Fluorescence phase-shifting interferometry for axial single particle tracking: a numerical simulation study.

Tracking of single fluorescent probes along the axial (depth) dimension is an important task in the biological and physical sciences. In this paper, we propose and analyze the use of fluorescence phase-shifting interferometry (FPSI) for axial single particle tracking (SPT) along 1 µm-depth (z) trajectories. FPSI is a photon-efficient, self-interference method that collects and coherently combines the 4π steradian emission wavefronts of a single fluorescent particle while introducing multiple phase shifts between the wavefronts to axially localize the particle with high precision over an extended depth-of-field. We employ vectorial imaging analysis and Monte-Carlo simulations of diffusive and directed motions to present a detailed comparative study of spatial and temporal FPSI for axial SPT based on simultaneous and time sequential collection of four phase-shifted interferograms using a single camera, respectively. The results of the numerical simulations show that for ≤0.105 µm2/s diffusion, spatial FPSI attains a maximal twofold improvement in the trajectory reconstruction precision at the expense of a fourfold reduced field-of-view compared to temporal FPSI. Furthermore, the analysis predicts that for sufficiently slow random linear motions, temporal FPSI is superior to spatial FPSI and achieves a smaller trajectory reconstruction error.

[Survival of a 300 gram infant].

Despite progress in neonatal medicine and the development of new methods of treatment such as surfactant administration and new modalities of ventilation, mortality remains significant among newborn infants weighing less than 500 gram. Neurodevelopmental outcome of infants born before 26 weeks gestation is perceived as very poor. As the result of recent reports, there have been calls for limitation of medical care for these infants. We report of only 4 infants weighing less than 400 grams, who have survived. Two of these infants developed respiratory failure and required aggressive conventional mechanical ventilation. We report on the survival of an infant delivered before the completion of 26 weeks gestation period and weighing 300 grams. The infant was ventilated by high frequency oscillatory ventilation for respiratory distress syndrome. She is the second smallest infant reported in the medical literature.

Early postnatal dexamethasone treatment and increased incidence of cerebral palsy.

OBJECTIVE: To study the long term neurodevelopmental outcome of children who participated in a randomised, double blind, placebo controlled study of early postnatal dexamethasone treatment for prevention of chronic lung disease. METHODS: The original study compared a three day course of dexamethasone (n = 132) with a saline placebo (n = 116) administered from before 12 hours of age in preterm infants, who were ventilated for respiratory distress syndrome and had received surfactant treatment. Dexamethasone treatment was associated with an increased incidence of hypertension, hyperglycaemia, and gastrointestinal haemorrhage and no reduction in either the incidence or severity of chronic lung disease or mortality. A total of 195 infants survived to discharge and five died later. Follow up data were obtained on 159 of 190 survivors at a mean (SD) age of 53 (18) months. RESULTS: No differences were found between the groups in terms of perinatal or neonatal course, antenatal steroid administration, severity of initial disease, or major neonatal morbidity. Dexamethasone treated children had a significantly higher incidence of cerebral palsy than those receiving placebo (39/80 (49%) v. 12/79 (15%) respectively; odds ratio (OR) 4.62, 95% confidence interval (95% CI) 2.38 to 8.98). The most common form of cerebral palsy was spastic diplegia (incidence 22/80 (28%) v. 5/79 (6%) in dexamethasone and placebo treated infants respectively; OR 4.45, 95% CI 1.95 to 10.15). Developmental delay was significantly more common in the dexamethasone treated group (44/80 (55%)) than in the placebo treated group (23/79 (29%); OR 2. 87, 95% CI 1.53 to 5.38). Dexamethasone treated infants had more periventricular leucomalacia and less intraventricular haemorrhage in the neonatal period than those in the placebo group, although these differences were not statistically significant. Eleven children with cerebral palsy had normal ultrasound scans in the neonatal period; all 11 had received dexamethasone. Logistic regression analysis showed both periventricular leucomalacia and drug assignment to dexamethasone to be highly significant predictors of abnormal neurological outcome. CONCLUSIONS: A three day course of dexamethasone administered shortly after birth in preterm infants with respiratory distress syndrome is associated with a significantly increased incidence of cerebral palsy and developmental delay.

Variations in neutrophil count in preterm infants with respiratory distress syndrome who subsequently developed chronic lung disease.

Neutrophil counts were studied in 62 preterm infants receiving mechanical ventilation for neonatal respiratory distress syndrome (NRDS). Exploratory analysis indicated that the severity of NRDS, as demonstrated by fractional inspired oxygen (FiO2), mean airway pressure (MAP), arterial-alveolar PO2 ratio (a/APO2) and oxygenation index (OI), was correlated with percentage change of neutrophil counts during the first 5 days of life. Further analysis demonstrated that infants with NRDS who subsequently developed chronic lung disease (CLD) (n = 21) had statistically significant differences in variation of neutrophil counts when compared with the remainder (n = 41) without CLD (-35.0% +/- 4.3 vs. -16.9% +/- 5.8, p < 0.02). It is concluded that significant variations in neutrophil counts during the first 5 days of life may be found in infants with NRDS who subsequently develop CLD and that these changes may have predictive value regarding the development of CLD.

Factors affecting plasma bilirubin in preterm infants ventilated for respiratory distress syndrome.

OBJECTIVE: To evaluate the contribution of various factors to plasma bilirubin level in preterm infants with a birth weight of < 1500 gm in need of mechanical ventilation for respiratory distress syndrome (RDS) during their first week of life. METHODOLOGY: A total of 50 very low birth weight (< 1500 gm) preterm infants consecutively admitted to the neonatal intensive care unit were studied. Plasma bilirubin levels were determined every 8 hours for the first week of life. Data relating to daily body weight, daily fluid intake, age at onset of gavage feeds, daily caloric intake, and grade of intraventricular hemorrhage (IVH) were collected. Data relating to mechanical ventilation were collected every 4 hours as follows: fractional inspired O2, arterial PO2, arterial PCO2, and mean airway pressure. An arterial/alveolar PO2 ratio and a corrected oxygenation index were computed for the first 2 days of life. A bilirubin index (BI), defined as the ratio of peak plasma bilirubin level to birth weight1/3, was used to study the association between bilirubin and the above variables. A BI was also used as a criterion for starting and discontinuing phototherapy. Multiple linear regression analysis was used to model BI. RESULTS: IVH (p < 0.0001), age at onset of gavage feeds (p < 0.003), oxygenation index (p < 0.007), and gestational age (p < 0.05) made a significant contribution to variations in BI (37.16%, 43.71%, 48.99%, and 53.33%, respectively). CONCLUSION: Hyperbilirubinemia in ventilated preterm infants with RDS is most likely multifactorial; entities quite distinct from RDS (such as nutrition and IVH) may significantly contribute to its variation.

A prospective search for urinary tract abnormalities in infants with isolated preauricular tags.

OBJECTIVE: To determine whether isolated preauricular tags are associated with urinary tract abnormalities. METHODOLOGY: Seventy consecutive infants with isolated preauricular tags were examined by ultrasonography for urinary tract abnormalities on day 3 or 4 of life between January 1993 and August 1999, after parental consent and ethics approval. Karyotype analysis was conducted in all infants with urinary tract abnormalities. The study group was compared with a control group of 69 infants without preauricular tags hospitalized during the same period. The control group consisted of infants who underwent urinary tract ultrasonography as part of an investigation for persistent regurgitation and/or vomiting associated with cyanotic spells. RESULTS: Urinary tract abnormalities were detected in 6 infants with isolated preauricular tags (6/70; 8.6%). Types of anomalies were as follows: hydronephrosis in 5 cases and horseshoe kidney in 1 case. The causes of hydronephrosis were ureteropelvic junction obstruction in 3 cases and vescicoureteric reflux in 2 cases. None of the infants in the control group had such abnormalities. All infants with urinary tract abnormalities had normal chromosomes. No statistically significant differences existed between groups concerning birth weight, gestational age, intrauterine growth, and male-to-female ratio. CONCLUSIONS: This study suggests a significant prevalence of urinary tract abnormalities in infants with preauricular tags. We recommend, therefore, that urinary tract ultrasonography be conducted in the routine assessment of infants with isolated preauricular tags.

Intrauterine growth retardation and brainstem auditory-evoked response in preterm infants.

Intrauterine growth retardation is frequently associated with intrauterine undernutrition, and can deleteriously affect brain function. Twenty-eight premature small for gestational age infants were compared with 28 premature appropriate for gestational age infants to determine whether intrauterine growth retardation was associated with abnormalities in the auditory pathway in the early neonatal period. The auditory pathway was studied between 4-18 wk of life by analysis of brainstem auditory-evoked potentials elicited by a 10/s 75 decibel above normal adult hearing level (dB nHL) click stimulus presented at the infants' ears. Peak latencies of components I, III and V, and interpeak latencies I-III, III-V and I-V, yielded no statistically significant differences between groups. The present study indicates that intrauterine growth-retarded premature infants may not have abnormalities of brainstem auditory-evoked response in the early neonatal period.

Brainstem auditory evoked response in newborns and infants.

Brainstem auditory evoked response studies were carried out on 105 neonates, with gestational ages ranging from 26 to 43 weeks. The mean chronologic and postconception ages of the subjects were 6.5 weeks and 40.6 weeks, respectively. Statistically significant relationships between brainstem auditory evoked response and gestational age, postconception age (gestational age plus chronologic age), and the 5-minute Apgar score, were demonstrated. Shortening of brainstem auditory evoked response as related to postconception age was demonstrated and this trend was statistically significant. However, of these factors a statistically significant shortening (maturation) of evoked response was demonstrated only in relation to postconception age.

Autologous umbilical cord blood transfusion.

The purpose of this study was to examine some aspects of umbilical cord blood collection for autologous transfusion in premature infants. All 120 microbacterial cultures (aerobic and anaerobic) of cord blood samples as well as 30 cultures of mycoplasma were treated. Cord prothrombin fragment (F 1 + 2) concentrations were quantified at one and 10 minutes after clamping of the cord. F 1 + 2 concentrations assessed on 25 newborn infants were similar and no linear association with time of clamping could be drawn. This means that cord blood thrombosis is not activated for at least 10 minutes following clamping of the cord. As far as is known, the first newborn infant to benefit from this method of transfusion is reported here. The premature infant received two portions of autologous blood (on days 5 and 7). No untoward effects were noted. Blood, collected from the umbilical cord, is a safe source for autotransfusion, provided that bacteriological testing has been carried out.

Predictive inability of cord zinc, magnesium and copper levels on the development of benign hyperbilirubinemia in the newborn.

Cord serum concentrations of zinc, magnesium and copper were determined in 90 healthy term infants. The infants were divided by peak bilirubin values into an icteric group (peak bilirubin > 136 mumol/l) (n = 21) and a control group (peak bilirubin < or = 136 mumol/) (n = 69). Mean cord serum zinc, magnesium and copper concentrations in the icteric group did not differ from those of the control group. Furthermore, no significant correlation was found between peak serum bilirubin concentrations and cord serum concentrations of these three elements. We conclude that cord serum concentrations of zinc, magnesium or copper are not useful in predicting which neonates will develop hyperbilirubinemia.

Transient neonatal hypothyroxinemia and the auditory brainstem evoked response.

Ten premature infants with low serum thyroxine levels (less than 84 nmol/L) were compared with 10 biochemically euthyroid infants to determine whether hypothyroxinemia in such infants can lead to alterations in the auditory pathway. The auditory pathway was studied between 6 and 11 wk of life by analyzing brainstem evoked potentials elicited by a 10/s, 75 dB above normal adult hearing level click stimulus presented at the infant's ears. Peak latencies of components I, III, and V and interpeak latencies I-III, III-V, and I-V did not yield statistically significant differences between groups. The present study indicates that untreated neonatal hypothyroxinemia does not lead to abnormalities of auditory brainstem evoked response.

Umbilical ascorbic acid levels in fetal distress.

Umbilical arterial and venous blood samples were obtained at birth immediately after clamping the cord in 38 infants. Simultaneously, maternal arterial samples were collected. Arterial blood samples were analyzed for acid-base blood gas content and venous blood samples were analyzed for plasma ascorbic acid levels. The umbilical plasma ascorbic acid level was significantly higher when compared with maternal plasma levels (172.9 +/- 39.2 vs. 57.8 +/- 21.0 mumol/liter, p < 0.0001). Correlations between maternal ascorbic acid levels and umbilical cord levels proved to be insignificant. Umbilical ascorbic acid levels in the 2 groups of infants characterized by the presence or absence of fetal distress showed significantly higher levels in the fetal distressed group (17 infants) when compared to the non-distressed group (21 infants)--191.9 +/- 36.0 vs. 157.4 +/- 34.6 mumol/liter, p < 0.005. The use of an umbilical cord ascorbic acid cut-off point of 95.8 mumol/liter gave a sensitivity of 76% and a specificity of 67% as predictors for the presence or absence of fetal distress (p < 0.025). The results of the present study demonstrate a substantial increase in ascorbic acid levels in infants exposed to intrapartum fetal distress, without any clinical sign of such insult at or after birth.

Preincubation with intravenous lipid emulsion reduces chemotactic motility of neutrophils in cord blood.

Neutrophils from cord blood of healthy term infants were isolated and incubated for 30 min with varying concentrations of intravenous lipid emulsion (ILE) solution (4, 8, 20 mg/ml). In vitro assay of chemotaxis was performed after incubation for 120 min with endotoxin-activated serum (EAS). Neutrophil random motility was unchanged after ILE incubation yet chemotactic factor (EAS)-stimulated motility was significantly reduced in a dose-related pattern.

Effect of gentamicin on the auditory brainstem evoked response in term infants: a preliminary report.

Seven essentially healthy term infants who received gentamicin starting on the 1st day of life for prolonged rupture of membranes and maternal fever were compared with nine healthy term infants to determine whether this drug induces alterations in the auditory pathway. The auditory pathway was studied on the 3rd day of life by analyzing brainstem auditory evoked potentials elicited by a click stimulus presented at the infant's ears. Latencies of components III and V, interval I-III, and interval I-V were significantly prolonged in the gentamicin group, indicating impairment of the central component of the auditory pathway. Peak and trough serum gentamicin levels all fell within the recommended therapeutic range. The study indicates that short course gentamicin therapy in healthy newborn infants can lead to abnormality of auditory function.

Platelet counts in maternal and umbilical venous blood at the time of delivery.

Platelet count in 38 paired maternal venous and umbilical venous specimens were determined at delivery. Umbilical values were significantly higher than simultaneous maternal values (p = 0.004), and a significant relationship was demonstrated between umbilical values and maternal values (r = 0.54, p = 0.0004). Associations between platelet counts and acid-base variables were found to be insignificant in the mother and the umbilical cord.

Somatostatin-like immunoactivity and biological activity is present in a human pheochromocytoma.

Somatostatin (SRIF)-like immunoreactivity (SRIF-LI) has previously been demonstrated immunohistochemically in sympathetic nerves and ganglia and in adrenal medullary cells. Studies were therefore performed to determine whether SRIF-LI was present in an adrenal pheochromocytoma. Acetic cid extracts of pheochromocytoma tissue contained high SRIF-LI concentrations (5.52 micrograms/g wet wt). On Sephadex G-75 gel filtration, the major peak of pheochromocytoma SRIF-LI coeluted with synthetic SRIF. SRIF-LI of a larger molecular size was also present in the tumor. Pheochromocytoma SRIF-LI coeluted with synthetic SRIF on reverse phase high pressure liquid chromatography. Pheochromocytoma SRIF-LI purified by high pressure liquid chromatography was equipotent to synthetic SRIF in inhibiting (Bu)2cAMP-stimulated GH release by rat pituitary cells in monolayer culture. Serum SRIF-LI was elevated in the patient before surgery and was restored toward normal after removal of the tumor. Serum levels of GH, TSH, and insulin were not obviously different before and after tumor removal. The results indicate that SRIF-LI is produced in excessive quantities by a pheochromocytoma. The immunological, chromatographic, and biological properties of the pheochromocytoma SRIF-LI suggest that it is indistinguishable from synthetic SRIF. This finding extends the list of peptides produced by pheochromocytoma and may provide an additional serum marker for the tumor in man.U