Low serum inhibin B levels as a marker of testicular damage after treatment for a childhood malignancy

The aim of this study was to evaluate the role of inhibin B and the determination of its concentration to diagnose testicular damage after treatment for a childhood malignancy. Thirty-seven males treated for Hodgkin disease (n=11) or non-Hodgkin lymphoma (n=26) were examined at a mean age of 16.9 ± 2.9 years. Mean age at the stop of therapy was 11.3 ± 3.0 years and in most cases the chemotherapy regimen included gonadal damaging alkylating agents. Thirty-three normal males (mean age 17.9 ± 4.1 years) were examined as controls. Serum samples were collected for determination of inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. Median inhibin values were significantly lower in patients than in controls (96.0 vs 225.0 pg/ml, P < 0.0001) and a strong negative correlation was found between inhibin B and FSH (r=−0.86, P < 0.0001), a weak correlation with LH (r = −0.32, P < 0.05) and no correlation with testosterone. In post-pubertal patients (i.e., over 16 years) a positive correlation was found between testicular size and inhibin level (r=0.53, P < 0.05), but not between testicular size and testosterone level. Pathological low levels (values that differed by more than 2 SD from the mean value of control subjects) were found in 20 patients for inhibin B and 8 for testosterone (P < 0.01) and pathological high values in 19 patients for FSH and 3 for LH. Conclusion This study confirms the role that inhibin B plays in the regulation of FSH secretion and provides further evidence of the utility of its evaluation as a direct indicator of male gonadal dysfunction. Received: 21 April 1999 / Accepted: 27 September 1999     

Changes in red cell phosphate metabolism of preterm and fullterm infants with perinatal problems during their first month of life

The effects of perinatal problems on red cell phosphate metabolism were studied in two groups of infants (preterms B and fullterms D) during the first month of life. All infants started milk feeding from day three after birth. The results were compared to those of healthy preterms (A) and fullterms (C), respectively. Comparisons were also made between the preterm and fullterm groups B and D. The preterms with perinatal problems (B) showed a significant delay in catching up with the plasma and red cell inorganic phosphate (Pi) levels of controls (A) throughout the first month of life (p < 0.05). In parallel, the erythrocyte 2,3 diphosphoglycerate (2,3-DPG) concentrations of the sick preterms lagged significantly behind those of controls (p < 0.001); but the ATP levels were comparable between the two groups. The fullterms behaved slightly differently. No significant differences in plasma Pi (Pl Pi) and red cell 2,3-DPG were seen between the sick and healthy neonates during the month of study, while red cell Pi (RBC Pi) and ATP were found to be lower in the sick ones (p < 0.05). The fullterms with perinatal problems (D) had significantly higher Pl Pi (p < 0.05) and RBC Pi (p < 0.01) than preterms with problems (B) from the first week of life and continued in a similar pattern until the end of the month. Red cell 2,3-DPG concentrations were found to be significantly correlated with Pl Pi and RBC Pi in both preterm groups (p < 0.01) and in the sick fullterms (p < 0.001) during the time of the study. In the healthy fullterms 2,3-DPG was found to correlate only with red cell Pi (p < 0.05). Perinatal problems seem to affect Pi metabolism to a different degree in preterm and fullterm neonates in the first month of life.     

The relation of germ cells per tubule in testes,serum inhibin B and FSH in cryptorchid boys

At bilateral orchiopexy bilateral biopsies may be indicated to determine fertility potential. It is currently unknown if the serum inhibin B levels at time of orchiopexy reflect the testicular status of the bilaterally cryptorchid child. The aim of this study was to relate the results of inhibin B and FSH measurements with testicular biopsy parameters in bilateral cryptorchid boys. Included were 25 boys with bilateral cryptorchidism, median 2.5 years (9 months to 5.5 years) at surgery for bilateral cryptorchidism with simultaneous testicular biopsies, and blood sample for inhibin B and FSH. The number of spermatogonia and gonocytes was measured in 100 tubular transverse sections, the S/T and the mean-S/T of the patient was found, and expressed as percent of lowest normal value. Inhibin B and FSH were measured and related to age-specific values. Forty percent (10/25) of the patients had very low mean-S/T (mean-S/T < 10% of lowest normal-value). Inhibin B was decreased in 24% (6/25) of the patients, all with decreased mean-S/T, predominantly with a mean-S/T < 10% of lowest normal-value (p < 0.05). There was a negative correlation between inhibin B and FSH (p < 0.05). In cases of mean-S/T<10% of lowest normal-value and decreased inhibin B, we found increased FSH in 9% (2/22) of the patients and hypergonadotropic hypogonadism was suspected. Low FSH was found in 5% (1/22) of the patients and hypogonadotropic hypogonadism was suspected. Low inhibin B predicts a serious condition in respect of infertility. Low FSH and inhibin B indicates examination for hypogonadotropic hypogonadism. In bilateral cryptorchid boys inhibin B levels correlated negatively to FSH.     

Do neonates with high serum cholesterol levels have a different high density lipoprotein composition?

In order to ascertain whether the high density lipoprotein (HDL) composition of neonates with high serum cholesterol levels (≥2.59 mmol/l or ≥100 mg/dl) differs from that of neonates with normal serum cholesterol levels (<2.59 mmol/l), 548 cord blood samples were examined from full-term newborns of the Toledo Study (Spain) of whom no perinatal factors were known which could alter cord blood lipid levels. Newborns were selected according to the following criteria: single and eutocic delivery with cephalic presentation, gestational age between the beginning of the 37th week and the end of the 41st week, body weight between 2.5 kg and 3.999 kg and an Apgar score of ≥7 and ≥9 at l min and 5 min, respectively. The prevalence of high serum total cholesterol (TC) level was greater (P < 0.02) in females than in males. Newborns with high TC levels had higher triglyceride (P < 0.01), HDL-cholesterol (P < 0.001) and apoprotein (Apo) A-I (P < 0.001) levels, and a higher TC/HDL-cholesterol ratio (P < 0.05), but a lower HDL-cholesterol/Apo A-I ratio (P < 0.05). ANOVA two-way analysis showed a significant effect of gender and serum cholesterol level and a statistical interaction of these two factors upon triglycerides, Apo A-I, and the HDL-cholesterol/Apo A-I ratio. However, HDL-cholesterol and the TC/HDL-cholesterol ratio were higher in neonates (males plus females) with high serum TC but they were not affected by sex. The larger HDL particles in males with high TC levels (HM) should be associated with the higher triglyceride level found in those individuals. Conclusion The composition of high density lipoproteins in newborns is influenced by the serum cholesterol level and by gender. Neonates with high total cholesterol have larger average high density lipoprotein (HDL) particles. If total cholesterol is elevated, HDL from males carries more cholesterol than HDL from females. Received: 26 November 1996 / Accepted: 7 January 1997     

Soluble Intercellular adhesion molecule-1 in newborn infants

The aim of this study was to evaluate the effect of increasing postnatal age on soluble intercellular adhesion molecule-1 (sICAM-1), a very early and sensitive marker of immune activation and response in the serum of newborn infants. Serum sICAM-1 was measured by EIA (T Cell Diagnostics) in 20 healthy adults (controls) and in 43 (24 females/19 males) healthy neonates, of whom 28 were full term, and 15 were born at a gestational age between 35 and 38 weeks of pregnancy, on the 1st, 5th and 30th day of life. Neonatal serum sICAM-1 values showed a very significant increase (P<0.01) from the 1st day (137.3 ± 62.0 ng/ml) to the 5th day (259.3 ± 124.0 ng/ml) and then to the 30th day of life (415.0 ± 114.0 ng/ml), being significantly lower on the 1st day (P<0.01), whereas significantly higher on the 30th day of life (P<0.05), than those in healthy adults (305 ± 195 ng/ml). Serum sICAM-1 values on the 1st day of life depended on both the mode of delivery (significantly higher in neonates born vaginally) and the gestational age at birth (significantly lower in those born at a gestational age over 38 weeks). A significant strong correlation was found in sICAM-1 values between the 1st and the 5th day following delivery (r _P =0.77, P<0.009). Conclusion The results of this study demonstrate a significant rise of serum sICAM-1 during the 1st month of life in healthy neonates suggesting a progressively increased activation of the neonatal immune system. Received: 20 June 1996 and in revised form: 24 March 1997 / Accepted: 24 April 1997     

Doppler evaluation of renal blood flow velocity as a predictive index of acute renal failure in perinatal asphyxia

Aim of our study was to evaluate Doppler renal blood flow velocity in asphyxiated neonates and to correlate renal function to Doppler findings. Doppler renal blood flow velocity was evaluated in 23 severely asphyxiated neonates born at a gestational age >32 weeks and compared to our standard Doppler data obtained in 25 healthy neonates comparable for gestational age and birth weight. Renal Doppler ultrasound was performed on the 1st and 3rd days of life. Renal function was investigated in the first 2 weeks of life. Asphyxiated neonates showed mean values of systolic velocity and mean velocity significantly reduced (P< 0.001) compared with our standard Doppler values on the 1st day of life. Seven out of the 23 asphyxiated neonates were affected by acute renal failure and 14 showed no renal involvement. Two neonates were oliguric but did not develop acute renal failure. On the 1st day of life, neonates with acute renal failure had significantly lower mean values of systolic velocity and mean velocity than the asphyxiated neonates without renal involvement (P< 0.01). All 7 neonates affected by acute renal failure showed a systolic velocity more than 2SD below the mean standard value, while only 4 of the 16 asphyxiated neonates (25%) without acute renal failure had low systolic velocity values on the 1st day of life. Doppler velocities in asphyxiated neonates were similar to standard values on the 3rd day of life. Renal failure recovered before the 11th day of life in all cases. Conclusion Our findings indicate that decreased Doppler renal flow systolic velocity observed in asphyxiated neonates on the 1st day of life is a useful predictive index for subsequent development of acute renal failure, with 100% sensitivity and 63.6% specificity. Received: 21 July 1997 / Accepted in revised form: 24 November 1997     

Sertoli cell markers in the diagnosis of paediatric male hypogonadism

During childhood, the pituitary-testicular axis is partially dormant: testosterone secretion decreases following a drop in luteinising hormone levels; follicle-stimulating hormone (FSH) levels also go down. Conversely, Sertoli cells are most active, as revealed by the circulating levels of anti-Müllerian hormone (AMH) and inhibin B. Therefore, hypogonadism can best be evidenced, without stimulation tests, if Sertoli cell function is assessed. Serum AMH is high from fetal life until mid-puberty. Testicular AMH production increases in response to FSH and is potently inhibited by androgens. Inhibin B is high in the first years of life, then decreases partially while remaining clearly higher than in females, and increases again at puberty. Serum AMH and inhibin B are undetectable in anorchid patients. In primary or central hypogonadism affecting the whole gonad established in fetal life or childhood, all testicular markers are low. Conversely, when hypogonadism only affects Leydig cells, serum AMH and inhibin B are normal. In males of pubertal age with central hypogonadism, AMH and inhibin B are low. Treatment with FSH provokes an increase in serum levels of both Sertoli cell markers, whereas human chorionic gonadotrophin (hCG) administration increases testosterone levels. In conclusion, measurement of serum AMH and inhibin B is helpful in assessing testicular function, without need for stimulation tests, and orientates the aetiological diagnosis of paediatric male hypogonadism.     

The moulded baby syndrome: incidence and risk factors regarding 1,001 neonates

Postural deformities are frequent in neonates. The moulded baby syndrome (MBS) comprises one or more of the following disorders: plagiocephaly, torticollis, congenital scoliosis, pelvic obliquity, adduction contracture of a hip and/or malpositions of the knees or feet. We analysed the incidence of MBS in healthy neonates and identified the risk factors of its composing elements. One thousand and one healthy neonates were examined on the second or third day of life by the same paediatrician. Familial, obstetrical, perinatal history and putative risk factors for postural deformities were collected. Families of newborns with a torticollis or plagiocephaly were given positioning advice and the outcome was evaluated by a phone survey 2 months later. MBS was detected in 107 neonates (10.7%): 97 plagiocephalies or torticollis, 25 congenital scoliosis or pelvic obliquities, and 13 malpositions of the knees or feet. We identified risk factors related to the mother (age: OR = 1.39, parity: OR = 0.643), to the obstetrical history (preterm labour: OR = 1.65, oligoamnios: OR = 10.179, breech presentation: OR = 2.746, pregnancy toxaemia: OR = 3.773, instrumental delivery: OR = 6.028) and to the newborn (male gender: OR = 1.982, birth length: OR = 1.196). The initial plagiocephaly or torticollis improved in 77% of infants after 2 months of stimulation and positioning measures. Paediatricians should be alert regarding the frequent but subtle MBS postural deformities and give positioning advice to the parents. A neonate of male gender or greater birth length, with an older primiparous mother, a history of preterm labour, oligoamnios or pregnancy toxaemia, a breech presentation or an assisted delivery is more likely to have MBS.     

Ionized magnesium and gestational age

Objective Investigation of magnesium (Mg) homeostasis has re-emerged as an area of interest in preterm born neonates who are at risk for brain pathology. However, data regarding the association between the biologically active ionized form of Mg and gestational age (GA) at an early stage of life in newborn infants are controversial. Methods We evaluated the total and ionized Mg electrolyte (TMg and IMg) as well as the calcium (TCa and ICa) and pH in the cord blood and on day 2 of life in 22 neonates born at different gestational ages (<32, 32–34, and ≥35 week) without magnesium tocolysis and absence of serious complications during pregnancy and delivery. Results The IMg fraction that accounted for 68.1+/−5.1% of the TMg in the cord blood and 67.9+/−4.5% of the TMg on day 2 of life, was significantly higher in very preterm infants (GA<32 week) as compared to neonates with GA ≥35 week. Higher IMg levels were correlated with the lower pH that was recorded in the cord blood of the very preterm infants (correlation coefficient, r=−0.80, p<0.0001) and ICa (r = −0.52, P<0.01). Lower pH also was correlated with the GA (P<0.0001). However, standard multiple regression analysis showed significant association between IMg levels and decreased pH but not the gestational age or ICa (beta=−1.10+/−0.21, p<0.00009). Conclusion Extremely preterm infants even without additional exposure to tocolytic magnesium are at risk for the lower pH associated elevation of ionized Mg, which should be considered during the management of these infants in order to prevent hypermagnesemia-related pathology.     

Abnormal umbilical artery Doppler waveforms and cord blood inhibin a and inhibin B levels

Inhibin A and inhibin B are glycoprotein hormones produced by human placenta and by several fetal organs during pregnancy. They are secreted in maternal circulation in increasing amounts from early until term pregnancy, and in umbilical cord blood levels are significantly lower than in maternal serum and do not differ from mid-pregnancy to term gestation. In the present study, we aimed to determine whether secretion of inhibin A and inhibin B into the fetal circulation is increased in pregnancies complicated by umbilical-placental vascular insufficiency. A group of women (n = 13) with abnormal Doppler umbilical artery flow velocimetry and a group of control women (n = 11) with uncomplicated term pregnancies and normal umbilical artery flow velocity waveforms were studied. In each woman, inhibin A and inhibin B concentrations were estimated in umbilical cord artery and vein. In the two groups of women, mean inhibin A levels did not differ between umbilical cord artery and vein. In addition, no difference was retrieved both in umbilical cord artery and vein values between healthy controls and patients with abnormal Doppler umbilical artery flow velocimetry. On the contrary, inhibin B levels were significantly higher in samples from umbilical cord vein than artery, in both groups of pregnant women (both p < 0.001). However, women with abnormal Doppler umbilical artery flow velocimetry had inhibin B levels significantly higher than healthy controls (p = 0.005) only in the umbilical cord artery, but not in the vein. In the presence of abnormal Doppler umbilical artery flow velocity, the concentrations of inhibin B are increased in the arterial umbilical circulation, suggesting that inhibin B is released from multiple fetal sources as a response to hypoxemic stress. As inhibins may affect the hypothalamus-pituitary-adrenal axis which plays an important role in the mechanisms of adaptations to the post-natal life, inhibin B in fetal circulation might then be beneficial to a fetus whose intrauterine survival is threatened by impaired umbilical-placental blood flow.     

Influence of open testicular biopsy in prepubertal rats on rats' adulthood fertility with correlation to serum levels of inhibin B and follicle stimulating hormone

ObjectiveOpen testicular biopsy (OTB) is one of the options to accurately assess fertility potential of the undescended testis. The aim of the study was to investigate consequences of OTB in prepubertal rats on their adulthood fertility.MethodsThirty-eight prepubertal male rats were divided into three groups depending on day 20 procedure. The first group was the control group, the second sham operated and the third has left OTB. Bilateral orchiectomy was performed on day 70 to all groups, with determination of serum inhibin B and follicle stimulating hormone (FSH). Removed testes were compared according to the weight, volume, spermatogenesis, histological and apoptotic changes in both testes with differences in serum levels of inhibin B and FSH.ResultsIpsilateral testicular weight, volume, and spermatogenesis reduction with a reduction of tubular number, diameter and germinative epithelium was found in OTB group. Significant increase in apoptotic index was found in biopsied testis without compensatory hypertrophy of contralateral testis. Differences of inhibin B and FSH were not statistically significant among three groups.ConclusionOTB in prepubertal rats has detrimental effects on fertility in adulthood. It does not cause compensatory hypertrophy of the contralateral testis nor does it disturb serum levels of inhibin B and FSH.     

Cord blood thyroid‐stimulating hormone and free T4 levels in Turkish neonates: Is iodine deficiency still a continuing problem?

Background: The objectives of this study were to determine the cord blood thyroid‐stimulating hormone (TSH) and free T₄ (FT₄) levels in Turkish neonates and to determine whether these variables reveal iodine deficiency. Methods: We collected 818 cords from healthy mothers at parturition and measured levels of FT₄ and TSH. We also measured cord blood FT₄ and TSH levels in different stages of gestation and gender. We grouped the neonates according to cord serum TSH levels, either being less (Group A) or greater (Group B) than 10 mIU/L. Group A included 589 neonates (300 girls [51%] and 289 boys [49%]) and Group B included 229 neonates (105 girls [45%] and 124 boys [55%]). Results: The percentage of subjects with cord blood TSH < 10 mIU/L and >10 mIU/L was 72% and 28%, respectively. Although cord TSH levels in Group B were greater than those in Group A (P < 0.001), cord blood FT₄ levels in Group B were lower than those in Group A (P < 0.05). There was no difference between both sex in terms of birthweight and maternal age. TSH and FT₄ levels did not vary according to neonate sex during gestation, except for from week 37 to 41. TSH levels of male neonates at the 41st week of gestation were higher than those of female neonates (P < 0.05). There were no effects of birthweight on TSH and FT₄ levels if the neonate was lighter than 2500 g at birth. TSH levels of male neonates were higher than those of female neonates when their birthweights were <2500 g (P < 0.05). There was no significant difference in TSH levels according to birthweights in male neonates. Conclusion: Our data provide the normative data for cord blood TSH and FT₄ levels in Turkish neonates and show that iodine deficiency is a still a public health problem in Turkey. These measurements can be useful for detection and verification of hypothyroidism in a screening program for congenital hypothyroidism as well as evaluation of the success of the iodination program.     

Elevated platelet activating factor in the tracheal aspirate at birth and signs of intra-uterine inflammation in infants with neonatal pulmonary emphysema

To investigate the pathophysiology of the neonatal pulmonary emphysema, we assayed platelet activating factor (PAF) in the tracheal aspirates of the low birth weight infants. A total of 29 neonates (birth weight <1750 g) who required mechanical ventilation were enrolled. Tracheal aspirates were obtained within 48 h and blood samples collected within 24 h of life. PAF was assayed on the basis of its ability to cause aggregation of washed rabbit platelets. PAF was significantly elevated in four infants who showed pulmonary emphysema within the 1st week of life (median 24 pg/g lipid phosphorus, range 9.9–200) compared with those detected in the other three groups of infants; infants with respiratory distress syndrome (RDS) in whom chronic lung disease (CLD) did not develop (median 1.8 pg/g lipid phosphorus, range 0–30; P < 0.05), infants without RDS nor CLD (median 0.64 pg/g lipid phosphorus, range 0–14; P < 0.05) and infants with other types of CLD (median 1.1 pg/g lipid phosphorus, range 0–1.8; P < 0.01). The four infants who developed pulmonary emphysema within the 1st week of life, had significantly elevated serum IgM and neutrophilia at birth. The increased amount of PAF in the tracheal aspirates shows the presence of inflammation in the lung at birth. The elevated serum IgM level and neutrophilia indicate that the inflammation begins in utero. Conclusion Our data suggest that neonatal pulmonary emphysema is caused by intra-uterine inflammation increasing platelet activating factor in the lungs. Platelet activating factor may play a role in aggravating the process of pulmonary emphysema. Received: 20 July 1998 / Accepted: 14 February 1999     

Renal injury in perinatal hypoxia: ultrasonography and changes in renal function

 We studied 12 hypoxaemic neonates (5 mature newborns, birth weight 2850–4200 g, gestational age 37–41 weeks; and 7 premature newborns, birth weight 770–1850 g, gestational age 27–34 weeks;) with repeated urine and blood chemistry on the 1st and 3rd days of life. Nephrosonographical examinations on the 1st, 3rd and 5–7th days of life were also performed. As controls, 12 healthy infants were examined (gestational age 36–42 weeks; birth weight 2450–4200 g). Hypoxic neonates had higher serum creatinine and blood urea nitrogen levels. Tubular markers also demonstrated renal tubular damage. Neonates in both hypoxic groups were hyperuricaemic and hyperuricosuric, and had higher urinary protein concentrations. All these infants exhibited an increased echogenicity of the renal cortex, and 11/12 showed the same finding in the medullary area. These findings disappeared within 1 week in all infants. Among the 12 healthy control infants, no cortical hyperechogenicity was found and only three of these infants displayed transient medullary renal hyperechogenicity. Conclusion Since the hypoxaemic infants demonstrated greatly increased urinary concentrations of uric acid and protein, we suggest that a temporary precipitation of these two agents may be responsible for the ultrasonographic findings. Circulatory redistribution might play a role in the phenomenon of cortical hyperechogenicity. Received: 23 March 2000 / Accepted: 14 March 2001     

Plasma RANTES increase during the first month of life independently of the feeding mode

The chemokine RANTES (regulated upon activation, normal T cell expressed and secreted) plays a significant role in the innate immunity, which is particularly important in the neonatal period. In this study, we aimed to investigate the ability of the neonate to increase plasma levels of RANTES in the first month of life, and the possible impact of breast feeding on this ability. The study population consisted of 125 healthy term neonates that were exclusively breast-fed (n = 62) or formula-fed (n = 63) for at least 1 month after birth. Plasma RANTES concentrations (ELISA) as well as circulating leukocytes and platelets were measured on days 1 and 30 of life. Median RANTES concentrations of the total group showed a significant increase between day 1 [1000 (448–2100) pg/mL] and day 30 [3688 (1488–5400) pg/mL, p < 0.0001], as did median total lymphocyte, T-cell, B-cell, NK-cell and eosinophil counts (all p values <0.0001). Monocyte and platelet counts did not change significantly over the neonatal period. Further analysis according to the mode of feeding showed that RANTES levels as well as leukocyte populations and platelet counts did not differ significantly between breast-fed and formula-fed neonates on either day 1 or 30. Healthy term neonates are capable of increasing plasma RANTES levels during the 1st month after birth independently of the mode of feeding.     

Prophylactic ibuprofen therapy of patent ductus arteriosus in preterm infants

This study was aimed at evaluating the efficacy of ibuprofen in the prophylaxis of patent ductus arteriosus (PDA) in very preterm neonates and at detecting eventual side-effects. A total of 46 preterm neonates with gestational age under 31 weeks were randomly assigned at 2 h of life: 23 to the prophylaxis group and 23 to the control group. The prophylaxis group received intravenous treatment with ibuprofen lysine (10 mg/kg), followed by 5 mg/kg after 24 h and 48 h. No placebo was given to the control group. No PDA was demonstrated at 72 h of life in 20 of the 23 babies in the ibuprofen group (87%) nor in 7 of the 23 control neonates (30.4%). All neonates with PDA received treatment with indomethacin. One neonate in the prophylaxis group and three in the control group underwent surgical ligation. Prophylaxis with ibuprofen was not associated with any significant side-effect except for food intolerance. Conclusion Ibuprofen prophylaxis seems to be efficient in closing patent ductus arteriosus and in reducing indomethacin treatment. No significant early side-effects were found due to ibuprofen. Received: 1 April 1999 / Accepted: 30 November 1999     

Perinatal stress influences lymphocyte subset counts in neonates. The generation R study

In the general population, it is unknown whether stress-related perinatal factors influence lymphocyte subset counts in neonates. The aim of this study was to assess the associations of perinatal factors related to stress and hypoxia (mode of delivery, Apgar scores, and umbilical cord blood pH) with absolute lymphocyte subset counts (T, B, NK, helper T, cytotoxic T, na?ve, memory T) in cord blood of 571 neonates. This study was embedded in a population-based prospective cohort study from fetal life onwards. All models were adjusted for gestational age, birth weight, gender, maternal fever, and each of the other perinatal stress-relating factors. Our results showed that increasing stress-related mode of delivery was positively associated with NK and memory T-lymphocyte subset counts (all p < 0.01). Effects of Apgar scores on lymphocyte subsets were explained by umbilical cord blood pH. Lower umbilical cord blood pH was associated with higher B, NK, and memory T-lymphocyte counts (all p < 0.05). Effects of mode of delivery and umbilical cord blood pH on other lymphocyte subsets were not observed. We conclude that, in the general population, lymphocyte subset counts in neonates increase with increasing stress- and hypoxia-related perinatal factors.     

Decreased serum inhibin B/FSH ratio as a marker of Sertoli cell function in male survivors after chemotherapy in childhood and adolescence

OBJECTIVE: Inhibin B produced by Sertoli cells may be an important marker of seminiferous tubule function in patients treated with chemotherapy (CT). The aim of this study was to evaluate the inhibin B/FSH ratio to detect male gonadal dysfunction in cancer survivors treated in childhood and adolescence. PATIENTS: Twenty-one male patients (group A) treated with 6-10 courses of CT for Hodgkin's disease during childhood and adolescence were examined 3-11 years after the conclusion of treatment. Twenty healthy young men (18-23 years old) were used as controls (group B). METHODS: Serum samples for the determination of inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), sex hormone-binding globulin (SHBG) and semen for analysis were collected. RESULTS: The median testicular volume of patients of group A was lower than those of group B (p = 0.001) and a positive correlation was found between testicular size and sperm count (r = -0.5, p = 0.01). Semen analysis revealed azoospermia in 11 patients, severe oligospermia in four and normal sperm count in three. No significant difference was found in the median of T, LH, SHBG, inhibin B concentrations and T/LH ratio between the groups. Serum inhibin B was correlated with the serum FSH levels (r = -0.5, p = 0.02). Median FSH was significantly higher (p = 0.0001), and median inhibin B/FSH ratio was significantly lower in group A than in controls (p = 0.0002), but the inhibin B/FSH ratio was higher in the patients with normal sperm count than in those with oligospermia (p = 0.00004). CONCLUSIONS: These results show that the cytotoxic effects of CT cause severe damage to the germinal epithelium with subtle effects on Sertoli cells. To assess Sertoli cell function in men with primary testicular damage after treatment with CT in childhood and adolescence, the inhibin B level needs to be interpreted in the context of the circulating FSH, especially when normal FSH levels are observed.     

The effectiveness of single and multiple applications of triple dye on umbilical cord separation time

The effectiveness of single and multiple applications of triple dye for umbilical cord care in the umbilical cord separation time (UCST) was evaluated in 180 neonates. Seven neonates were excluded, three where the cord stump separation time was uncertain and four to whom contact was lost. The participating neonates were randomly assigned to two groups. Group 1, 101 neonates, were treated with a regimen of a single application of triple dye. Group 2, 79 neonates, were treated with multiple applications of triple dye. Complete information was obtained from 97 neonates (96.2%) in group 1 and 76 (96%) in group 2. The UCST was 12.6 ± 0.45 (mean ± SE) days in group 1 and 16.68 ± 0.65 days in group 2 (P < 0.0001) and showed no significant association with infants' gender, mode of delivery, gravidity, gestational age, birth weight, or hospital stay. Conclusion A single application of triple dye may be a more favourable regimen with a similarly antimicrobial effect, a shorter UCST and may be more cost effective than multiple applications of triple dye in umbilical cord care. Received: 4 September 1997 / Accepted in revised form: 8 April 1998     

Severe neonatal hypercalcemia caused by subcutaneous fat necrosis without any apparent cutaneous lesion

Subcutaneous fat necrosis is a classic, albeit uncommon, cause of neonatal hypercalcemia. It occurs in newborn infants within the first month of life following a complicated delivery. The diagnosis is usually easy because of the presence of red-purple plaques in fatty areas along with firm subcutaneous nodules. A 1-month-old neonate, born strangled by her umbilical cord, presented with diarrhea and hypercalcemia (3.46 mM) with an initial physical examination considered normal. Her biological evaluations were as follows: P = 1.37 mM (1.6–2.2); PTH = 3 ng/L (12–65); 25-OH vitamin D = 87 nM (23–113); (1,25)-OH₂ vitamin D = 192 ng/L (20–46). The third day, a careful exam of the whole cutaneous surface revealed small firm subcutaneous nodules in the ischial region. Despite the absence of any visible skin modification, the association of perinatal stress and high (1,25)-OH₂ vitamin D level with subcutaneous nodules led to the diagnosis of subcutaneous fat necrosis. She was treated with oral prednisone for 45 days. Serum calcium levels normalized within a week, and the nodules disappeared without complications. Conclusion: Subcutaneous fat necrosis may induce severe hypercalcemia without any visible cutaneous lesion. No funding or grant was received for this study.