Delay in the Development of the Secondary Palate in Ay/a Mouse Embryos

The effects of the A^y gene on the normal development were investigated by using a inbred strain of C57BL/6 (a/a) and its congenic strain of C57BL/6-A^y (A^y/a) mice. Three mating groups (female× male), i. e., group I, a/a × a/a; group II, a/a × A^y/a; and group III, A^y/a × a/a, were set, and the rating of normal development was compared among the groups on gestation days 13, 14, 15 or 16 with special attention to the secondary palate. On day 13, the palates were wide-open and the palatal shelves were vertical in all embryos in all groups. In group I, both shelves became horizontal in 63.3% of the embryos on day 14. The incidences of embryos having completely closed palates were 95.8% and 100% on days 15 and 16, respectively. In group II, in which half of the embryos were expected to carry the A^y gene, the frequencies of shelf horizontalization on day 14 (31.1%) and of the complete closure on day 15 (74.3%) were significantly lowered as compared with those in group I, although the external morphological rating was comparable. On day 16, however, the palatal closure was completed in almost all embryos. In group III, in which maternal mice as well as half of their embryos carried the A^y gene, the external morphological rating was delayed as compared with that in either group I or II, and the frequencies of shelf horizontalization on day 14 and of the complete closure on day 15 were as low as 10.9% and 39.6%, respectively. The palatal closure was not yet completed in 15.3% of the embryos on day 16. These results indicate that the A^y gene causes a delay in shelf horizontalization and closure of the secondary palate of mouse embryos as compared with the a gene.     

Dietary exposure to low doses of bisphenol A: Effects on reproduction and development in two generations of C57BL/6J mice

The present study was conducted to examine the effects of low‐dose exposure to bisphenol A on reproduction and development in two generations of mice. Pregnant female C57BL/6J mice (F₀) were fed a diet containing low doses of bisphenol A (0, 0.33, 3.3, or 33 ppm) from gestational day 6 through postnatal day 22, and the weanlings (F₁ and F₂) from each F₀ and F₁ dam group, respectively, were also fed these same concentrations of bisphenol A ad libitum until sacrifice. There were no treatment‐related changes in body weight, body weight gain, food consumption, gestation length, or the number of live births on postnatal day 1 in F₀ dams between the control group and bisphenol A groups. Sex ratio and viability were similar in all F₁ pups. No treatment‐related changes were observed in body weight, food consumption, developmental parameters, anogenital distance, or weight of any of the organs (liver, kidney, heart, spleen, thymus, testis, ovary, or uterus) in F₁ and F₂ adults in either sex. The epididymis weight was slightly higher with 0.33 and 3.3 ppm in F₁ males, but this slight increase was neither dose dependent nor seen across generations. There were no treatment‐related effects of bisphenol A on cauda epididymal sperm count or sperm motility in F₁ or F₂ males. These findings indicate that dietary exposure to bisphenol A between 0.33 and 33 ppm does not adversely affect reproduction or development as assessed in two generations of mice.     

BUS/ldr, a Mutant Mouse Strain Exhibiting Abnormal Behaviors: Behavioral Similarities of BUS Mice and Chemically Labyrinthectomized Mice

The behavioral abnormalities of homozygotes (bus/bus) of mutant bustling mice, BUS/ldr, were characterized in comparison with those of heterozygotes (+/bus) and of chemically labyrinthectomized mice. Homozygotes were 4-fold more active than heterozygotes, as evaluated in an open field (11 × 17 cm) for 24 hr by means of Animex. Homozygotes revealed the lack of righting reflex and of head nystagmus on a rotating board, the frequent backward-moving and the inability to swim, in addition to characteristic behaviors such as circling, head bobbing and head tossing. Bilaterally labyrinthectomized mice behaviorally mimicked BUS homozygotes: The behavioral patterns of operated animals were essentially the same as those of BUS homozygotes with respect to all reflex and locomotor indices employed, suggesting that some peripheral vestibular dysfunction, though unidentified yet, is attributed to abnormal behaviors of BUS mice. Unilaterally labyrinthectomized mice were not hyperactive, nor exhibited circling behavior.     

Effects of the Ay Gene on the Sensitive Periods of Hydrocortisone-Induced Cleft Palate and Palatal Slit in Mice

The effects of the A^y gene on the sensitive periods of hydrocortisone-induced cleft palate and palatal slit were investigated in C57BL/6 (a/a) and its congenic strain of C57BL/6-A^y (A^y/a) mice by using the single-dose administration method. Matings were conducted as follows (femalex male): Group I, a/a × a/a; Group n, a/a ×A^y/a; and Group III, A^y/a × a/a. Pregnant females were subcutaneously given a single dose of 200 or 400 mg/kg of hydrocortisone on day 11, 12, 13 or 14 of pregnancy and killed on day 18 for examination of palatal defects of live fetuses. Cleft palate was produced in all groups by treatment on days 11–13 of pregnancy at a dose of 200 mg/kg without any increase in fetal mortality. In Group I, the maximum incidence was observed on day 11 and followed by a rapid decrease thereafter. In Group U, in which half of the fetuses were expected to carry the A^y gene, the incidence still remained high on day 12, although it was decreased to the level of Group I by day 13. In Group HI, in which maternal mice as well as half of their fetuses carried the A^y gene, significantly higher incidences were observed on days 12 and 13 with the maximum value on day 12 when compared with those in Groups I and/or II. Palatal slit was also induced in all groups on each of treatment days at a dose of 200 mg/kg. Although the incidences in both Groups I and II were high on days 11 and 12 and gradually decreased thereafter, the value on day 13 was significantly higher in Group II than in Group I. In Group IE, the maximum incidence was found on day 12 and the values on days 13 and 14 were still significantly higher than those in Groups I and/or II. These results indicate that the sensitive periods of hydrocortisone-induced cleft palate and palatal slit are prolonged into the later stage of embryonic development as a result of the A^y-gene effects.     

Normalization of Maximal Cardiovascular Variables for Body Size in Premenarcheal Girls

Previous studies have indicated the importance of allometric scaling of VO_2max for body size. However, no information is available on adjusting maximal cardiac output (Q _max) and stroke volume (SV_max) for body dimensions. The allometric exponent b was determined for the equation Y=aX ^b (where Y is the physiological outcome and X is the anthropometric variable) for VO_2max, Q _max, and SV_max relative to mass, height, and body surface area (BSA) in 24 premenarcheal girls (mean age 12.2 years) during cycle testing. Values for b were 1.08 and 1.05 for BSA relative to Q _max and SV_max, approximating that of 1.0 using the traditional ratio standard (cardiac index and stroke index). Exponents of body mass relative to VO_2max, Q _max, and SV_max (0.55, 0.55, and 0.59, respectively) eliminated the effects of body size, but the ratio standard (M ^1.0) did not. In this group of subjects, use of the ratio standard BSA was an appropriate means of adjusting maximal values of Q and SV for body size.     

Locus on chromosome 16 is significantly associated with increased tendency to lose pups in females of the RR/Sgn inbred mouse strain

Females of the inbred mouse strain RR/Sgn have an apparent tendency to lose pups during rearing. To identify genes underlying this abnormal maternal phenotype, we performed quantitative trait loci (QTL) mapping in 349 (C57BL/6 J × RR/Sgn) F₁ × RR/Sgn backcross mice and identified one significant and one suggestive QTL on chromosomes 16 and 4, respectively. We assigned the gene symbol nurturing ability QTL 3 (Naq3) to the QTL on chromosome 16. Twenty of the 21 mothers who lost entire litters were homozygous for RR/Sgn allele at Naq3; i.e., the significant association of Naq3 with pup loss was further confirmed by binomial tests. We tentatively propose that Mapk1, Kalrn, and Vps8 are potential candidate genes for Naq3.     

Neutrophil Receptors

We studied two interesting patients with neutrophil dysfunction: one is a patient with hyper-IgE syndrome with the serum inhibitor which belongs to IgE class and the other is characterized by defective phagocytosis confined to S. aureus. These patients suggested to us the presence of IgE receptors and receptors for S. aureus on neutrophils. The presence of IgE receptors on neutrophils was proved by the fact that neutrophils preincubated with 10 μg of pure IgE generated O^-₂ on stimulation with F(ab')₂, fragments of pure anti-K chain antibody or anti-K chain antibody. The presence of IgE receptors was also suggested by the suppressive effect of IgE soluble immune complexes on neutrophil chemotaxis. Neutrophils of the patient with defective phagocytosis confined to S. aureus could not generate O^-₂ with unopsonized S. aureus, while control neutrophils generated a significant amount of O^-₂ on addition of unopsonized S. aureus. Colchicine treated control neutrophils also could not generate O^-₂ by unopsonized S. aureus. These data suggested the presence of receptors for S. aureus on neutrophils.     

Effects of the Y‐chromosome and the dominant hemimelia mutation on the morphology of the mouse mandible

The aims of this study were to test whether the Y‐chromosome and the autosomal dominant hemimelia (Dh) mutation can affect mandible morphology in mice. I analyzed mandible size and shape using landmark‐based geometric morphometrics in 16 DH‐Chr Y^@‐+/+ (@ represents one of the inbred strain names) strains and observed significant differences in mandible size. The largest mandible was identified in strain DH‐Chr Y^C3H and the smallest in strain DH‐Chr Y^KK. Canonical variate and discriminant function analyses suggested that the mandible shapes of strains DH‐Chr Y^C3H and DH‐Chr Y^KK differed from those of the other strains. Because seven of the DH‐Chr Y^@‐+/+ strains were maintained with dominant hemimelia, I also analyzed the potential influence of dominant hemimelia on mandible morphology because dominant hemimelia is known to cause various skeletal malformations. There were no significant differences in mandible size in seven sets of DH‐Chr Y^@‐+/+ and DH‐Chr Y^@‐Dh/+ strains. However, canonical variate analysis mapped strains DH‐Chr Y^CAS‐Dh/+ and DH‐Chr Y^CBA‐Dh/+ mapped distantly from the rest. Additionally, I observed similar patterns of shape change between DH‐Chr Y^CAS‐+/+ and DH‐Chr Y^CAS‐Dh/+, and between DH‐Chr Y^CBA‐+/+ and DH‐Chr Y^CBA‐Dh/+. These data indicate that the Y‐chromosome affects the size and shape of the mouse mandible. Dominant hemimelia affects mandible shape but not size, and its effects emerge depending on the kinds of Y‐chromosomes.     

Adenovirus-mediated gene therapy in a mouse model of glycogen storage disease type 1a

Glycogen storage disease type 1a (GSD-1a), characterized by growth retardation, hypoglycemia, hepatomegaly, kidney enlargement, hyperlipidemia, hyperuricemia, and renal dysfunction, is caused by deficiencies in glucose-6-phosphatase (G6Pase), a key enzyme in glucose homeostasis. Over the last 20 years, dietary therapies have greatly improved the prognosis of GSD-1a patients. However, the underlying pathological process remains uncorrected and the efficacy of dietary treatment is frequently limited by poor compliance. Therefore, long-term complications till develop in adult patients. To develop future therapeutic approaches for GSD-1a, we have generatedG6Pase-deficient (G6Pase^-/-) mice that mimic the pathophysiology of human GSD-1a patients. To evaluate the feasibility of gene replacement therapy for this disorder, we have infused recombinant adenovirus containing murineG6Pase gene (Ad-mG6Pase) into G6Pase^-/- mice. While only 15% of G6Pase^-/- mice under glucose therapy survived weaning, a 100% survival rate was achieved when G6Pase^-/- mice were infused with Ad-mG6Pase and 90% of which lived to 3 months of age. Hepatic G6Pase activity in Ad-mG6Pase-infused mice was restored to 19% of that in G6Pase^+/+ mice at 7 through 14 post-infusion days. Ad-mG6Pase infusion also greatly improved growth of G6Pase^-/- mice and normalized plasma glucose, cholesterol, triglyceride, and uric acid profiles. Further, liver and kidney enlargement were less pronounced with near normal levels of glycogen depositions in both organs.Conclusion: our data demonstrate that a single administration of a recombinant adenovirus vector can alleviate the clinical manifestations of glycogen storage disease type 1a in mice, suggesting that this disorder in humans can potentially be corrected by gene therapy. Published online: 19 July 2002     

Validation of the Proximal Isovelocity Surface Area Method for Assessing Mitral Regurgitation in Children

The proximal isovelocity surface area (PISA) method for calculating volume flow through the regurgitant orifice has attracted significant attention. A number of in vitro studies and clinical studies in adults suggest that the method is accurate. However, when applying the method to children it must be noted that the absolute regurgitation volume is small, and the range of body sizes is wide. This study investigated the accuracy of the PISA method for quantitative assessment of the severity of mitral regurgitation in children. Twenty children aged 7 months to 12 years (average 4.7 years) with mitral regurgitation but without interventricular shunt or aortic stenosis were selected for this study. Underlying cardiac diseases included atrioventricular septal defects in nine, isolated mitral regurgitation in five, and association with other heart defects in six. The PISA radius (r) and the duration of regurgitation (T) were measured on color M-mode recordings, with the M line passing through the center of the PISA. Assuming that the PISA is a hemisphere, maximal regurgitant flow rate (MFR: ml/s) was calculated as MFR = 2π×~ r ²×~ V (r= maximal radius, V= aliasing velocity), and regurgitant stroke volume (RSVpisa) as RSVpisa = 2π×~ MSR ×~ V×~ T (MSR = mean square of the PISA radius during regurgitation). As a validating standard, total stroke volume (TSV) using two-dimensional echocardiography determined by the area–length volumetry method and forward stroke volume (FSV) by the pulsed Doppler method were measured, and regurgitant stroke volume (RSV_D: RSV_D= TSV − FSV) and regurgitant fraction (RF: RF = RSV_D/TSV) were calculated. A linear correlation was found between MFR, RSVpisa, and RSV_D (X) (MFR = 4.2X + 54.0, r= 0.84. RSVpisa = 1.0X + 9.8, r= 0.90), and both RSVpisa and MFR divided by body surface area (BSA: m²) revealed a significant correlation with regurgitant fraction (X) by nonlinear regression analysis (RSVpisa/BSA = 26.2 ×~ X/(1 − X) + 16.8, r= 0.85. MFR/BSA = 121.8 ×~ X/(1 − X) + 92.2, r= 0.79). It is concluded that maximal regurgitant flow rate, regurgitant stroke volume, and regurgitant fraction can be accurately predicted in children using the PISA method by Doppler echocardiography.     

Effect of surgery on ventilatory requirements in severe pulmonary interstitial emphysema

Pulmonary interstitial emphysema (PIE) is an acquired condition that can develop in premature infants with severe hyaline membrane disease (HMD) who require assisted ventilation. In this study, the effect of surgery on the ventilatory requirements of nine infants with severe and progressive PIE was established to determined the degree to which surgical intervention was beneficial. The median ventilation index for O₂([P_aO₂/(F₂O₂ × MAP)]) and median ventilation index for CO₂ ([PIP-PEEP] × RR × PCO₂) markedly improved following surgery. There was no difference in overall outcome between those infants who had a lobectomy and those who had pleurotomy with diathermy deflation of subpleural cysts (POD). Given that PIE is reversible, POD seems to be preferable to lobectomy because it preserves lung tissue. Correspondence to: S. W. Beasley     

Exposure to ethinyl estradiol prenatally and/or after sexual maturity induces endometriotic and precancerous lesions in uteri and ovaries of mice

Unrecognizable exposure to estrogenic substance may cause estrogen‐dependent diseases, endometriosis and cancer. Pregnant mice (ICR/Jcl, CLEA) were exposed to 0.01 mg ethinyl estradiol (EE₂)/kg per day or vehicle (olive oil) through oral intubation from day 11 to 17 of gestation. They delivered their offspring and raised them. When the experimental female F₁ mice were at 8 weeks of age, they were not exposed to EE₂ or to the same dose of EE₂ or to vehicle twice a week until 20 weeks of age. The control female F₁ mice were exposed to the same dose of EE₂ or vehicle alone, similarly. All mice were killed at 28 weeks of age. The resected uteri and ovaries were processed for microscopic examinations and for determination of the aromatase mRNA levels and aromatase protein through quantitative RT‐PCR and Western blotting, respectively. Adenomyosis and adenocarcinomatous changes were significantly discernible in the EE₂‐exposed uteri, and incidence of ectopic glands and serous cysts were significantly increased in the prenatally EE₂‐exposed ovaries as compared with respective controls. Significant upregulation of the aromatase mRNA was seen in the prenatally EE₂‐exposed uteri and in the EE₂‐exposed ovaries. The aromatase protein was identified in all ovaries examined, and in EE₂‐exposed uteri but not in controls and confirmed its localization in eutopic and ectopic glands, abnormally proliferated lesions and the lining of the cysts. Taken together, continuous EE₂ exposure may cause endometriotic and precancerous lesions due to excessive estrogen synthesis in both target organs.     

Growth references for height,weight, and head circumference for Argentine children with achondroplasia

In order to prepare growth references for height, weight, and head circumference for Argentine children with Achondroplasia, 228 children (114 boys) aged 0–18 years attending the Growth Clinic at Hospital Garrahan were measured between 1992 and 2009. Centiles were calculated by LMS, a method for summarizing growth data which adjusts for skewness. Curves for centiles are obtained using the formula: C_100a (t) = M(t)( 1 + L(t)S(t)Z_a )^1/L(t) {{\hbox{C}}_{{100}}}_\alpha (t){ = }M(t){\left( {{1 + }L(t)S(t){Z_\alpha }} \right)^{{1/}L(t)}} , where Z _α is the normal equivalent deviate for tail area α; C100α is the weight or height centile corresponding to Z _α , t is age in years, and L(t) is (skewness)(t), M(t) is median, S (t) is coefficient variation and C_100α (t) indicates the corresponding values of each curve at age t. Boys and girls centiles for height were similar to USA references in infancy and childhood but lower than that references at adolescence. Final height was 1.7 and 5.1 cm below USA achondroplasia references in girls and boys, respectively. Head circumference centiles were, at all ages, lower than USA references in both genders. Countries need national references for clinical growth assessment of their local population. Likewise, specific local growth references for children with some genetic conditions (such us achondroplasia) are valuable tools for detecting additional conditions affecting growth, for estimating final height and for evaluating the impact of growth-promoting treatments. Conclusion: references presented here can also be used in other countries with similar ethnographics characteristics.     

Estimating microsatellite based genetic diversity in Rhode Island Red chicken

This study aimed to estimate microsatellite based genetic diversity in two lines (the selected RIR^S and control line RIR^C) of Rhode Island Red (RIR) chicken. Genomic DNA of 24 randomly selected birds maintained at Central Avian Research Institute (India) and 24 microsatellite markers were used. Microsatellite alleles were determined on 6% urea-PAGE, recorded using GelDoc system and the samples were genotyped. Nei’s heterozygosity and Botstein’s polymorphic information content (PIC) at each microsatellite locus were estimated. Wright’s fixation indices and gene flow were estimated using POPGENE software. All the microsatellite loci were polymorphic and the estimated PIC ranged from 0.3648 (MCW0059) to 0.7819 (ADL0267) in RIR^S and from 0.2392 (MCW0059) to 0.8620 (ADL0136) in RIR^C. Most of the loci were highly informative (PIC>0.50) in the both lines, except for five loci in RIR^S and six loci in RIR^C line. Nei’s heterozygosity per locus ranged from 0.4800 (MCW0059) to 0.8056 (ADL0267) in RIR^S and from 0.2778 (MCW0059) to 0.875 (ADL0136) in RIR^C. Out of 24 loci, 15 (62.5%) in RIR^S and 14 loci (58.33%) in RIR^C revealed moderate to high negative F_IS index indicating heterozygote excess for these loci in corresponding lines, but the rest revealed positive F_IS indicating heterozygosity deficiency. A mean F_IS across the both lines indicated overall 10.77% heterozygosity deficit and a mean F_IT indicated 17.19% inbreeding co-efficient favoring homozygosity over the two lines. The mean F_ST indicated that 10.18% of the microsatellite variation between the two lines was due to their genetic difference.Key Words: F-statistics, Heterozygosity, Microsatellite allele, Polymorphic information content, Rhode Island Red chicken     

Effect of positive end expiratory pressure and mean airway pressure on respiratory compliance and gas exchange in children with liver disease

The effect of positive end expiratory pressure (PEEP) and mean airway pressure (MAP) on respiratory compliance and gas exchange was assessed in children with liver disease. In the first study of 12 patients, PEEP was decreased either by 3 cmH₂O below the baseline level (the child's original level) or to 0 cmH₂O and then increased to 3 cmH₂O above the baseline. Decreasing PEEP impaired compliance (P<0.01), and oxygenation (P<0.05), whereas increasing PEEP improved compliance (P<0.05) and oxygenation (P<0.05). Neither increasing nor decreasing PEEP caused significant changes in the carbon dioxide levels. In the second study, 24 children were studied at their baseline settings and then after increasing the PEEP by 3 cmH₂O while simultaneously lowering the peak inspiratory pressure (PIP) to maintain MAP constant (12 children had lung function measurements). In the group overall increasing PEEP while decreasing PIP resulted in an insignificant change inp _aO₂, but a significant increasep _aCO₂ (P<0.01) and reduction in tidal volume (P<0.01), the change in compliance was not significant. After a second period at the baseline settings, in 12 children inspiratory time (T_I) was increased while keeping MAP constant by reducing PIP. No significant change inp _aO₂ or compliance was experienced, butp _aCO₂ increased (P<0.05) and tidal volume decreased (P<0.01). In the other 12 children MAP was increased by prolonging T_I. Increasing MAP had a variable effect and the changes inp _aO₂ andp _aCO₂ were not significant. No critical MAP level with regard to oxygenation was demonstrated. We conclude that in children with liver disease, increasing PEEP can improve oxygenation and compliance, but the MAP level alone does not determine oxygenation.     

The use of pulse oximetry in the prevention of hyperoxaemia in preterm infants

When deciding an appropriate upper limit for pulse oxygen saturation (SpO₂) in preterm infants the usefuleness of current data is limited by the fact that previous studies have examined a population of more mature infants and children or have applied various exclusion criteria which produce results unrepresentative of clinical practice. We tested the hypothesis of previous workers that maintaining the SpO₂ below 98% would ensure an arterial oxygen tension (PaO₂) less than 12 kPa. A total of 477 simultaneous measurements ofPaO₂ and SpO₂ were made using Ohmeda Biox oximeters on 43 infants who were less than 33 weeks gestation and receiving supplementary oxygen. Of 435 measurements performed when the SpO₂ was 97% or less, 26 (6%) had aPaO₂ greater than 12 kPa. Further examination of the data showed that of 108 estimations performed when the SpO₂ was less than 94%, none had aPaO₂ greater than 12kPa.Conclusion When using Ohmeda Biox pulse oximeters an upper limit of 97% for SaO₂ is not effective in preventing hyperoxaemia; however, a linit of 93% is likely to maintain thePaO₂ below 12 kPa.     

Effect of pre-immunization by killed Mycobacterium bovis and vaccae on immunoglobulin E response in ovalbumin-sensitized newborn mice

A recently advanced hypothesis suggests that decreased exposure to T-helper (Th) 1-inducing agents cause Th2-biased differentiation in response to concomitant allergens. We therefore examined the effect of pre-immunization with killed Mycobacterium bovis and killed M. vaccae which are known to be very potent inducers of Th1 immune response, on serum IgE response in ovalbumin (OVA)-sensitized newborn mice. Eighty-four newborn Balb/c mice were divided into four groups and were immunized intraperitoneally 24 h after birth with 50 µl of 5 × 10⁴ colony-forming units (c.f.u.) of killed M. bovis in group I (M. bovis group, n = 19), with 25 µl of 2.5 × 10⁸ c.f.u. of killed M. vaccae plus 25 µl of 5 × 10⁴ c.f.u. of killed M. bovis in group II (M. vaccae+ M. bovis group, n = 28) and with 50 µl of only phosphate-buffered saline (PBS) in group III (no mycobacterial immunization, n = 18). No injection was applied to mice in group IV (control group, n = 19). Starting from 8 weeks of age, all mice except the control group were sensitized with 0.5 ml of 20 mg/ml OVA administered intraperitoneally 7 times every other day. Thirty days after the final injection, all animals except those in the control group were challenged with an aerosol of 2 mg/ml OVA. Forty-eight hours later, blood was collected from all mice for determination of serum IgE levels. A statistically significant difference was observed in the serum total IgE levels between groups III and IV (p = 0.0099), indicating that the mice were successfully sensitized with OVA. Serum total IgE values of the female mice in M. bovis group were found to be significantly lower than group III (p = 0.009), while no difference was observed in males. Serum total IgE levels of the M. vaccae+M. bovis group were found to be significantly lower than group III both in male and female mice (p < 0.0001 and p = 0.0001, respectively), showing even lower values in females in comparison with controls (p = 0.0092). Pre-immunization in the newborn period with killed M. bovis alone or in addition to M. vaccae may potentially be helpful in down-regulating an IgE response.     

Hypoxia-induced free iron release in the red cells of newborn infants*

Heparinized blood samples were obtained at birth from 164 newborn infants (101 full term; 63 preterm). Intra-erythrocyte free iron concentration and hypoxanthine plasma levels were determined by high-pressure liquid chromatography. Intra-erythrocyte free iron concentration was higher in preterm than in full term babies (p < 0:0001) and adults (p < 0:0001). Statistically significant correlations were observed between intra-erythrocyte free iron concentration and hypoxanthine levels (r = 0:66; p= 0:0001), pH (r = - 0:76; p = 0:0001), base excess (r = - 0:79; p= 0:0001), and gestational age (r = - 0:44; p= 0:0001) in both infant populations. Multiple regression analysis between intra-erythrocyte free iron concentration in cord blood, as an independent variable, and Apgar score at 1 min, pH, base excess, hypoxanthine values, FiO₂ needed for resuscitation immediately after delivery, and gestational age, as dependent variables, identified hypoxanthine levels (p= 0:0003; partial F-test = 15.4) as the best single predictor of intra-erythrocyte free iron concentration. In conclusion, hypoxia induces intra-erythrocyte free iron release, and therefore enhances the risk of oxidative injury due to hydroxyl radical generation.     

Chronic night cough and asthma severity in children with stable asthma

The relationship between night cough and other indices of asthma severity was studied in 21 children with clinically stable asthma and persistent night cough. Overnight cough was quantified and related to symptom scores, oxygen saturation (S_aO₂) during sleep, evening and morning peak flow recordings and daytime tests of lung function. In the index group the median number of coughing episodes was 23 (range 1–158). Only 4 children had counts of <10 overnight, similar to the comparison group of 12 children all of whom had counts of <10. There was a trend towards the association of overnight cough with reduced evening peak flow (r=–0.407,P=0.07) and reduced S_aO₂ (r=–0.36,P=0.10). Abnormalities in daytime tests of lung function were observed in 13 children. There was no relationship between night cough and daytime indices of lung function abnormality although children with more severe daytime abnormalities also had significant night cough. Conversely, five children with chronic night cough had normal daytime function.Conclusion Night-time cough in children with asthma is not simply a reflection of daytime lung function status, whereas, overnight S_aO₂ correlates well. Other factors need to be explored to explain the variability of night-time cough in these children.