Modelling induced resistance to plant diseases.

Plant disease control has traditionally relied heavily on the use of agrochemicals despite their potentially negative impact on the environment. An alternative strategy is that of induced resistance (IR). However, while IR has proven effective in controlled environments, it has shown variable field efficacy, thus raising questions about its potential for disease management in a given crop. Mathematical modelling of IR assists researchers with understanding the dynamics of the phenomenon in a given plant cohort against a selected disease-causing pathogen. Here, a prototype mathematical model of IR promoted by a chemical elicitor is proposed and analysed. Standard epidemiological models describe that, under appropriate environmental conditions, Susceptible plants (S) may become Diseased (D) upon exposure to a compatible pathogen or are able to Resist the infection (R) via basal host defence mechanisms. The application of an elicitor enhances the basal defence response thereby affecting the relative proportion of plants in each of the S, R and D compartments. IR is a transient response and is modelled using reversible processes to describe the temporal evolution of the compartments. Over time, plants can move between these compartments. For example, a plant in the R-compartment can move into the S-compartment and can then become diseased. Once in the D-compartment, however, it is assumed that there is no recovery. The terms in the equations are identified using established principles governing disease transmission and this introduces parameters which are determined by matching data to the model using computer-based algorithms. These then give the best match of the model with experimental data. The model predicts the relative proportion of plants in each compartment and quantitatively estimates elicitor effectiveness. An illustrative case study will be given; however, the model is generic and will be applicable for a range of plant-pathogen-elicitor scenarios.

Lipid-Based Natural Food Extracts for Effective Control of Botrytis Bunch Rot and Powdery Mildew on Field-Grown Winegrapes in New Zealand.

Synthetic controls of crop pathogens are increasingly associated with harm to the environment and human health, and pathogen resistance. Pesticide residues in crops can also act as non-tariff trade barriers. There is therefore a strong imperative to develop biologically based and natural product (NP) biofungicides as more sustainable alternatives for crop pathogen control. We demonstrate the field efficacy, over multiple seasons, of NP biofungicides, NP1 (based on anhydrous milk fat) and NP2 (based on soybean oil), on two major diseases of winegrapes-Botrytis bunch rot (Botrytis) and powdery mildew (PM). The NPs were integrated into a season-long integrated disease management programme that has produced chemical-residue-free wines. Efficacies for Botrytis control on three different varieties were: 63-97% on Chardonnay, 0-96% for Sauvignon Blanc and 46-58% on Riesling; with 65-98% PM control on Chardonnay and Riesling. NP2 exhibited the significant control of Botrytis latent infections, making it a viable alternative to mid-season synthetic fungicides. Disease control was significantly better than the untreated control and usually as efficacious as the synthetic fungicide treatment(s). Yields and wine quality in NP-treated crops were normally equivalent to those in the synthetic fungicide treatments. The results indicate that NP-mediated disease control of Botrytis and powdery mildew can be obtained in the vineyard, without synthetic fungicide input.

Integrated Use of Aureobasidium pullulans Strain CG163 and Acibenzolar-S-Methyl for Management of Bacterial Canker in Kiwifruit.

An isolate of Aureobasidium pullulans (strain = CG163) and the plant defence elicitor acibenzolar-S-methyl (ASM) were investigated for their ability to control leaf spot in kiwifruit caused by Pseudomonas syringae pv. actinidiae biovar 3 (Psa). Clonal Actinidia chinensis var. deliciosa plantlets ('Hayward') were treated with ASM, CG163 or ASM + CG163 at seven and one day before inoculation with Psa. ASM (0.2 g/L) was applied either as a root or foliar treatments and CG163 was applied as a foliar spray containing 2 × 107 CFU/mL. Leaf spot incidence was significantly reduced by all treatments compared with the control. The combination of ASM + CG163 had greater efficacy (75%) than either ASM (55%) or CG163 (40%) alone. Moreover, treatment efficacy correlated positively with the expression of defence-related genes: pathogenesis-related protein 1 (PR1), ß-1,3-glucosidase, Glucan endo 1,3-ß-glucosidase (Gluc_PrimerH) and Class IV chitinase (ClassIV_Chit), with greater gene upregulation in plants treated with ASM + CG163 than by the individual treatments. Pathogen population studies indicated that CG163 had significant suppressive activity against epiphytic populations of Psa. Endophytic populations were reduced by ASM + CG163 but not by the individual treatments, and by 96-144 h after inoculation were significantly lower than the control. Together these data suggest that ASM + CG163 have complementary modes of action that contribute to greater control of leaf spotting than either treatment alone.

Fetal growth retardation: femurs, fontanels, and follow-up.

Sixty-three term newborn infants with fetal growth retardation were evaluated within three days of birth. They were classified by length and head circumference. In group 1, both length and head circumference were less than the tenth percentile; in group 2, either length or head circumference was less than the tenth percentile; and in group 3, both length and head circumference were greater than the tenth percentile. Ponderal index (weight/length ratio), anterior fontanel size, and amount of epiphyseal ossification were also determined. Significantly lower birth weights and decreased ossification were found when groups 1 or 2 were compared separately with group 3. These differences were most marked when the weight/length ratio was less than 2.25. When the ponderal index was less than 2.0, epiphyseal ossification was usually absent (suggesting a chronic process). Epiphyseal ossification was positively correlated with birth weight and length but was unrelated to anterior fontanel size. Ossification was more often absent in males than females. There was a negative (inverse) correlation between birth weight and anterior fontanel size. Follow-up of 32 of these infants at age 1 year showed marked individual variations, but there were significant differences in incremental linear growth between groups 1 and 3, a finding which supports results of animal studies showing that catch-up growth may be related to skeletal immaturity. Physical measurements at birth in the individual baby with fetal growth retardation do not reliably predict subsequent growth.

Oxygen plus pressure plus time: the etiology of bronchopulmonary dysplasia.

Ten infants developed the chronic pulmonary syndrome designated bronchopulmonary dysplasia, following artificial (assisted) ventilation using a volume-regulated positive-pressure respirator. Despite previous reports implicating elevated oxygen concentrations for prolonged periods of time, only two infants required more than 80% oxygen for more than 24 hours, and only one infant required 60% oxygen for more than 100 hours. "Immature" lungs when exposed to inspired oxygen concentrations over 40% for as little as three days via positive-pressure ventilation may develop bronchopulmonary dysplasia. The role of the underlying disease and the relationship with Wilson-Mikity syndrome remain uncertain.

Prolonged dexamethasone therapy reduces the incidence of cryotherapy for retinopathy of prematurity in infants of less than 1 kilogram birth weight with bronchopulmonary dysplasia.

To determine whether prolonged dexamethasone therapy, used in the treatment of bronchopulmonary dysplasia (BPD), affects the incidence of cryotherapy for retinopathy of prematurity, the authors conducted a retrospective review of all infants admitted to a neonatal intensive care unit between October 1988 and October 1990 (n = 957) whose birth weights were less than 1 kg (n = 90). All admissions were reviewed to determine birth weight, gestational age, survival, incidence of BPD and cryotherapy, use and duration of dexamethasone therapy, length of mechanical ventilation, continuous positive airway pressure, and additional supplemental oxygen. Of all neonatal intensive care unit admissions, 9.4% weighed less than 1 kg, and 64% survived for greater than 28 days (n = 58). Of the survivors, 82% had BPD. Cryotherapy for retinopathy of prematurity was used only in those with birth weights of less than 1 kg and with BPD. All those treated with dexamethasone (n = 23) had BPD and significantly lower gestational ages (25.6 vs 26.4 weeks) (P = .05) and birth weights (759 vs 824 g) (P < .05) than those not treated (n = 25). Dexamethasone was used in 23 of 48 infants (9 for < or = 24 days, 14 for > 24 days). Eleven required cryotherapy: 5 of 25 with no dexamethasone, 5 of 9 treated for 24 days or less, and 1 of 14 treated for longer than 24 days (P < .04). In those treated with prolonged (> 24 days) dexamethasone, cryotherapy was significantly reduced compared with those treated for shorter periods. Although the probability was significant, the 95% confidence intervals were wide.(ABSTRACT TRUNCATED AT 250 WORDS)

Early increase in intracranial pressure in preterm infants.

Noninvasive measurement of intracranial pressure is now available via the anterior fontanel in newborn infants. We measured intracranial pressure during the first week of life in 18 preterm infants and found a statistically significant increase from birth to age 24 hours and a significant decrease by 48 hours (13.8 vs. 24.4 vs. 14.3 cm H2O). This did not seem to be the result of postnatal head shrinkage. There were no other apparent correlations. We suspect that hypoxia may play an important role in the etiology of increased intracranial pressure. We believe that these findings may have important implications for intracranial hemorrhage in preterm infants.

Early diagnosis of neonatal sepsis.

To better define the need for antibiotic therapy, several tests recommended as helpful in diagnosing neonatal sepsis were evaluated in 376 neonates during the first week after birth. The five most useful tests (with definitions of abnormality) were: band/total neutrophils (greater than or equal to 0.2); leukocyte count (less than 5,000/cu mm); latex-C-reactive protein (positive greater than 0.8 mg/100 ml); ESR (greater than or equal to 15 mm for the first hour); and latex haptoglobin (positive greater than 25 mg/100 ml). When these five tests were applied early (at the time infection was suspected and blood culture sent), 28 of 30 cases (93%) subsequently proven to have infection had two or more abnormal tests. This compares with only 24 of 320 babies (8%) with no subsequently documented evidence of infection. Of all babies who had two or more tests positive (n = 71), 39% had proven sepsis, and an additional 23% had "very probable" infection. The combination of leukopenia and an elevated band/total neutrophil ratio seems to be particularly predictive of sepsis (13 of 17 babies with this combination had proven sepsis). When less than two tests were positive, the probability that sepsis was not present was 99%. These simple, rapid tests require no special laboratory facilities and provide a valuable adjunct in the early detection of the neonate with sepsis.

Excessive handling as a cause of hypoxemia.

Continuous transcutaneous oxygen (TcPo2) monitoring was used to study low-birth-weight infants (15 control, 15 experimental) during their stay in the intensive care nursery (ICN). Twenty hours of continuous recordings were made of heart rate, respiratory rate, and TcPo2 in the first five days after birth. Personnel caring for the control infants were blind to the TcPo2 measurements. Those caring for the experimental group were instructed in the operation of the TcPo2 monitor and used the device to modify the timing and extent of procedures to minimize "undersirable time" (TcPo2 less than 40 or greater than 100 torr). Control group infants had an average of 40 min/20 hr in "undesirable time." When personnel used TcPo2 monitoring to modify care this "undesirable time" was reduced to 6 min/20 hr. This difference was statistically significant (P less than .001). Infants in the control group were handled more frequently, and experienced more hypoxemia. Of the hypoxemic time suffered by the control infants 75% was associated with handling. Only 5% of the hypoxemia or hyperoxemia was detected by blood Pao2 analysis or conventional monitors. Intermittent arterial blood gas sampling is an inadequate method for monitoring arterial oxygenation in low-birth-weight infants since hypoxemia and hyperoxemia are often missed. Continuous TcPo2 monitoring improves care by diminishing "undesirable time."

Effect of application force on noninvasive measurements of intracranial pressure.

Application of the Ladd fiberoptic sensor to the anterior fontanel of the human newborn has been used as a method for monitoring intracranial pressure noninvasively. This study measures the effect of varying the force with which the sensor is applied to the fontanel. The Ladd sensor readings of five preterm human infants were continuously monitored while sensor application force was increased in a stepwise manner. The Ladd sensor readings for each infant varied with the force applied. In one infant sensor application was gradually increased while direct measurements of lumbar CSF pressure were made. Ladd sensor readings in this infant increased with increasing application force, while lumbar CSF pressure remained unchanged. It is concluded that readings obtained with the Ladd sensor applied to the anterior fontanel of the human infant depend on the force with which the sensor is applied. The effect of application force must be taken into account if noninvasive measurements of intracranial pressure are to be made with the Ladd device.

Transcutaneous oxygen monitoring in aminophylline-treated apneic infants.

Transcutaneous PO2 (tcPO2) monitoring offers a new approach to the evaluation of drug effects. We investigated the effect of theophylline on ten premature infants with apnea. Theophylline was administered as aminophylline, 8 mg/kg per rectum every 12 hours for two doses and 4 mg/kg every 12 hours for a total of two or five days (short and long courses). The tcPO2, heart rate (beat-to-beat), and thoracic impedance were continuously monitored during each of three 4-hour study periods: 12 hours before theophylline administration, 12 hours after initiation of theophylline therapy, and 24 to 48 hours after discontinuing the drug's use. Plasma levels were measured by a radioimmunoassay developed in our laboratory. Polygraphic recordings were analyzed without knowledge of treatment for frequency of apneic spells, mean duration of apneas, total duration of hypoxemia (tcPO2 less than or equal to 40 torr), total duration of hyperoxemia (tcPO2 greater than or equal to 100 torr), basal tcPO2, heart rate, and respiratory rate. In each case during theophylline use, cardiorespiratory patterns were altered, respirations were more regular, apneic spells were reduced, PO2 was stabilized with less hypoxia and hyperoxia, and bradycardic episodes were decreased. There was considerable variation in the response of the ten infants and a significant difference in the frequency of return of symptoms between those receiving short-term therapy and those receiving the longer course.

Intraventricular hemorrhage in preterm infants: declining incidence in the 1980s.

Ultrasound has been routinely used since late 1979 to diagnose periventricular-intraventricular hemorrhage in infants whose gestational age was 34 weeks or less. During the years 1980 to 1987 the ultrasound scans were interpreted by one person, and a steady decline in incidence of periventricular-intraventricular hemorrhage was observed. Both for infants of 34 weeks or less and for very low birth weight (less than 1500 g) infants, periventricular-intraventricular hemorrhage incidence decreased, respectively, from 34% and 39% in 1980 to 1981 to 19% and 25% in 1986 to 1987. This decrease was confined to true intraventricular hemorrhages, which decreased from 22% in 1980 to 1981 to 7% in 1986 to 1987 for infants of less than or equal to 34 weeks' gestation. These results were not influenced by a change in the distribution of birth weights or gestational ages of the infants evaluated nor by a change in the inborn to outborn ratio. The incidence of periventricular-intraventricular hemorrhage was lower in infants born by cesarean section than those delivered vaginally, but the decrease could not be attributed to an increased number of deliveries by cesarean section. Although there were undoubtedly changes in neonatal care during this time period, no planned intervention occurred. It was concluded that pharmacologic intervention studies must be interpreted with caution.

Neonatal mortality risk for the eighties: the importance of birth weight/gestational age groups.

Since 1976 a computerized data base has been used to store information on babies admitted to two intensive care nurseries serving the Vermont/New Hampshire region. The data base now allows reporting "neonatal" mortality by birth weight/gestational age (BW/GA) groupings for 1976--1979. For all BW/GA groups, except the most immature infants, there has been marked improvement compared to data gathered in the sixties (ie, mortality has decreased). These data are probably applicable to most other centers providing neonatal intensive care. The use of BW/GA categories provides the most reliable way of objectively comparing statistics from one center to another. Differences between two centers were observed when birth weight specific rates were used, but were largely abolished by using BW/GA groups. Data gathered in this way will be increasingly important for comparisons between centers and across years and when evaluating the effectiveness of new therapeutic interventions.

Ultrasound detection of changing ventricular size in posthemorrhagic hydrocephalus.

Real time ultrasonography has been used to follow sequentially the changing size of the cerebral ventricles in an infant with posthemorrhagic hydrocephalus. A method for quantitating ventricular size is presented and the rapidity with which ventricular size decreases following removal of cerebrospinal fluid is demonstrated.

Low-dose indomethacin and prevention of intraventricular hemorrhage: a multicenter randomized trial.

OBJECTIVES: Parenchymal involvement of intraventricular hemorrhage (IVH) is a major risk factor for neurodevelopmental handicap in very low birth weight neonates. Previous trials have suggested that indomethacin would lower the incidence and severity of IVH in very low birth weight neonates. METHODS: We enrolled 431 neonates of 600- to 1250-g birth weight with no evidence for IVH at 6 to 11 hours of age in a prospective, randomized, placebo-controlled trial to test the hypothesis that low-dose indomethacin (0.1 mg/kg intravenously at 6 to 12 postnatal hours and every 24 hours for two more doses) would lower the incidence and severity of IVH. Serial cranial ultrasound examinations and echocardiographs were performed. RESULTS: There were no differences in the birth weight, gestational age, sex, Apgar scores, and percent of neonates treated with surfactant between the indomethacin and placebo groups. Within the first 5 days, 25 (12%) indomethacin-treated and 40 (18%) placebo-treated neonates developed IVH (P = .03, trend test). Only one indomethacin-treated patient experienced grade 4 IVH compared with 10 placebo-treated neonates (P = .01). Sixteen indomethacin-treated neonates and 29 control neonates died (P = .08); there was a difference favoring indomethacin with respect to survival time (P = .06). Eighty-six percent of all neonates had a patent ductus arteriosus on the first postnatal day; indomethacin was associated with significant ductal closure by the fifth day of life (P < .001). There were no differences in adverse events attributed to indomethacin between the two treatment groups. CONCLUSIONS: Low-dose prophylactic indomethacin significantly lowers the incidence and severity of IVH, particularly the severe form (grade 4 IVH). In addition, indomethacin closes the patent ductus arteriosus and is not associated with significant adverse drug events in very low birth weight neonates.

The changing face of neonatal infection: experience at a regional medical center.

The incidence, etiology and timing of neonatal infection were assessed in a regional neonatal intensive care unit from 1983 through 1992. Infection onset was considered as very early (< 24 hours), early (1 to 7 days) or late (8 to 60 days). Case-fatality rates were determined for different weight groups and time periods (1983 to 1987 vs. 1988 to 1992). Overall neonatal sepsis incidence changed very little, but there was a marked decrease in very early onset sepsis in 1988 to 1992 especially in very low birth weight (< 1500 g) infants, possibly attributable to increased use of prenatal antibiotics. There was an accompanying increase in late onset sepsis, primarily nosocomial infection associated with improved survival of tiny infants, most striking after exogenous surfactant became readily available. During 1988 to 1992, because of very few very early-onset cases, very low birth weight infants had overall case fatality rates of about 10%, which were the same as for larger infants. The predominant organism in very early onset infection was Group B Streptococcus (GBS) (27 of 58) and in late onset infection was coagulase-negative staphylococcus (57 of 103). More cases of early onset GBS pneumonia were seen in the last 5 years. Neonatal meningitis was seen rarely during this decade, with only one case documented in the first 24 hours of life.

Coagulase-negative staphylococci as true pathogens in newborn infants: a cohort study.

We examined the pathogenicity of coagulase-negative staphylococci (CONS) in newborn infants by comparing presenting nonspecific signs of infection in infants with and without CONS bacteremia. During a 6-month period 799 blood cultures were obtained in a tertiary care nursery; 81 (10.1%) grew CONS and 25 (3.0%) grew other bacteria. A comparison group of 121 infants was selected randomly from ill patients whose blood cultures were negative. In addition 70 well infants were matched to CONS-positive cases. Abnormal clinical signs, complete blood cell counts, C-reactive protein, alpha-1-acid glycoprotein and prealbumin were determined at the time of culture. Signs that discriminated best between infants with and without CONS bacteremia were identified by logistic regression analysis. Infants with CONS bacteremia did not differ from infants with sepsis caused by recognized pathogens, except for lethargy, which was significantly more common in unequivocal infection. Infants with presumed infection but negative blood cultures, and noninfected control patients had abnormal signs significantly less often than CONS-positive infants. C-reactive protein, hyperthermia, increased oxygen requirements and lethargy were the most useful signs in identifying neonatal bloodstream infection. This cohort study provides objective evidence for the pathogenicity of CONS in newborn infants.

Does cesarean section protect against intraventricular hemorrhage in preterm infants?

A declining incidence of periventricular-intraventricular hemorrhage (PV-IVH) in preterm infants less than 35 weeks' gestational age during the years 1980 through 1987 led us to investigate the role of the route of delivery. Routine cephalic ultrasound was used to detect PV-IVH in 490 vaginal and 411 cesarean section deliveries. A lower incidence of all PV-IVH and severe PV-IVH was noted in cesarean section deliveries for each 2-year period, with a decline in all PV-IVH in vaginal and cesarean section deliveries from 39% and 31%, respectively, in 1980-1981 to 23% and 11% in 1986-1987. Striking differences were noted for infants less than 1500 g, less than 1000 g, or less than 27 weeks' gestation. For example, in infants less than 1000 g, the incidence of all PV-IVH was 52% in vaginal (n = 101) and 25% in cesarean section deliveries (n = 88), and of severe PV-IVH was 26% and 11%, respectively. These differences did not seem to be influenced by presence or absence of labor, breech presentation, or low Apgar scores. Route of delivery should be considered as an important variable in pharmacologic intervention studies.

Noninvasive monitoring of intracranial pressure: a new approach for neonatal clinical pharmacology.

Measurements taken with the pressure-activated fiberoptic sensor should provide better insight into the relative usefulness of various agents such as glycerol and corticosteroids in the reduction of intracranial pressure. It is also useful in monitoring pressure changes during asphyxia-hypoxia, convulsions, and anesthesia, and in demonstrating the effects of drugs such as furosemide on intracranial pressure.

Neonatal cerebral pathology diagnosed by ultrasound.

This article discusses cranial ultrasonography in various clinical settings. Since 1979, the authors have screened all preterm infants for intracranial hemorrhage, and here they present their experience with hemorrhage and its sequel, ventricular dilatation. Also discussed is the use of cranial ultrasonography in infants with seizures and encephalopathy and in infants with abnormal head growth or suspected cerebral malformations.