Changes in the concentration and distribution of immunoglobulin-producing cells in SIDS palatine tonsils

Seventeen sudden infant death syndrome (SIDS) cases and 9 controls, were examined immunohistochemically with regard to the presence of IgA-, IgM-, IgD, and IgG, as well as for thesubtypes IgG₁, IgG₂-, IgG₃-, and IgG₄-immunocytes. Differences in compartmentalization were also investigated. Differences were demonstrated between SIDS and controls in total number of IgG cells per 0.1 mm² tissue area (median: 18.3, range: 12.3-30.2 versus median: 6.3, range: 2.0-14.6) (p<0.01), and for IgA immunocytes (median: 3.9, range: 2.4-5.0 versus median: 1.5, range: 1.1-3.7) (p<0.05), while no differences were demonstrated for IgM cells (median: 1.8, range: 1.2-3.3 versus median: 1.8, range: 0.7-5.6) or IgD cells (median: 1.9, range: 0.8-2.9 versus median: 1.6, range: 0.7-2.4). Differences were demonstrated between SIDS and control IgG plasma cells in all the four palatine tonsillar compartments; germinal centre (p<0.01), mantle zone (p<0.05), interfollicular area (p<0.01) and reticular epithelium (p<0.01). Furthermore, the number of IgA cells was higher in SIDS vs. controls in both the germinal centre (median: 1.4, range: 0.6-2.1 versus median: 0.6, range: 0.3-1.3) (p<0.05) and in the interfollicular area (median: 2.2, range: 1.1-3.1 versus median: 0.5, range: 0.4-2.0) (p<0.01). For IgM immunocytes, differences were demonstrated in the germinal centre (median: 1.0, range: 0.4-1.6 versus median: 0.4, range: 0.3-1.3) (p<0.01) as well as in the germinal centre (median: 0.6, range: 0.5-0.8 versus median: 0.4, range: 0.3-0.7) (p<0.01) and in the interfollicular area (median: 1.2, range: 0.8-1.6 versus median: 0.5, range: 0.5-0.7) (p<0.01) in the IgD immunocyte group. The total number of IgG₁- and IgG₃-immunocytes were increased in SIDS (median 15.6, range: 5.3-58.9 versus median: 2.5, range: 1.5-8.4) (p<0.01) and (median: 3.6, range: 0.4-8.6 versus median: 1.1, range: 0.4-1.3) (p<0.01) respectively. Furthermore, significantly increased numbers of these two subclasses, were seen in all the four compartments in the SIDS cases. The palatine tonsillar immune system is stimulated in SIDS. Furthermore, the changes being predominantly in the germinal centres and interfollicular areas, are indicating a recent stimulation, and the IgG-subgroup response pattern makes a viral protein antigen the most likely stimulant.;     

Control of ventilation in subsequent siblings of victims of sudden infant death syndrome

To learn whether the ventilatory responses to hypoxia (17% O2) and hypercapnea (4% CO2) differ in the subsequent siblings of sudden infant death victims (SIDS), we studied seven normal control infants, nine infants who had had a prolonged apneic spell (apneic infants), and 10 subsequent siblings of SIDS (mean ages 10.4 weeks, 15 weeks, and 10 weeks, respectively). With inhalation of 17% O2, one of seven controls, two of nine apneic infants, and seven of 10 siblings of SIDS breathed periodically (controls vs siblings, P less than 0.04). Heart rate and end-tidal PCO2 did not change, but respiratory rate decreased in the siblings (45 to 31 breaths per minute, P less than 0.001). Arousal occurred during 25% of the hypoxic challenges in the controls and apneic infants but was not seen in the siblings of SIDS (control vs siblings P less than 0.08, apneic vs siblings P less than 0.05). With inhalation of 4% CO2 there was a similar increase in estimated ventilation among the three groups. Arousal occurred 33% of the time in all three groups. Our findings show that, after 5 weeks of age, siblings of SIDS have a normal response to hypercapnea but respond to mild hypoxia with periodic breathing.     

Reduced bone mineral density and increased bone turnover in Prader-Willi syndrome compared with controls matched for sex and body mass index--a cross-sectional study

OBJECTIVES: To study bone mineral status, body composition, and biochemical markers of bone turnover in Prader-Willi syndrome (PWS). STUDY DESIGN: Eight subjects with PWS (three males, five females; mean age, 24 years [range 16-41]) were included. Each subject was compared with an age-, sex- and body mass index-matched control randomly drawn from the background population. Bone mineral density (BMD), lean body mass, and fat mass were measured. Plasma PINP, PIIINP, osteocalcin, total alkaline phosphatase, bone-specific alkaline phosphatase, C-terminal telopeptide of type I collagen, and urine cross-linked N-terminal telopeptide of type I collagen were measured as biochemical markers of bone and collagen turnover. RESULTS: The PWS patients had significantly lower whole-body BMD (mean +/- SD, 1.020 +/- 0.041 vs 1.237 +/- 0.118 g/cm(2); 2p <.01) than controls due to lower bone mineral content (BMC: 2291 +/- 607 vs 2825 +/- 409 g; 2p=.02). Resorptive and formative bone markers were significantly elevated in patients compared with controls. Plasma testosterone was low in male patients (3.50 +/- 4.97 vs 19.2 +/- 8.78 nmol/L, 2p=.05), whereas no difference in plasma estradiol was present. CONCLUSIONS: The patients had a low BMD due to a high bone turnover. This high turnover was probably linked to sex steroid deficiency.     

Pulmonary neuroendocrine cells and neuroepithelial bodies in sudden infant death syndrome: potential markers of airway chemoreceptor dysfunction.

Pulmonary neuroendocrine cells (PNEC), including neuroepithelial bodies (NEB), are amine- and peptide (for example, bombesin)-producing cells that function as hypoxia/hypercapnia-sensitive chemoreceptors that could be involved in the pathophysiology of sudden infant death syndrome (SIDS). We assessed morphometrically the frequency and size of PNEC/NEB in lungs of infants who died of SIDS (n = 21) and compared them to an equal number PNEC/NEB in lungs of age-matched control infants who died of accidental death or homicide, with all cases obtained from the San Diego SIDS/SUDC Research Project database. As a marker for PNEC/NEB we used an antibody against chromogranin A (CGA), and computer-assisted morphometric analysis was employed to determine the relative frequency of PNEC per airway epithelial area (% immunostained area, %IMS), the size of NEB, the number of nuclei/NEB, and the size of the NEB cells. The lungs of SIDS infants showed significantly greater %IMS of airway epithelium (2.72 +/- 0.28 [standard error of the mean, SEM] versus 1.88 +/- 0.24; P < 0.05) and larger NEB (1557 +/- 153 microm(2) versus 1151 +/- 106 microm(2); P < 0.05) compared to control infants. The size of NEB cells was also significantly increased in SIDS cases compared to the controls (180 +/- 6.39 microm(2) versus 157 +/- 8.0 microm(2); P < 0.05), indicating the presence of hypertrophy in addition to hyperplasia. Our findings support previous studies demonstrating hyperplasia of PNEC/NEB in lungs of infants who died of SIDS. These changes could be secondary to chronic hypoxia and/or could be attributable to maturational delay. Morphometric assessment and/or measurement of the secretory products of these cells (for example, CGA, bombesin) could provide a potential biological marker for SIDS.     

Circulating leptin levels and bone mineral density in children with biliary atresia

AIM: To investigate circulating leptin levels in biliary atresia (BA) patients and the association of leptin with bone mineral density (BMD) and the severity of BA. METHODS: We have examined 50 patients with BA and 15 matched healthy controls. Serum leptin, osteocalcin and C-terminal telopeptide of type I collagen (CTX) levels were measured by sandwich enzyme-linked immunosorbent assay (ELISA). BMD of the lumbar spine was measured by dual energy X-ray absorptiometry. RESULTS: Serum leptin levels of BA patients were lower than those of healthy controls (2.7 +/- 0.3 vs. 7.1 +/- 1.7 ng/mL, p = 0.0001). Among the BA patients, serum leptin levels were significantly lower in patients with jaundice than patients without jaundice (1.7 +/- 0.2 vs. 3.4 +/- 0.4 ng/mL, p = 0.001). BMD of BA patients was correlated (p < 0.001) with leptin levels, age and BMI (r = 0.55, r = 0.75 and r = 0.58, respectively). The serum CTX levels were significantly higher in jaundice patients compared with jaundice-free patients and the healthy controls (0.6 +/- 0.2 vs. 0.2 +/- 0.1 ng/mL, p = 0.01), whereas the serum osteocalcin levels in BA patients were not different from those in the controls. CONCLUSION: Circulating leptin levels are correlated with BMD and the presence of jaundice in BA, suggesting that the leptin may play a physiological role in maintaining bone mass of BA patients with jaundice.     

Lung maturation in the hyperinsulinemic rat fetus

Hyperinsulinemic rat fetuses were obtained either by repeated in utero injections of long-acting insulin (resulting in fetal hypoglycemia) or by chronically infusing intravenous glucose to the mother (resulting in fetal hyperglycemia). Fetuses were examined at term. In insulin-injected fetuses (n = 15), surfactant (S) fraction phosphatidylcholine (PC) and disaturated phosphatidylcholine (DSPC) were significantly decreased (3.6 +/- 0.1 nmol Pi/mg tissue; p less than 0.001 and 2.8 +/- 0.1 nmol/mg; p less than 0.025, respectively) as compared with their saline-injected controls (4.8 +/- 0.2 and 3.3 +/- 0.1 nmol/mg, respectively, n = 19). However, residual (R) fraction was unchanged, and there was no difference in whole-lung phospholipids (combined S and R fractions). These results are consistent with morphological data showing a lower lamellar body area per type II cell profile in insulin-injected fetuses as compared with their controls [1.41 +/- 0.13 micron 2 (n = 72) versus 1.99 +/- 0.14 micron 2 (n = 129) p less than 0.01]. Glycogen content was slightly higher in insulin-injected fetuses (18.5 +/- 1.0 micrograms/mg, n = 17) than in their controls (15.1 +/- 0.8 micrograms/mg, n = 18; p less than 0.05). In the second model, changes in S fraction PC and DSPC were similar to those observed after insulin-injections: 4.3 +/- 0.25 and 3.4 +/- 0.2 nmol Pi/mg in fetuses of glucose-infused rats (n = 10) versus 5.7 +/- 0.45 and 4.3 +/- 0.3 nmol Pi/mg, respectively, in controls (n = 10, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Tissue mineral levels in victims of sudden infant death syndrome I. Toxic metals--lead and cadmium

Lung, liver, kidney, and rib specimens were obtained at autopsy from 66 sudden infant death syndrome (SIDS) infants and 23 infants who died suddenly from other causes between the ages of 4-26 wk. Tissue levels of lead and cadmium were measured by atomic absorption spectroscopy and are expressed as microgram/g dry weight. Because these metals are cumulative with age in storage tissues, the levels were corrected for age (adjusted to age 13 wk). The SIDS liver and rib specimens contained significantly more lead than non-SIDS tissues (liver, 1.095 microgram/g versus 0.761 microgram/g, P less than 0.05; rib, 1.754 microgram/g versus 1.041 microgram/g, P less than 0.01, respectively). There were no significant differences in cadmium concentration between the SIDS and non-SIDS tissues. All four tissues showed significant increases with age in both lead and cadmium concentrations in SIDS. The increase in lung lead concentration with age was significantly greater in SIDS than in non-SIDS cases, P less than 0.05. In non-SIDS only kidney cadmium showed an increase with age (P less than 0.0001). These data collectively suggest an increased exposure of the SIDS infant to lead either prenatally and/or postnatally. Any physiologic effects of the increased tissue lead levels are unknown. They may be only a marker of the known epidemiology of SIDS.     

Circadian variations in sudden infant death syndrome: associations with maternal smoking, sleeping position and infections. The Nordic Epidemiological SIDS Study

AIM: To study circadian variation in the sudden infant death syndrome (SIDS) and possible associations with risk factors for SIDS. METHODS: A questionnaire-based case-control study matched for place of birth, age and gender was conducted in Denmark, Norway and Sweden: The Nordic Epidemiological SIDS Study. The study comprised 244 SIDS victims and 869 control infants between September 1992 and August 1995. The main outcome was hour found dead. RESULTS: A significant circadian pattern was observed among the 242 SIDS victims with a known hour found dead, with a peak at 08.00-08.59 in the morning (n = 33). Of the SIDS victims, 12% were found dead at 00.00-05.59, 58% at 06.00-11.59, 21% at 12.00-17.59 and 9.0% at 18.00-23.59. When comparing night/morning SIDS and day/evening SIDS (found dead 00.00-11.59 and 12.00-23.59, respectively), the proportion of night/morning SIDS was high among infants of smoking mothers (81% vs 53%, p < 0.001), infants with a reported cold (82% vs 64%, p = 0.007) and infants sleeping side/supine (81% vs 60%, p < 0.001). No associations were observed between hour found dead and other sociodemographic risk factors for SIDS. Risk (odds ratio and 95% confidence interval) of night/morning SIDS and day/evening SIDS was 7.0 (4.5-10.9) and 1.5 (0.8-2.5), respectively, for maternal smoking, 2.2 (1.5-3.1) and 0.6 (0.3-1.3), respectively, if the infant had a reported cold, 3.7 (2.1-6.6) and 3.1 (1.1-8.4), respectively, if the infant was put to sleep in the side position (supine reference), and 11.0 (5.9-20.2) and 21.6 (7.6-60.8), respectively, if the infant was put to sleep in the prone position. CONCLUSION: The observed higher proportion of night/morning cases in SIDS if the mother smoked, if the infant was reported to have a cold and if the infant was sleeping side/supine may contribute to the understanding of some epidemiological characteristics of SIDS.     

Weight gain and sudden infant death syndrome: changes in weight z scores may identify infants at increased risk.

AIMS: To investigate patterns of infant growth that may influence the risk of sudden infant death syndrome (SIDS). DESIGN: Three year population based case control study with parental interviews for each death and four age matched controls. Growth was measured from prospective weight observations using the British 1990 Growth Reference. SETTING: Five regions in England (population greater than 17 million, more than 470 000 live births over three years). SUBJECTS: 247 SIDS cases and 1110 controls. RESULTS: The growth rate from birth to the final weight observation was significantly poorer among the SIDS infants despite controlling for potential confounders (SIDS mean change in weight z score (deltazw) = -0.38 (SD 1.40) v controls = +0.22 (SD 1.10), multivariate: p < 0.0001). Weight gain was poorer among SIDS infants with a normal birth weight (above the 16th centile: odds ratio (OR) = 1.75, 95% confidence interval (CI) 1. 48-2.07, p < 0.0001) than for those with lower birth weight (OR = 1. 09, 95% CI 0.61-1.95, p = 0.76). There was no evidence of increased growth retardation before death. CONCLUSIONS: Poor postnatal weight gain was independently associated with an increased risk of SIDS and could be identified at the routine six week assessment.     

The brain‐derived neutrophic factor val66met polymorphism and sudden unexpected infant death

Aim: Findings of hypoxia prior to death and involvement of a dysregulation of the serotonergic network in sudden infant death syndrome (SIDS) may indicate that brain‐derived neutrophic factor (BDNF) also is of importance with regard to sudden unexpected infant death. Based on this, the purpose of this study was to investigate the BDNF val66met polymorphism in SIDS cases, cases of infectious death and controls. Methods: The polymorphism was investigated in 163 SIDS cases, 34 cases of infectious death and 121 controls, using real‐time PCR and fluorescence melting curve analysis. Results: There were no differences in val66met genotype distribution between neither the SIDS cases nor the cases of infectious death and controls (p = 0.95 and p = 0.52, respectively). Conclusion: The study indicates that the val66met polymorphism is not important for sudden unexpected infant death. However, several other SNPs in the BDNF gene, as well as in other genes involved in this pathway, including G‐protein, have to be investigated to fully exclude any involvement of BDNF in SIDS.     

Weight gain and sudden infant death syndrome: changes in weight z scores may identify infants at increased risk

AIMS—To investigate patterns of infant growth that may influence the risk of sudden infant death syndrome (SIDS).DESIGN—Three year population based case control study with parental interviews for each death and four age matched controls. Growth was measured from prospective weight observations using the British 1990 Growth Reference.SETTING—Five regions in England (population greater than 17 million, more than 470 000 live births over three years).SUBJECTS—247 SIDS cases and 1110controls.RESULTS—The growth rate from birth to the final weight observation was significantly poorer among the SIDS infants despite controlling for potential confounders (SIDS mean change in weight z score (δzw) = ?0.38 (SD 1.40) v controls = +0.22 (SD 1.10), multivariate: p < 0.0001). Weight gain was poorer among SIDS infants with a normal birth weight (above the 16th centile: odds ratio (OR) = 1.75, 95% confidence interval (CI) 1.48-2.07, p < 0.0001) than for those with lower birth weight (OR = 1.09, 95% CI 0.61-1.95, p = 0.76). There was no evidence of increased growth retardation before death.CONCLUSIONS—Poor postnatal weight gain was independently associated with an increased risk of SIDS and could be identified at the routine six week assessment.     

Maternal and perinatal risk factors for SIDS: a novel analysis utilizing pregnancy outcome data

A number of maternal and perinatal factors to increase an infant’s risk of sudden infant death syndrome (SIDS) have been found in past investigations. We analysed data for potential SIDS risk factors including the presence of complications or conditions considered as detrimental to the infant’s or mother’s health. The data for 118 SIDS cases and 227 matched controls were obtained from a state pregnancy outcome unit. SIDS was found to be significantly more common in cases where the infant’s mother was not in a relationship (i.e. divorced, separated or never married) (p?=?0.005), if the infant was not the first born (p?=?0.0001) and when the mother resided in a socioeconomically disadvantaged area (p?=?0.03). Conclusion: Overall, this SIDS cohort appears to display classical SIDS associations, and our findings are consistent with those from other regions. This novel epidemiological tool opens the way for a national Australia-wide study using pregnancy outcome data collected by the individual states and could be helpful in assessing maternal and fetal risk factors for other paediatric medical conditions.     

婴儿猝死综合征血中抗Ro和抗La自身抗体的检查

目的 探讨婴儿猝死综合征的死因。方法 应用重组Ｒｏ５２，Ｒｏ６０和Ｌａ融合蛋白，以ＥＬＩＳＡ，免疫印迹和免疫沉降法检查了南澳大利亚州的２４０例ＳＩＤＳ患儿血中的自身抗体。同时取１００例成人及３２例正常婴儿作为正常对照组。结果 在２４０例ＳＩＤＳ患儿中，ＥＬＩＳＡ法发现１６．３％，具有抗Ｒｏ５２．７％具有抗Ｒｏ６０，０．８％有抗Ｌａ自身抗体，部分阳性血清通过免疫和印记法加以证明。     

Decreased lung surfactant disaturated phosphatidylcholine in sudden infant death syndrome

The lipid composition of lung surfactant obtained by lung lavage at autopsy in 40 infants dying from the sudden infant death syndrome (SIDS), was compared to that obtained from 12 infants dying from other causes (control group). Analysis of the lipids from the two groups showed no major difference in the proportions of the various phospholipid classes particularly the predominant component, phosphatidylcholine (PC), which was present at 60.7 +/- 0.9% (mean +/- S.E.) of the total phospholipids in the SIDS group and 57.9 +/- 2.9% in the control group. However the proportion of the PC present as the disaturated form (DSPC), was significantly (P less than 0.01) reduced in the SIDS group (65.8 +/- 1.6%) in comparison to the control group (77.4 +/- 3.5%). The proportion of DSPC present in the PC fraction of SIDS infants in the high-risk age range of 1-26 weeks (63.9 +/- 1.9%) was also significantly reduced (P less than 0.01) in comparison to the total control group of infants. For infants older than 26 weeks, significant differences in the proportion of DSPC in PC were not observed between SIDS and control groups. A functional consequence of the observed reduction in the DSPC content of lung surfactant of SIDS infants could be a greater degree of fluidity of the surfactant, particularly at exhalation. Such a biophysical change in surfactant properties could have a profound influence on lung function and be a causative factor in sudden infant death.     

Lung tissue concentrations of nicotine in sudden infant death syndrome (SIDS)

OBJECTIVE: To compare lung concentrations of nicotine and cotinine in cases of sudden infant death syndrome (SIDS) and controls. DESIGN/METHODS: We measured lung tissue concentrations of nicotine and cotinine in SIDS (n = 44) and non-SIDS cases (n = 29) stratified according to household smoking status. RESULTS: When all the SIDS and non-SIDS cases were compared regardless of smoking status, there was a significantly higher nicotine concentration in the SIDS cases than in the non-SIDS cases, (P =.0001). Upon stratifying for smoking status, there was a nonsignificant trend toward more nicotine in SIDS versus non-SIDS lungs that had come from a reported smoking environment. In the nonsmoking group, there were significantly higher nicotine concentrations in SIDS than non-SIDS cases (P =.001). CONCLUSIONS: Children who died from SIDS tended to have higher concentrations of nicotine in their lungs than control children, regardless of whether smoking was reported. These results are based on an objective, biochemical test rather than history, and they further support the relationship between environmental tobacco smoke and the risk of SIDS.     

Ghrelin levels in young children with Prader-Willi syndrome

OBJECTIVE: To explore the hypothesis that high ghrelin levels contribute to obesity in Prader-Willi syndrome (PWS), we assessed whether the increased levels observed in older persons with PWS exist in very young children, before the onset of hyperphagia. STUDY DESIGN: We measured ghrelin levels in nine children with PWS (17-60 months of age) and eight healthy control subjects of equivalent body mass index (BMI), age, and sex. RESULTS: PWS and control groups had equivalent BMI (16.8 +/- 1.4 vs 16.1 +/- 0.9 kg/m(2), respectively; P = .24), age (37.8 +/- 15.4 vs 50.3 +/- 17.7 months; P = .14), and sex. PWS and control groups also had equivalent fasting levels of total ghrelin (787 +/- 242 vs 716 +/- 135 pg/mL, respectively; P = .24), bioactive ghrelin (102 +/- 35 vs 91 +/- 23 pg/mL; P = .45), insulin, and glucose. Ghrelin correlated negatively with BMI among controls (r = -0.760, P = .029) but not PWS (r = 0.015, P = .97). CONCLUSIONS: Children <5 years of age with PWS, who had not yet developed hyperphagia or excessive obesity, had normal ghrelin levels, in contrast with the hyperghrelinemia of older, hyperphagic people with PWS. It is possible that ghrelin levels increase suddenly before hyperphagia develops.     

Steroid hormone may modulate hepatic somatomedin C production in newborn calves

We have studied the possible influence of steroid hormones and a beta-agonist (clembuterol) on hepatic insulin-like growth factor 1 (IGF1) production in young calves. For this purpose nine 20- to 40-day-old Holstein X Friesian male calves were fitted with chronically indwelling catheters in hepatic and portal veins and hepatic artery. Estradiol induced a simultaneous increase in plasma growth hormone (GH nmol/l) and IGF1 (nmol/l) levels (0.35 +/- 0.05 vs. 0.10 +/- 0.01 in control calves; 9.5 +/- 1.0 vs. 5.9 +/- 0.5 in controls, respectively). In the same way, 90 min after starting testosterone treatment, plasma GH levels increased from 0.21 +/- 0.08 to 1.30 +/- 0.40 while plasma IGF1 concentrations began to rise only 240 min after starting infusion (8.4 +/- 1.0) to reach maximal values at 300 min (10.7 +/- 1.1). Cortisol and clembuterol did not significantly modify either plasma GH levels or plasma IGF1 concentrations. Our results indicate that in young calves gonadal steroids exert their anabolic action through GH and IGF1.     

Hypothalamic-pituitary-testicular function in prepubertal children with chronic liver disease

Adult patients with chronic liver disease (CLD) show clinical and biochemical signs of hypogonadism and estrogenization. However, no information is available on hypothalamo-pituitary-testicular function in prepubertal or early pubertal children with CLD. Eighteen prepubertal children with CLD, aged 5.8+/-5.5 years (mean +/- SD; range 0.32-12.8), were studied. Most of them had moderate liver function abnormality. Height was slightly decreased (SDS: -1.44-/+1.88) but weight for height was adequate. Serum gonadotropins were evaluated as a function of age. In the age group younger than 1 year (n = 7), serum LH was elevated (4.88+/-6.22 IU/l) when compared with a group of 39 control children (1.2+/-1.65), while serum FSH was normal. In this young group, serum testosterone was normal, but serum estradiol was significantly increased (24.1+/-19.7 pg/ml) when compared with the control group (6.5+/-3.54). In contrast, in the age group older than 2 years, no difference between patients with CLD and controls was observed, either in serum gonadotropins or in serum sex hormones. Taking the 18 patients with CLD together, serum SHBG (113.7+/-51 nmol/l; mean +/- SD) was significantly higher than in normal controls (76+/-38 nmol/l, n = 91, p <0.001). Moreover, and different from normal controls, no change with age was observed in serum SHBG, total testosterone or bioavailable testosterone (non-SHBG-bound). Normal testosterone response to hCG stimulation (>1 ng/ml) was found in a subgroup of 11 children with CLD. By contrast, eight of 11 patients with CLD had an inadequate decrease in SHBG after androgen stimulation. In conclusion, we observed that during the first year of life, a period which includes the postnatal activation of the hypothalamo-pituitary-testicular axis, there is an elevation of serum LH and serum estradiol that suggests the existence of a moderate deficiency of Leydig cell function. This disorder is no longer observed in older prepubertal children. Similar to reports in adults, children with CLD have elevation of serum SHBG levels. Furthermore, the lack of SHBG decrease and bioavailable testosterone increase with age, probably modulated by GH, suggests some degree of hepatic GH resistance in prepubertal patients with CLD.     

Why do ALTE infants not die in SIDS?

Aim: To compare known risk factors for sudden infant death syndrome (SIDS) amongst infants with apparent life threatening events (ALTE) with their matched controls, and ALTE infants who subsequently died of SIDS with infants surviving an ALTE.
Methods: Questionnaires with replies were obtained from 58 ALTE infants and 56 sex and age matched ALTE control infants. 244 SIDS cases and 868 SIDS controls were used as comparison.
Results: The incidence of ALTE was found to be 1.9% among SIDS controls, but 7.4% among infants who later on died of SIDS. The parents sought medical advice in 0.9% vs 3.7%. ALTE infants did not differ from their matched controls. In the ALTE group 13.3% of the survivors had the combination of prone sleeping and maternal smoking compared with 33.3% of those who became SIDS victims.
Conclusions: Our results show some major differences between the ALTE infants and SIDS victims not supporting that these conditions belong to the same entity. However, we cannot exclude the possibility that there is a subpopulation of ALTE infants who did not die in SIDS due to that they were sleeping on the back and not exposed to nicotine.     

Epidemiology of sudden infant death syndrome in Japan

An epidemiological survey was carried out to examine the present situation with respect to sudden infant death syndrome (SIDS) in Kanagawa Prefecture. Questionnaires on sudden unexpected death of infants aged < 1 year in 1990-91 were sent to the hospitals and clinics in Kanagawa Prefecture which may take care of such infants. By analysing information from 10 485 replies, 48 out of 73 reported sudden infant deaths were confirmed to be SIDS, although autopsy was not performed in 13 cases (27%). The incidence of SIDS per 1000 live births in Kanagawa Prefecture was 0.29 in 1990 and 0.31 in 1991; and if limited to autopsy cases 0.19 and 0.25, respectively. Sudden infant death syndrome cases in Japan were found to occur more frequently when infants were < 6 months old, at home and sleeping alone, but less in the winter and between midnight and early morning. There was little difference between the numbers in prone and supine sleeping positions at discovery. It was not clear whether SIDS occurred more often to babies sleeping prone than supine, because there were no controls matched with the SIDS cases. In future, continuous epidemiological surveys of SIDS in Japan should be carried out.