Annual summary of vital statistics--1991.

Between 1990 and 1991, provisional data show that the infant mortality rate decreased again, from 9.1 to 8.9, a decline of 2% in contrast to the 7% decline from 1989 to 1990. Birth, death, and marriage rates were also lower, but the divorce rate stayed at about the same level as in 1990. Natural increase in the population, excess of births over deaths, was less than 2 million, 4% less than the increase in 1990. Detailed analysis of changes and of the influence of factors like age and race requires final data; at the time of preparation of this report final birth and death data were available only through 1989. For a variety of reasons, including staff shortages and delays in receipt of state data by the National Center for Health Statistics (NCHS), final data for 1990, which would usually have been available in late August 1992, are not expected before early 1993. Unlike recent years, the decline in the infant mortality rate was only in the neonatal component, which decreased 3.6%. Postneonatal mortality increased, for the first time in many years, by 1.6%, suggesting that the decline in the total is related more to therapeutic advances in neonatology than to improved prevention. Internationally, newly independent Latvia was added to the list of countries with rates less than 15, but Costa Rica was deleted. With the reunification of Germany the list shrank to 28 and, by default, the United States moved up from 21st to 20th. Some 12.5 million births, less than 9% of the world total, took place in countries with under-5 mortality rates of less than 20 per 1000. At the other end of the scale, 42% of the world's births occurred in countries with under-5 mortality rates of more than 140 per 1000. The median under-5 mortality rate for those countries in 1990 was 189 per 1000, meaning that almost 20% of the infants born alive in these countries died before their fifth birthday.


Fever phobia: the pediatrician's contribution.

Fever phobia, the exaggerated fear of fever, is found among parents of all socioeconomic classes. Pediatricians may inadvertently contribute to fever phobia if their practice and educational message are incongruent. To determine how pediatricians treat fever in their practice, the authors sent a self-administered questionnaire to a sample of members of the American Academy of Pediatrics who lived in Massachusetts. Pediatricians were asked (1) how dangerous they believed fever to be, (2) how they treated fever in their practice, and (3) what types of educational information they gave families regarding fever. One-hundred seventy-two of the 234 (74%) eligible pediatricians returned the survey; 151 were completed. Sixty percent of the respondents were male, and 75% practiced some form of primary or episodic care. Ninety-eight (65%) believed that fever itself could be dangerous to a child, with 58 (60%) of the original 98 citing that a temperature of 104 degrees F or greater could lead to complications such as seizures, brain damage, or death. In practice, 108 (72%) always or often recommended treatment to reduce fever and 96 (89%) of the 108 did so at temperatures between 101 degrees and 102 degrees F. One hundred thirty-one (88%) respondents agreed that a sleeping child with fever should be left undisturbed. One hundred twenty-one (80%) pediatricians always or often tried to educate families about fever during sick-child visits, yet only 38% addressed the dangers of fever.(ABSTRACT TRUNCATED AT 250 WORDS)


Low-level lead exposure, intelligence and academic achievement: a long-term follow-up study.

The implications of low-level lead exposure for children's intellectual and academic performance at school age are uncertain. This issue was investigated in a prospective study of middle-class and upper-middle-class children with low lifetime exposures to lead. A battery of neuropsychological tests was administered at age 10 years to 148 children whose lead exposure and cognitive function had been previously assessed at ages 6, 12, 18, 24, and 57 months. Primary endpoints were Wechsler Intelligence Scale for Children-Revised (WISC-R) and the Kaufman Test of Educational Achievement (K-TEA). Higher levels of blood lead at age 24 months, but not at other ages, were significantly associated with lower global scores on both the WISC-R and the K-TEA after adjustment for potential confounders. Over the range of approximately 0 to 25 micrograms/dL, a 0.48-mumol/L (10 micrograms/dL) increase in blood lead at 24 months was associated with a 5.8-point decline in WISC-R Full-Scale IQ (95% confidence interval: 1.7 to 9.9, P = .007) and an 8.9-point decline in K-TEA Battery Composite score (95% confidence interval: 4.2 to 13.6, P = .0003). Mean blood lead level at age 24 months was 0.31 mumol/L (6.5 micrograms/dL; SD: 4.9, 90% percentile: 12.5). Slightly elevated blood lead levels around the age of 24 months are associated with intellectual and academic performance deficits at age 10 years.


Poisoning prevention knowledge and practices of parents after a childhood poisoning incident.

This study investigated the effectiveness of a poison center-initiated mailed intervention on improving the preventive practices of families whose preschool child had recently experienced a poisoning incident. A low-cost, mailed poisoning prevention packet consisting of telephone stickers, a +f41 coupon for syrup of ipecac, one slide-style cabinet lock, a nine-step checklist for "poison-proofing" the home, pamphlets, and a cover letter was tested prospectively on a population of parents calling a poison center for advice about possible poisoning exposures involving their preschool children. Parents without ipecac 1 week after the incident were randomized so that half received the mailed intervention. A "blind" follow-up telephone interview was conducted 3 months later. Of the 336 original families enrolled in the study, 301 (90% retention) completed the follow-up interview. Those who had received the intervention were more likely to have a telephone sticker than control families (78% vs 39%; P < .0001) and were more likely to be using at least one slide lock in the home (59% vs 40%; P < .001). However, intervention families were no more likely to have ipecac on hand than control families (57% vs 52%; P = not significant) and did not indicate a higher rate of compliance with suggested changes in other behaviors and practices to prevent poisonings. A poisoning recurrence rate of 3.7% was seen in the total sample during the 3-month period of surveillance; there was no difference between groups in recurrence rate. Even after a poisoning event, parents may not be sufficiently motivated to take poisoning prevention measures on their own.(ABSTRACT TRUNCATED AT 250 WORDS)


Improving influenza vaccination rates in children with asthma: a test of a computerized reminder system and an analysis of factors predicting vaccination compliance.

Fewer than 10% of children with moderate or severe asthma receive an annual influenza vaccination despite their heightened susceptibility to severe infections and recommendations by the American Academy of Pediatrics and the Immunization Practices Advisory Committee that all such children be vaccinated annually. Patient, provider, and system factors leading to this poor vaccination rate are not well understood. This study tested the effectiveness of a computerized reminder system in improving influenza vaccination rates in children with asthma and examined patient barriers to vaccination at one pediatric clinic in an urban teaching hospital. A computer database identified 124 children with moderate or severe asthma. Patients were randomly assigned either to study group (n = 63), who were sent a personalized letter reminder about the need for an influenza vaccination, or to a control group (n = 61), who received no reminder. Study group mothers were interviewed 2 months after the letter was sent to assess factors associated with receipt of vaccination, including demographic features, parental worry about asthma and vaccine side effects, the four dimensions of the Health Belief Model, and health locus of control beliefs. Nineteen study group patients (30%) received an influenza vaccination, compared with only 4 control patients (7%) (P < .01). Forty-three mothers of children in the study group were interviewed; 14 (33%) of these children had received the vaccination. Of the characteristics investigated, two significantly correlated with vaccination compliance: high levels of parental worry about asthma (positively correlated: odds ratio = 23.3, P < .01) and high levels of parental worry about vaccine side effects (negatively correlated: odds ratio = 0.087, P = .025).(ABSTRACT TRUNCATED AT 250 WORDS)


Pediatric residency training: ten years after the Task Force report.

A sample of 3000 pediatricians who had completed their residency training in 1978 or later were surveyed regarding the perception of the adequacy of their residency training in specific aspects of pediatric practice and in a number of subspecialty areas. The survey was almost identical with the one that formed the basis for the American Academy of Pediatrics Task Force on Pediatric Education report in 1978. The results revealed relatively little change in the high rates of perceived "insufficient training" in all the areas of pediatrics described as "underemphasized" in the Task Force report. However, those residents who received their training during the second half of the 10 years since the Task Force survey reported significant improvement in the previously underemphasized areas of developmental and behavioral pediatrics and adolescent medicine. Results also revealed a significant increase in the number of pediatricians who identify either a subspecialty interest or subspecialty practice in developmental or behavioral pediatrics. The increase in pediatric subspecialists and the improved training experience since 1984 indicate that the Task Force report may have had a positive impact on residency training in developmental and behavioral pediatrics.


Relationship of intraventricular hemorrhage or death with the level of umbilical artery catheter placement: a multicenter randomized clinical trial. Umbilical Artery Catheter Trial Study Group.

Umbilical artery catheters are frequently used in the care of very low birth weight neonates to monitor arterial blood gas values. Historically, catheters with the tip placed low, in the abdominal aorta, have been associated with an increased risk of peripheral vascular complications. Recently, a report suggested that catheters placed high, in the thoracic aorta, were associated with an increased risk of intraventricular hemorrhage. To determine whether there is an association between the placement of an umbilical artery catheter high, in the thoracic aorta, and the occurrence of intraventricular hemorrhage (grades II through IV) or death within the first 5 days of life, a multicenter randomized trial was conducted. Nine hundred seventy neonates weighing 500 through 1499 g were randomly assigned to receive either high catheters, in the thoracic aorta closest to the sixth to eight thoracic vertebra, or low catheters, in the abdominal aorta closest to the third to fifth lumbar vertebra. The incidence of the primary outcome (intraventricular hemorrhage grades II through IV and/or death) was 25.8% among newborns with high catheters and 23.1% in those with low catheters (relative risk = 1.12, 95% confidence interval = 0.89, 1.39). However, a significant interaction was observed between the level of catheter placement and birth weight for neonates weighing 750 through 999 g and those weighing 1000 through 1499 g. The subgroup of neonates weighing 750 to 1000 g had a relative risk of the primary outcome of 0.72 (95% confidence interval = 0.49, 1.07), while those weighing 1000 through 1499 g had a relative risk of 2.02 (1.21, 2.36).(ABSTRACT TRUNCATED AT 250 WORDS)


Excess morbidity associated with interhospital transport.

A prospective study was performed to determine whether excess morbidity occurred in critically ill and injured pediatric patients during interhospital transport compared with morbidity in a control group. Control observations were made during the first 2 hours of pediatric intensive care unit (PICU) care of patients emergently admitted from within the same institution and not requiring interhospital transport. The first 2 PICU hours of control patients corresponded to the interval of transport in those who required interhospital transfer. Transport care was provided by nonspecialized teams from referring hospitals. Morbidity occurred in 20.9% of 177 transported patients, exceeding the morbidity rate of 11.3% in 195 control patients (P < .05). The difference in morbidity was due to intensive care-related adverse events (eg, plugged or dislodged endotracheal tubes, loss of intravenous access) in 15.3% and 3.6% of transported and control patients, respectively (P < .05). Physiologic deterioration occurred at similar rates of 7.9% and 8.7% in transported and control patients, respectively (P > .05). Slightly greater pre-ICU severity of illness in transported than control patients (median Pediatric Risk of Mortality Score = 10 and 7, respectively, P < .05) and greater pre-ICU therapy relative to severity (P < .05) in control patients are potential confounding sources of the morbidity differences. If patients are stratified into subgroups of similar pre-ICU severity, an excess of intensive care-related adverse events in transported patients remains evident in the severe subgroup (P < .05). Further investigation is warranted to determine whether specialized transport teams can reduce the excess morbidity associated with interhospital transport of critically ill and injured pediatric patients.


Persistent pulmonary hypertension in premature neonates with severe respiratory distress syndrome.

Cardiac catheterization studies have demonstrated that Doppler-derived flow velocities in the ductal flow jet and the left pulmonary artery accurately predict the aortopulmonary pressure difference and left-to-right shunt size in newborns. To assess the presence of persistent pulmonary hypertension in premature newborns with various degrees of respiratory distress syndrome (RDS) severity, we estimated pulmonary artery pressure from the aortopulmonary pressure difference and pulmonary blood flow from the left pulmonary artery flow velocity with color-flow-directed, pulsed Doppler echocardiography. Seventy-nine premature neonates were divided into three groups--no or mild RDS (n = 27), severe RDS (n = 38), and fatal RDS (n = 14)--and compared with a group of healthy term neonates (n = 34). In premature and term neonates with no/mild RDS the mean +/- SEM aortopulmonary pressure difference increased from 7.3 +/- 0.4 and 6.6 +/- 0.5 mm Hg to 22.8 +/- 1.4 and 21.4 +/- 1.1 mm Hg over the first 24 hours (P < .001). The mean aortopulmonary pressure difference was 0.9 +/- 0.3 mm Hg during the first 72 hours in neonates with fatal RDS, but increased from 1.5 +/- 0.3 mm Hg at 4 hours to 7.4 +/- 0.6 at 24 hours and 21.5 +/- 0.7 mm Hg at 72 hours of age in neonates with severe RDS. Left pulmonary artery velocity time integrals were 18.3 +/- 0.5 cm in premature and 18.8 +/- 0.5 cm in term neonates with no/mild RDS at 12 hours vs 11.2 +/- 0.4 cm in neonates with severe and 9.9 +/- 0.5 cm in neonates with fatal RDS (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)


Relationship of sudden infant death syndrome to maternal smoking during and after pregnancy.

Sudden infant death syndrome (SIDS) is associated with maternal smoking during pregnancy. However, the relationship between tobacco exposure during infancy and SIDS is unknown. The examination of infants whose mothers smoked only after pregnancy will help determine the relationship between passive cigarette exposure during infancy and SIDS risk. This case-control analysis used data on normal birth weight (> or = 2500 g) infants included in the National Maternal and Infant Health Survey, a nationally representative sample of approximately 10,000 births and 6000 infant deaths. Infants were assigned to one of three exposure groups: maternal smoking during both pregnancy and infancy (combined exposure), maternal smoking only during infancy (passive exposure), and no maternal smoking. SIDS death was determined from death certificate coding. Logistic regression was used to adjust for potentially confounding variables. Infants who died of SIDS were more likely to be exposed to maternal cigarette smoke than were surviving infants. Among black infants the odds ratio was 2.4 for passive exposure and 2.9 for combined exposure. Among white infants the odds ratio was 2.2 for passive exposure and 4.1 for combined exposure. After adjustment for demographic risk factors, the odds ratio for SIDS among normal birth weight infants was approximately 2 for passive exposure and 3 for combined exposure for both races. These data suggest that both intrauterine and passive tobacco exposure are associated with an increased risk of SIDS and are further inducement to encourage smoking cessation among pregnant women and families with children.


Pediatric submersions: prehospital predictors of outcome.

This retrospective cohort study was conducted to test prehospital prognostic indicators in pediatric submersion victims. The authors studied all less than 20 years old victims submerged in the non-icy waters of King County, WA who were treated by Seattle or King County Emergency Medical Services between 1985 and 1989 and were hospitalized or died. Seventy-seven victims were identified from emergency medical services incident logs, hospital discharge records, and medical examiner's registries. Outcome predictors were correlated with the victim's condition at hospital discharge. Of 29 victims in cardiac arrest, 13 had return of spontaneous circulation following field resuscitation. Of these, 6 (21%) survived, with mild (n = 2) and severe (n = 4) neurologic impairment at hospital discharge. The best outcome predictors were obtained in the field. These were, for death or severe neurologic impairment, submersion durations > 10 minutes (6/6) and resuscitation durations > 25 minutes (17/17), and for good outcome, sinus rhythm (37/37), reactive pupils (43/43), and neurologic responsiveness (40/40) at the scene. Field-determined factors were reproducibly good outcome predictors. Aggressive emergency medical services may save the lives of pediatric victims in cardiac arrest following short submersion durations. The data support pronouncing dead in the field those pediatric victims of non-icy submersions who do not respond to advanced life support within 25 minutes.


Outlook for the child with a cephalocele.

Specific information on the outcome for a child with a cephalocele can be difficult to find and interpret. To update outcome information for the child with a cephalocele, the investigators compared outcome of 34 infants from their institution with that of those in previously published series. For the infants from the investigators' institution, overall mortality was 29% and was confined to infants with posterior defects, which was consistent with other published series. Additional major congenital abnormalities were present in nearly half the infants, and these were an important factor in contributing to a poorer prognosis as well as whether the defect could be operatively reduced. Seizures and hydrocephalus were often secondary problems in those infants who did worse. In addressing outlook for the infant with the cephalocele, primary factors to be considered are operability and the presence of additional major abnormalities, both intracranial and extracranial.


Efficacy of adding nebulized ipratropium bromide to nebulized albuterol therapy in acute bronchiolitis.

Nebulized ipratropium bromide is though to be synergistic with albuterol in therapy for acute childhood asthma. Because the efficacy of ipratropium in bronchiolitis is uncertain and some infants with bronchiolitis do not respond to nebulized albuterol alone, the following study was undertaken. In this double-blind, placebo-controlled trial, 69 infants between 6 weeks and 24 months of age who exhibited the first episode of acute bronchiolitis were randomly assigned to receive either nebulized albuterol (0.15 mg/kg per dose) and ipratropium bromide (250 micrograms per dose) (group A, n = 36) or nebulized albuterol and normal saline (placebo) (group B, n = 33) for two doses, 1 hour apart. The two groups were comparable at baseline. Both therapies resulted in clinically significant improvement. However, the addition of ipratropium resulted in no additional benefit with respect to decrease in the respiratory rate (mean decreases 10.6/min vs decreases 8.6/min, P = .86), accessory muscle score (range 0 through 3) (decreases 0.92 vs decreases 0.82, z = -0.44), wheeze score (range 0 through 3) (decreases 0.94 vs 0.85, z = -0.20), oxygen saturation (increases 0.25% vs increases -0.33%, P = .86), or hospitalization rate (17 vs 10). The number of "nonresponders" and "clear responders" was also very similar in both groups. No toxicity was noted. The increase in heart rate was mild and similar in both groups (increases 6.7 vs increases 11.1). The power of the study to detect a difference between the two treatment groups in the respiratory rate change > or = 8/min is greater than 90%.(ABSTRACT TRUNCATED AT 250 WORDS)


Systemic infections due to Streptococcus pneumoniae relatively resistant to penicillin in a children's hospital: clinical management and outcome.

Streptococcus pneumoniae isolates relatively (0.1 microgram/mL < minimum inhibitory concentration < or = 1.0 microgram/mL) resistant to penicillin (RRP) have been recovered worldwide, but reports of therapy and outcome of systemic infections due to these strains are limited. This retrospective study of prospectively identified patients reviews the clinical features, management, and outcome of 19 children with systemic infections due to S pneumoniae. From January 1, 1989 to December 31, 1991, 13 of 244 blood (5.3%) and 4 of 32 cerebrospinal fluid (12.5%) pneumococcal isolates were relatively resistant to penicillin. The serotypes were as follows: 14 (12 isolates), 6 (4 isolates), 19 (2 isolates), 23 (1 isolates). One peritoneal fluid isolate and one joint fluid isolate were also relatively resistant to penicillin. The mean age of the 19 patients was 30 months (range 5 to 104 months), and five children had underlying disorders. Eleven children (nine inpatients) were treated initially with a parenteral cephalosporin. Six patients were treated as outpatients, and all had (occult) bacteremia. Three of these patients received ceftriaxone intramuscularly in the emergency department; five were treated with amoxicillin/clavulanic acid, and one received amoxicillin. Seven of 13 children treated in the hospital became afebrile in 48 hours. Three others were afebrile from the time of admission. Repeat blood cultures obtained within 24 to 48 hours after therapy was initiated were sterile in 10 children. All but one child responded to initial therapy. The recovery of S pneumoniae isolates relatively resistant to penicillin has increased in our hospital during the last 3 years.(ABSTRACT TRUNCATED AT 250 WORDS)


Milk production by mothers of premature infants: influence of cigarette smoking.

The volume of milk produced by mothers who smoked cigarettes (n = 11) and control subjects who did not smoke (n = 29) was compared after the delivery of their preterm infants (28 to 32 weeks gestation). Milk production was significantly less among those who smoked, with or without adjusting for age, race, parity, gravidity, weight-for-height, prior nursing experience, customary alcohol and caffeine intake, infant birth weight, and pumping frequency. Each mother maintained her milk production using an electrical breast pump and without the stimulus of her infant suckling at the breast. Daily frequency and duration of breast pump usage were similar in the two groups. At 2 weeks postpartum, 24-hour milk volumes were 406 +/- 262 mL for mothers who smoked and 514 +/- 338 mL for control subjects. Between 2 to 4 weeks postpartum, the mean change in 24-hour milk volume (milliliters per 24 hours) of control subjects increased (+113 +/- 179 mL, P < .005), whereas milk volume of mothers who smoked cigarettes remained unchanged (-47 +/- 122 mL, P = .25). The percentage change in milk volume between 2 and 4 weeks for the combined groups was significantly related to four factors: pumping frequency, change in daily pumping frequency, day of initiation of pumping, and smoking status. Total and protein nitrogen, lactose, calcium, and phosphorous concentrations did not differ in milks from mothers who smoked cigarettes and mothers who did not smoke.(ABSTRACT TRUNCATED AT 250 WORDS)


School functioning of US children with asthma.

Data from the 1988 US National Health Interview Survey on Child Health, a nationally representative cross-sectional survey, were used to determine national estimates of school outcomes (grade failure, learning disabilities, and suspension/expulsion) and mean number of absences for children with asthma (CWA) compared to well children without current health conditions. Families indicated that 536 (4.9%) of the 10,362 survey children in grades 1 through 12 had had asthma in the previous 12 months. Families reported 18% of CWA vs 15% of well children had grade failure, 9% of CWA vs 5% of well children had learning disabilities, and 5% of CWA vs 6% of well children had been expelled or suspended. Children with asthma averaged 7.6 school days absent compared with 2.5 days for the well group. Multiple logistic regression was used to compare the odds of grade failure, learning disabilities, and suspension/expulsion among CWA and well children, overall and stratified by income. Similar methods were used to assess the role of health status among asthmatic children. After adjustment for demographic factors, CWA had similar risks of grade failure and suspension/expulsion, but 1.7 times the risk of learning disability compared with well children. Also, among families with incomes below $20,000, CWA had twice the odds of grade failure compared with well children. For asthmatic children, reported health status was an important predictor of learning disability. Ten percent of CWA were reported to be in fair-poor health. After adjustment for demographic factors, those in fair-poor health were twice as likely to have a reported learning disability compared with those in good-excellent health.(ABSTRACT TRUNCATED AT 250 WORDS)


Detection of IgM rheumatoid factors by enzyme-linked immunosorbent assay in children with juvenile rheumatoid arthritis: correlation with articular disease and laboratory abnormalities.

This study was undertaken to determine the clinical relevance of IgM rheumatoid factors (RFs) detected by enzyme-linked immunosorbent assay (ELISA) in children with juvenile rheumatoid arthritis (JRA) by examining their association with severity of acute articular disease. ELISAs for IgM-RF were performed on serum specimens from 65 children with JRA. Activity of articular disease was estimated by an arbitrary scoring system. Significant differences were seen in articular disease activity between the group of children with polyarticular disease who were IgM-RF-positive by ELISA compared with those who were IgM-RF-negative (P = .0003). When a small group of individual children with polyarticular disease were followed longitudinally, similar correlations were found between severity of acute disease and the presence of IgM-RFs detected by ELISA. In children with pauciarticular JRA, expression of IgM-RFs appeared to be a transient phenomenon with no correlation with either articular disease or laboratory abnormalities.


Epidemiology of juvenile chronic arthritis in southwestern Sweden: a 5-year prospective population study.

Previous epidemiological studies of juvenile chronic arthritis (JCA) report divergent results owing to differences in diagnostic criteria, patient retrieval, and study designs. To investigate incidence and prevalence of JCA in a total population, this prospective survey was performed in southwestern Sweden between 1984 and 1988. Cases were identified using the European League Against Rheumatism criteria for JCA and were reported annually from eight pediatric departments and local pediatricians in the studied area. During the 5 years, 213 new cases of JCA were found, corresponding to an incidence of 54.6 per 100,000 children younger than 16 years of age. The average annual incidence was 10.9 per 100,000. The peak incidence rate, 18.3 per 100,000 was found in girls 0 through 3 years old. The lowest incidence rate, 6.4 per 100,000, was found among boys 12 through 15 years old. In December 1988, 334 cases of JCA were recorded, giving a prevalence of 86.3 per 100,000. When patients in remission were omitted the prevalence was 64.1 per 100,000. The monoarticular+pauciarticular onset type constituted 68.3% of the prevalence cases, while 21.9 were polyarticular and 6.6% had systemic onset. To avoid underestimation of incidence and prevalence, and to get a correct picture of disease patterns, epidemiological surveys of JCA should be population-based rather than referral center-based. Further descriptive studies of JCA in different well-defined geographic areas are important to make valid comparisons. Such comparisons could give clues to etiological factors, both genetic and environmental.


Database use in neonatal intensive care units: success or failure.

The purpose of this national survey was to define the extent and features of database use by 445 tertiary level neonatal intensive care nurseries in the United States. Of the 305 centers responding to our survey, 78% had a database in use in 1989 and 15% planned to develop one in the future. Nurseries varied remarkably in the volume of data collected, the amount of time devoted to completing data collection forms, and the personnel involved in data collection. Although data were used primarily for statistical reports (93% of nurseries), quality assurance (73%) and research activities (61%) were also enhanced by database information. Neonatal databases were used to generate reports for the permanent medical record in 38% of centers. Satisfaction with the database was dependent on how useful the database information was to centers which collected and actually used a large volume of information. Overall, nurseries expressed a high degree of confidence in the data they collected, and 65% felt their neonatal database information could be used directly in publication of research. It was disturbing that accuracy of data was not monitored formally by the majority of nurseries. Only 27% of centers followed a routine schedule of data quality assurance, and only 53% had built in error messages for data entry. We caution all who receive database information in the form of morbidity and mortality statistics, clinical reports on patients cared for in neonatal units, and published manuscripts to be attentive to the quality of the data they consume. We feel that future database design efforts need to better address data quality control. Our findings stress the importance and need for immediate efforts to better address database quality control.


Stimulus mislocalization depends on spatial frequency.

It was previously reported that briefly presented peripheral stimuli are perceived closer to fixation than continuously presented stimuli at the same eccentricity; this effect has, however, not proved consistently replicable. In this study it was investigated whether the misperception of location might depend upon the spatial frequency content of the stimulus. Spatial-frequency-filtered vertical bars were displayed briefly and their locations were judged relative to continuously visible comparison spots. For monocular stimuli, a significant foveopetal mislocalization of the bar was obtained that increased in size as spatial frequency was lowered. Even larger mislocalizations were obtained for dichoptically presented horizontally disparate pairs of bars, and this effect also increased at low spatial frequencies. Possible underlying mechanisms are discussed, and spatial frequency is suggested to have been the confounding factor in previous studies.


Asymmetric interactions in the processing of the visual dimensions of position, width, and contrast of bar stimuli.

The processing of different dimensions of a single stimulus may be either integral or separable. Dimensions are called integral if correlated variation of one improves discrimination on the basis of the other and random variation of one interferes with discrimination on the basis of the other. For separable dimensions on the other hand, subjects can attend to one dimension and disregard variations in the other. These discrimination tests were used to find the interactions between the processing of the visual dimensions of position, width, and contrast of a light bar stimulus. The relations between these dimensions were found to be asymmetric: judgments of position and width are independent of contrast variations, but variations in these dimensions influence contrast discriminations. Furthermore, position variations influence width judgements more than vice versa. The data were analyzed for repetition effects, and it was found that this model is not sufficient to explain all the interaction phenomena. The asymmetries found may be related to the different ways these dimensions are mapped onto cortical neuron responses.


Neon flank and illusory contour: interaction between the two processes leads to color filling-in.

Two aspects of neon color spreading, local color spreading (neon flank) and illusory contour, were investigated by dichoptic viewing. Neon flank was not observed under appropriate dichoptic stimulation, suggesting that input to the process for local color spreading is based on monocular configuration. However, illusory contours were formed according to the interocularly combined configuration rather than according to each monocular configuration, suggesting that input to the process responsible for illusory contours should be ocularly-nonselective and binocular, rather than monocular. The possibilities of artifacts such as those arising from interocular rivalry were appropriately eliminated, and thus, it is tentatively concluded that the process underlying local color spreading is monocularly driven, whereas the process underlying illusory contours is binocularly driven. Furthermore, a new demonstration is presented that indicates that interocularly-induced illusory contours 'capture' and extend the monocularly-induced local color spreading, resulting in global color spreading (neon color spreading). These results support our hypotheses that neon color spreading involves two separable processes in the early visual processing, the feature detection process (for local color spreading) and the illusory contour process, and that these two processes interact with each other at later stages of cortical processing. The relation of local color spreading and illusory contours to surface separation is also discussed.


Amodal completion, depth stratification, and illusory figures: a test of Kanizsa's explanation.

Subjective contours have been explained by Kanizsa as being a consequence of amodal completion of incomplete figures. According to the theory of amodal completion, figural incompleteness triggers the emergence of an illusory object superimposed on the gaps in the inducers, which in turn hide parts of the pattern, thus suggesting that the plane of the illusory object must always be seen to be above the plane of the inducers. A figure was created in which subjective contours are seen despite the fact that the perceived depth relationships run counter to that required by the theory of amodal completion. In four experiments, this depth relationship is confirmed by using direct and indirect measures which assess both registered and apprehended depth. By emphasizing a logical inconsistency in the explanation based on amodal completion, the results show that amodal completion, at least in Kanizsa-like patterns, cannot be considered as a causal factor for subjective contour figures.


Linear vection in the central visual field facilitated by kinetic depth cues.

Illusory self-motion (vection) is thought to be determined by motion in the peripheral visual field, whereas stimulation of more central retinal areas results in object-motion perception. Recent data suggest that vection can be produced by stimulation of the central visual field provided it is configured as a more distant surface. In this study vection strength (tracking speed, onset latency, and the percentage of trials where vection was experienced) and the direction of self-motion produced by displays moving in the central visual field were investigated. Apparent depth, introduced by using kinetic occlusion information, influenced vection strength. Central displays perceived to be in the background elicited stronger vection than identical displays appearing in the foreground. Further, increasing the eccentricity of these displays from the central retina diminished vection strength. If the central and peripheral displays were moved in opposite directions, vection strength was unaffected, and the direction of vection was determined by motion of the central display on almost half of the trials when the centre was far. Near centres produced fewer centre-consistent responses. A complete understanding of linear vection requires that factors such as display size, retinal locus, and apparent depth plane are considered.


Orientation selectivity in infancy: behavioural evidence for temporal sensitivity.

One-month-old infants were tested with a habituation-recovery paradigm to determine whether they could discriminate phase-shifting grating patterns that switched between two orientations, three or eight times a second, from grating patterns that only shifted in phase. The infants were found to discriminate patterns switching orientation at the lower temporal rate of 3 reversals s-1, but not 8 reversals s-1. This finding supports the idea that orientation-selective mechanisms improve in their temporal sensitivity during early infancy. Where they can be compared, the results from behavioural and electrophysiological studies agree as to the course of this development.


Gaze angle explanations of the induced effect.

Mayhew and Longuet-Higgins formulated a computational explanation of the induced effect which successfully predicts the conditions under which the induced effect will occur. Underlying their theories are the assumptions that disparity information is separated into horizontal and vertical components and that the vertical disparities are used to calculate the gaze angles. An implementation of the fusional explanation introduced by Petrov makes similar predictions for the induced effect, but does not depend on these two assumptions.


The effect of defocusing the image on the perception of the temporal order of flashing lights.

The temporal interval between flashing lights that is required to perceive nonsimultaneity decreases as the refractive error increases from 0 to +2 diopters. The interval then remains constant with further increases to 3 and 4 diopters. The results are discussed in terms of the relative increase of transient to sustained visual channels and of the increase in apparent movement.


Recognising faces: effects of lighting direction, inversion, and brightness reversal.

When information about three-dimensional shape obtained from shading and shadows is ambiguous, the visual system favours an interpretation of surface geometry which is consistent with illumination from above. If pictures of top-lit faces are rotated the resulting stimulus is both figurally inverted and illuminated from below. In this study the question of whether the effects of figural inversion and lighting orientation on face recognition are independent or interactive is addressed. Although there was a clear inversion effect for faces illuminated from the front and above, the inversion effect was found to be reduced or eliminated for faces illuminated from below. A strong inversion effect for photographic negatives was also found but in this case the effect was not dependent on the direction of illumination. These findings are interpreted as evidence to suggest that lighting faces from below disrupts the formation of surface-based representations of facial shape.


A case of a dual frame of reference.

It is demonstrated that observers may relate to two parts of the same object by using two different frames of reference. Subjects were asked to indicate directions within a model of a hallway in which signs were posted on a single prism. The majority of subjects interpreted a sign frontally facing them as indicating the direction which is ahead of them, yet they interpreted an adjacent sign that was slanted with respect to the frontal plane as indicating a direction which is at the same side of the line of sight as the sign is. This manifests a mixture of an egocentric and an object-centred frame of reference, that is reminiscent of the mixture of local spatial interpretations in impossible pictures. It is suggested that frames of reference are not necessarily unique in a given percept, and that they are not derived from a global computation.


Sighting-down and the Poggendorff illusion: a mystery within a mystery.

As reported before, sighting-down one of the diagonal lines on a typical Poggendorff pattern will reduce the illusion even if that situation is only pictorial. But here it is also argued that sighting-down itself requires further understanding.


The first pictures: perceptual foundations of Paleolithic art.

Paleolithic representational art has a number of consistent characteristics: the subjects are almost always animals, depicted without scenic background, usually in profile, and mostly in outline; the means of representation are extremely economical, often consisting of only a few strokes that indicate the salient features of the animal which are sufficient to suggest the whole form; and it is naturalistic to a degree, but lacks anything like photographic realism. Two elementary questions are raised in this essay: (i) why did the earliest known attempts at depiction have just these characteristics and not others? and (ii) how are objects so minimally represented recognizable? The answers seem to lie with certain fundamental features of visual perception, especially figure-ground distinction, Gestalt principles of closure and good continuation, line surrogacy, component feature analysis, and canonical imaging. In the earliest pictures the graphic means used are such that they evoke the same visual responses as those involved in the perception of real-world forms, but eschew redundancies of color, texture, linear perspective, and completeness of representation.


Spectral content as a cue to perceived auditory distance.

Changes in the spectral content of wide-band auditory stimuli have been repeatedly implicated as a possible cue to the distance of a sound source. Few of the previous studies of this factor, however, have considered whether the cue provided by spectral content serves as an absolute or a relative cue. That is, can differences in spectral content indicate systematic differences in distance even on their first presentation to a listener, or must the listener be able to compare sounds with one another in order to perceive some change in their distances? An attempt to answer this question and simultaneously to evaluate the possibly confounding influence of changes in the sound level and/or the loudness of the stimuli are described in this paper. The results indicate that a decrease in high-frequency content (as might physically be produced by passage through a greater amount of air) can lead to increases in perceived auditory distance, but only when compared with similar sounds having a somewhat different high-frequency content, ie spectral information can serve as a relative cue for auditory distance, independent of changes in overall sound level.


Perspective, orientation disparity, and anisotropy in stereoscopic slant perception.

Stereoscopic depth estimates are not predictable from the geometry of point disparities. The configural properties of surfaces (surface contours) may play an important role in determining, for example, slant responses to a disparity gradient, and the marked anisotropy in favour of slant around a horizontal axis. It has been argued that variation in slant magnitude are attributable to the degree of perspective conflict present and that anisotropy is attributable to orientation disparity, which varies with the axis of slant. Three experiments were conducted in which configural properties were varied to try and tease apart the respective roles of orientation disparity and conflicting perspective in determining stereoscopic slant perception and slant axis anisotropy. The results could not be accounted for by the magnitude of the orientation disparities present. Conflicting perspective cues appeared to play a role but only for slant around a vertical axis. It was concluded that there are important configural effects in stereopsis attributable neither to orientation disparity nor to perspective.


Convergent and divergent perspective.

Use of divergent (or inverse) perspective in pictures is often regarded as arbitrary or even as erroneous in spite of the fact that entire schools of art exist in which this kind of perspective is regularly used. An experiment is reported which shows that a significant trend towards divergent perspective is experienced by subjects viewing laterally displaced three-dimensional arrays. Centrally viewed arrays show the expected perceptual convergence. It is therefore argued that divergent perspective, under appropriate conditions, is as perceptually legitimate an experience as convergent perspective.


Spatial gating effects on judged motion of gratings in apertures.

Wallach has described in qualitative terms the movement of lines behind apertures. We related the data he obtained to the aperture problem, constructed a model of movement perception, and carried out tests of the model. Experiment 1 was a parametric study, and showed the conditions under which a reliable illusion (the barber pole illusion) of diagonal movement of lines along an aperture could be obtained, and when fluctuating judgements or veridical percepts were obtained. On the basis of this study a dipole model was constructed. The model was further developed and tested. In experiment 2 the effects of total area of stimulation were examined: diagonal gratings were viewed behind multiple apertures. In experiment 3 the effects of local signs were examined: diagonal gratings were viewed in an aperture which had edges cut in small steps and stairs, with the risers parallel to the grating, and the treads parallel to the direction of motion of the grating. Experiment 4 was designed to test a prediction about the motion aftereffect of dots near and far from the point of fixation, and the results confirmed the model. It was concluded that the model accounts for the barber pole illusion and, generally, for the movement of gratings in apertures.


Curvature is a basic feature for visual search tasks.

A curved target can be found efficiently among straight distractors in a visual search task. This could reflect the status of curvature as a basic feature for visual search. Alternatively, curvature could be detected as a locus of high variation in orientation. In a series of experiments it is shown that efficient search for curvature is possible even if local variation in orientation is eliminated as a cue. This suggests that curvature is part of the set of basic features for visual search and that this set is derived relatively late in the course of visual processing.


Seeing lumps, sticks, and slabs in silhouettes.

Marr has suggested that we see three-dimensional (3-D) shapes in silhouettes because we make the implicit assumption that the viewed shapes are generalized cones. One difficulty with this suggestion is that it cannot deal with silhouettes of irregular 3-D shapes like clouds and trees; another is that it only applies to generalized cones with a relatively high length:width ratio. An alternative explanation, suggested by evidence from cross-cultural studies of language, from children's early speech, and from children's early drawings, is that the scene primitives actually used by humans are not generalized cones but 'lumps', 'sticks', and 'slabs', that is, primitives whose only shape properties are their relative extensions in 3-D space. In this paper it is proposed that the implicit assumption we make in interpreting silhouettes is that the extendedness of the silhouette reflects the extendedness of the viewed shape, so that a round region is seen as a lump and a long region is seen as a stick; and that such views seem "natural" because they are the views most likely to be encountered in normal environments. This account is more general than that of Marr because it explains how we interpret silhouettes of all kinds of 3-D shapes, even very irregular ones. Unlike Marr's account, it also deals with flat shapes like slabs and discs, and shows why it is difficult to see these shapes in silhouettes.


Use of preferential inspection to define the viewing sphere and characteristic views of an arbitrary machined tool part.

Measurements were made of the way human subjects visually inspected an idealized machined tool part (a 'widget') while learning the three-dimensional shape of the object. Subjects were free to rotate the object about any axis. Inspection was not evenly distributed across all views. Subjects focused on views where the faces of the object were orthogonal to the line of sight and the edges of the object were aligned parallel or at right angles to the gravitational axis. These 'face' or 'plan' views were also the easiest for subjects to bring to mind in a mental imagery task. By contrast, when subjects were instructed to imagine the views displaying the most structural information they visualized views lying midway between face views.


Serial pattern complexity: irregularity and hierarchy.

In perception research, various models have been designed for the encoding of, for example, visual patterns, in order to predict the human interpretation of such patterns. Each of these encoding models provides a few coding rules to obtain codes for a pattern, each code expressing regularity and hierarchy in that pattern. Some of these models employ the minimum principle which states that the human interpretation of a pattern is reflected by the simplest code for that pattern, ie the simplest code according to a given complexity metric. In this paper a new complexity metric is proposed. This metric is based on a formal analysis of the concept of regularity. Some conclusions of this analysis are sketched. The new metric does not depend on artifacts of the coding rules. It accounts for the amounts of irregularity and hierarchy as represented in a code of a pattern, such that these two amounts can be added to determine the complexity of a code. An experiment is discussed that shows that the new metric performs significantly better than the metrics used previously. In particular, the new metric predicts more local pattern organizations than the old metrics. This implies that various local pattern organizations do not falsify the minimum principle anymore.


Attention and interference in prospective and retrospective timing.

Subjects listened to a series of musical selections and then judged the duration of each selection. Some subjects were informed beforehand that timing was involved (prospective timing) whereas others were informed afterwards (retrospective timing). Half the groups performed a concurrent proofreading task during stimulus presentation. The results showed a trade-off between temporal and nontemporal task performance: prospective-timing groups were more accurate in judging time and were worse at proofreading, whereas retrospective-timing groups were relatively poor at judging time but better at proofreading. This pattern is consistent with Michon's notion of an essential equivalence between temporal and nontemporal processing, and supports the predictions of an attentional allocation model of timing. The proofreading task interfered both with prospective and with retrospective timing, and both types of time judgments were influenced in the same way by effects of stimulus context. These results imply that similar timing processes operate under prospective and retrospective conditions.


Feature analysis and the role of similarity in preattentive vision.

Texture arrays of line elements at various orientations were used to study three phenomena of preattentive vision. Subjects were asked (1) to discriminate texture areas and to distinguish their form (experiments on texture segmentation); (2) to detect salient or vertical line elements (experiments on pop-out); and (3) to identify configurations of similar or or dissimilar targets (experiments on grouping). Within the patterns, line orientation was systematically varied to distinguish the effect of differences between areas from the effect of similarity within areas. In all of the experiments, performance was found to depend on local orientation contrast at texture borders rather than on the analysis of line orientation itself. Texture areas were correctly identified only when the orientation contrast at the border well exceeded the overall variation of line orientation in the pattern. Similarly, only target elements with high local orientation contrast were detected fast and "in parallel". Targets with an orientation contrast lower than background variation required serial search. Preattentive grouping was found to depend on saliency, as defined by local orientation contrast, but not on the similarity of line elements. In addition to local orientation contrast, which played an important role in all of the visual phenomena studied, influences from the alignment of line elements with the outline of a figure were also seen.


The effects of experimental variables on the perception of American English /r/ and /l/ by Japanese listeners.

The effects of variations in response categories, subjects' perception of natural speech, and stimulus range on the identification of American English /r/ and /l/ by native speakers of Japanese were investigated. Three experiments using a synthesized /rait/-/lait/ series showed that all these variables affected identification and discrimination performance by Japanese subjects. Furthermore, some of the perceptual characteristics of /r/ and /l/ for Japanese listeners were clarified: (1) Japanese listeners identified some of the stimuli of the series as /w/. (2) A positive correlation between the perception of synthesized stimuli and naturally spoken stimuli was found. Japanese listeners who were able to easily identify naturally spoken stimuli perceived the synthetic series categorically but still perceived a /w/ category on the series. (3) The stimulus range showed a striking effect on identification consistency; identification of /r/ and /l/ was strongly affected by the stimulus range, the /w/ identification less so. This indicates that Japanese listeners tend to make relative judgments between /r/ and /l/.


On the relation between auditory spatial attention and auditory perceptual asymmetries.

Laterality investigators have typically interpreted any perceptual asymmetry as a direct expression of the functional organization of the brain. However, many other confounding factors, including the asymmetric distribution of attention, may also contribute to either the magnitude or the direction of any of these advantages. In two experiments, attention was manipulated in a dichotic listening paradigm by presenting a preexposural tone cue to the ear from which the subject was required to report. The time available to orient attention was manipulated by varying the time period between the onset of the cue and the onset of the trial (stimulus onset asynchrony, or SOA). Results indicated that a right ear advantage for the identification of verbal material obtained at a 150-msec SOA was almost completely eliminated at an SOA of 450 msec. In addition, the direction of the ear advantage for emotion identification was found to depend on task difficulty. A left ear advantage, apparent when task difficulty was minimal, was reversed to a right ear advantage when difficulty was increased. These data are taken as evidence that, when subjects are faced with a difficult dichotic task, there is a general tendency for right-handed subjects to bias their attention toward the right ear. Such a tendency is shown not only to have likely seriously compromised the results of past investigations of functional perceptual asymmetries but also to be inconsistent with previously proposed theories of dichotic listening performance.


Coherence and transparency of moving plaids composed of Fourier and non-Fourier gratings.

We examined the perceptual coherence of two-component moving plaids. The gratings that constituted the plaids were either standard Fourier gratings (F), in which luminance was determined by a drifting sinusoid, or non-Fourier gratings (NF), in which the contrast of a random background was modulated by a drifting sinusoid. These NF gratings are examples of stimuli that generate a compelling percept of motion, even though they fail to elicit a motion signal from motion analyzers based on standard cross-correlation (Chubb & Sperling, 1988). Naive observers viewed three types of stimuli consisting of superpositions of these two components: (1) two standard drifting gratings (F/F), (2) two non-Fourier drifting gratings (NF/NF), and (3) one standard and one non-Fourier drifting grating (F/NF). As expected, the F/F stimulus yielded a compelling percept of coherent motion. The dominant percept of all the observers for the NF/NF stimulus was one of coherent motion, provided that both gratings were visible and of approximately equal contrast. None of the observers reported a dominant percept of coherent motion for the F/NF condition, over a wide range of contrasts for the two grating components and across two varieties of NF gratings. In view of the results of Albright (1992) and Albright and Chaudhuri (1989), that show that single cells in macaque V1 and MT respond to both F and NF motion, one cannot interpret our findings as evidence that F and NF motion are processed independently. Alternative, "higher level" interpretations based on the intrinsically ambiguous nature of the stimuli and physical laws governing the appearance of transparent objects are discussed.


Properties of the recombination of one-dimensional motion signals into a pattern motion signal.

We have examined the human ability to determine the direction of movement of a variety of plaid patterns. The plaids were composed of two orthogonal sine-wave gratings. When the plaid components are of unequal spatial frequency or sometimes of unequal contrast, observers judge the direction of movement incorrectly. In terms of the two-stage model of Adelson and Movshon (1982), these errors may result from either a misjudgment in the perceived speeds of each of the components or a failure in the combination of one-dimensional component movements into a coherent direction of motion of the two-dimensional plaid pattern, or both. A comparison of the perceived direction of motion of plaids with the relative perceived speeds of the plaid component gratings suggest that both failures occur, but in different circumstances. The relative perceived speed of the plaid components was measured with a spatial and a temporal forced-choice technique, the former leading to larger differences. Our results support the notion that the visual system decomposes a moving plaid into oriented components and subsequently recombines the component motions.


Information tradeoffs in complex stimulus structure: local and global levels in naturalistic scenes.

An information tradeoff is an increased processing or utilization of information from one stimulus source at the expense of processing or utilization of information from a different source. An experiment was conducted to determine whether information tradeoffs occurred when subjects attended selectively to one of two different structural levels of naturalistic scenes. The subjects' attentional focus was directed to either the global or local structure of a scene (i.e., the scene or an object in the scene, respectively) either before or after presentation of a scene. They then had to use the information obtained from a 100-msec exposure of the scene to choose between two forced-choice alternatives that described one of the levels. The nature of the alternatives was such that both alternatives adequately characterized one of the structural levels on the basis of physical and semantic relations within the scene. Results showed that the subjects were significantly slower and less accurate when their attentional focus and the forced-choice alternatives were at different levels of stimulus structure than when they were at the same level, providing evidence of an information tradeoff when different types of information from a scene were used. When processing information from a particular structural level, information from the other level either was less available or was not used efficiently. Furthermore, the information tradeoffs were more severe in the precue than in the postcue condition, indicating differences in the efficiency of the selectivity process. The results are interpreted with respect to the role of selective attention in processing complex stimuli such as naturalistic scenes.


The effect of amplitude comodulation on auditory object formation in sentence perception.

To comprehend speech in most environments, listeners must combine some but not all sounds from across a wide range of frequencies. Three experiments were conducted to examine the role of amplitude comodulation in performing an essential part of this function: the grouping together of the simultaneous components of a speech signal. Each of the experiments used time-varying sinusoidal (TVS) sentences (Remez, Rubin, Pisoni, & Carrell, 1981) as base stimuli because their component tones are acoustically unrelated. The independence of the three tones reduced the number of confounding grouping cues available compared with those found in natural or computer-synthesized speech (e.g., fundamental frequency and simultaneity of harmonic onset). In each of the experiments, the TVS base stimuli were amplitude modulated to determine whether this modulation would lead to appropriate grouping of the three tones as reflected by sentence intelligibility. Experiment 1 demonstrated that amplitude comodulation at 100 Hz did improve the intelligibility of TVS sentences. Experiment 2 showed that the component tones of a TVS sentence must be comodulated (as opposed to independently modulated) for improvements in intelligibility to be found. Experiment 3 showed that the comodulation rates that led to intelligibility improvements were consistent with the effective rates found in experiments that examined the grouping of complex nonspeech sounds by common temporal envelopes (e.g., comodulation masking release; Hall, Haggard, & Fernandes, 1984). The results of these experiments support the claim that certain basic temporal-envelope processing capabilities of the human auditory system contribute to the perception of fluent speech.


Visual and nonvisual information disambiguate surfaces specified by motion parallax.

Motion parallax has been shown to be an effective and unambiguous source of information about the structure of three-dimensional (3-D) surfaces, both when an observer makes lateral movements with respect to a stationary surface and when the surface translates with respect to a stationary observer (Rogers & Graham, 1979). When the same pattern of relative motions among parts of the simulated surface is presented to a stationary observer on an unmoving monitor, the perceived corrugations are unstable with respect to the direction of the peaks and troughs. The lack of ambiguity in the original demonstrations could be due to the presence of (1) non-visual information (proprioceptive and vestibular signals) produced when the observer moves or tracks a moving surface, and/or (2) additional optic flow information available in the whole array. To distinguish between these two possibilities, we measured perceived ambiguity in simulated 3-D surfaces in situations where either nonvisual information or one of four kinds of visual information was present. Both visual and nonvisual information were effective in disambiguating the direction of depth within the simulated surface. Real perspective shape transformations affecting the elements of the display were most effective in disambiguating the display.


Salience of stimulus and response features in choice-reaction tasks.

A pattern of differential reaction time (RT) benefits obtained in spatial-precuing tasks has been attributed to translation processes that operate on mental codes formed to represent the stimulus and response sets. According to the salient-features coding principle, the codes are based on the salient stimulus and response features, with RTs being fastest when the two sets of features correspond. Three experiments are reported in which the stimulus and response sets were manipulated using Gestalt grouping principles. In the first two experiments, stimuli and responses were grouped according to spatial proximity, whereas in the last experiment, they were grouped according to similarity. With both types of manipulations, the grouping of the stimulus set systematically affected the pattern of precuing benefits. Thus, in these experiments, the organization of the stimulus set was the primary determinant of the features selected for coding the stimulus and response sets in the translation process.


Discrimination tests of visually influenced syllables.

In the McGurk effect, perception of audiovisually discrepant syllables can depend on auditory, visual, or a combination of audiovisual information. Under some conditions, visual information can override auditory information to the extent that identification judgments of a visually influenced syllable can be as consistent as for an analogous audiovisually compatible syllable. This might indicate that visually influenced and analogous audiovisually compatible syllables are phonetically equivalent. Experiments were designed to test this issue using a compelling visually influenced syllable in an AXB matching paradigm. Subjects were asked to match an audio syllable/va/either to an audiovisually consistent syllable (audio/va/-video/fa/) or an audiovisually discrepant syllable (audio/ba/-video/fa/). It was hypothesized that if the two audiovisual syllables were phonetically equivalent, then subjects should choose them equally often in the matching task. Results show, however, that subjects are more likely to match the audio/va/ to the audiovisually consistent/va/, suggesting differences in phonetic convincingness. Additional experiments further suggest that this preference is not based on a phonetically extraneous dimension or on noticeable relative audiovisual discrepancies.


Effects of context on sweet and bitter tastes: unrelated to sensitivity to PROP (6-n-propylthiouracil).

In a double-shifting context paradigm, subjects gave magnitude estimates of the perceived intensity of qualitatively dissimilar taste substances (saccharin and quinine, sucrose and quinine) or qualitatively similar ones (saccharin and sucrose), with each pair of substances taking on different contextual sets of concentrations in different sessions. The dissimilar pairs produced substantial differential effects of context (e.g., a particular concentration of saccharin or sucrose was judged more intense than a particular quinine in one contextual setting, less intense in another), but the similar pair did not. This result accords with the hypothesis that differential context effects depend on qualitative similarity. Contrary to expectations, however, the magnitude of the context effect did not differ in tasters and nontasters of the bitter substance 6-n-propylthiouracil (PROP), groups previously shown to differ in sensitivity to bitterness in saccharin. Similarity judgments suggest that saccharin and sucrose were qualitatively alike for all subjects, regardless of sensitivity to PROP.


Surface perception in pictures.

Subjects adjusted a local gauge figure such as to perceptually "fit" the apparent surfaces of objects depicted in photographs. We obtained a few hundred data points per session, covering the picture according to a uniform lattice. Settings were repeated 3 times for each of 3 subjects. Almost all of the variability resided in the slant; the relative spread in the slant was about 25% (Weber fraction). The tilt was reproduced with a typical spread of about 10 degrees. The rank correlation of the slant settings of different observers was high, thus the slant settings of different subjects were monotonically related. The variability could be predicted from the scatter in repeated settings by the individual observers. Although repeated settings by a single observer agreed within 5%, observers did not agree on the value of the slant, even on the average. Scaling factors of a doubling in the depth dimension were encountered between different subjects. The data conformed quite well to some hypothetical fiducial global surface, the orientation of which was "probed" by the subject's local settings. The variability was completely accounted for by single-observer scatter. These conclusions are based upon an analysis of the internal structure of the local settings. We did not address the problem of veridicality, that is, conformity to some "real object."


The differentiation of rhythmic structure.

Listeners judged whether two five-tone nonmetric rhythms were the same or different. Each rhythm was presented one, two, or four times to study the process of perceptual differentiation. The results indicated that the listeners perceived these rhythms in terms of the grouping of the tones, and not in terms of the timing between the groups. Two rhythms that had the same perceptual grouping were judged as being identical, even if the timing between the groups was different. The perception of the groupings of tones developed gradually. If each rhythm was presented only once, then the listeners had only a global percept, focused on groups (runs) of three elements, and often judged two different rhythms as being identical. If the rhythms were presented two or four times, then the grouping of the tones became more differentiated and the listeners were less likely to judge different patterns as being identical. Thus, perception of auditory rhythmic structure appears to follow the same developmental process as the perception of visual spatial structure.


Temporal factors in the discrimination of coherent motion.

When observers view the relative movements of a pair of bars defined by the difference of spatial Gaussian functions (DOGs), they can accurately discriminate coherent movements over a range of temporal frequencies and temporal asynchronies. Of particular interest is the fact that performance accuracy is maintained even when the two bars differ in spatial-frequency content and contrast. On each trial, observers viewed two brief presentation intervals in which a pair of vertically oriented DOGs moved randomly back and forth within a restricted range. During one observation interval, both elements moved in the same direction and by the same magnitude (correlated), and in the other interval, the movements were independent (uncorrelated). Temporal asynchronies were introduced by delaying the displacement of the right bar relative to that of the left bar in each interval. Observers were able to discriminate correlated versus uncorrelated movements up to a 45-60-msec temporal delay between the two elements' relative displacements. If motion processing is accomplished by mechanisms operating over multiple spatial and temporal scales, the visual system's tolerance of temporal delays among correlated signals may facilitate their space-time integration, thereby capitalizing on the perceptual utility of coherent-motion information for image segmentation and interpolating surface structure from the movements of spatially separated features.


Infants' responsiveness to the auditory and visual attributes of a sounding/moving stimulus.

Responses to unimodal and multimodal attributes of a compound auditory/visual stimulus were investigated in 4-, 6-, 8-, and 10-month-old infants. First, infants were habituated to a compound stimulus consisting of a visual stimulus that moved up and down on a video monitor and a sound that occurred each time the visual stimulus reversed direction at the bottom. Once each infant met a habituation criterion, a series of test trials was administered to assess responsiveness to the components of the compound stimulus. Response was defined as the total duration of visual fixation in each trial. In the two unimodal test trials, the rate at which the component was presented was changed while the rate of the other component remained the same, whereas in the bimodal test trial the rate of both components was changed simultaneously. Results indicated that infants at each age successfully discriminated the bimodal and the two unimodal changes and that regression to the mean did not account for the results. Results also showed that disruption of the temporal relationship that accompanied the change in rate in the two unimodal test trials was also discriminable, but rate changes appeared to play a greater role in responsiveness than did synchrony changes. Considered together with results from similar prior studies, the current results are consistent with the modality appropriateness hypothesis in showing that discrimination of temporal changes in the auditory and visual modalities is dependent on the specialization of the sensory modalities.


Differential thresholds for limb movement measured using adaptive techniques.

Differential thresholds for limb movement were measured in 10 subjects, using the transformed up-down procedure. Subjects were required to indicate which of two random displacement perturbations delivered to their forearms had the larger standard deviation (SD). The SD of the reference signal was fixed for each experimental condition at one of seven values ranging from 0.05 to 3.2 mm. THe SD of the other signal varied depending on the subject's response. Using this procedure, the differential threshold for limb movement was calculated to be 8%, which is very similar to the thresholds estimated previously for changes in limb position (9%) and force (7%). The sensitivity of the human proprioceptive system to changes in limb displacement was much greater than anticipated, with subjects being able to resolve a 5-microns difference between two perturbations delivered to their arms.


The linkage between stimulus frequency and covert peak areas as it relates to monaural localization.

Head-related transfer functions for differently centered narrow noise bands were obtained on 6 subjects. Derived from these measurements were covert peak areas (CPAs), defined as the spatial constellation of loudspeakers that generates maximal sound pressure at the entrance of the ear canal for specific bands of frequency. On the basis of previous data, we proposed that different frequency bands served as important spectral cues for monaural localization of sounds from different loci and that location judgments were directed toward the CPAs associated with the different bands. In the first study, the stimuli were bandpass filtered so that they contained only those frequencies whose associated CPAs occupied either the monaural listener's "upper" or "lower" spatial regions. Loudspeakers, separated by 15 degrees, were stationed in the left hemifield, ranging from 0 degree to 180 degrees azimuth and -45 degrees to 60 degrees elevation. Subjects reported the loudspeaker from which the sound appeared to originate. Judgments of the sound's elevation were in general accord with the CPAs associated with the different frequency segments. In the second study, monaural localization tests were administered in which different 2.0-kHz-wide frequency bands linked with specific CPAs were notch filtered from a 3.5-kHz highpass noise band. For the control condition, the highpass noise was unfiltered. The data demonstrated that filtering a frequency segment linked with specific CPAs resulted in significantly fewer location responses directed toward that particular spatial region. These results demonstrate in greater detail the relation between the directional filtering properties of the pinna and monaural localization of sound.


Intrusion patterns in rapid serial visual presentation tasks with two response dimensions.

A rapid serial visual presentation (RSVP) paradigm using both one and two response dimensions was used to test parallel processing models of stimulus dimensions. Fifty subjects were asked to report the identity and/or color of a target uppercase word inserted in a series of lowercase words. The results produced a predominance of posttarget intrusions for color responses and a predominance of pretarget intrusions for identity responses. The requirement of a response to a second dimension impaired hit rates but did not change the pattern of intrusions. An examination of the distributions of intrusions in each response dimension as a function of the response given to the other dimension showed an unexpectedly high percentage of simultaneous hits, a moderate covariation between both responses, and the same patterns of intrusions when compared with the general distributions. While these results seem to be compatible with parallel models of processing for stimulus dimensions, two modifications to this model are suggested. First, the processing of response dimension(s) needs some attentional resources. Second, provision for a mixed model is indicated, which would include trials where no illusory conjunctions are formed.


Episodic effects on the visual comparison of letters in words.

In two experiments, subjects compared the identity of either the first letters of displays or all the letters in displays. Words yielded faster decisions than did pseudowords (pronounceable items derived by changing a vowel in a word) only when entire displays were compared. In a training phase run before the comparison task, subjects had written down either the first letters or entire displays. Relative to items that had not appeared in the training phase, prior experience at writing entire displays facilitated same decisions about entire displays and interfered with different decisions about entire displays. Prior experiences did not moderate the processing of first-letter identities. It was concluded that episodic effects arise from the interaction of higher order information underlying lexical encoding. Prelexical processing of letters is not sensitive to episodic effects.


Local brightness mechanisms sketch out surfaces but do not fill them in: psychophysical evidence in the Kanizsa square.

In two experiments, brightness enhancement of the illusory surface in the Kanizsa square was investigated by means of a brightness matching procedure. The results show that specific properties of the inducing elements such as size, spacing, and luminance have effects on the matching threshold that are similar to those previously obtained in experiments on simultaneous contrast. The data from a third experiment demonstrate that increment thresholds measured within the Kanizsa square are elevated when the target is flashed on a position close to the inducing elements. The thresholds decrease considerably in the center of both test and control figures (representing or not representing an illusory square). These observations suggest that low-level mechanisms are likely to explain local brightness differences within the configurations but not global figure brightness. In other words, local contrast seems to generate brightness information that "sketches out" surfaces at their surrounds but does not "fill" them "in."


Perceptual processing of adjacent and nonadjacent tactile nontargets.

Previous research has shown that subjects appear unable to restrict processing to a single finger and ignore a stimulus presented to an adjacent finger. Furthermore, the evidence suggests that, at least for moving stimuli, an adjacent nontarget is fully processed to the level of incipient response activation. The present study replicated and expanded upon these original findings. The results of Experiment 1 showed that an equally large response-competition effect occurred when the nontarget was presented to adjacent and nonadjacent fingers (on the same hand). The results of Experiment 2 showed that the effects observed in Experiment 1 (and in previous studies) were also obtained with stationary stimuli. Although small, there was some indication in the results of Experiment 2 that interference may dissipate more rapidly with distance with stationary stimuli. An additional finding was that interference effects were observed in both experiments with temporal separations between the target and nontarget of up to 100 msec. In Experiment 3, target and nontarget stimuli were presented to opposite hands. Although reduced, interference was still evident with target and nontarget stimuli presented to opposite hands. Varying the physical distance between hands did not produce any change in the amount of interference. The results suggest that the focus of attention on the skin extends nearly undiminished across the fingers of one hand and is not dependent upon the physical distance between sites of stimulation.


Improvement in line orientation discrimination is retinally local but dependent on cognitive set.

The ability of human observers to discriminate the orientation of a pair of straight lines differing by 3 degrees improved with practice. The improvement did not transfer across hemifield or across quadrants within the same hemifield. The practice effect occurred whether or not observers were given feedback. However, orientation discrimination did not improve when observers attended to brightness rather than orientation of the lines. This suggests that cognitive set affects tuning in retinally local orientation channels (perhaps by guiding some form of unsupervised learning mechanism) and that retinotopic feature extraction may not be wholly preattentive.


Testing models of the redundant-signals effect: a warning concerning the combination-rule regression analysis.

The redundant-signals effect is the observed RT advantage for trials presenting two or more targets, as compared with trials with only one target. Two general classes of parallel-processing model have been proposed to explain this effect: race models (e.g., Raab, 1962) and coactivation models (e.g., Miller, 1982). Various distributional analyses have been used in work aimed at discriminating between these two model classes. The present study reexamined one of these tests--the combination-rule regression analysis based on variable-criterion theory (Grice, Canham, & Boroughs, 1984)--by applying it to the data from two sets of simulated experiments. One set of simulations assumed coactivation; the other set assumed an independent race on redundant-target trials. Nearly identical combination-rule values were observed in the two sets of simulations. This finding shows that the combination rule of variable-criterion theory does not discriminate between models capable of explaining the redundant-signals effect. The implications of this finding are briefly discussed.


Putative therapeutic applications of calmodulin antagonists.

Calmodulin is the most important intracellular receptor protein for the second messenger calcium. The calcium-calmodulin complex regulates a number of physiological processes. An increasing number of pharmaceutical products is reported to interfere with the calcium-calmodulin complex. Despite the fact that the precise mechanisms of action of these so-called calmodulin antagonists await further clarification, reports accumulate in the literature indicating a broadening spectrum of putative therapeutic applications of calmodulin antagonists. Some of these applications, such as in cell proliferation, hypertension, congestive heart failure, arrhythmia and gastro-intestinal disorders, are discussed in the present review.


Current status of interferon alpha in the treatment of chronic hepatitis B.

Interferon alpha is the only available therapy for patients with chronic hepatitis B. With interferon alpha 3-15 MU thrice weekly or 5 MU daily during 3-6 months one-third of the patients achieve seroconversion of HBeAg and HBV-DNA together with normalization of aminotransferases and slight improvement of histology. Loss of HBsAg is reported in a minority of responders during treatment, but increases during follow-up. Patients with baseline alanine aminotransferase of at least twice the upper limit of normal and low HBV-DNA concentration achieve the best response rates. HIV-positive patients with low CD4 counts and Asians are poor responders. As side-effects influenza-like symptoms are experienced by almost all patients. Mild leukopenia, thrombocytopenia and decreased hairgrowth are frequently reported. Severe depression, depersonalization and psychosis are reported in a small number of patients but tend to be poorly recognized in some studies. The decision whether dose reduction is indicated seems strongly related to the opinion of the investigator. Although long-term effects on the occurrence of cirrhosis and the development of hepatocellular carcinoma are not available yet, the achieved results are promising.


Knowledge of medication in hospitalized chronic respiratory patients.

Object of the study was to assess educative needs in the field of drug therapy among 99 chronic patients with advanced chronic lung disease admitted to the Respiratory Service of the Hospital Sta. Creu i Sant Pau (Barcelona, Spain). The knowledge of the patients about their previous drug treatment, sources of information as well as patients' conception of side-effects, was gathered from medical records and by means of a questionnaire. The majority of patients studied were male (63%), aged over 60 years (average 63 +/- 12), illiterate or with basic education (88%), had a chronic obstructive, pulmonary disease (76%) and with an important degree of chronicity. They had been treated for their condition during a mean of 8.4 years and took an average of 4.6 drugs. 31% Of patients did not answer any question about their medication properly and only 17% gave a correct answer to all the questions. The lower the age and the higher the educational level, the higher the proportion of correct answers to knowledge questions. 35% Of the patients stated not to have been informed about their medication and 55% stated that they had read the patient package inserts.


Comparative study on protective gloves for handling cytotoxic medicines: a model study with carmustine.

The quality of protective gloves was studied. Protective gloves are part of the personal safety equipment for staff handling cytotoxic drugs. A study using raster electron microscopic photography, measurement of thickness by micrometer screw and permeability of carmustine by high pressure liquid chromatographic assay was carried out. The results show differences between different types of gloves.


Disposition of quinine in rats with induced renal failure.

Aetiologically different models of experimental acute renal failure were induced in rats by the administration of glycerol, mercuric chloride and gentamicin, respectively, to different groups. Quinine levels in plasma and urine of the rats with induced renal failure were determined and pharmacokinetic parameters (elimination t1/2, CLp, V, CLR AUC0-infinity) of the drug were derived and compared with values obtained from control rats following intraperitoneal administration of a 10 mg/kg body-weight dose of quinine. Results showed that each of the three compounds caused an up to 25-fold increase in the plasma levels of the drug and a marked decrease in the levels of the metabolite 3-hydroxyquinine. All the pharmacokinetic parameters determined for the rats with renal impairment were markedly different when compared to control. The high plasma quinine levels observed in the rats with renal failure could be largely due to the marked decrease in V and reduced metabolism. Also, in the rats with renal impairment, no correlation was observed between the increased plasma urea levels and plasma quinine levels or disposition of the drug. The results of the study suggest that quinine should be used with caution in patients with renal impairment. The plasma urea levels, as a measure of renal function, might not provide a suitable index for determining quinine dosage.


Clearance of indomethacin occurs predominantly by renal glucuronidation.

In this report we describe the conditions of collection, storage and handling of urine samples, collected after oral dosing with indomethacin in man, in order to maintain the integrity of the labile glucuronide formed. We found that the body clearance occurs predominantly by renal metabolism, due to glucuronidation in the human kidney. These glucuronides may be converted to isomeric glucuronides and/or the parent compound indomethacin during the residence time in the bladder.


Stability of sufentanil citrate in a portable pump reservoir, a glass container and a polyethylene container.

The stability of sufentanil citrate (100 ml, 5 micrograms/ml) in an admixture with sodium chloride 0.9% injection was investigated when filled in a portable pump reservoir with PVC wall, a glass container and a polyethylene container, at 32 degrees C, 4 degrees C and -20 degrees C for up to 21 days. No change in colour was visually observed in any of the samples during the 21-day storage period. A slight precipitation was noticed in three out of nine portable pump reservoirs, one at each storage temperature. There was a slight rise in pH at each storage temperature in all samples. There was approximately 13% loss of sufentanil citrate in the portable pump reservoirs stored at 32 degrees C during 2 days and 60% loss after 21 days, due to absorption of sufentanil citrate in the reservoir wall. No loss of sufentanil citrate could be detected in the portable pump reservoirs when stored at -20 degrees C and 4 degrees C. However, a serious inhomogeneity of the sufentanil citrate solution occurred after thawing at room temperature in the portable pump reservoirs which had been kept at -20 degrees C. The homogeneity could be restored by shaking for approximately 10 min. There was no change in the sufentanil citrate concentrations in the glass containers and polyethylene containers stored at the three temperatures. The portable pump reservoirs stored at 32 degrees C also showed a significant loss of vehicle due to evaporation (1.0 +/- 0.1 ml a week). This could not be detected in any of the other samples.


Future developments in the pharmacotherapy of lung disease.

Future advances in the pharmacotherapy of lung disease will occur mainly in the treatment of asthma, and will include the development of new long-acting beta 2-agonists, long-acting parasympatholytics, phosphodiesterase inhibitors, corticosteroids with fewer systemic side-effects, and other antiinflammatory drugs. Free radicals play an important role in most lung diseases, including asthma, emphysema, fibrosis, and adult respiratory distress syndrome. The search for free radical scavengers is now in progress. Replacement therapy with alpha 1-antitrypsin and surfactant is now possible. Progress in this area stems principally from a better understanding of the pathogenesis of lung disease.


Dealing with sadness, madness and hostility. New psychotropic drug remedies for the future.

The objective of this article is to present an overview of new forms of psychotropic drug therapy that may be expected to play a role in psychiatric practice in the 1990s. In predicting these future developments, three lines of approach have been followed. Firstly, progress in elucidating basic neuronal mechanisms is described. The radioligand receptor binding technique has proved to be an especially powerful tool in the search for novel psychoactive compounds. Secondly, those mental health problems most likely to undergo intensive study are discussed. It is likely that special attention will be devoted to organic mental disorders related to aging (dementia) or chronic exposure to toxic substances. In addition, research will be aimed at explaining and reducing the occurrence of auto-aggressive and hetero-aggressive behaviour. Thirdly, the types of newly designed agents and treatment strategies currently under investigation are outlined. In particular, the development of pharmacological agents that interfere with serotonergic molecular mechanisms has opened the way to improving existing psychotropic drugs, to inventing drugs that achieve known clinical effects via different mechanisms of action, and even to discovering entirely new categories of psychotropic drugs.


Cardiovascular drugs.

Since the category of cardiovascular drugs comprises a considerable number of pharmacotherapeutic groups, an overview of future developments must necessarily be limited to those areas in which innovations are most likely to occur. Further extension of our knowledge of thrombolytic therapy may eventually lead to new choices of primary drugs. In the area of antiarrhythmic therapy, the clinical use of a number of drugs has been hampered by the pro-arrhythmogenic actions of these agents. The development of new class III anti-arrhythmics will continue, probably giving rise to new therapeutic options. In the vascular area a new group of drugs, the renin inhibitors, is likely to emerge for the treatment of hypertension. Moreover, exciting discoveries in vascular pharmacology should eventually translate into new pharmacotherapeutic approaches. Finally, the large-scale availability of blood fractions (coagulation factors) prepared by recombinant technology may help solve current shortages of products derived from donated blood.


Immunomodulators. Future prospects.

The future role of the immunomodulators in medical practice is yet to be defined. The key question is whether these new substances will bring remarkable progress in transplantation or in the treatment of such conditions as cancer, AIDS, and autoimmune diseases, or whether they will be of only minor adjunctive importance. As background to the discussion of immunomodulating agents, the immune system is explained, with emphasis on the roles of T and B lymphocytes, macrophages, phagocytes, human leukocyte antigen and the complement system. Special attention is given to the cytokines, particularly the lymphokines. The immunomodulators can be divided into three main groups: immunosuppressive agents, such as FK 506 and rapamycin; immunostimulating agents, of which BCG vaccine is most important; and the remaining immunomodulators, which include the biological response modifiers. The last group, which encompasses the colony-stimulating factors (GM-CSF, G-CSF, and M-CSF), the interleukins, the interferons, and the tumour necrosis factors, is described in detail. Innovative research and medical applications of these cytokines, including indications, contraindications, and adverse reactions, are discussed. The role of monoclonal antibodies against endotoxins is also described.


Future directions in antimicrobial chemotherapy.

New developments in the treatment of bacterial infections are discussed. The most important developments include oral broad-spectrum cephalosporin derivatives and extended-spectrum injectable cephalosporins with improved activity against Gram-positive bacteria. Meropenem is a new carbapenem agent with markedly improved activity against Gram-negative bacteria. Many fluoroquinolones are in various phases of development. The most interesting new compound is sparfloxacin. Azithromycin is a new macrolide which, because of its very long half-life, attains very high levels in most tissues. Potential uses of the newer agents are discussed.


Delivery of hormones: some new concepts.

Some new concepts in the delivery of hormones are described. Transmucosal or transdermal penetration of hormones can be facilitated, often by the use of absorption enhancers. Studies of nasal insulin delivery are described. Recently developed iontophoretic delivery devices can be useful for pulsatile transdermal administration of peptide hormones. A self-regulating delivery system releasing insulin in response to glucose levels is described. A vaginal ring releasing ethinylestradiol and 3-ketodesogestrel is a new concept in long-acting contraception. A nasal estradiol formulation, containing the absorption enhancer dimethyl-beta-cyclodextrin, is an interesting alternative to oral and transdermal delivery of female sex hormones.


New cytotoxic drugs and targets in oncology.

New agents in the preclinical and early clinical pipeline (phases I and II) are described and some of the problems associated with their development are reviewed. The article focuses on tubulin poisons such as taxol, topoisomerase inhibitors, such as topotecan, and drugs such as bryostatin 1 and miltefosin, which interfere with specific signal transduction pathways involved in malignant cell growth.


Future prospects in antiviral therapy.

Two important stumbling blocks to the development of effective and nontoxic antiviral drugs are the intracellular localization of the virus and the fact that a virus uses host cell functions to multiply. Therefore, new antiviral drugs must act on a virus-specific function. Most currently available useful antiviral drugs are the result of compound screening of large numbers of possible agents. Advances in our understanding of the molecular biology and biochemistry of the viral multiplication cycle and new laboratory techniques for determining the molecular sites of action have now made it possible to develop and screen new antiviral drugs in a more purposeful manner. Another possible option in antiviral therapy is combination therapy using drugs that enhance the therapeutic effect or diminish side-effects. The most promising new antiviral drugs are discussed according to the different steps they affect in the viral multiplication process. Combination therapy is also reviewed.