster analysis based on the normal anatomy of the retinal nerve fibre layer. A fundamental approach in the collection of normative data and the selection of glaucoma cases used in this project has been to select subjects using non-perimetric criteria (except for the removal of large field defects). Our objective here was to reduce bias from pre-conceived ideas of visual fields. This approach was used for (1) empirical studies on physiological variability, (2) development of analysis methods, and (3) evaluation of such methods. Glaucoma patients were selected based on evaluations of optic disc appearance. Normal subjects were never eliminated on the basis of perimetric results alone. The new methods developed in these studies have significantly improved discrimination between normal and glaucomatous field results, as compared with previously available techniques. Our results indicated that the usage of probability scores was the main source of this improvement, and that the location of observed field abnormalities and spatial modelling were other important factors. Candidate methods which did not properly combine spatial and normative analyses resulted in false positive defects in the mid-periphery and/or underestimated paracentral glaucomatous field defects. Similar approaches based on classification of visual field results in terms of significances, and on recognition of specific spatial patterns of field loss could be used for other groups of diseases having visual field abnormality as an important diagnostic sign.(ABSTRACT TRUNCATED AT 400 WORDS)


Race and ethnicity as biological constructs. For some time, biologists and anthropologists have overwhelmingly rejected the partitioning of modern humans into biological "races." An examination of recent human evolutionary history suggests that the zoological definition of race, based on significant genetic differences, cannot be legitimately applied to contemporary humans. Extensive past hybridization, plasticity of the human phenotype, the presence of ecotypes, the lack of extensive molecular information, and the lack of longitudinal multigenerational evaluations of diverse groups contribute to ambiguity in taxonomic assignment. Although biological aggregates do exist, they represent variation below the subspecies level, and, as such, are much more tenuous over evolutionary time. The persistent reference to quasibiological constructs such as ethnicity and race in the lay and scientific literatures requires that ethnicity be scrutinized for possible biological dimensions. The Diop model of ethnicity suggests that at least three components contribute to its formation: a historical factor, a linguistic factor, and a psychological factor, each of which can be examined for possible biological dimensions. Presumed biological affinities may allow certain groups to expand and extend their collective history and amplify their kin networks, possibly improving group biological fitness. Individual and group initial language of acquisition may influence brain physiology and organize the template for interpretation and behavior, creating greater consistency of response across otherwise divergent biological aggregates. Psychological continuity in particular behavioral traits, particularly repetitive multigenerational responses, may have an adaptive aspect at the group level. While ethnicity remains primarily a sociocultural category, it has biological precursors, parameters, and consequences for both individuals and groups. The genetic components of these biological dimensions remain to be identified and quantified.


Black-White differences in blood pressure: the role of social factors. This review summarizes current knowledge about the social sources of differences in blood pressure between blacks and whites in the United States. Genetic variables may play some role in explaining black-white differences in blood pressure, but social factors are more important than genetic ones. I review evidence linking stress, social integration, coping styles, and health behavior (including obesity) to high blood pressure, emphasizing that the distribution of these risk factors is shaped by larger social structures and processes. Effective efforts to reduce stress and improve health practices must not focus only on the individual but must seek to alter the social, economic, and political structures and arrangements that produce disease.


Models for dietary and weight change in African-American women: identifying cultural components. This paper explores cultural factors that potentially influence the effectiveness of weight-control programs for African-American women and attempts to challenge the perception that such programs operate in a culture-free context. The prevalence of obesity and related chronic conditions is notably higher among African-American than among white women. A larger net weight gain during adulthood among African-American women is associated at least in part with a lesser likelihood of losing weight. Evidence from clinical trials also suggests that African-American women have difficulty in losing weight. Cultural variables are thought to limit the intensity of weight-loss motivations among African-American women, but it is also possible that unrecognized cultural variables within behavioral weight-control programs limit their applicability to persons who do not fit a typical middle-class white American prototype. Many perspectives that differ between African-American and American cultures are directly relevant to the tasks and expectations involved in conventional behavioral therapy. Thus, efforts to make programs culturally appropriate for African-American women may need to go beyond superficial adaptations (eg, logistical accommodations) toward a behavioral analysis of weight control as it is likely to be approached by African-American women within their cultural context.


Community organization to reduce the risk of non-insulin-dependent diabetes among low-income African-American women. Non-insulin-dependent diabetes mellitus is epidemic among African-American women in the United States; reports of its prevalence among African Americans range from 50% to 60% higher than among whites. African Americans also incur higher rates of diabetes-related complications such as blindness, end-stage renal disease, and amputations. Data indicate that non-insulin-dependent diabetes among African Americans is associated with lower socioeconomic status and with obesity. Because obesity has been hypothesized as contributing to the growing numbers of non-insulin-dependent diabetics among African-American women, new strategies are urgently needed to promote weight loss in this population. Community organization can broaden health education and facilitate behavior change toward development of life- and self-mastery skills. Specific strategies of this approach include (1) integrating community values into health messages, (2) facilitating neighborhood "ownership" and decision-making, (3) utilizing existing formal and informal networks, and (4) empowering individuals and community. Community organization may be a promising strategy among low-income minority communities to reduce the risk of non-insulin-dependent diabetes by promoting changes in dietary patterns, because it ensures that the health messages and programs that emerge will be consistent with existing sociocultural norms and beliefs.


The weathering hypothesis and the health of African-American women and infants: evidence and speculations. Observed variation between populations in fertility-timing distributions has been thought to contribute to infant mortality differentials. This hypothesis is based, in part, on the belief that the 20s through early 30s constitute "prime" childbearing ages that are low-risk relative to younger or older ages. However, when stratified by racial identification over the predominant first child-bearing ages, maternal age patterns of neonatal mortality vary between groups. Unlike non-Hispanic white infants, African-American infants with teen mothers experience a survival advantage relative to infants whose mothers are older. The black-white infant mortality differential is larger at older maternal ages than at younger ages. While African Americans and non-Hispanic whites differ on which maternal ages are associated with the lowest risk of neonatal mortality, within each population, first births are most frequent at its lowest-risk maternal ages. As a possible explanation for racial variation in maternal age patterns of births and birth outcomes, the "weathering hypothesis" is proposed: namely, that the health of African-American women may begin to deteriorate in early adulthood as a physical consequence of cumulative socioeconomic disadvantage.


Patterns of blood lead levels in US black and white women of childbearing age. While high-dose lead exposure has long been known to be detrimental to reproductive functioning, several recent studies have reported adverse effects such as shortened gestation, decreased birthweight, and increased incidence of spontaneous abortion in association with maternal blood lead levels as low as 0.48 to 0.72 mumol/L (10 to 15 micrograms/dL). Using data from the second National Health and Nutrition Examination Survey, we examined patterns of blood lead levels by age for US black and white women of childbearing age. We found that sizable percentages of women have blood lead levels that may place them at risk for poor reproductive outcomes and that disparities exist between the racially identified groups. Black women tend to have higher lead levels than white women, and the magnitude of this difference is larger among older compared to younger age-groups of reproductive-age women. This disparity may reflect the cumulative effect of differential environmental exposure to lead and may have implications for the excessive incidence of adverse reproductive outcomes currently seen in US black women.


Similarities in cardiovascular reactivity to behavioral stressors in African-American and white males. This study examines the influence of ethnicity (African-American vs white) and family history of hypertension on the blood pressure and heart rate responses of healthy, unmedicated men, aged 21 to 39 years, to a variety of stressors that are hypothesized to elicit beta-adrenergic or alpha-adrenergic reactivity. Cardiovascular reactivity data were also obtained in response to ischemic exercise (handgrip), and a structured interview was designed to measure anger. On the basis of previous research, we predicted that African Americans would show greater responses to the alpha-adrenergic tasks (cold pressor test) and smaller cardiovascular responses to the beta-adrenergic tasks (math challenge) compared to whites. The results indicated no significant differences between African-American and white blood pressure or heart rate responses to either of the tasks. On the other hand, both African-American and white men with family histories of hypertension had significantly higher systolic and diastolic blood pressure responses during exposure to each of the stressors than did men with negative family histories of hypertension. Parental history did not significantly influence heart rate responses to the stressors or resting plasma catecholamine levels in either group. African Americans had significantly lower erythrocyte lithium-sodium exchange rates and significantly higher intracellular sodium concentration compared to whites; parental history of hypertension did not influence these measures. Finally, the blood pressure responses to stress were not modified by the erythrocyte lithium-sodium exchange rate, intracellular sodium concentration, or plasma concentrations of catecholamines.


HIV risks among minority drug users in a small city. In 1989, African-American and Mexican-American drug users (n = 220) in a small southern city were interviewed, in street settings, about their HIV behavioral risks and their readiness to reduce risks. Both ethnic groups contained large numbers of cocaine and heroin users. Mexican Americans were more likely to use heroin, prefer injection, and share needles with other drug users than were African Americans. Sexual risk-taking in both groups was high, with very low levels of condom use, high levels of exchanging sex for drugs and money, and high levels of having multiple sexual partners. Mexican Americans were more likely than African Americans to have regular partners who used drugs. Intravenous drug users in both ethnic groups were at high risk for HIV infection, reporting high levels of multiple drug use, daily drug use, needle sharing, never cleaning needles, and exchanging sex for drugs or money. Readiness to reduce HIV risks was also high in both groups, as evidenced by the response to questions about the use of free preventive services, HIV testing, and concern about AIDS. Implications for research and preventive programs among minority drug users in small cities are discussed.


Health survey methods with minority populations: some lessons from recent experience. Until recently, minority populations have been inadequately or inaccurately represented in health research. Researchers are now recognizing the need to improve the validity and reliability of data on the health status and health-related behaviors of minorities. This paper discusses important methodological issues in conducting health survey research in minority communities: construction of an appropriate sampling frame, response rates, attrition from panel studies, and response patterns. These themes are illustrated with data from three field studies at the New England Research Institute. Two of these studies focus on inner-city Puerto Rican youth, a group rapidly increasing in size. The extent and multiplicity of problems experienced by this group affect the complexity of survey protocols. The third study is a random-digit-dial telephone survey on health care utilization for coronary heart disease by black and white adults from three inner-city neighborhoods in Boston. The conclusions drawn from the Institute's experience are corroborated by other scientific studies. First, the sociocultural characteristics of the community or group selected for study must be considered in planning and implementing any survey research on minority populations. Second, ensuring the quality of field work with minority groups may be expensive because of high residential mobility and lack of preexisting sampling frames. Third, there is no reason to expect any diminution of data quality with minority groups, provided the resources for data collection are adequate. The quality of data is undoubtedly proportional to the field efforts expended, but the costs of high-quality survey work are often not appreciated. The paper questions the utility of the term "minority research," for it disregards the considerable variation between and within minority groups and subcultures.


A partnership with minority populations: a community model of effectiveness research. This paper describes a community-based approach, including a partnership of an academic medical institution and a high-risk, urban, African-American population, directed at decreasing premature morbidity and mortality and enhancing health and functional status. The intervention approach is based on a model of community-based leadership and "ownership" of interventions and programs to enhance sustainability of effective approaches, and it follows specific stages to assure appropriate assessment and evaluation. Initial efforts were directed at the control of hypertension and were coordinated through decentralized mayor's stations in Baltimore, Maryland. This approach was successful in significantly enhancing control of hypertension and reducing related morbidity and mortality. Over time, an enhanced partnership has been coordinated through churches in the community and organized around a program entitled "Heart, Body, and Soul." Current efforts are directed at the major risk factors and preventable and/or controllable problems in the population, such as hypertension, smoking, obesity, diabetes, hyperlipidemia, and cervical and breast cancer. Key components include the training of neighborhood health workers to provide screening, counseling, monitoring, support, and follow-up; enhanced access to care; training of high school students as health counselors; and use of media to promote healthier life-styles.


An evaluation of rectal epithelial proliferation measurement as biomarker of risk for colorectal neoplasia and response in intervention studies. Colorectal carcinogenesis is preceded by a phase of epithelial hyperproliferation. Detection and measurement of this hyperproliferation could be useful as a marker of risk for neoplasia or a measure of response to intervention therapy. Today, bromodeoxyuridine labelling and immunohistology is the easiest to perform and most standardized technique for evaluating proliferation in experimental and human studies. In general, measurement of proliferation has fulfilled expectation in experimental studies, however, in humans it has been less conclusive. The reasons are multifactorial and include: limitations in obtaining tissue samples and sampling error, the type of labelling technique used, lack of an objective method for quantifying proliferation and confounding factors influencing the degree of proliferation. The use of matched controls, sophisticated statistical analysis and the search for trends and not just statistical significance, is to be recommended. At present, evaluation of rectal epithelial proliferation is of limited value in assessing risk for colorectal neoplasia in the individual. On the other hand, it seems a useful biomarker of response within the context of a matched control intervention trial.


Endogenous plasma sex hormones in pre- and postmenopausal women with breast cancer: results from a case-control study in Moscow. Plasma sex hormone-binding globulin (SHBG), testosterone, total oestradiol (E2) and proportion of E2 not bound to blood proteins (percentage free E2) have been measured in a case-control study to test whether any of these factors are related to the risk of breast cancer. The cases studied were 27 premenopausal and 34 postmenopausal women with newly diagnosed localized breast cancer who were admitted to the All-Union Cancer Research Centre, Moscow. The controls were an equivalent number of women from the same neighbourhood. These were matched for age (within 2 years) and menopausal status. The average levels of E2 in cases were significantly higher than controls (p = 0.004 and p < 0.001 for pre- and postmenopausal groups, respectively). Percentage free E2 was significantly raised only in premenopausal cases (p = 0.019). The plasma concentrations of testosterone and SHBG were similar for both pre- and postmenopausal groups. Raised E2 or percentage free E2 was associated with an increased relative risk of breast cancer. However, only E2 levels (crude or adjusted for body build) were significantly related to risk in the two menopausal sets (p = 0.022 and p = 0.002, respectively). High percentage free E2 was associated with almost a threefold increase in the risk of breast cancer in premenopausal women; however, this increase was not statistically significant (p = 0.083). The levels of SHBG or testosterone, crude or adjusted for body build and E2 concentration, were not related to risk of breast cancer.


Do general practitioners facilitate the breast screening programme? Mammography uptake has been discouragingly low since the introduction of breast cancer screening in Northern Ireland. This questionnaire survey was undertaken to appraise the views of participating general practitioners (GPs) about mammography and the extent to which they followed good practice in facilitating the screening programme. Of 173 GPs, 152 returned a questionnaire. Approximately three-quarters of these GPs believed the screening programme was worthwhile for the eligible women on their list. When sent the prior notification lists from the screening unit, less than half of the GPs always checked the accuracy of patients' addresses. Fifty-five per cent of the GPs said they routinely took opportunities (as they arouse) during normal surgeries to counsel women about mammography and 90% did so in health promotion or well-woman clinics. Despite this, only 56% routinely recorded non-attendance in patients' case notes and less than 20% contacted non-attenders to advocate mammography. Such a pro-active approach was more commonly adopted with women who had not attended when invited for a cervical smear. There was no significant difference in mammography uptake among the women on the lists of GPs with differing views or whose doctors differed in their degree of active commitment to the programme. The results point to a need for the screening unit to evaluate its own advocacy role to GPs and for Health Board to devise effective appraisal strategies for health promotion clinics in primary care.


Physical characteristics and factors related to sexual development and behaviour and the risk for prostatic cancer. A case-control study of prostatic cancer was carried out to examine the association between selected physical characteristics and factors related to sexual development and behaviour and the risk for this disease. In consideration of an endocrinologic mechanism for these putative risk factors, the association between selected factors and serum hormone level in a comparison group, free of prostate cancer, was also examined. One-hundred cases and 113 controls were included for study. An elevated risk for prostatic cancer was found for those currently married (odds ratio (OR) = 4.0), those who had been married once (OR = 2.8), and those who were currently practising a religion (OR = 2.0). Compared to subjects with one child, those with more than one child and those with no children were more common among cases than controls. Prostatic cancer risk was associated with large body size and, in particular, with greater weight (p < 0.01). Early age at attainment of adult height was also associated with prostatic cancer risk (p < 0.01). Only moderate associations were found between increased frequency of sexual intercourse and prostatic cancer risk. The levels of testosterone (T), dihydrotestosterone, salivary testosterone and T/SHBG (sex hormone binding globulin) did not vary with age. Older men had higher oestradiol levels. Further, little association between hormone levels and risk factors was found, except for married subjects having increased serum androgens (p < 0.05) and heavy subjects having decreased serum androgens (not significant).


Prediction of cancer mortality in the Nordic countries in 2005: effects of various interventions. Rough estimates of the effect in 2005 of various preventive measures aimed at reducing cancer mortality in the Nordic countries were made using the American software CAN*TROL. The effect was measured as the percentage reduction in cancer mortality in 2005. The calculations were performed for changes in the smoking, dietary and sunbathing habits of the population (primary prevention), earlier diagnosis (secondary prevention) and improvements in survival resulting from better treatment (tertiary prevention). The calculations incorporate many assumptions, some of them more firmly based than others, such as uniformity of incidence trend in all the Nordic countries and also concerning the causality of various relations. For lack of evaluated Nordic data, we have used American figures concerning stage distributions and stage-specific relative survival rates. These assumptions should be borne in mind when drawing conclusions from the results obtained. The results show that there is a potential of up to several tens of percent for reducing total cancer mortality by the year 2005.


Cancer of the oesophagus: a global overview. The geographical distribution of cancer of the oesophagus shows wide inter- and intra-national variation both in mortality and sex ratio. Numerous analytical studies have demonstrated alcohol and tobacco as important risk factors. Poor diet, particularly those lacking fresh fruit and vegetables, appears to be an equally important determinant in certain areas. In addition to alcohol and tobacco, Maté drinking in Southern South America independently increases risk. The possible role of thermal injury when Maté is drunk hot is still being investigated. Analysis of incidence data by histological subtype and site of disease has revealed rising rates for adenocarcinomas, generally of the lower third of the oesophagus, and predominantly in males. These data are paralleled by increasing rates of adenocarcinoma of the cardia of the stomach. The aetiology of these tumours in adjacent sites remains to be fully investigated but one known predisposing factor is the presence of Barrett's oesophagus. This poor prognosis disease does not appear amenable to widespread screening. Preventative measures would necessarily incorporate plans to reduce alcohol and tobacco use while improving the marginal diets of many populations.


The rising trend in oesophageal adenocarcinoma and gastric cardia. The incidence of cancer of the oesophagus and stomach in the West Midlands region of England have been analysed for the 25 years 1962-86. Overall, cancer of the oesophagus is increasing (from 3.45 per 100,000 in 1962-66 to 4.37 in 1982-86) and stomach cancer is decreasing (19.22 and 16.54 respectively). However, when analysed by histological type and subsite the picture is very different. In oesophagus, squamous cell carcinoma shows only a slight increase whereas for adenocarcinoma the increase is highly significant (from 0.14 to 0.76). In stomach, cardia shows a very similar pattern to adenocarcinoma of oesophagus (increasing from 0.75 to 2.96) but pyloric antrum is decreasing (from 2.63 to 2.32). The rapid changes in investigative procedures over the period have resulted in increasing numbers with histological confirmation and subsite specification but despite these confounding factors, comparative analyses still indicate a real increase in adenocarcinoma of oesophagus and cardia. Although the incidence of both are greater in men than in women, the proportional rates of increase, particularly for cardia, are very similar in both sexes, indicating a common aetiological factor or factors. Analysis by social-economic group reveals that the increases observed are not uniform throughout the population but are relatively higher in professional classes (1 and 2).


Trends in registered incidence of oesophageal and stomach cancer in the Oxford region, 1974-88. In the Oxford region 8,903 residents with oesophageal or gastric cancers were registered by the Oxford Cancer Registry between 1974 and 1988. For most of this time the Registry's practice was to code all adenocarcinomas of the oesophagus as adenocarcinomas of the cardia of stomach. There was a significant increase over time in the registered incidence of adenocarcinoma of the cardia, no appreciable change in the incidence of oesophageal cancers registered as such, and a decline in registered incidence of cancers of the stomach other than cardia.


Oesophageal cancer in France and Switzerland: recent time trends. This paper reports the incidence of oesophageal carcinoma in five cancer registries from France and in a further two from the francophone regions of Switzerland. The cancers are segregated into the two main histological types (squamous cell carcinoma and adenocarcinoma). In Belgium the proportion of adenocarcinomas is much higher than in any of the French registries. A study of time trends shows no clear trend in overall incidence of oesophageal cancer. There is a trend towards an increasing proportion of adenocarcinomas with time, that is most apparent in Doubs, Dijon and Vaud registries.


Breast cancer in Europe: the importance of factors operating at an early age. Breast cancer incidence varies considerably among European countries, with highest rates found in western and northern and lowest rates in eastern and southern European countries. The objective of this ecological correlation study was to investigate to what extent variation in breast cancer incidence within Europe can be attributed to differences in the prevalence of the following risk factors: age at menarche, age at first birth, parity, body height and body weight. The results of the study showed that particularly age at first birth and body height correlated positively and significantly with breast cancer incidence. If in eastern and southern European countries changes take place with respect to reproductive behaviour and nutritional status in the same way as has happened in western and northern European countries, breast cancer incidence in the countries included in this study may increase by 11%. This means that, by the time the 0- to 10-year-old female population in the European countries being studied reaches the age of 64, the number of women with breast cancer may be 1,198,369, which is almost 135,000 higher than would be the case if breast cancer risk remained stable.


Colorectal carcinoma in Indian patients with idiopathic ulcerative colitis. In contrast to reports from Western countries, the incidence of colorectal carcinoma among patients with idiopathic ulcerative colitis is considered to be low in the Indian subcontinent. In order to assess the risk of carcinoma in Indian patients, a retrospective analysis of 436 cases of idiopathic ulcerative colitis seen by us over a period of 12 years was carried out. Eight cases of colitis carcinoma (1.8%) were encountered during the study period. Pancolitis was present in six of them while colitis was of limited extent in two cases. The mean duration of colitis prior to development of carcinoma was 12.1 (range 7-25) years. While four of these patients were on our follow-up list and were diagnosed to have carcinoma at the time of a medical or surgical complication, four others first presented to us with a surgical complication of colitis carcinoma. We conclude that colitis carcinoma is not a rare entity among Indian patients with idiopathic ulcerative colitis. We feel that until proved otherwise, patients with idiopathic ulcerative colitis from the Indian subcontinent should not be denied the benefits of a cancer surveillance programme.


Dietary practices in households as risk factors for stomach cancer: a familial study in Poland. In the framework of a nationwide case-control study of risk factors for stomach cancer, a household survey was conducted on those food habits at the family level which were considered relevant for stomach cancer. The practices of 741 case and 741 control households were compared and relative risks calculated by the unconditional maximum likelihood method. For each household, the person responsible for cooking completed the survey. Respondents to the household survey were 35% of the cases and 40% of the controls of the case-control study and otherwise other household members. Case households relied more frequently on their own gardens as a major source of vegetables and fruit, and they cooked their vegetables more often than control households. The vegetable and fruit consumption during the summer period per family member was significantly less in case households compared to control households. The difference in per capita vegetable and fruit consumption between case and control households persisted, but was considerably less pronounced when the consumption of the index person (case or control) was subtracted from the household consumption. The consumption of mainly wholemeal bread showed a relative risk (RR) of 0.18 (95% CI 0.07-0.44) compared with mainly white bread consumption, whereas frequent frying and stewing of meat was associated with an increased risk compared to boiling of meat (RR = 2.06, 95% CI 1.48-2.87). No association with risk was found for long-term refrigerator use or other storage modalities.(ABSTRACT TRUNCATED AT 250 WORDS)


Science as cancer prevention for American inner city residents. Eighty parents and guardians of high-risk elementary school children from Hartford, America's fourth poorest city, participated in a 12-week Saturday programme of science and cancer risk reduction while their children participated in a science programme designed to be interesting and fun. The children learned to enjoy biology as innovative recreation. Their parents and guardians learned to appreciate the health risks associated with passive thinking. Cigarette advertisements and misleading food claims were exposed to scientific scrutiny with the result that parents and guardians came to view scientific thinking as a means to protect their children and themselves from cancer. They also learned to reduce cancer risk through proper nutrition. Attendance was excellent and the majority of parents and guardians completing the programme believed they had learned to identify and avoid cancer risks.


Attitude or access: reasons for not attending mammography in Northern Ireland. Maximizing the uptake of mammography among the eligible population will be critical to the success of the national breast cancer screening programme. Although compliance may vary for different reasons from area to area, it has been suggested that making screening clinics more accessible may be an effective means of enhancing uptake. In the present study we undertook 600 interviews with women who had been invited for mammography to determine the main reasons given by women in Northern Ireland for not attending for mammography when invited, how these may have related to access factors and to discover their views on how the service might be improved. The most frequently cited reasons for non-attendance were related to feelings of indifference or ignorance of screening issues and to fear of pain or embarrassment. Although more non-attenders did not have access to private transport, few women (23/600) expressed a preference for more accessible clinics. The fact that non-attenders were more likely not to have had a recent cervical smear, adds weight to the notion that attitudes rather than access played the predominant role in influencing uptake in this sample. We have concluded that investment in flexible mobile screening units cannot replace the continued need for delivering effective advocacy to eligible women.


Histological and cytological diagnosis of carcinoma of the oesophagus. Endoscopic examination of the oesophagus accompanied by histological examination of biopsies or cytological examination of smears enables a confident diagnosis of carcinoma to be established within a period of 24-48 h and in the case of cytology within 15-60 min. Squamous cell carcinoma and adenocarcinoma are easily identified in biopsies or smears taken directly from the lesion. The histopathologist should be alerted to the possible diagnosis of Barrett's adenocarcinoma provided adequate information is given regarding the level of the squamo-columnar junction and the level of the targeted lesion. Unusual tumours are encountered rarely and they include carcinosarcoma, mucoepidermoid carcinoma, adenocystic carcinoma, carcinoid, malignant melanoma, oat cell carcinoma, spindle cell sarcoma, malignant lymphoma, Kaposi's sarcoma, etc. Special stains and multiple levels from the biopsies will be required for accurate identification of these tumours. Dysplasia constitutes a difficult diagnostic problem with reference to its significance regarding surveillance and treatment. Low grade dysplasia represents a recommendation for surveillance provided that the patient is regarded as a good surgical risk if cancer should develop at a later stage. High grade dysplasia is associated with a high risk of invasive cancer and close surveillance is required for the detection and treatment of invasive cancer provided also that the patient is a good surgical risk.


Barrett's oesophagus.

Barrett's oesophagus. Barrett's oesophagus or columnar lined epithelium of the oesophagus (CLO) is a metaplastic condition associated with excessive gastro-oesophageal reflux. It is found in 15% of patients with reflux oesophagitis. In a detailed study of 115 CLO patients dysplasia was found in 46%; 13.9% were moderate or severe dysplasia, usually found in intestinal type CLO. Fifty patients were endoscoped annually to determine the natural history of the disease. The incidence of adenocarcinoma was 1 in 52 patient-years, a 125-fold excess risk. A dysplasia-carcinoma sequence was seen in the five who developed carcinoma. Patients with early carcinoma were treated surgically with 12% postoperative mortality and 100% survival for 24-70 months.


The early diagnosis of oesophageal adenocarcinoma by endoscopic screening. Oesophageal carcinoma has a very poor prognosis unless detected at a pre-symptomatic stage. This can only be done by screening and patients with Barrett's columnar lined epithelium of the oesophagus (CLO) are high risk candidates for an endoscopic screening programme. Surveillance studies in CLO patients, when reviewed, showed that the incidence of adenocarcinoma was between 1 in 52 and 1 in 81 patient years, with a mean of 1 in 76. This paper describes the Nottingham experience with an endoscopic screening programme that was established in 1976. To date it has detected four adenocarcinomas at a mean cost similar to that of detecting breast cancer by screening.


Surgery in Barrett's oesophagus.

Surgery in Barrett's oesophagus. Surgical treatment for a columnar-lined oesophagus (CLO) may be considered in terms of indications, procedures and risks. Reflux may be an indication for surgery, but does not lead to reversal of epithelium, nor does it eliminate malignant potential. Whether it reduces such potential is not certain. Anti-reflux surgery is therefore based on reflux-related criteria, and not as a treatment for a CLO. Dysplasia is a possible indication for surgery, but as progression to carcinoma may be slow, must not be considered an absolute indication in an elderly, frail patient. Malignancy is a clear indication for operation in a patient deemed fit enough to withstand it. Anti-reflux operations have been standardized over recent years, and aim at exclusion of gastric juice from the oesophagus. Another approach is to alter refluxed material qualitatively by a duodenal diversion procedure. This eliminates bile and pancreatic juice from the oesophagus, with dramatic effects on inflammation but without reversal of a CLO. Reversal of inflammation may facilitate endoscopic surveillance. Either dysplasia or carcinoma are treated by oesophagogastric resection. Newer forms of laparoscopic or thoracoscopic dissection may be particularly applicable with dysplasia or early carcinoma in CLO. Palliative surgery for advanced tumours is not often required today. Risks of anti-reflux surgery must be balanced against symptoms. Risks are reduced if splenectomy is avoided, and operations avoided where possible in the elderly. Resection for dysplasia or carcinoma is high-risk surgery. In the young there is much to gain, and the risks are lower. In the elderly, in the absence of other treatment, risks must be balanced against general health and life expectancy.


Case management lessons from a public/private partnership to finance long-term care. In June of 1987, Connecticut's State Task Force on Private and Public Responsibilities for Financing Long-Term Care for the Elderly released its final report. This Governor's Commission, concluding that neither the private nor the public sector had much short-term hope of solving this difficult problem alone, recommended the creation of a public/private partnership. As this partnership was forged, some unique insights were gained into the functions of case management. This case study shows how case management can help coordinate the private and public roles, but it also raises some research questions which must be tackled before case management can fulfill its promise to help stretch and conserve scarce resources.


Eldercare. An issue for corporate america. The aging of America is taking its toll on employers in a variety of ways. Growing numbers of employees are also part-time or full-time caregivers for older relatives or friends. These employees' caregiving responsibilities contribute to absenteeism, tardiness, increased use of health benefits, and decreased productivity. Following a landmark study by The Travelers in 1985, it and other corporations have begun to offer a variety of programs to address the concerns of caregivers. Among the services being offered are information fairs, counseling and referral assistance, flexible spending accounts, support groups, and adult daycare.


Case management. The wave of the future. Nurses and social workers are often placed in case management positions without an understanding of the basic philosophy or skills necessary for functioning effectively in this role. While the general components of the case management process are familiar to people from both professions, the specific procedures and goals of the process are quite different from those the participants learned during their basic educational preparation. This article explores the growing need for case management and offers a plan for effective training and skills necessary for the successful case manager. It describes the effects of case management on resource allocation, on the quality of its clients' lives, and on the systems within which it operates. It provides a clear overview of the important role that the case manager plays in sustaining the independence of older persons.


What price quality? Assuring the quality of case-managed in-home care. Case managed community-based long-term care has now become an established component of the service delivery system in the United States. As case management has developed, it has gone through an evolutionary process. In the initial phase of case management, considerable attention was placed on gaining access to resources by the case manager. This article addresses issues of assuring the quality of case-managed care. It focuses on the current concerns and potential problems associated with evaluating the effectiveness of services arranged by case managers, and describes a model, developed in Ohio, to ensure the quality of care. In addition, it discusses the continued challenges for and costs of quality assurance and notes the difficulty of obtaining empirical data in the effort to assure quality.


Developing consumer-centered quality assurance strategies for home care. A case management model. Despite a growing interest in home care quality assurance, models for effective quality assurance systems are in short supply. This article describes such a model, developed after a literature review; interviews with business leaders and with home care consumers and their families; and focus groups with consumers, case managers, and home health nurses. The Consumer-Centered, Negotiated Model for Home Care Quality integrates quality assurance into the case management process, focusing on the entire plan of care, not simply individual services. In this model, quality assurance is a regular and ongoing process, utilizing standards that are consumer-oriented, specific, and measurable.


A clinical collaboration of a psychiatrist and a geriatric care manager. Older persons often need an integrated support system to enable them to remain in the community. This is particularly true for elderly patients with multidimensional disorders. This article describes an effective collaboration between a psychiatrist and geriatric care manager in treating six such patients.


Case management services for children with special health care needs. A family-centered approach. The Coordinating Center for Home and Community Care (CCHCC) has developed a comprehensive, multidisciplinary case management model that facilitates the discharge of technology-assisted children from hospital to home. Coordination of the variety of services necessary for optimal medical, educational, and psychosocial development of the child and family is provided with an emphasis on cost containment. The hallmark of this program is its ability to locate, coordinate, and monitor the quality, continuity, provision, and cost of services at home. The CCHCC model was designed to enable children who would otherwise remain hospitalized at a substantial cost to third party payers to move home, providing a humane choice for families while requiring less costly care for funders.


A case management agency and bank create a service innovation. Connecticut Community Care, Inc. (CCCI), a statewide, nonprofit case management agency, in collaboration with Connecticut National Bank (CNB), developed a unique model of delivering case management services to bank trust clients. No reports of such a collaborative model have been found in the published literature in the United States. The article presents a historical overview of this innovative initiative; the identification of the target population; the delivery of the assessment, coordination, and monitoring services; and the marketing techniques. Utilization statistics, a synopsis of the model outcomes as viewed by the trust officers, and suggestions for replication are also presented.


Have we oversold case management as a "quick fix" for our long-term-care system? Case management has become a core component in almost every community-based, long-term-care program. Yet it is, at best, a piecemeal response to an enormous health and social services problem. Fragmented funding, ill-considered public health policy, and short-range planning assure that no single system, even one as ubiquitous as case management, will eliminate the serious problems plaguing our health care system.


A taxonomy of ethical issues in case management of the frail older person. Present-day case managers find themselves facing a broad range of ethical issues and value conflicts. For managers of the frail older person, these issues may relate to (a) the client, (b) the client's family, (c) the manager's agency, (d) interdisciplinary interactions, (e) interagency dynamics, and (f) the entire service system. An eight-point strategy for conflict resolution can be effectively applied to these ethical conflicts.


Case management in long-term care: it can be ethical and efficacious. The present-day concept of case management combines two opposing functions, advocacy and gatekeeping, which creates an ethical tension. To maintain a balance between these activities and thus avoid untenable ethical situations, long-term-care programs must at the very least have sufficient dollars to provide required services, those dollars must be committed to the program and not subject to allocation elsewhere, and the services must be distributed fairly among those who need them. Various case management models attempt to separate the advocacy and gatekeeping functions with varying degrees of success.


Individual advocacy as a governing principle. Many case managers have two roles, that of gatekeeper and that of advocate, that often conflict. A true advocate adopts the client's perspective as the guide for activity. Many advocacy models exist, notably those of physician/patient and lawyer/client. The client's rights to an informed choice and to strict confidentiality are fundamental to these advocacy models and must be incorporated into any advocacy model of case management.


Ethical issues in case management from a political and systems perspective. This article has been excerpted from a talk which provided a description of the systemic context in which case management operates in relation to other services and provides an overview of the political context in which the system of services for older people operates. The ethical issues of case management, which are discussed elsewhere in this issue, are imposed in part by the role of case managers in the system as a whole, which in turn reflects our society's political consensus on how older persons will be served and at what cost.


The Person-In-Environment System for classifying client problems: A new tool for more effective case management. This article outlines the application of the Person-In-Environment system for the classification of problems which clients bring to case managers. The PIE system, sponsored by the National Association of Social Workers, Inc., concisely describes social role, environmental, mental health, and physical health problems in a format that allows for a clear delineation of the appropriate targets for case management intervention. The article also illustrates the system's use with three case management vignettes involving child protective services, the chronically mentally ill, and older adults.


A quantitative method for measuring regional in vivo fatty-acid incorporation into and turnover within brain phospholipids: review and critical analysis. An experimental method and its associated mathematical model are described to quantitate in vivo incorporation rates into and turnovers of fatty acids (FAs) within stable brain metabolic compartments, particularly phospholipids. A radiolabeled FA is injected i.v. in a rat, and arterial plasma unacylated FA radioactivities and unlabeled concentrations are sampled until the animal is killed after 15 min, when the brain is analyzed biochemically or with quantitative autoradiography. Unbound unacylated label in blood easily crosses the blood-brain barrier; rapidly equilibrates in the unacylated FA, acyl-CoA and phosphatidate-diacylglycerol brain pools; then is incorporated into phospholipids and other stable metabolic compartments. Uptake and incorporation of labeled FAs are independent of cerebral blood flow at constant brain blood volume. Different labeled FAs enter specific sn positions of different brain phospholipids, suggesting that a combination of probes can be used to investigate metabolism of these phospholipids. Thus, [9,10-3-H]palmitate preferentially labels the sn1 position of phosphatidylcholine; [1-14C]arachidonate the sn2 positions of phosphatidylinositol and phosphatidylcholine; and [1-14C]docosahexaenoate the sn2 positions of phosphatidylethanolamine and phosphatidylcholine. The FA model provides an operational equation for rates of incorporation of FAs into brain phospholipids, taking into account intracerebral recycling and de novo synthesis of the FA, as well as entry into brain of FA from acylated blood sources. The equation is essentially independent of specific details of the proposed model, and can be used to calculate turnovers and half-lives of FAs within different phospholipid classes. For the model to be most applicable, experiments should satisfy conditions for pulse-labeling of the phospholipids, with brain sampling times short enough to minimize exchange of label between stable metabolic compartments. A 15-20 min sampling time satisfies these criteria. The FA method has been used to elucidate the dynamics of brain phospholipids metabolism in relation to brain development, brain tumor, chronically reduced auditory input, transient ischemic insult, axotomy with and without nerve regeneration, and cholinergic stimulation in animals with or without a chronic unilateral lesion of the nucleus basalis magnocellularis.


Increased cognitive sensitivity to scopolamine with age and a perspective on the scopolamine model. 18 older normal volunteers (mean age = 66.5 +/- 7.9 years) and 46 younger volunteers (mean age = 27.0 +/- 6.1 years) were administered the anticholinergic drug scopolamine (0.5 mg i.v.) followed by a battery of cognitive tests evaluating attention, learning and memory. The older subjects were significantly more impaired than the younger by scopolamine on some tests of learning and memory. This increased sensitivity of the older group to scopolamine is consistent with studies in animals and humans showing decreased cholinergic system function with age. The findings also indicate that age is an important variable to consider in using the scopolamine model of memory impairment. The cognitive impairment caused by scopolamine in younger subjects in this and prior studies is similar to some, but not all aspects of the impairment which occurs in normal aging. Scopolamine also caused impairments on digit span and word fluency tasks, which are not consistent with normal aging changes. In the older group of subjects, scopolamine produced aspects of the cognitive impairment which occurs in AD on tests of episodic memory and learning, vigilance-attention, category retrieval, digit span, and number of intrusions. Other areas of cognition that are of relevance to aging and AD such as psychomotor speed, praxis, concept formation and remote memory were not evaluated in this study. Some of these are being evaluated in ongoing studies, along with additional and more specific tests of retrieval from knowledge memory, implicit memory and attention. The scopolamine model has provided a fruitful pharmacologic starting point for the study of a number of cognitive operations. The idea of dissecting apart aspects of memory systems pharmacologically depends on the availability of neurochemically specific drugs and on the specificity and sensitivity of neuropsychological tests for distinct cognitive operations or domains. Further studies using such tools will aid not only in the understanding of the impairments which occur in aging and in AD, but also of the conceptualization of memory and other cognitive operations and ultimately the physiological mechanisms involved in memory and learning.


Activity-dependent development of spinal cord motor neurons. Patterned neuronal activity in early postnatal life can regulate the acquisition of the mature morphological and electrophysiological properties of neurons. Many properties of motor neurons are developmentally regulated and may be influenced by epigenetic factors. The pattern of activation of motor neurons can regulate axon terminal morphology and synaptic efficacy at the neuromuscular junction. Motor neuron morphology and synaptic connections can also be modified by exposure to specific hormones in the early postnatal period. The acquisition of mature physiological and anatomical properties is paralleled by the acquisition of specific molecular properties. Recent experiments using molecular markers for motor neuron differentiation indicate that motor neurons undergo activity-dependent development during a circumscribed period in early postnatal life. Normal motor neuron differentiation requires a normal pattern of neuronal activity in early postnatal life. Differentiation also requires activation of the NMDA receptor over the same time period. The activity-dependent development of morphological, electrophysiological and molecular properties of motor neurons is similar to activity-dependent development in the vertebrate visual system. The neuromuscular system may provide an accessible system for characterizing the molecules subserving the translation of patterned neuronal activity into mature neuronal phenotype.


Management of depression in the elderly. Depressive illness in late life may present to doctors in the community or on general hospital wards. Management often involves physical treatments, but social and psychological approaches may also be important. This article considers acute treatment, continuation treatment (to prevent relapse) and the treatment of resistant depressive illnesses.


Management of adults with cystic fibrosis. Many patients with cystic fibrosis now survive into adulthood seeking continuation of their care from adult physicians rather than paediatricians. Attention to detail is the key to successful management of this complex multisystem disorder; care is best provided in the context of a multidisciplinary, team-oriented approach.


Clinical manifestations of African AIDS. AIDS (acquired immunodeficiency syndrome) is now the greatest cause of death in many African countries. Any traveller from sub-Saharan Africa may present with an AIDS-related condition. This article provides a brief introduction to the problems posed by AIDS and AIDS-related conditions and their recognition.


Intravenous chlormethiazole.

Intravenous chlormethiazole. Intravenous chlormethiazole is widely used for its sedative and anticonvulsant action in patients with acute alcohol withdrawal, status epilepticus, pre-eclampsia and eclampsia. Concern remains over its safety if it is given carelessly and without careful monitoring.


Clinical applicability of inorganic phosphate measurements. Many articles have warned of the dangers of too much and/or too little potassium, calcium or sodium in the blood, but phosphate has not received similar attention. Yet, because of its pivotal role in intermediary metabolism and its close solubility product relationship with ionized calcium, disordered phosphate homeostasis can have profound clinical effects.


Guide to postgraduate exams: multiple-choice questions. Multiple-choice questions are among the most common components of medical exams. They are potentially very reliable and are easy and accurate to mark. Their validity leaves much to be desired, however, and the common practice of negative marking is ill considered.


Central administration of 5-HT activates 5-HT1A receptors to cause sympathoexcitation and 5-HT2/5-HT1C receptors to release vasopressin in anaesthetized rats. 1. The effects of intracerebroventricular injections to the right lateral ventricle (i.c.v.) of 5-hydroxytryptamine (5-HT, 40 and 120 nmol kg-1), N,N-di-n-propyl-5-carboxamidotryptamine (DP-5-CT; 3 nmol kg-1), 5-carboxamidotryptamine (5-CT; 3 nmol kg-1), 8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT; 3, 40 and 120 nmol kg-1) and 1-(2,5-di-methoxy-4-iodophenyl)-2-aminopropane (DOI; 40 and 120 nmol kg-1) on renal sympathetic nerve activity, blood pressure, heart rate and phrenic nerve activity were investigated in normotensive rats anaesthetized with alpha-chloralose. 2. 5-HT caused a long lasting pressor response which was associated with an initial bradycardia and renal sympathoinhibition followed by a tachycardia and renal sympathoexcitation. Pretreatment with the 5-HT2/5-HT1C receptor antagonists, cinanserin (300 nmol kg-1, i.c.v.) or LY 53857 (300 nmol kg-1, i.c.v.) reversed the initial bradycardia and sympathoinhibition to tachycardia and sympathoexcitation. Combined pretreatment with LY 53857 (300 nmol kg-1, i.c.v.) and the 5-HT1A antagonist, spiroxatrine (300 nmol kg-1, i.c.v.), blocked the effects of 5-HT on all the above variables. 3. Pretreatment with the vasopressin V1-receptor antagonist, beta-mercapto-beta,beta-cyclopentamethylene-propionyl1, O-Me-Tyr2, Arg8-vasopressin [(d(CH2)5Tyr(Me)AVP, 10 micrograms kg-1, i.v.] did not affect the magnitude but reduced the duration of the pressor response produced by i.c.v. 5-HT and reversed the initial bradycardia and renal sympathoinhibition to tachycardia and sympathoexcitation. 4. 1-(2,5-Di-methoxy-4-iodophenyl)-2-aminopropane (DOI) caused a pressor effect which was associated with a bradycardia and sympathoinhibition. These effects were blocked by pretreatment with BWSOlC67 (0.1 mg kg-', i.v.), a peripherally acting 5-HT2/5-HTc receptor antagonist. However,BWSOlC67 (0.1 mg kg-', i.v.) failed to block the effects of i.c.v. 5-HT.5. DP-5-CT, 5-CT and 8-OH-DPAT (3 nmol kg-', i.c.v.) caused sympathoexcitation, tachycardia and a rise in blood pressure. Pretreatment with methiothepin (1 mg kg-', i.v.) or spiroxatrine (300 nmol kg-',i.c.v.) attenuated the response to i.c.v. DP-5-CT.6. It is concluded that i.c.v. administration of 5-HT activates 5-HTlA receptors to cause sympathoexcitation and 5-HT2 or 5-HT1c receptors to cause the release of vasopressin.


Withdrawing medical treatment: implications of the Bland case. The question of whether it is possible to withdraw a feeding system from a patient who is in a persistent vegetative state raises serious legal and ethical issues which have recently been discussed in the High Court. This article discusses the issues and the Court's conclusions in this particular case.


Mechanisms of the biphasic responses to endothelin-3 in dog coronary arteries. 1. Endothelin-3 (ET-3) elicited relaxations at low concentrations (up to 10(-8) M) and contractions at higher concentrations in dog isolated coronary arteries precontracted with prostaglandin F2 alpha (PGF2 alpha). The relaxation by ET-3 was not affected by endothelium denudation nor treatment with NG-nitro-L-arginine, but was abolished or reversed to a contraction by treatment with indomethacin and markedly suppressed by tranylcypromine, a PGI2 synthetase inhibitor, or diphloretin phosphate, a prostaglandin receptor antagonist. ET-1 produced only concentration-dependent contractions. 2. BQ-123, a new selective ETA receptor antagonist, caused relaxation of the strips contracted with ET-3 in a dose-dependent manner and prevented the ET-3-induced contraction but did not affect the contraction produced by PGF2 alpha. The relaxation caused by ET-3 was enhanced by treatment with BQ-123. 3. It is concluded that the relaxations elicited by ET-3 in dog coronary arteries are mediated via liberation of PGI2 by activation of non-ETA receptors, located in subendothelial tissues, possibly smooth muscle cells, whereas the peptide-induced contractions are mediated via ETA receptors.


Cardiovascular selectivity of adenosine receptor agonists in anaesthetized dogs. 1. In order to determine the relevance of adenosine (Ado) receptor classification obtained from in vitro methods to the cardiovascular actions of Ado agonists in vivo, the cardiovascular effects of adenosine 5'-monophosphate (AMP), N6-cyclohexyladenosine (CHA, 400 fold A1-selective), 5'-N-ethyl-carboxamidoadenosine (NECA, A1 approximately A2) and 2-phenylaminoadenosine (PAA, 5 fold A2-selective) were compared in open-chest, fentanyl-pentobarbitone anaesthetized dogs. 2. Graded doses of CHA (10 to 1000 micrograms kg-1), NECA (0.5 to 100 micrograms kg-1) or PAA (0.1 to 20 micrograms kg-1) were administered intravenously and changes in haemodynamics and myocardial contractility were assessed 10 min following each dose. The effects of graded infusions of AMP (200 to 1000 micrograms kg-1 min-1) were also evaluated. 3. AMP and each of the Ado analogues (NECA > PAA > CHA) increased the systemic vascular conductance index (SVCI) in a dose-dependent manner and reduced mean arterial pressure (MAP). At doses causing similar increases in SVCI, these agonists caused (i) similar reflex increases in heart rate (HR) and cardiac index (CI) and decreases in AV conduction interval (AVi) and (ii) similar increases in coronary vascular conductance (CVC). 4. After cardiac autonomic blockade with atropine (0.2 mg kg-1) and propranolol (1 mg kg-1), AMP, CHA and PAA still increased SVCI and CVC and decreased MAP. CHA and PAA had no marked effects on HR, CI or AVi. As in the absence of cardiac autonomic blockade, equieffective vasodilator doses of CHA and PAA had identical effects on CVC, CI and AVi. 5.Myocardial contractility, as assessed by E,,,,, measurements, was stimulated by AMP in control animals. Following cardiac autonomic blockade, PAA increased contractility while AMP and CHA had no significant effects.6. Despite marked.differences in receptor selectivity in vitro, no marked differences between the actions of these Al- and A2-selective Ado receptor agonists on the cardiovascular system in vivo were apparent.Difficulties therefore exist in the application of in vitro Ado receptor selectivity data to the prediction of the cardiovascular effects of Ado agonists in vivo.


Stereospecific antiarrhythmic effects of naloxone against myocardial ischaemia and reperfusion in the dog. 1. The effects of both the (-)- and (+)-stereoisomers of naloxone in anaesthetized dogs with arrhythmias induced by acute coronary artery occlusion followed by reperfusion were investigated. 2. Following coronary artery occlusion and reperfusion, all dogs in the control group developed ischaemia- and reperfusion-induced cardiac arrhythmias, bradycardia and hypotension. 3. The opiate antagonist (-)-naloxone prevented the arrhythmias, bradycardia and hypotension due to myocardial ischaemia and reperfusion. 4. The (+)-stereoisomer of naloxone, which is inactive as an opiate antagonist, was without beneficial effects. 5. These results indicate a possible involvement of endogenous opioid peptides in the cardiac effects due to myocardial ischaemia and reperfusion, mediated by opiate receptors through opiate antagonism.


Lack of effect of potassium channel openers on ATP-modulated potassium channels recorded from rat ventromedial hypothalamic neurones. 1. Single neuronal cells were freshly isolated from the ventromedial hypothalamic nuclei (VMHN) of the rat brain. Currents through ATP-modulated and large conductance (160 and 250 pS) calcium-activated potassium channels were recorded by the cell-attached and excised inside-out patch techniques. 2. BRL38227 (lemakalim; 30-90 microM) applied to the superfusing medium produced no change in firing rate of isolated glucose-receptive VMHN neurones in cell-attached recordings. 3. BRL38227, at concentrations of between 30-100 microM applied to the intracellular (cytoplasmic) aspect of inside-out patches, had no effect on the activity of ATP-sensitive K+ channels in the absence of ATP or in the presence of a sub-maximal inhibitory concentration (3 mM) of ATP. Cromakalim, pinacidil, minoxidil sulphate and diazoxide also produced no effect under these conditions. 4. The potassium channel openers (KCO's) were tested on ATP-activated potassium channels recorded from a further subpopulation of VMHN neurones. Application of BRL38227 (up to and including 100 microM) to this channel in inside-out patches either in the absence of ATP or when activated by 5 mM ATP had no effect on channel activity. Identical results were obtained with cromakalim and pinacidil. 5. BRL38227 had no effect on either of the large conductance (250 pS and 160 pS) calcium-activated potassium channels in VMHN neurones. 6. Intracellular recordings were made from glucose-receptive VMHN neurones in rat brain slices. Cromakalim (50 microM) or diazoxide (60 microM) did not alter the firing rate or passive membrane properties of these neurones demonstrated to be sensitive to tolbutamide (0.1 mM). 7. These results show that the KCO's tested in this study have no effect either on VMHN neurones contained in brain slices or on the activity of any of the ATP-modulated potassium channels under isolated patch conditions associated with these neurones.


Inositol 1,4,5-trisphosphate generation and calcium mobilisation via activation of an atypical P2 receptor in the neuronal cell line, N1E-115. 1. Alterations in the levels of intracellular calcium ([Ca2+]i) and D-myo-inositol-1,4,5-trisphosphate (InsP3) were measured in the murine neuroblastoma cell line clone, N1E-115, by use of the calcium-sensitive dye, fura-2 and a radioreceptor assay, respectively. 2. Exposure of the cells to ATP (100 microM) elicited rapid and transient increases in [Ca2+]i and InsP3, with both responses reaching a maximum between 10-20 s after agonist addition. 3. Investigation of concentration-response data by use of various analogues of ATP suggests the presence of an extracellular receptor which fails to fit into the current classification of purinoceptors. 4. Cross-desensitization experiments suggest that the same receptor can also be activated by the structurally different pyrimidine base, UTP. 5. Application of the tumour-promoting agent, beta-phorbol-12,13 dibutyrate (PDBu) caused a reduction in the increases in both [Ca2+]i and InsP3, suggesting a role for protein kinase C in feedback inhibition of purinoceptor responses in this cell line. 6. In summary, we present the first evidence for the existence of an atypical purinoceptor on a cell line of CNS origin. This receptor is linked to stimulation of phosphoinositide turnover and subsequent mobilisation of intracellular calcium.


L-leucyl-L-arginine, naltrindole and D-arginine block antinociception elicited by L-arginine in mice with carrageenin-induced hyperalgesia. 1. Intraplantar injection of carrageenin into the mouse hind paw produced hyperalgesia when measured by the paw pressure test (Randall & Selitto method). 2. Subcutaneous administration of L-arginine (100-1,000 mg kg-1), a possible precursor of kyotorphin which is an endogenous analgesic neuropeptide, inhibited carrageenin-induced hyperalgesia in a dose-dependent manner. This effect was blocked by subcutaneous administration of naloxone, naltrindole, a selective delta-opioid receptor antagonist (enkephalin antagonist), and D-arginine. 3. Intracerebroventricular administration of L-leucyl-L-arginine inhibited the antinociceptive effect of systemically administered L-arginine in hyperalgesic mice. 4. Intracerebroventricular administration of L-arginine (3 and 30 micrograms per mouse) and kyotorphin (300 ng-3 micrograms per mouse) produced antinociception in hyperalgesic mice. The antinociceptive effects of L-arginine but not kyotorphin were blocked by intracerebroventricular administration of D-arginine. 5. These results suggest that L-arginine-induced antinociception is mediated by activation of 'kyotorphinergic' nerves followed by activation of the 'opioidergic' (possible 'enkephalinergic') nerves in the central nervous system.