[Immunopsychiatry and SARS-CoV-2 pandemic: Links and possible consequences]. / Immuno-psychiatrie et pandémie de SARS-CoV-2 : liens et possibles conséquences.

OBJECTIVE: The SARS-CoV-2 (or COVID-19) pandemic has been propagating since December 2019, inducing a drastic increase in the prevalence of anxious and depressive disorders in the general population. Psychological trauma can partly explain these disorders. However, since psychiatric disorders also have an immuno-inflammatory component, the direct effects of the virus on the host's immune system, with a marked inflammatory response, but also the secondary inflammation to these psychosocial stressors, may cause the apparition or the worsening of psychiatric disorders. We describe here the probable immunopsychiatric consequences of the SARS-CoV-2 pandemic, to delineate possible screening actions and care that could be planned. METHOD: Data from previous pandemics, and existing data on the psychopathological consequences of the SARS-CoV-2 pandemic, allowed us to review the possible immunopsychiatric consequences of the SARS-CoV-2 pandemic, on the gestational environment, with the risk of consecutive neurodevelopmental disorders for the fetus on one hand, on the children and adults directly infected being at increased risks of psychiatric disorders on the other hand. RESULTS: As in previous pandemics, the activation of the immune system due to psychological stress and/or to infection during pregnancy, might lead to an increased risk of neurodevelopmental disorders for the fetus (schizophrenia and autism spectrum disorders). Furthermore, in individuals exposed to psychological trauma and/or infected by the virus, the risk of psychiatric disorders, especially mood disorders, is probably increased. CONCLUSION: In this context, preventive measures and specialized care are necessary. Thus, it is important to propose a close follow-up to the individuals who have been infected by the virus, in order to set up the earliest care possible. Likewise, in pregnant women, screening of mood disorders during the pregnancy or the postpartum period must be facilitated. The follow-up of the babies born during the pandemic must be strengthened to screen and care for possible neurodevelopmental disorders.

Hormone ontogeny in the ovine fetus and neonate. XXII. The effect of somatostatin on the growth hormone (GH) response to GH-releasing factor.

We postulated that an increase in the biological effectiveness of somatostatin (SRIF) accounts, at least in part, for the decrease in basal and GRF-induced ovine GH (oGH) secretion observed around birth in the ovine fetus and neonate. To test this hypothesis, SRIF (SRIF-14; given as 30 micrograms/kg iv bolus, followed by 2 micrograms/kg.min for 75 min) was infused into chronically catheterized fetal and neonatal lambs, and the oGH response induced by GRF [GRF-(1-44) amide; 1 microgram/kg] in the presence of exogenous SRIF was compared to the oGH response induced by GRF in saline-infused controls. In fetuses of 115-122 days gestation, SRIF had no detectable effect on the oGH response to GRF [peak incremental oGH response (mean +/- SEM), 527 +/- 124 vs. 562 +/- 103 ng/ml in controls]. In neonatal lambs (3-17 days old), SRIF completely suppressed the immediate oGH response to GRF (peak incremental response, 0.8 +/- 1.3 vs. 111 +/- 34 ng/ml in controls; P less than 0.02). In late gestational fetuses (126-139 days old), a transitional pattern was observed (peak incremental oGH response, 207 +/- 56 vs. 324 +/- 30 ng/ml in controls; P less than 0.04). In the second part of this study, we explored, in the neonatal lamb, the hypothesis that SRIF withdrawal plays a role in pulsatile GH secretion and that the amount of GRF to which the somatotrope is exposed before SRIF withdrawal is a major factor in determining the amplitude of GH bursts. SRIF (SRIF-14; a 30 micrograms/kg bolus, followed by 2 micrograms/kg.min) was infused iv for 40 min, GRF [GRF-(1-44) amide; 1 microgram/kg] was injected iv 20 min after starting the SRIF infusion, and the oGH rise after SRIF withdrawal was evaluated. In one series of controls GRF was replaced by saline, and in the other SRIF was replaced by saline. The oGH rise during recovery after SRIF alone was lower than that after the combined administration of SRIF and GRF (peak oGH increment, 8 +/- 3 vs. 38 +/- 12 ng/ml; P less than 0.04). The amplitude of the GH pulse after SRIF and GRF was similar to the immediate oGH response to GRF alone. These studies show that SRIF is unable to suppress the immediate oGH response to GRF in the ovine fetus, and that the suppressive effect of SRIF on the immediate oGH response to GRF increases gradually in late gestation and sharply at birth.(ABSTRACT TRUNCATED AT 400 WORDS)

Hormone ontogeny in the ovine fetus and neonatal lamb. XX. Effect of age, breeding season, and twinning on the growth hormone (GH) response to GH-releasing factor: evidence for a homeostatic role of fetal GH.

The ovine GH (oGH) response to GRF (1-44 amide) was evaluated in 74 chronically catheterized fetal and neonatal lambs. After a 1-h control period, GRF was administered iv, and the oGH response was studied during the next 60 min. The following variables were analyzed: GRF dose, fetal or neonatal age, breeding season, and singleton or multiple pregnancy. One and 10 micrograms/kg GRF elicited a similar oGH response, which was greater (P less than 0.001) than the response to 0.1 microgram/kg GRF. GRF-stimulated oGH release was strikingly age dependent. The mean peak incremental oGH response in fetuses of 89-122 days gestation (294 +/- 55 ng/ml) was higher (P less than 0.05) than that in fetuses of 127-145 days gestation (136 +/- 19 ng/ml); the fetal response was much greater (P less than 0.005) than the mean peak increment in neonatal lambs (46 +/- 7 ng/ml). A remarkable difference in basal and GRF-induced oGH secretion was observed in both fetuses and lambs of ewes bred in the normal breeding season (on-season) and those bred out of season (off-season). In the neonatal lamb, the mean basal oGH concentration was higher (P less than 0.005) in the on-season (12 +/- 2 ng/ml) than in the off-season (7 +/- 0.5 ng/ml) neonatal lambs, as was the mean peak incremental oGH response to GRF (70 +/- 12 vs. 33 +/- 7 ng/ml; P less than 0.01). In contrast, in singleton, late gestational fetuses (127-145 days), the mean basal oGH concentration was lower (P less than 0.03) in the on-season (74 +/- 9 ng/ml) than in the off-season (124 +/- 18 ng/ml) fetuses, as was the mean peak incremental oGH response to GRF (136 +/- 9 vs. 292 +/- 41 ng/ml; P less than 0.005). Further, compared to the on-season, late gestational singletons, on-season twin fetuses had higher (P less than 0.0001) basal oGH levels (199 +/- 19 ng/ml) and peak incremental oGH responses (248 +/- 11 ng/ml). Moreover, off-season twin fetuses had the highest basal GH concentrations and the most striking increment in GH concentration after GRF treatment of any of the groups. The strikingly age-dependent pattern of the GRF-induced oGH response in fetal and neonatal lambs is compatible with the concept that the inhibitory influences or their effects on the somatotrope increase gradually during late gestation and sharply at birth.(ABSTRACT TRUNCATED AT 400 WORDS)

Role of surgical resection in the treatment of hypothalamic hamartomas causing precocious puberty. Report of six cases.

Hypothalamic hamartomas (HHs) are benign tumors that are often associated with central precocious puberty. Resection of HHs has been recommended as a treatment option for selected cases of pedunculated lesions, especially in young children. The role of surgery has to be evaluated in the light of the availability of effective medical treatment with gonadotropin-releasing hormone analogs (GnRHas). The authors report the long-term results of total resection of HHs in two children with central precocious puberty and compare it with medical management in four children. The two surgically treated patients underwent total resection of pedunculated HHs at 1.75 (Case 1) and 3.25 years (Case 2) and have received follow-up care for 9 and 8 years, respectively. There were no postoperative complications and computerized tomography scanning confirmed complete tumor removal in both patients. Both patients subsequently experienced some regression of secondary sexual characteristics. The response of luteinizing hormone to GnRH became prepubertal in one patient and was diminished in the other. However, the growth velocity remained elevated (> 7 cm/year), bone age remained advanced (> +2 standard deviations) 5 years after surgery, decreasing adult height prediction. In one child, GnRHa therapy was initiated 7 years postsurgery. Four children were treated solely with GnRH agonists and have received follow-up care for 2.3, 6, 9, and 9 years, respectively. These patients have had a complete regression of endocrinological abnormalities, including a normalization of growth velocity and reduction in the rate of skeletal maturation. No side effects were noted with decapeptyl treatment, and one child developed sterile abscesses while receiving Lupron-Depot. The proven efficacy of GnRHa in suppressing puberty and reducing bone age advancement leads the authors to advise against surgery as the initial management of central precocious puberty caused by HHs.

Transient neonatal diabetes mellitus and macroglossia.

Transient neonatal diabetes mellitus is an uncommon disorder. Macroglossia in association with transient neonatal diabetes mellitus has been reported only twice before. We report the case of a 21-day-old male infant referred from a peripheral hospital for management of hyperglycemia. The mother was a 21-year-old primigravid in good health. There was no history of diabetes or drug or alcohol exposure. The pregnancy was complicated by intrauterine growth retardation and oligohydramnios from 30 weeks' gestation and the birth weight at 38 weeks' gestation was only 1480 gm. Physical examination revealed dysmorphic features and asymmetric growth retardation. The admission weight (1840 gm) and length (40.5 cm) were 5 SDs less than the mean and head circumference (32.5 cm) was 1 SD less than the mean. Dysmorphic features included macroglossia, large fontanelles, hypospadias, umbilical hernia, and bilateral inguinal hernias. Hyperglycemia had been noted on day 1 of life with an initial blood glucose value of 16 mmol/L (288 mg/dl). Despite treatment with regular insulin blood glucose control continued to be erratic. Therefore a regimen of daily NPH insulin was begun, which has a smoother action. Interestingly, from day 41 to day 47 the infant did not receive insulin and a crude control of the blood glucose was demonstrated. Peak levels of blood glucose in excess of 20 mmol/L (360 mg/dl) were followed by drops to levels less than 2 mmol/L (36 mg/dl) without insulin administration. This abnormal pattern of glucose control may represent poorly regulated release of endogenous insulin. However, because of unsatisfactory glucose levels administration of daily NPH insulin was reintroduced. The infant was discharged from the hospital on day 50 and administration of insulin was discontinued uneventfully at 9 months. At 1 year the hemoglobin A1c level was still normal and the infant's weight was at the 10th percentile. Macroglossia was less pronounced. Development showed mild delay in gross motor milestones.

Vitamin D deficiency in pregnant and breast-feeding women and their infants.

We describe the cases of five consecutive infants with symptomatic vitamin D deficiency and their mothers. Four of the infants were light skinned, all had poor sunlight exposure, and all were breast-fed or had diets low in vitamin D. All mothers had vitamin D deficiency. Regardless of race, infants with poor sunlight exposure and diets lacking in vitamin D are at risk for vitamin D deficiency. Mothers of these infants should be evaluated for vitamin D deficiency. Vitamin D supplementation of the breast-feeding mother at risk and her infant is recommended.

Ethics and the management of the patient with intersex: a middle way.

We review the controversies surrounding the management of patients born with ambiguous genitalia to determine the strengths and weaknesses of recommendations for clinical practice. Traditional practice involves paternalistic decision making by medical practitioners, including the use of deception and/or incomplete communication of facts about the infant's condition and early surgical intervention to make a "definitive" sex and gender assignment. However, modern scientific evidence about sex-role determination refutes earlier theories supporting the appropriateness and need for early decisions. Some intersex individuals have begun to speak out against their treatment, denouncing the secretive approaches and cosmetic surgery without the specific consent of the (mature) affected individuals. They argue for complete disclosure of information regarding the condition and deferral of all surgery until at least adolescence. The traditionalist practices no longer conform to modern legal or ethical standards of care. The position of some intersex activists ignores the potential for psychosocial harm to intersex children and our society's general and strong deference to parental discretion in decisions for and about their children. We argue for a middle way, involving shared decision making with parents of children with intersex and the honoring of parental preferences for or against surgery.

Abnormalities of water metabolism after surgery for optic/chiasmatic astrocytomas in children.

A major concern during the early postoperative period after surgical resection of optic chiasmatic gliomas is the derangement of sodium and water metabolism which may add to the morbidity of the procedure. The purpose of this study was to characterize the abnormalities of water and sodium metabolism in children with optic chiasmatic gliomas treated surgically at British Columbia's Children's Hospital and to identify therapeutic modalities which might prevent or ameliorate the development of these complications. A retrospective chart review of children with optic/chiasmatic gliomas undergoing operations on the tumor was performed and the pre- and postoperative radiographs reviewed by an independent neuroradiologist. There were 11 patients who underwent 13 operations for either resection (n = 9) or biopsy (n = 4) of their optic chiasm tumor. The extent of resection in patients undergoing more than simple biopsy ranged from 83 to 99%, and all patients with resection had exophytic tumor extending into the hypothalamus. Postoperative syndrome of inappropriate antidiuretic hormone secretion (SIADH) and/or diabetes insipidus occurred after 8 of the 9 tumor resections and was associated with significant morbidity. No disturbance of water metabolism occurred after biopsy only. In patients with SIADH, the urinary sodium level rose markedly 6-12 h prior to the development of hyponatremia, and it was concluded that this was a valuable predictor of impending hyponatremia. Replacement of urine output was noted to be the most reliable way to avoid rapid fluctuations in serum sodium and to avoid the morbidity of diabetes insipidus or SIADH and is recommended in the postsurgical patients who cannot regulate fluid intake.

The management of type 2 diabetes in children and adolescents.

The medical community faces an emerging epidemic of type 2 diabetes (T2DM) in children and adolescents with a disproportionate increase among certain ethnic groups. T2DM represents one arm of the metabolic syndrome and parallels an increasing prevalence of obesity. The metabolic syndrome includes insulin resistance, hyperlipidemia, and hypertension with a consequent risk of early cardiovascular disease. Thus, treatment of T2DM and the metabolic syndrome pose a challenge for pediatric endocrinologists and represent an enormous public health issue. This review presents information about the treatment of childhood T2DM.

Neonatal hypoglycemia caused by hypopituitarism in infants with congenital syphilis.

Two infants with congenital syphilis and persistent hypoglycemia were found to have hypopituitarism. Hypopituitarism should be recognized as a potential complication of congenital syphilis; affected infants with persistent hypoglycemia should receive a prompt evaluation of pituitary function.

[The relation of the short radial extensor muscle of the wrist with the deep branch division of the radial nerve. Its significance in the physiopathology of elbow pain]. / Les rapports du muscle court extenseur radial du carpe avec la branche de division profonde du nerf radial. Intérêt dans la physiopathologie des épicondylalgies.

Since Roles and Maudsley's publication, in 1972, it has been admitted that the entrapment of the posterior interosseous nerve (PION) is a possible cause of lateral elbow pain. In the radial tunnel, at least 4 or 5 compressive structures have been described. The arcade of Frohse is a well known compressive cause while the medial edge of the extensor radialis brevis (ECRB) muscle is less frequently incriminated. An anatomic study of 45 supper limbs from 40 cadavers was performed to analyse the relations between the medial edge of the ECRB and the PION. The medial edge of the ECRB was a real fibrous arch in 43 cases (95%). It crossed over the PION in 42 cases, 9 mm more proximally than the arcade of Frohse. So the relationships between the ECRB and PION are very close in 93% of cases. The proximal edge of the supinator muscle was fibrous in 40% of cases but always supple. These findings suggest that the ECRB is a possible cause of PION entrapment. Its role is underestimated in pathology. The frequent association between lateral epicondylitis and PION compression can be explained by the presence of this fibrous structure. Lateral elbow pain must be considered as a regional pathology. The treatment has to deal with every pathological aspect.

Association of autoimmunity with IgG2 and IgG4 subclass deficiency in a growth hormone-deficient child.

An association between humoral immune deficiency and childhood autoimmune disease has been previously established. We describe a 7-year-old male with severe autoimmune disease, recurrent infections, a marked deficiency of IgG2 and IgG4, and an inability to respond to polysaccharide antigens. This child was also found to have isolated growth hormone (GH) deficiency. Laboratory results included a positive anti-smooth muscle antibody, a positive Raji-cell assay for immune complexes, and normal levels of IgG, IgM, and IgA. IgG subclasses revealed an IgG1 of 1225 (normal for age, 280-1120 mg/dl), IgG2 of less than 10 (30-630 mg/dl), IgG3 of 36 (40-250 mg/dl), and IgG4 of less than 4 (11-620 mg/dl). No increase in antibody titer was noted to either Pneumovax or unconjugated Haemophilus influenzae vaccine. Numbers of circulating B cells (CD19) were markedly diminished (less than 0.5%). Liver biopsies have shown chronic active hepatitis. Somatomedin C was 0.28 U/ml (normal for age, 0.5-2.06 U/ml). Challenge with either L-dopa or clonidine produced a peak GH response of 2.3 ng/ml (normals = greater than 7 ng/ml). Children with autoimmune disorders should be evaluated for IgG subclass deficiencies and ability to make antibody in response to antigen challenge regardless of the serum immunoglobulin levels. Growth failure in immune-deficient children should not be assumed to be due to chronic illness or recurrent infections. Other etiologies for growth failure should be sought.

Growth and growth factors in premature infants receiving dexamethasone for bronchopulmonary dysplasia.

Physical growth and the serum growth factors, insulin growth factor 1 (IGF1) and its binding protein (IGFBP3) were measured weekly during dexamethasone treatment and for 3 weeks after stopping therapy in 10 ventilated babies [median (range) birth weight 860 g (640-1210); median (range) gestational age 26 weeks (24-29)] with bronchopulmonary dysplasia (BPD). The mean (+/- SE) rates of change of all physical measures except crown-rump length (CRL) increased significantly after stopping dexamethasone: weight gain 13.2 (+/- 1.5) on versus 1.0 (+/- 1.9) g/day off treatment; occipital-frontal circumference 0.7 (+/- 0.1) cm/week; CRL 0.5 (+/- 0.1) versus 0.7 (+/- 0.1) (TBL) 0.7 (+/- 0.1) versus 1.1 (+/- 0.1) cm/week; CRL 0.5 (+/- 0.1) versus 0.7 (+/- 0.1) cm/week, and knee-ankle length (KAL) 0.13 (+/- 0.02) versus 0.36 (+/- 0.04) cm/week. Mean serum IGF-1 (1.57 +/- 0.13 versus 3.56 +/- 0.41 nmol/L) and IGFBP3 (0.94 +/- 0.03 versus 1.12 +/- 0.05 mg/L) levels also increased off treatment. The weekly dose of dexamethasone (mg/kg) was significantly negatively correlated with all physical growth measures (P < 0.01), but showed no correlation with growth factors. Protein intake (g/kg/day) was significantly correlated (P < 0.01) with weight gain (r = 0.28), changes (TBL) (r = 0.32), serum IGF1 levels (r = 0.60), and IGFBP3 levels (r = 0.37). All aspects of physical growth are compromised during dexamethasone treatment for BPD. Poor growth during steroid treatment is associated with lower IGF1 and IGFBP3 levels. Further study is needed to examine the effect of varying dexamethasone dosage regimes and nutritional intake on the growth process in BPD.

Adrenal suppression in children with the human immunodeficiency virus treated with megestrol acetate.

Symptoms and laboratory evidence of adrenal suppression developed in 2 children with the human immunodeficiency virus after megestrol acetate (MA) therapy was discontinued; both required transient glucocorticoid replacement therapy. High-dose corticotropin stimulation testing performed on children with the human immunodeficiency virus treated or not treated with MA showed that baseline and post-corticotropin cortisol levels were extremely low in 7 of 10 treated patients and normal in 10 of 10 members of a control group (P <.01). MA may suppress adrenal function, and replacement glucocorticoids may prevent or relieve associated symptoms at times of severe stress or on discontinuation of MA therapy.