Projections of cervical cancer mortality and incidence in New Zealand: the possible impact of screening. The aim was to estimate the likely burden of cervical cancer in New Zealand over the next two decades, according to whether cervical screening services are made more effective. The study was based on national mortality and incidence data for the periods 1954-87 and 1954-86, respectively. An age-period-cohort model was used to estimate the contributions of age, time period, and birth cohort effects to the occurrence of cervical cancer. Using age specific estimates of the future female population of New Zealand, projections of cervical cancer mortality and incidence until the year 2008 were derived from the model. Projections were made assuming either that screening services will not be improved, or that an immediate improvement in the organisation of screening will lead to a decline in period effects for incidence of 15% per five year time period (with a slightly delayed effect on mortality). It was also assumed either that the risk in new birth cohorts will be similar to that in recent cohorts, or that their risk will be halved as a result of changes in sexual behaviour (due to education about AIDS or other factors). Combining these assumptions produced four sets of estimates, reflecting a range of possible scenarios. Both the data used and the projections obtained related to the entire population of New Zealand women. For both mortality and incidence, projections were made of age specific rates, cumulative rates, and absolute numbers of deaths or new cases. With the first assumption about new birth cohorts, it was estimated that both mortality and incidence rates will increase if screening services are are not improved. In absolute terms, the present 100 deaths per year could increase to about 148 deaths per year, while there could be a much larger increase in incidence from 235 per year to about 440 per year). With improved screening, there could be a reduction in age specific mortality rates and a modest decline in the number of deaths, while a reduction in incidence rates would be accompanied by about the same number of new cases as at present. In comparison with improvements in screening, changes in the underlying risk in new birth cohorts would have much smaller effects on the occurrence of cervical cancer over the next two decades. Plausible improvements in cervical screening are likely to be accompanied by only small changes in the burden of cervical cancer over the next two decades. If screening services are not improved, however, there will be striking increases in both mortality and incidence.


Social class, marital status, and cancer of the uterine cervix in England and Wales, 1950-1983. The aim was to investigate whether trends in mortality from cancer of the cervix uteri by age, marital status, and social class are compatible with current beliefs about the epidemiology of the disease. Data on mortality from cancer of the cervix for single and married women by age and social class were obtained from the Registrar General's Decennial Supplements on occupational mortality for the years 1950-53, 1959-63, 1970-72, and 1979, 1980, 1982, and 1983. Age standardised mortality rates were calculated directly by social class and marital status. The data relate to all cases of carcinoma of the cervix reported in England and Wales in the years studied. There was a marked convergence of mortality between single and married women over the period within every social class grouping examined. The social class differential, however, remained essentially unchanged for both single and married women considered separately. Trends in mortality by marital status appear to reflect accurately the changes in the pattern of marriage and sexual behaviour that have taken place in the post-war period, whereas the patterns of other risk and protective factors such as screening explain these trends less well. In contrast, it seems likely that factors other than patterns of sexual behaviour and screening operate to maintain the social class differential in England and Wales.


Further evidence of benefits of a (non-randomised) breast cancer screening programme: the DOM project. The aim was to demonstrate the benefits of breast cancer screening on mortality. The study was an evaluation of a breast cancer screening programme by means of different approaches: (1) a case-control study, breast cancer deaths being the cases; (2) comparing the numbers of breast cancer deaths in screened and unscreened women; (3) comparing breast cancer mortality before and after start of the programme; (4) comparing breast cancer mortality in different large cities; (5) comparing screening activity with mortality reduction. The setting was a breast cancer screening programme in the city of Utrecht, the DOM project, for women aged 50-64 years old at intake, birth cohort 1911-1925. The programme started in 1974, and there were five screening rounds up to 1984. Participation rate in the first round was 72% (14,697 women). (1) Screening was protective against dying from breast cancer, odds ratio 0.52, with a stronger effect in older women and no evidence of confounding; (2) risk ratio of dying from breast cancer for women in the response group was the same as the odds ratio, 0.52; (3) breast cancer death rate after the start of the project was nearly 20% lower than before the project started; after correcting for women who could not have benefited from screening the reduction was 33%; (4) a rise in breast cancer mortality in birth cohort 1911-1925 seen in other large cities without a screening programme due to aging of the cohort was not seen in the city of Utrecht; (5) mortality reduction followed the screening activity with a time lag of approximately 5 years. Early diagnosis of breast cancer by mammography reduces breast cancer mortality in women 50-64 years old at intake; different approaches to the evaluation of the project give different estimates of the screening effect, making clear that the effect depends on the intensity of the programme.


Contributions of incidence and case fatality to mortality from bladder cancer in the south Thames Regions. The aim was to assess the individual contributions of incidence and case fatality to variations in bladder cancer mortality between districts in the South Thames Regions. The standardised mortality ratios for bladder cancer were calculated for the health districts in the South Thames Regions using data from the Thames Cancer Registry. The results were compared with the standardised registration ratios, used as a measurement of incidence, and survival hazard function, used as a measurement of case fatality. As one determinant of case fatality is the severity at presentation, mortality was also compared with the standardised proportion of cases with advanced disease at diagnosis. The study took place in the 28 health districts in South East and South West Thames regional health authorities. Subjects were 3271 cases of bladder cancer aged 15-74 years resident in one of the two South Thames regional health authorities at diagnosis and registered between 1982 and 1985. The standardised mortality ratios for the different districts varied from 62 to 139. The standardised registration ratios, the survival hazard functions adjusted for age and stage of disease at diagnosis, and the proportion of cases with severe disease at diagnosis were all independently and significantly related to the standardised mortality ratios in each district. Mortality from bladder cancer was significantly related to measurements of incidence, case fatality, and severity at presentation. These relations have implications for the health services. The incidence of disease may be modified through preventative measures, the case fatality through improved quality of care, and severity at presentation possibly through prompt management of patients with haematuria. Further studies are needed to investigate why these factors have high values in some districts.


Racial differences in ill defined cancer mortality in the United States and in the District of Columbia. The aim was to examine the epidemiology of unknown primary cancer mortality in the USA during 1979 to 1988 by age, sex, race, year, and geographical area. National (US) and state data were abstracted for deaths due to ill defined cancer (ICD-9 195.0 to 199.1) and all cancers combined (ICD-9 140.0-209.9). Age adjusted mortality rates were calculated using the 1980 USA population as the standard, and standardised rate ratios were derived. National total cancer incidence data were obtained from the surveillance, epidemiology and end results (SEER) program, and age and sex specific relative (black/white) cancer incidence rates were derived and compared to relative (black/white) mortality rates for ill defined cancer. State and regional median family income levels were obtained from the 1980 census and compared to corresponding mortality rates. This study used data for the US population, the 50 states, and the District of Columbia. During 1984-1988, ill defined cancers accounted for an average of 34,921 deaths each year in the USA (13.7 per 100,000 population). The mortality rate due to ill defined cancers is greater among blacks (19.3 per 100,000) than whites (13.2 per 100,000) (RR = 1.5) and has not declined since 1979. There is considerable geographical variation in the ill defined cancer mortality rate. Thus among blacks the highest rates were clustered in the central states (23 per 100,000) and the lowest rates were seen in the mountain and western states (17 per 100,000). The District of Columbia had the highest overall rate (21.7 per 100,000) when compared to all other states. The black/white relative mortality rate due to ill defined cancer was consistently greater than the black/white relative incidence of all cancers. Ill defined cancer mortality is the fourth leading site of cancer mortality in the USA, and accounts for 7.4% of cancer deaths annually. The large proportion of ill defined cancer deaths may have biased the accuracy of national and local cancer incidence and mortality statistics. The higher mortality of ill defined cancer among blacks is not explained by the higher overall cancer incidence among blacks and suggests the influence of socioeconomic or cultural barriers that may result in underutilisation of health services or substandard health care. Ill defined cancer mortality may be a sentinel indicator of deficiencies in the health care delivery system as well as a measure of progress against cancer.


Adding years to life: effect of avoidable mortality on life expectancy at birth. The aim was to determine the number of years that could be gained by preventing avoidable deaths. The study arose from the concept of avoidable causes of death and life expectancy at birth. Four abbreviated life tables were computed. The first included all causes of death; the second excluded all avoidable causes of death; the third and fourth excluded respectively primary and secondary avoidable causes of death. Mortality and population data were taken from Mortality Statistics Offices in Valencia Region, Spain. Life expectancy at birth (LEB) was 75.7 years. After removing all avoidable deaths, LEB increased by 1.74 years. This improvement is attributed to avoidable deaths by primary prevention (1.09 years) and avoidable death by secondary prevention (0.37 year). According to these results the greatest improvement in LEB would be gained by primary prevention.


Childhood blood pressure, body build, and birthweight: geographical associations with cardiovascular mortality. The aim was to examine whether blood pressure, body build, and birthweight differ between areas of England and Wales with widely differing adult cardiovascular mortality rates. This was a cross sectional survey of children in five towns with exceptionally high and five towns with exceptionally low current adult cardiovascular mortality. The study was a school based survey. 3842 children aged 5.0-7.5 years were selected by stratified random sampling of primary schools (response rate 76%). Blood pressure, pulse rate, height, and weight were measured and birthweight was assessed by maternal recall. Children in towns with high cardiovascular mortality rates were significantly shorter than those in towns with low cardiovascular mortality rates (mean difference 0.9 cm, 95% confidence interval 0.4 to 1.4 cm) and had slightly higher body mass indices (mean difference 0.12 kg/m2, 95% CI -0.03 to 0.27 kg/m2). Mean birthweights were slightly lower in high mortality towns (mean difference 34 g, 95% CI -10 to 78 g), while the proportion of children with low birthweight (< 2500 g) (8.1%) was significantly higher than that in low mortality towns (5.5%) (p = 0.005). Mean differences in blood pressure between high and low mortality towns were small and non-significant, even after adjustment for height. The differences in height between high and low mortality towns were largely independent of social class. However, differences in mean birthweight were markedly reduced once social class was taken into account. No geographical relationship between childhood blood pressure and adult cardiovascular mortality was detected. Although it is possible that the differences in mean height and body mass index between towns with differing adult cardiovascular mortality may have implications for future patterns of health in these towns, the absence of marked differences in birthweight and blood pressure suggests that hypotheses proposing a direct relationship between intrauterine experience and adult cardiovascular mortality will have limited relevance to geographical variation in cardiovascular disease in this generation.


Level of education, lifestyle, and morbidity in two groups of white collar workers. The aim was to examine the relationship between level of education, lifestyle, and morbidity in two groups of male white collar workers, and to determine whether any differences found could be related to objective differences in working conditions. The study was a survey of a random sample of commercial travellers and a sample of men with sedentary occupations, representing two different groups of white collar workers. Survey interviews were conducted during the annual compulsory medical examination. Subjects were classified into three levels of education and differences according to level of education were studied in relation to 40 frequent health problems, lifestyle variables, body mass index, height, and working conditions. There were 1364 men in the commercial traveller group, mean age 39.5 years, and 525 men in the sedentary group, mean age 36.2 years. There were 22 exclusions because of unclassifiable levels of education and four refused to be interviewed. The study took place in 11 towns in France. When age was taken into account there were only minor differences in the prevalence of health disorders. Lifestyle variables and height were clearly related to the level of education. Observed differences could not be explained by constraints or declared difficulties in working conditions. Differences in health practices related to level of education are observed even in groups that are relatively homogeneous socially. Lifestyle may be important as an intermediate determinant of health disorders among less educated people.


Public health implications of dietary differences between social status and occupational category groups. As there is a social status gradient in chronic disease mortality in Australia, this study aimed to establish whether there were substantial differences among socioeconomically defined groups with respect to food choice and nutrient intake, in the context of risk of nutrition related chronic diseases. Cross sectional data were collected from a randomly selected population sample of 1500 urban Australian adults. Data were collected by postal questionnaire, which included an assessment of dietary intake and questions on sociodemographic details. Three measures of social position were collected: occupation, educational status, and income status. Occupation was interpreted both on a continuous, prestige scale, and also as categorical occupational groupings. The study achieved a 70% response rate. Higher social status was generally associated with healthier dietary intakes, with lower fat and refined sugar densities, and higher fibre densities, but also with higher alcohol density. No differences were found in salt, polyunsaturated fat, protein, or complex carbohydrate densities across groups. Food intake differences were also found between occupational status groups, with the upper social groups tending to consume more wholegrain cereal foods, low fat milk, and fruit, and less refined cereal foods, full cream milk, fried meat, meat products, and discretionary sugar; but also more cheese and meat dishes. Although this study did show statistically significant differences across social status groups in relation to nutrient and food intakes, these differences were small compared to the disparity between intakes of all groups and the recommended patterns of intake, and did not appear to be great enough to be a major explanatory variable in differences in disease risk across groups.


Clustering of dietary variables and other lifestyle factors (Dutch Nutritional Surveillance System). The aim was to investigate whether dietary factors cluster in a favourable or unfavourable way and to characterise the groups identified by lifestyle and sociodemographic variables. This cross sectional study was based on data of the 1987-1988 Dutch national food consumption survey (DNFCS), obtained from a panel by a stratified probability sample of the non-institutionalised Dutch population. 3781 adults (1802 males and 1979 females) of the DNFCS, aged 19 to 85 years, were studied. To estimate dietary intake two day food records were used. Lifestyle factors were collected by structured questionnaire and sociodemographic variables were available from panel information. Cluster analysis was used to classify subjects into groups based on similarities in dietary variables. Subsequently, these groups were characterised by sociodemographic and lifestyle factors as well as by the consumption of food groups. Eight clusters were found. In comparison with the guidelines, the dietary quality in four clusters was poor. The cluster with the poorest dietary intake (high intake of fat, cholesterol, and alcohol; low intake of dietary fibre) showed on average a high consumption of animal products (except milk), fats and oils, snacks, and alcoholic beverages, and a low consumption of fruit, potatoes, vegetables, and sugar rich products. Smoking, body mass index, dietary regimen on own initiative, hours of sleep, gender, age, socioeconomic status, and day of the week were found to discriminate among the clusters. Cluster analysis resulted in substantial differences in mean nutrient intake and seems useful for dietary risk group identification. Undesirable lifestyle habits were interrelated in some clusters, but an exclusive lifestyle for health risk has not been found.


Fair, and still a sun lover: risk of gallstone formation. The aim was to evaluate the hypothesis that sunlight exposure leads to the development of gallstones in people with a sun sensitive skin. This was a case-control study among 206 white patients referred for an ultrasound examination of the gallbladder. Sunlight exposure and skin sensitivity were retrospectively assessed by a structured questionnaire. The questionnaire was taken before the outcome of the ultrasound examination was known, so that the patients and the interviewers were blind to the outcome. The main outcome measure was gallstones in the gallbladder detected by ultrasound. 87 patients had gallstones (cases), 119 had none (controls). In subjects with a skin sensitive for sun (Fitzpatrick skin type I) a positive attitude to sunbathing was associated with a higher risk of gallstones than a negative attitude. In subjects with an insensitive skin (skin type IV) no association was found. This study confirms a hypothesis which was based upon metabolic research. However it is too early to upgrade the first "F" in the traditional adage that gallstone patients are "fair, fat, female, fertile and forty". Since both epidemiological and pathobiological evidence is scarce, the role of sun and/or (ultraviolet) light exposure and skin sensitivity in the aetiology of gallstones should be confirmed by further research.


Channelling of controlled release formulation of ketoprofen (Oscorel) in patients with history of gastrointestinal problems. The aim was to determine if a new controlled release formulation (Oscorel) of the non-steroidal anti-inflammatory drug (NSAID) ketoprofen has been preferentially prescribed in patients with prior history of gastro-intestinal disturbances. The study was a pharmacy records based comparison of the rates of prior prescribing of drugs indicated for peptic ulcer treatment in first recipients of Oscorel in 1989 versus recipients of other NSAID products. A representative panel of Dutch community pharmacies serving approximately 425,000 people was used. Oscorel was launched in January 1989. Data on prescriptions dispensed in 1987-1988 to a total of 837 first users of Oscorel were analysed and compared with the dispensing history of a reference population including 30,787 patients who did not receive a prescription for Oscorel during 1989. Compared to the reference population, first users of Oscorel included a greater proportion of females, of patients 75 years and older, of heavy users of NSAIDs, and of patients switching among different NSAIDs. A total of 24.1% of first users of Oscorel had received peptic ulcer therapy in 1987-1988, versus 15.7% of the reference population. The rate ratio was 1.54, with 95% confidence interval of 1.36-1.74. Adjustment for stratifying variables caused only minor changes in the rate ratio, which remained stable on 1.5. Oscorel appears to have been channelled into use in patients with recognised risk factors for gastrointestinal toxicity. This preferential prescribing probably resulted from expectations and claims that this product has a lower risk of such toxicity.


Changing incidence of peptic ulcer--facts or artefacts? A cohort study from Tromsø. The aim was to estimate the age and sex specific incidences of duodenal and gastric ulcers censored for death and migration. A population based cohort was followed seven years through records of x ray examinations, endoscopies, and operations in the only hospital serving the area. The study was conducted in the municipality of Tromsø, Northern Norway, where all men aged 20 to 54 years and women aged 20 to 49 years in 1980, a total of 21,440, were included. We found an incidence of 1.47 (95% CI 1.21-1.76) and 0.88 (0.67-1.14) per 1000 person-years for gastric and 1.98 (1.69-2.31) and 0.85 (0.64-1.11) for duodenal ulcers in men and women, respectively. A small and insignificant sex difference for gastric ulcer was noted. The duodenal preponderance in men was only recognised among the ulcers identified by x ray, not among ulcers diagnosed by endoscopy. This population based study has, in contrast to recent studies from other areas, revealed an unchanged high incidence of gastric and duodenal ulcer in both sexes. Compared to earlier studies from this area it indicates a preponderance of duodenal ulcers. The study also shows the impact of attendance rate, death, and migration, and of diagnostic methods on the incidence estimates. Ignoring these potential biases may lead to conclusions on peptic ulcer trends that reflect artefacts rather than real changes in peptic ulcer occurrence.


Pulmonary function development in children with past history of asthma. The aim was to examine whether or not the children with a past history of asthma but free from asthmatic attacks for several years show a different growth pattern in pulmonary function from control children. A community based cohort was surveyed three times during a four year follow up period. Kashima district in Ibaraki prefecture, Japan. In 1980, 441 primary school children between 113 and 124 months of age were enrolled as an initial cohort; 325 of these provided reliable results in each of the three surveys. A level and a slope of FVC, FEV1, Vmax50, and Vmax25 were calculated for each child, based on a general linear model analysis. Past histories of each child were determined from a standardised questionnaire. The children with a history of doctor diagnosed asthma showed a lower Vmax50 level (p < 0.005) and a lower level and slope of Vmax25 (p < 0.005, p < 0.01) than control children, even when only those who did not suffer from wheezing attacks during the follow up period were considered. Indices of peripheral airways function in children with an asthmatic history were reduced even if they had been in remission for several years. The difference in pulmonary function in comparison to control children might become greater at the time of the adolescent growth spurt.


Impact of headache on sickness absence and utilisation of medical services: a Danish population study. The aim was to study the extent and type of health service utilisation, medication habits, and sickness absence due to the primary headaches. This was a cross sectional epidemiological survey of headache disorders in a general population. Headache was diagnosed according to a structured interview and a neurological examination using the criteria of the International Headache Society. A random sample of 25-64 year-old individuals was drawn from the Danish National Central Person Registry. All subjects were living in the Copenhagen County. 740 subjects participated (76% of the sample); 119 had migraine and 578 had tension type headache. Among subjects with migraine 56% had, at some time, consulted their general practitioner because of the migraine. The corresponding percentage among subjects with tension type headache was 16. One or more specialists had been consulted by 16% of migraine sufferers and by 4% of subjects with tension type headache. The consultation rates of chiropractors and physiotherapists were 5-8%. Hospital admissions and supplementary laboratory investigations due to headache were rare (< 3%). Half of the migraine sufferers and 83% of subjects with tension type headache in the previous year had managed with at least one type of drug in the current year. Acetylsalicylic acid preparations and paracetamol were the most commonly used analgesics. Prophylaxis of migraine was used by 7%. In the preceding year 43% of employed migraine sufferers and 12% of employed subjects with tension type headache had missed one or more days of work because of headache. Most common was 1-7 days off work. The total loss of workdays per year due to migraine in the general population was estimated at 270 days per 1000 persons. For tension type headache the corresponding figure was 820. Women were more likely to consult a practitioner than men, whereas no significant sex difference emerged as regards absenteeism from work. The impact of the headache disorders on work performance in the general population is substantial, and the disorders merit increased attention.


The problem of diagnostic variability in general practice. The aim was to examine the scale, source, and relevance of variation between general practices in respect of the rates with which patients consulted with illnesses falling in each of several diagnostic groups. This study involved a general practice morbidity survey conducted over two years, 1970-72. All patients who consulted their general practitioners were identified and the number of these who consulted with diagnoses attributable to each of the 18 main chapters of the International classification of diseases were counted. Patients who consulted for more than one diagnosis within a chapter were counted once only; those who consulted for one or more diagnoses in each of several chapters were counted once for each chapter. This was a national survey involving general practitioners in England and Wales. The study involved 214,524 patients from 53 selected general practices (115 doctors) who were registered with their general practitioners for the whole of the year 1970-71 and for whom their morbidity data had been linked with their social data from the 1971 census. Using the numbers of patients on the practice lists as denominators, practice patient consulting rates (PPCR) were calculated for each practice and for each ICD chapter. Variability in chapter PPCR was examined by calculating coefficients of variation and, after allowance for random variation, coefficients of residual variation. There were large interpractice (doctor) variations in all chapter rates. These variations were only marginally attributable to: chance; different age, sex and social class mixes of practice populations; geographical locations; and practice organisation. The rates were, however, consistent from one year to the next for any one practice. Approximately half of the interpractice (doctor) diagnostic variability was associated with overall patient consulting behaviour. When the effects of this behaviour were discounted, any major residual diagnostic variability was confined largely to ICD chapters I-V, XVI, and XVII, ie, those chapters where aetiology forms the basis of classification. Variations in recorded diagnostic rates are mainly due to the consistent but idiosyncratic and selective exclusion by practitioners of some components from the total set which often coexist in a new diagnosis. Because of the scale of interpractice diagnostic variability, the use of algorithms and information technology is largely precluded from outcome studies, auditing procedures, and studies of practice work loads in general. However, (1) the consistency of any individual doctor's pattern of diagnostic recording from one year to another permits studies of trends; and (2) given a reasonable number of recording practices, the population mean practice consulting rates can be estimated with sufficient accuracy for many epidemiological research and administrative uses.


Demographic characteristics and health behaviours of consenters to medical examination. Results from the Welsh Heart Health Survey. The aim was to compare the demographic characteristics and health related behaviours of people who consented to a medical examination as part of a population survey with those who did not. The study formed part of the (1985) Welsh Heart Health Survey, which comprised a three stage design involving household interview, self completion questionnaire, and medical examination. Subjects for medical examination were selected from responders to the questionnaire survey (67%). Sixty six per cent of this group consented to medical examination (n = 11,637). Odds ratio analysis techniques were used to compare consenters and non-consenters. The analysis was based on self reported information available from previously completed questionnaires, and from personal interviews. The study supported the findings of previous research indicating that consenters to medical examination are more likely to be from non-manual social groups, to be aged 25-44 years, to be educated beyond school age, and to be married. Individuals with healthy lifestyle characteristics (diet, physical activity) were overrepresented among consenters. The only exception to this finding was in relation to excessive alcohol consumption. These findings emphasise the importance of maximising response rates in all forms of social research including surveys with a clinical component. They also have methodological and analytical implications for the Welsh Heart Health Survey.


Calcium and potassium currents in leg motoneurons during postembryonic development in the hawkmoth Manduca sexta. During insect metamorphosis the nervous system is reorganized to accommodate changes in behavior. In the hawkmoth, Manduca sexta, many identified larval motoneurons persist to innervate new adult muscles, while undergoing changes in dendritic morphology and synaptic connections. The thoracic leg motoneurons, for example, innervate different sets of muscles in the larva and adult and participate in distinct types of locomotor behavior in the two stages of life. To determine whether changes in the biophysical properties of these motoneurons accompany the structural and functional modifications that have been described, we used the whole-cell voltage-clamp technique to compare the Ca2+ and K+ currents expressed by leg motoneurons isolated from the larval, pupal and adult stages of Manduca. After 24 h in culture, the somata of leg motoneurons isolated from all three stages expressed voltage-sensitive Ca2+ currents that could be blocked by Cd2+, Co2+ or Ni2+. The currents were larger with Ba2+ as the charge carrier. The Ca2+ current density was significantly lower in these motoneurons during the early pupal stage than in either the larva or adult. Similar experiments revealed both transient and sustained K+ currents in the leg motoneurons that could be blocked with Cs+. There was a significant decrease in the density of the transient, inactivating outward current in leg motoneurons isolated from the early pupal stage. Thus, the levels of some types of ionic currents are modulated during metamorphosis. These changes may be important for the developmental or behavioral changes that accompany metamorphosis.


The influence of temperature on power output of scup red muscle during cyclical length changes. To gain insight into how temperature affects locomotory performance, we measured power output of scup red muscle during oscillatory length changes at 10 degrees C and 20 degrees C. When we optimized work loop parameters, we found that maximum power was 27.9 W kg-1 at 20 degrees C and 12.8 W kg-1 at 10 degrees C, giving a Q10 of 2.29. Maximum power was generated at a higher oscillation frequency at 20 degrees C (5 Hz) than at 10 degrees C (2.5 Hz), and the Q10 for power output at a given oscillation frequency ranged from about 1 at 1 Hz to about 5 at 7.5 Hz. An analysis of the results in terms of crossbridge kinetics suggests that the higher power output at 20 degrees C is associated with both a higher Vmax (i.e. more power per cycling crossbridge) and faster activation and relaxation (i.e. a greater number of cycling crossbridges). To obtain a more realistic understanding of the functional importance of temperature effects on muscle, we imposed on isolated muscle in vivo length changes and oscillation frequencies (measured during previous experiments on swimming scup) and the in vivo stimulus duty cycle (measured from electromyograms in this study). At 20 degrees C, muscle bundles tested under these in vivo conditions produced nearly maximal power, suggesting that the muscle works optimally during locomotion and, thus, important contractile parameters have been adjusted to produce maximum mechanical power at the oscillation frequencies and length changes needed during swimming. At 10 degrees C, muscle bundles tested under in vivo conditions produced much less power than was obtained during the 'optimized' work loop experiments discussed above. Furthermore, although 'optimized' work loop experiments showed that maximum power output occurs at 2.5 Hz, scup do not appear to swim with such a low tailbeat frequency. Although the reason for these apparent discrepancies at 10 degrees C are not known, it shows that simple extrapolation from isolated muscle to the whole animal, without knowledge of how the muscle is actually used in vivo, can be misleading.


Constrained and flexible features of rhythmical hindlimb movements in chicks: kinematic profiles of walking, swimming and airstepping. Although studies of walking have generated many of the principles for motor control, walking is but one of the many behaviors that an animal produces. This study investigates the relationships among the kinematic profiles of three behaviors in chicks: walking, swimming and airstepping. In addition to describing features of the hindlimb movements, such as retraction and protraction, we also examined the intra- and interjoint coordination patterns at the hip, knee and ankle. By using multiple levels of analysis, we identified some features that are common to all three behaviors, and therefore appear to be constrained, as well as some dissimilar or flexible features. Specifically, we show that resistance differentially affects the hip, knee and ankle joints. Our results also show that each joint plays a distinctive role in these behaviors. For example, we suggest that the hip stabilizes the hindlimb and regulates the rhythmicity of its movements. We also show that movement at the knee consistently precedes movement at the other joints in each behavior. Finally, differences in ankle movements are the key features that discriminate one behavior from another. Continuity among prenatal, perinatal and postnatal behaviors in chicks is discussed.


Evidence that fin whales respond to the geomagnetic field during migration. We challenge the hypothesis that fin whales use a magnetic sense to guide migration by testing for associations between geophysical parameters and the positions where fin whales were observed over the continental shelf off the northeastern United States. Monte Carlo simulations estimated the probability that the distribution of fin whale sighting was random with respect to bottom depth, bottom slope and the intensity and gradient of the geomagnetic field. The simulations demonstrated no overall association of sighting positions with any of these four geophysical parameters. Analysis of the data by season, however, demonstrated statistically reliable associations of sighting positions with areas of low geomagnetic intensity and gradient in winter and fall, respectively, but no association of sighting positions with bathymetric parameters in any season. An attempt to focus on migrating animals by excluding those observed feeding confirmed the associations of sighting positions with low geomagnetic intensity and gradient in winter and fall, respectively, and revealed additional associations with low geomagnetic gradients in winter and spring. These results are consistent with the hypothesis that fin whales, and perhaps other mysticete species, possess a magnetic sense that they use to guide migration.


The dissociation of repetition priming and recognition memory in language/learning-disabled children. Recent research has found that the performance of learning-disabled and non-disabled children is dissociated on explicit and implicit tests of memory (Lorsbach & Worman, 1989). The current study further examined this phenomenon by comparing language/learning-disabled (L/LD) and nondisabled children (NLD) on tasks measuring primed picture-naming and item recognition. Included within the design of the experiment was the manipulation of both presentation format (pictures or words) and retention interval (immediate or 1 day). Children were initially presented with pictures and words. Performance was measured both immediately and following a 1-day retention interval on a picture naming task, an item recognition task, and a supplementary measure of memory for presentation format. The magnitude of facilitation associated with primed picture-naming was found to be independent of item recognition performance. In addition, the effects of population (L/LD and NLD) and retention interval (immediate test or 1 day) each produced dissociations between the magnitude of naming facilitation and item recognition performance. Results were discussed in terms of their implications for our understanding of the nature of memory difficulties in L/LD children.


Whole words and decoding for short-term learning: comparisons on a "talking-computer" system. Low-and average-ability readers in first and second grade studied a list of 36 words using a "talking-computer" system. The system highlighted and simultaneously pronounced orthographic units in the words when the children touched the words with a light pen. During two training sessions, the computer presented four groups of 9 words each, one group as whole words, one in syllabic units, one in subsyllabic units, and one as single grapheme-phoneme units. All children learned the least words with single grapheme-phoneme units, having had the greatest difficulty blending the units into words during training. The other presentation units did not differ significantly from each other for most students on post-testing. However, the low first-grade readers learned fewer words segmented and presented by subsyllables than by syllable or word units, but only for multisyllabic words. Monosyllabic words were blended and learned as easily with onset-rime segmentation as with whole word units, for all children.


Perception of multidimensional stimuli: a differential-sensitivity account of cognitive processing and development. A differential-sensitivity account of cognitive processing is described that emphasizes the development of perceptual sensitivity to object relations that are directly perceived. Four experiments are presented that investigate this account and compare it to the integrality-separability view of development and the view that younger children are nonselective in their processing of multidimensional stimuli. Results show that stimulus differences are more salient than identities (Expt. 1), younger as well as older children are highly selective in their perception and classify stimuli by separate dimensions (Expt. 2), differential sensitivity affects the perceived magnitude of stimulus differences (Expt. 3), and younger and older children perceive separate dimensions in speeded classifications (Expt. 4). The importance of considering individual patterns of responses in cognitive and developmental research is also demonstrated.


Studies in space orientation. II. Perception of the upright with displaced visual fields and with body tilted. To overcome certain disadvantages of the tilted-mirror situation as a technique for separating visual and postural determinants of the perceived upright, a new procedure was developed. The S was presented with a small tilted room, on the back wall of which was a rod which he had to adjust to the true upright. In a first test, judgments of the rod were obtained with body upright, and under three different conditions of the field: (a) The S, standing at a distance from the tilted scene, viewed it through a tube which restricted his view to the interior of the scene. (b) The S stood directly in front of the scene without a tube. (c) The S stood at a distance from the scene, without a tube, so that he saw not only the tilted scene but the outer upright room as well. Under all three conditions the perceived vertical and horizontal were displaced significantly in the direction of the axes of the tilted scene. When an outer upright field was present, as in the third condition, the effect of the tilted scene upon the perceived upright diminished. In another experiment, judgments of the rod were obtained with body tilted, both to the same side as the field and to the opposite side. It was found that tilting the body resulted in an increased tendency to accept the tilted field as a basis for judging the upright. Not only were the perceived vertical and horizontal displaced further in the direction of the tilted scene, but a number of Ss perceived the tilted scene as fully upright. In another experiment there was found a tendency for the tilted scene to right itself with prolonged observation. In some cases the righting was complete, so that at the end of the observation period, the tilted scene was perceived to be fully upright. Under all conditions, striking individual differences were found in the extent to which the perceived upright was affected by the surrounding tilted field. There is evidence of considerably consistency in a person's performance under the different conditions employed.


Tolman's cognitive analyses: predecessors of current approaches in psychology. Hindsight is always helpful. I hope that I have provided some appreciation of why the experiment by Tolman et al. (1946) is a classic and deserves to be included in this series. Evaluating the extent to which this particular experiment actually influenced the development of all of the endeavors described above is difficult, and I leave it to those individuals who have an interest in the history of science to draw the appropriate conclusions. Even without direct causality, the continued relevance of this experiment is striking. We might all wish that we have sufficient foresight to investigate significant problems in such a way that our own contributions are still considered important almost 50 years after we make them.


Studies in spatial learning. I. Orientation and the short-cut. 1946. 1. The original rough formulation of the expectancy theory is difficult to distinguish from the alternative stimulus-response doctrines. Part of this difficulty results from the fact that implicit in this rough formulation, is a definition of the matrix "x expects a goal at location L," which makes it equivalent to the matrix "x runs down the practiced path," when certain conditions are fulfilled. Because of this difficulty, we have rejected this definition. 2. We have suggested instead a definition of the matrix "x expects a goal at location L" which makes it equivalent to the matrix "x runs down the path which points directly to the location L," when certain conditions are fulfilled. 3. To determine whether rats will run down such a path, whenever the original path is blocked, we have run 56 female rats in a situation which conformed to these conditions. 4. Thirty-six percent of the rats chose the path which pointed directly towards the location of the goal. The remaining rats were distributed over the other paths in a chance fashion. 5. We have concluded (1) that rats do learn to expect goals in specific locations, (2) that there are important similarities between this behavior and human symbolic behavior, and (3) that these similarities justify our using the word 'expectation' as a name for the disposition to short-cut when the original patch is blocked.


Textons, visual pop-out effects, and object recognition in infancy. Five experiments were conducted to determine whether primitive perceptual features, or textons, which Julesz (1984) identified in studies of texture segregation with adults, also affect object recognition early in development. Three-month-old infants discriminated Ts and Ls composed of overlapping line segments from +s but not from each other in a delayed-recognition test after 24 hr; however, Ts and Ls were discriminated from each other after only 1 hr. In a priming paradigm, Ts, Ls, and +s were discriminated from one another after 2 weeks. In succeeding experiments, infants exhibited adultlike visual pop-out effects in both delayed recognition and priming paradigms, detecting an L in the midst of 6 +s and vice versa; these effects were symmetrical. The pop-out effects apparently resulted from parallel search: Infants failed to detect 3 Ls among 4 +s. Clearly, some of the same primitive units that have been identified as the building blocks of adult visual perception underlie object recognition early in infancy.


Structure and process in semantic memory: evidence from event-related brain potentials and reaction times. Through scalp measurements of the electrical activity of the brain (event-related potentials, or ERPs) recorded while subjects verified the truth of sentences relating exemplars and categories (e.g., ALL DOGS ARE ANIMALS), inferences were made about aspects of semantic processing that were not directly reflected by overt responses. In particular, it is suggested that a negative ERP component that peaks about 400 ms after the onset of the sentence predicate (i.e., N400) is sensitive to structural aspects of semantic memory. The amplitude of this component was modulated by the relatedness of the subject and predicate terms, as well as the hierarchical level of both these terms, but was not sensitive to the truth value of a sentence.


Optimizing the use of information: strategic control of activation of responses. Recent studies indicate that subjects may respond to visual information during either an early parallel phase or a later focused phase and that the selection of the relevant phase is data driven. Using the noise-compatibility paradigm, we tested the hypothesis that this selection may also be strategic and context driven. At least part of the interference effect observed in this paradigm is due to response activation during the parallel-processing phase. We manipulated subjects' expectancies for compatible and incompatible noise in 4 experiments and effectively modulated the interference effect. The results suggest that expectancies about the relative utility of the information extracted during the parallel and focused phases determine which phase is used to activate responses.


The role of spatial attention in visual word processing. Subjects made lexical decisions on a target letter string presented above or below fixation. In Experiments 1 and 2, target location was cued 100 ms in advance of target onset. Responses were faster on validly than on invalidly cued trials. In Experiment 3, the target was sometimes accompanied by irrelevant stimuli on the other side of fixation; in such cases, responses were slowed (a spatial filtering effect). Both cuing and filtering effects on response time were additive with effects of word frequency and lexical status (words vs. nonwords). These findings are difficult to reconcile with claims that spatial attention is less involved in processing familiar words than in unfamiliar words and nonwords. The results can be reconciled with a late-selection locus of spatial attention only with difficulty, but are easily explained by early-selection models.


Involuntary covert orienting is contingent on attentional control settings. Four experiments tested a new hypothesis that involuntary attention shifts are contingent on the relationship between the properties of the eliciting event and the properties required for task performance. In a variant of the spatial cuing paradigm, the relation between cue property and the property useful in locating the target was systematically manipulated. In Experiment 1, invalid abrupt-onset precues produced costs for targets characterized by an abrupt onset but not for targets characterized by a discontinuity in color. In Experiment 2, invalid color precues produced greater costs for color targets than for abrupt-onset targets. Experiment 3 provided converging evidence for this pattern. Experiment 4 investigated the boundary conditions and time course for attention shifts elicited by color discontinuities. The results of these experiments suggest that attention capture is contingent on attentional control settings induced by task demands.


Asymmetry in visual search for targets defined by differences in movement speed. Perception of motion speed was investigated with the visual search paradigm, using human Ss. When searching for a fast target among slow distractors, reaction time was minimally affected as the number of distractors was increased. In contrast, reaction time to detect a slow target among fast distractors was slow and linearly related to the number of distractors. The effect cannot be attributed to differences in temporal frequency, discriminability, or one type of representation that might result from spatiotemporal filtering. An alternative hypothesis that can account for the asymmetry is that speed detectors operate as high-pass filters in the velocity domain. This hypothesis is in agreement with results obtained in psychophysical studies on motion adaptation as well as data from single-cell recordings in nonhuman species.


Making two responses to a single object: implications for the central attentional bottleneck. Experiments with two stimuli and two responses have revealed a central attentional bottleneck and pointed to response selection as its primary locus; however, little has been said about the underlying reasons for this bottleneck. Here we explore these reasons. In the first three experiments, Ss made two separate responses to different aspects of the same object. Interference between selection of the responses persisted, ruling out the possibility that the dual-task bottleneck is caused by the input to the response-selection mechanism being limited to one object at a time. The next four experiments examined what happens when two responses are made to the same attribute of a single object. These experiments show that only one response selection occurred. Hence, the central mechanism is not limited to picking one motor action at a time. Several possible theories about the nature of the bottleneck are discussed.


Intertrial interval and sequential effects in magnitude scaling. The intertrial interval (ITI) was varied within subjects in magnitude estimation and cross-modality matching experiments. Fits of a recently proposed time series regression model show that the influence of the previous stimulus intensity on the current response decreases when the ITI is increased. The results can be interpreted as showing that an assimilative or additive perceptual or memory effect decreases with an increase in ITI. Fits of an earlier model, on the other hand, suggest that the influence of the previous stimulus intensity increases with an increase in ITI, which is counter to expectations. The new regression model (a) provides a simple explanation for the counterintuitive results obtained with the earlier model, (b) shows that assimilation in perception or memory can appear as contrast, and (c) reduces to a simpler model for longer ITIs.


Inverse duration effects in partial report. In partial-report experiments, an array of stimuli is displayed briefly, followed by a probe indicating the items to be reported. When exposure duration of the array is increased, 2 contrasting outcomes have been found: Some experiments find that performance improves (direct-duration effect); others find that it deteriorates (inverse-duration effect). The objective here was to identify the reasons for the discrepant results. This was done by investigating the roles played by 5 factors that differed between the 2 sets of contrasting studies. An inverse-duration effect was obtained in each of 6 experiments; its magnitude was affected by retinal eccentricity and by the number of items denoted by the probe. The effect was independent of array configuration and of number of items in the array. The direct-duration effect was shown to arise from a confounding of exposure duration and brightness.


A psychophysiological study of the use of partial information in stimulus-response translation. Ss performed a hybrid go/no-go reaction task in which colored letters were assigned in various ways to 4 finger responses, 2 on each hand. In addition to reaction time, psychophysiological measures were used to assess the duration of stimulus identification and the onset of central and peripheral motor activity. The results suggest that response selection can begin on the basis of 1 stimulus dimension (e.g., color), while the other dimension (e.g., letter form) has not yet been identified. Other results are discussed with regard to "selection for action" (Allport, 1987) and the importance of stimulus-response translation strategies in the use of partial information.


Effects of preliminary perceptual output on neuronal activity of the primary motor cortex. Observations of single neurons in the primary motor cortex of 1 monkey provided evidence that preliminary perceptual information reaches the motor system before perceptual analysis is complete. Neurons were recorded during a task in which 1 stimulus was assigned to a wrist flexion response and another was assigned to wrist extension. Two stimuli were assigned to a no-go response; each was visually similar to either the flexion or the extension stimulus. When a no-go stimulus was presented, neurons responded with weaker versions of the discharge patterns exhibited to the visually similar stimulus requiring a movement, suggesting that neurons receive partial perceptual information favoring that movement. Functionally separable neuronal populations were identified, and differences in the activations of these provide evidence about the functional effects of preliminary perceptual output on movement control processes.


Position-linked interference in forming simple visual groups. Experiments with 2-element visual groups reveal a form of interference that has several interesting properties. Observers judged the orientation of an imaginary line formed by 2 pixels (the target) while attempting to ignore a third pixel (the noise). Noise interfered with performance, even when it was made distinct from the target in various ways. This interference was strongly position linked; a single equation described the interference pattern for many different target-noise configurations. Maximum interference was observed not when the noise was closest to the target but when it was at a distance of half the separation between target pixels. Some initial findings were consistent with the idea that visual grouping reflects the operation of visual channels with Gabor-like receptive-field profiles. But subsequent results implicated processes that automatically construct visual boundaries.


Do recognizable figures enjoy an advantage in binocular rivalry? Five experiments examined whether recognizable stimuli predominate in binocular rivalry. It was found that a face predominated more than did a pattern equated for spatial frequency, luminance, and contrast; an objective reaction time procedure confirmed predominance of the face. The face was still liable to fragmentation as stimulus size increased. Observers tracked exclusive dominance of a picture of a camouflaged figure (a Dalmatian dog) prior to and then following discovery of the figure's presence; control observers received the same protocol with a scrambled version of the dog stimulus. Compared with control results, predominance of the dog picture was higher even before observers knew of the camouflaged figure. Inversion of the dog figure reduced its predominance. Binocular rivalry is sensitive to object-related, configural properties of a stimulus.


Testing a semistochastic variant of the interactive activation model in different word recognition experiments. A semistochastic variant of the interactive activation (IA) model of context effects in letter perception (McClelland & Rumelhart, 1981) was used to simulate response time distributions and means in different experiments investigating the effects of word frequency, neighborhood size and frequency, and orthographic priming in visual word recognition. The results provide evidence in favor of the connectivity assumption underlying the model but question the necessity of the interactivity assumption for simulating latencies in word recognition tasks. Together with those of a recent study by McClelland (1991), the present results suggest that 10 years after its appearance, the IA model's potential for testing hypotheses about the structure and dynamics of basic phenomena of human information processing in a variety of perceptual and cognitive tasks is not yet fully exploited.


How do somersaulters land on their feet? Body movements of trampolinists landing upright from forward somersaults, with eyes open and closed, were analyzed to test a theory of how braking and timing of actions are conjointly controlled. In regulating landing, rotation has to be slowed by extending the body so that it reaches the upright just as the feet hit the trampoline. Extending a theory of visual control of linear braking, it was hypothesized that upright landing is achieved by perceptually regulating body extension so as to keep the ratio angle of body to upright: rate of change of angle (the tau function of the angle) proportional to time-to-landing. The data support the hypothesis, indicate that vision improves precision of control, and argue further for the value of the tau function in the perceptual regulation of action.


Selective reaching: evidence for action-centered attention. Most studies of selective attention briefly present static 2-dimensional stimuli and require arbitrary responses such as verbal naming or a keypress. Many of our perceptual-motor interactions with the environment, however, require reaching directly toward an object while ignoring other objects in the scene. A series of experiments examines selective attention in the latter reaching situation. Effects previously observed in the traditional experimental procedures were obtained, suggesting that the models developed (which propose inhibitory mechanisms, e.g.) apply to ecologically valid situations. Attention accesses action-centered internal representations during such tasks.


Visual space perception and visually directed action. The results of two types of experiments are reported. In 1 type, Ss matched depth intervals on the ground plane that appeared equal to frontal intervals at the same distance. The depth intervals had to be made considerably larger than the frontal intervals to appear equal in length, with this physical inequality of equal-appearing intervals increasing with egocentric distance of the intervals (4 m-12 m). In the other type of experiment, Ss viewed targets lying on the ground plane and then, with eyes closed, attempted either to walk directly to their locations or to point continuously toward them while walking along paths that passed off to the side. Performance was quite accurate in both motoric tasks, indicating that the distortion in the mapping from physical to visual space evident in the visual matching task does not manifest itself in the visually open-loop motoric tasks.


Adaptive modification of saccadic eye movements. Experiments are reported in which the target for a saccadic eye movement was displaced during the saccade. Subjects adapted to the displacement by altering the amplitudes of subsequent saccades to compensate for it. Analysis of kinematic details of the saccade trajectories revealed that the adaptation did not arise from a simple remapping of perceived target locations. Instead, the adaptation appeared to be accomplished by a change in the gain of the saccadic system. The gain change arose primarily from a change in the magnitude of the force pulse for the saccade, not a change in the duration of the pulse. These results have implications for the mechanisms that underlie saccades in normal situations. In particular, people can separately adjust the magnitudes and durations of the force pulses used to produce saccades.


Temporal patterning in cascade juggling. A key variable in cascade juggling is the proportion of time that a juggler holds onto a juggled object during a hand cycle, that is, the time from catch to throw in relation to the time from catch to catch. Space-time constraints and principles of frequency locking suggest 3/4 as the primary ratio and 2/3 and 5/8 as the most accessible options. In 5 experiments, object number, mass, and type (ball or scarf) were manipulated together with the frequency at which the objects were juggled. With 5 or 7 balls, the ratio was 3/4, independent of frequency. With 3 balls, the ratio decreased with frequency, with 3/4, 2/3, and 5/8 tending to predominate independently of the force variations induced by variation in object mass. With 3 scarves, ratios varied inversely with frequency and often exceeded 3/4. Implications for a dynamical theory of juggling were discussed with the issue of relative timing in coordination and the manipulation of task constraints as an experimental strategy.


Rubbing your stomach while tapping your fingers: interference between motor planning and semantic judgments. Previous research (Klatzky et al., 1989) shows that the time required to make sensible/nonsensible judgments about an action-object phrase (e.g., "rub your stomach") is reliably faster when the phrase is preceded by a cure representing a specific prototypical hand shape (vs. a neutral cue). The current experiments investigated the effects of preparing for an alternate task (finger tapping vs. syllable vocalization) on facilitatory priming of sensibility judgments. Preparation for finger tapping reduced the magnitude of the priming effect more than preparation for vocalization, suggesting that resources accessed during semantic processing of action-object phrases are also used during manual response preparation. The results support the existence of a system representing manual actions that is limited in the number of activities that can be represented at one time and that is not so general that it represents manual and vocal tract movements.


Semantic congruity effects and theories of the comparison process. Two experiments requiring comparisons of point locations on the line demonstrate that the magnitude of the response-time-based congruity effect parallels the form of the macro and the micro speed-accuracy trade-off function. This is predicted from the evidence accrual class of theories but is contrary to either the propositionally based semantic coding theory or the expectancy view. Very large accuracy-based congruity effects with comparisons of point locations in the plane are evident. Congruity effects arise because the duration of each evidence accrual is increased and the quality of the information is reduced as the distance of the stimulus representations from the instruction-activated reference point increases. This evidence accrual view is extended to account for the properties of perceptual and symbolic comparisons.


Prevalence of lifetime sexual victimization among female patients. State and federal statistics describe a lower incidence of rape and child abuse than is suggested by community prevalence rates. Victims of sexual assault may experience numerous short-term and long-term effects on psychosocial and physical health. They tend to use medical services more than nonvictims and are also more likely to seek medical care than mental health services. This study seeks to determine the prevalence of sexual victimization in a family practice setting. Women 18 years of age or older presenting to a combined family practice and university student health center for a routine Papanicolaou smear or a health maintenance visit voluntarily completed an anonymous sexual experiences questionnaire of 28 close-ended items. Of 416 consecutive women, 405 agreed to participate. Of 147 family practice patients, 47.6% reported some type of contact sexual victimization during their lifetimes; 25.2% reported rape or attempted rape. Of 258 student health service patients, 57% had experienced contact sexual victimization, and 28.7% reported rape or attempted rape. Of those who reported unwanted sexual contact, 30% of the family practice patients felt they would not be comfortable discussing the experience with medical personnel, and 44.9% of the student health service patients would not feel comfortable doing so. Women with a history of unwanted sexual contact may be common in family practice and student health settings. Although treatment can be beneficial, many of these patients are not comfortable discussing their experiences with medical personnel. These findings suggest that there is potential benefit in obtaining a sexual victimization history as part of routine care, but further research will be necessary to assess the clinical benefit of such an approach.


A comparison of the gastrointestinal side effects of two forms of erythromycin. The gastrointestinal (GI) side effects of erythromycin frequently limit therapy and compliance. PCE Dispertab, a more expensive brand of erythromycin, has been promoted as a well-tolerated new dosage form; however, no studies compare its GI side effects with those of other forms of erythromycin. We compared erythromycin PCE (particles-in-tablet) with E.E.S. (erythromycin ethylsuccinate) to determine whether there is a difference in the incidence and severity of GI side effects. This was a multicenter, prospective, single-blind, randomized trial. Observers, but not participants, were blinded to the brand of erythromycin taken until after data analysis. We enrolled ambulatory patients who were at least 18 years old and weighed at least 90 lb for whom erythromycin had been prescribed at a dosage of 1.0 g/d. Subjects were given either the particles-in-tablet form, 333 mg three times daily, or the ethylsuccinate form, 400 mg four times daily, for 10 days and asked to report efficacy, compliance, and the frequency and severity of four GI symptoms (abdominal pain, nausea, vomiting, and diarrhea) in a daily diary. There were no significant differences between the particles-in-tablet and ethylsuccinate forms in incidence of GI side effects (63% and 61%, respectively), average daily GI symptom severity score (0.62 and 0.68, respectively), and GI-related discontinuations (8.5% and 8.2%, respectively). The incidence of moderate or severe nausea was 5% for the particles-in-tablet form and 25% for the ethylsuccinate form (P < .001). Although ethylsuccinate caused a higher incidence of moderate to severe nausea, there were no differences in the three main outcome measures: incidence of GI side effects, average daily GI-symptom severity score, and GI-related discontinuations. Therefore, we support prescribing erythromycin ethylsuccinate as a first line of treatment because it costs less.


The many-voiced cultural story line of a case of diabetes mellitus. An ethnographic approach is used to conduct and describe my research into a case of chronic illness and to assist the family physician's interventions. What at first appeared to be a frustrating, difficult-to-control case of diabetes mellitus was later revealed to be an intricate drama involving multiple voices and issues: marital, life stage, family, religious, occupational, regional, economic, and physician family-of-origin. Questions such as who has the disease?, what is the disease?, what keeps the disease going?, who is the patient?, and who is the clinician? are explored in the context of this case. The case was "solved" when the loss and sadness of aging was discovered and accepted during a cathartic session involving the diabetic patient, her husband, their family physician, and myself, a consultant.


Body mass and weight as indicators for cholesterol screening. Universal screening of serum cholesterol levels in adults has been recommended but not achieved. We were interested in factors that affected screening rates, and whether obese patients were more likely to have elevated cholesterol levels than other patients in our practice. A sequential sample of charts was reviewed for height, weight, race, sex, diagnosis of hypertension or diabetes, and evidence of cholesterol screening. Of 604 adult patients, 32% had serum cholesterol measurements. No correlation was found between weight or body mass index and cholesterol levels. Patients with hypertension or diabetes were more frequently screened. Sex and race did not influence screening rates. In this population neither weight nor body mass index was associated with elevated serum cholesterol levels, suggesting that screening must be offered without regard to level of obesity in order to find those patients who will benefit from intervention.


Contractual arrangements between residency programs and HMOs. Although one out of seven health maintenance organizations (HMOs) is directly involved in graduate medical education (GME), either as an accredited sponsoring organization or through a contractual agreement with an academic medical center or teaching hospital to serve as an ambulatory rotation site, relatively little is known about the extent to which HMOs have provider contracts with faculty or residents of GME programs. Such provider contracts are not agreements to collaborate on the education of residents, but rather contractual arrangements under which individual physicians or groups (who happen to be residents or faculty) agree to provide services to HMO enrollees in return for some form of compensation. In 1990, the Group Health Association of America conducted a survey of a sample of residency training programs in family medicine, internal medicine, and pediatrics to ascertain the extent to which (1) residents and faculty of residency training programs are participating physicians in HMOs; and (2) HMO enrollees are serving as the patient base for GME in ambulatory settings. Overall, 42% of the residency program respondents indicated that they contract with HMOs to provide services to enrollees. Nearly two thirds (64%) of family practice programs have provider contracts as compared with 28% of pediatrics programs and 24% of internal medicine programs. Provider contracts with independent practice associations are by far the most common, followed by group, network, and staff model contracts, in that order. It is apparent that provider contractual arrangements between HMOs and primary care residency programs are quite common, especially in the area of family practice. These contractual arrangements have probably resulted in a more predictable and stable patient revenue base for residency programs. The long-term effects on provider practice styles and the financing of graduate medical education are less clear.


Family physicians, chiropractors, and back pain. In this article, major aspects of back care provided to patients by family physicians and chiropractors are reviewed, and the recent guidelines on spinal manipulation therapy are discussed. These guidelines should be useful for family physicians wishing to refer patients to chiropractors.


The computer-based medical record: current status. At the turn of the century, neither hospitals nor physicians routinely kept clinical records. Since then, the medical record has gradually evolved. More recently, as society and medicine have become more complex and sophisticated, inadequacies of the paper medical record have become increasingly apparent. The computer-based medical record addresses many of the deficiencies of the paper record. Meanwhile, barriers to computer-based records have decreased; hardware has become more affordable, powerful, and compact, and software has been refined. Socially, the major payers for health care are demanding verification of the effectiveness and quality of care, information that involves data-intensive research. The electronic medical record promises to improve quality of care by providing point-of-care reminder and decision support tools as well as a database for substantiating the effectiveness of care. In conjunction with the growing integration of computers into all facets of life, government agencies, computer giants, and medical organizations are currently laying the groundwork for the development of standardized elements and formats for computer-based medical information systems. As part of the continuing evolution of the medical record, we foresee these forces culminating in the computerization of the clinical record. In this review, we briefly describe the developments that led us to this conclusion and describe computer-based clinical record systems in use in two family practice settings.


Anterior shoulder dislocations.

Anterior shoulder dislocations. The glenohumeral joint of the shoulder is the most commonly dislocated joint in the body. When dislocation occurs, it is usually anterior. The primary care physician usually sees the patient after reduction has been performed. Thus, treatment is directed at recovery of function and preventing recurrences. The prognosis and likelihood of recurrence in a first-time anterior dislocation depends on the mechanism of injury, treatment, rehabilitation, sex, age, and complications. Non-operative treatment after reduction usually involves immobilization and rehabilitation. Studies to date seem to indicate that age and activity level are more important factors for recurrence than length of immobilization. Traditionally, if there are recurrences after conservative treatment, then surgery is contemplated.


Supraventricular tachycardia resistant to treatment in a pregnant woman. Supraventricular tachycardia is relatively common in pregnancy, and is related to the normal physiologic changes of the cardiovascular system in the gravid state. When the arrhythmia is secondary to an ectopic atrial focus of automaticity, it can be particularly difficult to convert to a normal sinus rhythm with medications or DC cardioversion. A case of supraventricular tachycardia complicating a normal pregnancy and resistant to treatment is presented, with particular attention devoted to flecainide and propranolol, agents ultimately effective in this patient.


Sulfoconjugation of steroids and the vascular pathway of communication in dogfish testis. The zonal testis of the dogfish (Squalus acanthias) has proven advantageous to study biochemical changes in relation to stage of spermatogenesis, including information on steroidogenic enzymes and steroid receptors. To investigate whether sulfotransferase is part of a mechanism regulating the availability of biologically active hormone in close proximity to receptors, we measured in vitro conversion of [3H]estrone (E1) to sulfoconjugated metabolites in cytosolic subfractions of testes grossly dissected according to germ cell composition (premeiotic-PrM, meiotic-M, and postmeiotic-PoM stages). Assays were carried out in the presence of adenosine 3'-phosphate 5'-phosphosulfate (PAPS) at 22 degrees C and optimized for time (60 min) and protein (500 micrograms/ml). Michaelis-Menten kinetics and saturation analysis gave the following reaction constants for [3H]E1: Km = 0.33 microM, Vmax = 2.5 pmol/min/mg; and for PAPS: Km = 33 microM, Vmax = 1.1 pmol/min/mg; competition studies carried out in the absence or presence of 1- or 5-fold excess radioinert steroids indicated that estrogen (E2 > E1) as well as androgens (T = DHEA > 5 alpha dihydrotestosterone, DHT) were effective inhibitors. Sulfotransferase activity was found to be stage-related, being highest in PoM regions (2.31 +/- 0.24 pmol/min/mg protein) when compared to M and PrM regions (1.22 +/- 0.22 and 1.28 +/- 0.21 pmol/min/mg protein, respectively). Sulfoconjugation and the intratesticular distribution of steroid sulfates were also measured in vivo by perfusion of the intact testis with [3H]androgen or -estrogen. The pathway of blood flow via the genital artery was epigonal organ-->PoM-->M-->PrM (mature-->immature). Perfused [3H]E2, T, and DHT were all extensively metabolized in a one-pass, 1 hr perfusion, less than 10% of perfused [3H] steroid being recovered from testicular tissues as unchanged steroid. In general, recovery of polar metabolites was greater than non-polar metabolites from all three substrates. Sequential hydrolysis with glucuronidase and glusulase indicated that sulfoconjugation is a minor component (< 20%) of several "inactivating" pathways, which include glucuronide conjugation, 17-ketosteroid synthesis, and pathways leading to unidentified polar metabolites. No consistent stage-related distribution patterns were observed for any of the metabolite subfractions; however, total recovered radioactive steroid (polar plus non-polar) formed a decreasing concentration gradient from point of entry of perfusate (PoM region) to point of exit (PrM region). These data support the conclusion that access to receptors by steroid ligands may be controlled by a balance between activating and inactivating pathways.(ABSTRACT TRUNCATED AT 400 WORDS)


Anti-P450lpr antiserum inhibits specific monooxygenase activities in LPR house fly microsomes. Monooxygenase activity in microsomes from the LPR strain of house fly (Musca domestica L.) was inhibited by anti-P450lpr, and antiserum specific for house fly cytochrome P450lpr. Anti-P450lpr did not inhibit house fly cytochrome P450 reductase or rat cytochrome P450 monooxygenase assays, consistent with specific inhibition of P450lpr. Anti-P450lpr inhibited the ability of cytochrome P450 reductase to reduce carbon monoxide treated LPR microsomal cytochrome P450, up to 49% of the total, showing that inhibition of cytochrome P450 reduction is the major mechanism of inhibition. Anti-P450lpr inhibited 98% of methoxyresorufin-O-demethylase activity and all the benzo(a)pyrene hydroxylase activity in LPR microsomes, but none of the pentoxyresorufin-O-dealkylase activity. The antiserum partially inhibited ethoxyresorufin-O-dealkylase and ethoxycoumarin-O-dealkylase activity. These results demonstrate that methoxyresourfin-O-demethylase activity and benzo(a)pyrene hydroxylase activity are characteristic substrates for P450lpr activity in the LPR strain of house fly.


Inhibitory role of sex steroid in the regulation of ovarian follicle-stimulating hormone receptors during pregnancy. The present study was conducted to determine the role of sex steroids in the regulation of FSH receptors in pregnant rats. In the normal physiological condition, FSH bindings per unit ovarian weight (density of binding) and per 2 ovaries (total binding) increased during days 14-21 gestation. Scatchard plot analyses of the binding suggested that the increase in FSH binding was due to an increase in the number of FSH-binding sites. The plasma FSH concentration in pregnant rats was stable during the receptor change. In contrast, the plasma estradiol-17 beta concentration continuously increased from gestation day 14 to 21, and the testosterone level showed a large peak on gestation day 18. Estradiol-17 beta (one silastic plate containing 13 mg crystal)-implanted pregnant rats during 14-21 days of gestation induced significant decreases in the total FSH binding and ovarian weight on gestation day 21. Estradiol administration increased the plasma estradiol level 2.3-fold but did not change the FSH level. Testosterone or 5 alpha-dihydrotestosterone, a nonaromatizable androgen, did not influence the binding level under the same dose treatment. In contrast, continuous treatment with aminoglutethimide (2 plates containing 20 mg crystal), an inhibitor of adrenocortical steroidogenesis, for 7 days significantly increased the total FSH binding without a significant change in the ovarian weight. The plasma titers of estradiol and testosterone in pregnant rats treated with aminoglutethimide were reduced by 37% and 51%, respectively. Aminoglutethimide did not influence plasma FSH levels. These results suggest that circulating estradiol acts as a negative factor in the regulation of ovarian FSH receptors, at least during the second half of pregnancy. Other factor(s) that is (are) independent of sex steroids and FSH may contribute to FSH receptor induction.


Sex differences in adrenal function in the lizard Cnemidophorus sexlineatus: I. Seasonal variation in the field. In order to document sex differences in adrenal function and how this relates to gonadal function during the period of seasonal activity, blood samples from male and female six-lined racerunners, Cnemidophorus sexlineatus, were taken immediately after capture in the field for determination of plasma corticosterone and gonadal steroid concentrations. Plasma testosterone and dihydrotestosterone levels for males, and 17 beta-estradiol and progesterone levels for females, were measured. Trends in the concentration of plasma corticosterone differed significantly between males and females. In males the highest concentrations of corticosterone were measured in late spring and the lowest concentrations were measured in late summer. Whereas half of the variation in corticosterone levels among males could be explained as seasonal change, less than 1% of the variation among females could be explained as seasonal change. In males plasma corticosterone and androgens exhibited similar seasonal decreases. Corticosterone levels for females were not correlated with progesterone or 17 beta-estradiol levels. Sex differences in seasonal variation in plasma corticosterone concentrations suggest that corticosterone may be involved in the different reproductive strategies and energy requirements of males and females during the seasonal period of activity.


Sex differences in adrenal function in the lizard Cnemidophorus sexlineatus: II. Responses to acute stress in the laboratory. Circulating concentrations of plasma corticosterone and gonadal steroids were measured in intact and gonadectomized male and female lizards (Cnemidophorus sexlineatus) following acute stress (handling) in the laboratory. There was a significant increase in plasma corticosterone after stress. Whereas intact females exhibited greater concentrations of corticosterone relative to intact males, ovariectomized females exhibited lower concentrations of corticosterone relative to castrated males. In addition to sex differences in corticosterone responses to gonadectomy, progesterone was elevated by stress in both intact and ovariectomized females but not in males. Corticosterone adjusted for castration and handling in males was negatively correlated with the plasma androgen level. The adrenal responsiveness of males to acute stress may be attenuated by androgens presumably secreted by the testis. Not only does adrenal function influence reproduction, but adrenal responses differ between males and females, and appear to be influenced by the gonadal axis. The sex differences in adrenal responses to stress likely reflect different reproductive strategies and nutritional requirements of males and females during the breeding season.


Genetic and experimental studies on a new pigment mutant in Xenopus laevis. White lethal (wl) is a recessive mutation affecting the differentiation of the three types of chromatophores in Xenopus laevis and eventually leading to the death of the mutants around stage 50. Melanophores appear at st. 33 but differentiate abnormally, remaining pale grey, and do not proliferate after st. 41. The rare xanthophores present contain only a few differentiated pterinosomes, and the iridophores consist of noniridescent white dots. When the albino gene (ap) is combined with wl, melanophores do not differentiate. Reciprocal heterotopic and orthotopic trunk neural crest grafts have shown that the defect is intrinsic to the neural crest cells but is not due, in the case of melanophores, to a tyrosinase deficiency as revealed by the dopa reaction. The mode of action of the gene, the abnormal pattern, and lethality are discussed.


Protein kinase C modulators influence meiosis kinetics but not fertilizability of mouse oocytes. The role of protein kinase C (PKC) in the successive steps of mouse oocyte meiotic process was investigated. We have used either OAG, an analog of diacylglycerol, or mezerein, a nonphorbol ester diterpene, less tumor promoting than phorbol esters, as PKC activators, and staurosporine as PKC inhibitor. Cumulus-free oocytes were cultured in minimum essential medium with each of these PKC modulators and maturation stages were screened every two hours until the end of the process. Both PKC activators prevented GVBD at each tested dose for 4 hr (OAG) and 8 hr (mezerein), and decreased the frequencies of PB oocytes. The inhibitory effects of both activators were dose dependent and reversible. The addition of OAG to the culture medium after GVBD occurrence (i.e., after 4 hrs) did not affect PB extrusion whereas similar addition of mezerein significantly decreased the frequency of PB oocytes. Inhibition of PKC by staurosporine accelerated GVBD and increased the frequency of PB extrusion. When staurosporine was added after GVBD, PB extrusion occurred earlier but PB oocyte frequency was not increased. Fertilizability was not affected when oocyte maturation occurred in the presence of any of these substances despite the delay in maturation process. These results clearly indicate that the PKC pathway is involved in mouse oocyte meiotic process: activation of the enzyme would arrest meiotic process whereas its inhibition would participate in meiosis induction.


Culture of postimplantation rat embryos in rabbit serum for the identification of the growth factor in fractionated rat serum. The growth factor for postimplantation rat embryos was investigated on the basis of the serum species-specificity in supporting embryonic development in culture. We used rabbit serum as a basal medium for the culture of head-fold stage rat embryos, and examined the effects of various fractions of rat serum on their development. In rabbit serum alone, rat embryos developed poorly. With the rat serum ultrafiltrate of molecular weight (MW) < 300,000, embryonic development improved, but not with the ultrafiltrate of MW < 100,000. With dialyzed rat serum or the globulin fraction of rat serum, embryonic development improved, but the albumin fraction had no effect. It was concluded from these results that some macromolecular growth factor for cultured postimplantation rat embryos was present in the globulin fraction of rat serum. The molecular weight of this growth factor was estimated to be between 65,000 and 300,000. Rabbit serum was considered to be suitable as a medium for the identification of this growth factor.


The ionophore-induced acrosome reaction differs structurally from the spontaneous acrosome reaction. The ultrastructure of the spontaneous acrosome reaction in ram spermatozoa has been compared with that induced by the ionophore, A23187. The spontaneous event was dependent on incubation for 4 h, on the temperature, and on dilution. Apart from the more rapid occurrence of the ionophore-induced event, the mean diameter and distribution of vesicle size was also different. The ionophore-induced vesicles were larger, more irregular, and heterogeneous in size compared with those occurring in the spontaneous acrosome reaction (average diameter 84 nm vs. 60 nm in the spontaneous acrosome reaction). These observations are interpreted in relation to capacitation.


The role of hypoglossal sensory feedback during feeding in the marine toad, Bufo marinus. Behavioral observations demonstrate that bilateral deafferentation of the hypoglossal nerves in the marine toad (Bufo marinus) prevents mouth opening during feeding. In the present study, we used high-speed videography, electromyography (EMG), deafferentation, muscle stimulation, and extracellular recordings from the trigeminal nerve to investigate the mechanism by which sensory feedback from the tongue controls the jaw muscles of toads. Our results show that sensory feedback from the tongue enters the brain through the hypoglossal nerve during normal feeding. This feedback appears to inhibit both tonic and phasic activity of the jaw levators. Hypoglossal feedback apparently functions to coordinate tongue protraction and mouth opening during feeding. Among anurans, the primitive condition is the absence of a highly protrusible tongue and the absence of a hypoglossal sensory feedback system. The hypoglossal feedback system evolved in parallel with the acquisition of a highly protrusible tongue in toads and their relatives.


Assembly and disassembly of axonal microtubules of the toad Xenopus laevis under the effect of temperature. In toads Xenopus laevis living at 11 degrees (winter), the microtubular density of 4-microns myelinated axons of lumbosacral nerves was assessed with the electron microscope. In controls, the density was 11.2 microtubules/microns2. In nerves incubated at 0 degrees, microtubules decreased following a simple exponential curve with a half time of 4.7 min (k = 0.149 min-1); residual microtubules were 4.5%. After rewarming, the full complement of microtubules reappeared within 60 min. In steady state, the microtubular density exhibited a linear relationship with temperature (range: 0-22 degrees; slope 0.94 microtubules/microns 2 per degree; r, 0.96). After heating the nerve by 11 degrees above the physiological temperature, microtubules increased by 83%, whereby the pool of unpolymerized tubulin was at least 2.7 mg/ml of axoplasm. A seasonal variation of the microtubular density was observed which accorded with the environmental temperature. The macroscopic kinetics of microtubule disassembly in the axoplasm is similar to that reported for purified tubulin but that of assembly is slower. Microtubules of peripheral axons of Xenopus are cold-labile and vary during the annual cycle.


Formation of the peripheral nervous system during tail regeneration in urodele amphibians: ultrastructural and immunohistochemical studies of the origin of the cells. In the regenerating newt tail, epimorphic regeneration--which recapitulates morphologically normal embryonic development--proceeds along a rostrocaudal differentiation gradient. Innervation of the new myomeres results from the spinal roots of segments rostral to the amputation plane and from ventral roots emerging from the lateroventral region of the regenerating spinal cord, in which motor neurons are differentiating. Electron microscopy and an indirect immunofluorescence study with anti-glial fibrillary acid protein (GFAP) confirm that the ventrolateral part of the regenerated ependymal tube gives rise to cells of the ventral root sheath and the spinal ganglia. Anti-GFAP and anti-neurofilament antibodies showed that ependymoglial cells and Schwann cells may play a role in neuronal pathfinding by helping guide and stabilize pioneering axons as they extend toward the myomeres. The carbohydrate epitope NC-1 is expressed in the spinal cord, in sheath cells of the spinal ganglia and in the non-myelin-forming Schwann cells of the peripheral nervous system. L1, a Ca++ independent neural cell adhesion molecule, was detected in the axonal compartments of the regenerating spinal cord, on immature and/or non-myelin-forming Schwann cells within the peripheral nervous system (PNS), and on nerve fibers within the regenerate. These immunohistochemical observations collectively support the hypothesis that Schwann cells already present in the blastema could be involved in organizing neural pathways.


Pregnancy-associated murine protein-1 (PAMP-1) in wild rodents. The presence of pregnancy-associated murine protein-1 (PAMP-1) in a number of wild rodent species was examined using tandem crossed immunoelectrophoresis and anti PAMP-1 antisera raised in rabbits. PAMP-1 is a protein present in female laboratory mice and rats; analogues were readily detected in the following species: Musculus domesticus, M. musculus, Apodemus sylvaticus, A. agrarius, A. flavicollis, and Microtus arvalus. Immunologically, cross-reacting proteins could not be detected in the laboratory hamster and laboratory guinea pig. Maternal PAMP-1 serum levels were recorded throughout pregnancy in the two species of house mouse: M. domesticus and M. musculus. Both proteins exhibited maximum concentration at day 11 of gestation. During early pregnancy, M. domesticus females had significantly higher serum levels than those of M. musculus females.


Initial evaluation of the diving accident victim. Diving accidents include air embolism and decompression sickness. Both require early stabilization and initiation of therapy before transfer to a definitive medical center for recompression therapy. Initial treatment consists of hydration, oxygen therapy and often steroids and antithrombosis therapy. Symptoms must be separated from other related conditions including myocardial infarction.


Recreational scuba injuries.

Recreational scuba injuries. Decompression illness, which includes decompression sickness and arterial gas embolism, can be a complex and difficult diagnostic dilemma. The signs and symptoms are not well known and mimic other illnesses which often results in delay when seeking medical evaluation. Additionally, most physicians are not exposed to diving medicine and may not recognize a decompression illness injury. The Divers Alert Network (DAN) offers information to the diving public and telephone consultation for physicians who require assistance in the evaluation of scuba divers and management of dive accident cases. Divers Alert Network also publishes the national annual report on scuba diving morbidity and mortality. Services provided without charge are sponsored by the DAN membership. This article introduces the physician to decompression illness and the basic care and treatment of the injured scuba diver.


Pathophysiology and treatment of decompression sickness and gas embolism. Decompression sickness and cerebral gas embolism can present as dramatic and profound sudden onset injuries in patients engaged in tunnel work and compressed gas diving, including scuba. The history and management of these illnesses span centuries. The pathophysiology relates to occurrence of gas bubbles in extrapulmonic sites. Decompression sickness is due to supersaturation of the tissue with dissolved gas and subsequent evolution of gas bubbles. Gas embolism results from the direct transit of molecular gas from a pulmonary or intravascular origin into the arterial circulation causing occlusion of a distal locus. Treatment relates to increasing hydrostatic pressure, thus maximizing the gradient for gas reabsorption and dissolution and subsequently gas excretion via the lungs.


Bodies in water. Solving the puzzle.

Bodies in water. Solving the puzzle. The enigma produced by a body found in water is clarified only by a total circumstantial investigation correlated with autopsy findings. Multiple factors, human, equipment and environmental, must be considered before opinions are expressed. The conclusion that death is due to drowning does not address the true needs which are to determine why a victim got into difficulty and could not escape.


How plastic is the central nervous system? Ramon y Cajal expressed the fatalistic view in 1928, of the central nervous system's response to damage that "...once the development was ended, the fonts of growth and regeneration of the axons and dendrites dried up irrevocably. In adult centers, the nerve paths are something fixed, ended, immutable. Everything may die, nothing may regenerate." Recently, however, new techniques for studying the nervous system have led to a reversal of thought. It is now clear the central nervous system (CNS) is remarkably plastic. While neurons cannot be replaced once they are lost through traumatic damage, the action of neurotoxins or disease processes, remaining neurons are capable of a remarkable array of responses under the appropriate conditions. The lines of research that led to this new concept are briefly explored and also current directions being pursued to understand factors that control CNS plasticity.