Serum osteocalcin levels in hyperthyroidism before and after antithyroid therapy

Hyperthyroidism is characterized by accelerated bone turnover, caused from direct stimulation of bone cells by increased thyroid hormones. In this study, we aimed to investigate serum osteocalcin levels as a bone formation marker, before antithyroid (propylthiouracil) therapy at hyperthyroid stage and after antithyroid therapy at euthyroid stage of the patients. Twenty four hyperthyroid patients (18 females, 6 males) and 20 (13 females, 7 males) healthy controls were included into this study. Blood and urine samples were taken before medical treatment at hyperthyroid state, and after the antithyroid therapy until the patients reached the euthyroid state. Serum alkaline phosphatase, osteocalcin, calcium, phosphorus, Free T3, Free T4, TSH and urine calcium/creatinine levels were assessed. We found a significant decrease in serum osteocalcin (p=0.006), urinary calcium/creatinine (p=0.004), and serum phosphorus (p=0.038) levels in euthyroid state in comparison to hyperthyroid state. The increases in serum bone formation marker osteocalcin and bone resorption marker urinary calcium/creatinine levels in hyperthyroid state compared to euthyroid state in our study confirmed that hyperthyroid patients have high bone turnover. We conclude that, hyperthyroid patients has high bone turnover of formation and resorption even after attainment of euthyroidism. Osteocalcin and urine calcium/creatinine are sensitive markers in documenting bone remodeling during treatment of hyperthyroidism.     

Similar antibody concentrations in Filipino infants at age 9 months, after 1 or 3 doses of an adjuvanted, 11-valent pneumococcal diphtheria/tetanus-conjugated vaccine: a randomized controlled trial

In Filipino infants, 1 dose of an adjuvanted, 11-valent pneumococcal conjugate vaccine (serotypes 1, 4, 5, 7F, 9V, 19F, and 23F conjugated to tetanus protein; and serotypes 3, 6B, 14, and 18C conjugated to diphtheria toxoid) administered alone at age 18 weeks (11PncTD1) elicited similar antibody concentrations at age 9 months as those elicited by 3 doses (11PncTD3) administered concomitantly with national program vaccines, at ages 6, 10, and 14 weeks. Geometric mean antibody concentrations ranged from 0.36 microg/mL (for serotype 18C) to 5.81 microg/mL (for serotype 4), for the 11PncTD1 vaccine, and from 0.32 microg/mL (for serotype 18C) to 5.01 microg/mL (for serotype 19F), for the 11PncTD3 vaccine. The proportion of infants with threshold antibody concentrations > or =0.35 microg/mL was also similar (ranges, 55.6%-100% for the 11PncTD1 vaccine and 42.9%-100% for the 11PncTD3 vaccine). The functional activity of antibodies expressed as opsonophagocytic activity titers was similar in the 11PncTD1 and 11PncTD3 groups. This finding is an important one for countries with financial constraints and high pneumococcal disease burden.     

Inhibins in childhood and puberty

Inhibin is a heterodimeric glycoprotein that consists of an alpha-subunit linked to either a betaA subunit (inhibin A) or to a betaB subunit (inhibin B) and it exists in at least six different isoforms. These isoforms can not be measured separately by immunoassays. In boys, serum inhibin B levels change in concert with the increase in gonadotrophins. Associated with the postnatal activation of gonadotrophin secretion, the early inhibin B secretion is sustained until the age of 18-24 months; thereafter serum concentrations subside. In boys, between Tanner stages G1 and G2, serum inhibin B concentration again increases, but then plateaus. Inhibin A levels in human males are below the detection limit, but in girls, during the postnatal activation of gonadotrophin secretion, both serum inhibin A and inhibin B concentrations are measurable. Serum inhibin B levels correlate positively with age several years before the clinical onset of puberty, suggesting increasing follicular activity in late prepuberty. During female puberty, the inhibin B level increases from Tanner stage B1 through stage B3, suggesting high follicular activity before the development of ovulatory menstrual cycles, but serum inhibin A levels become measurable later in puberty, in agreement with the idea that inhibin A is mainly produced by the corpus luteum.     

Effects of Angiotensin-converting enzyme inhibition and statin treatment on inflammatory markers and endothelial functions in patients with longterm rheumatoid arthritis

OBJECTIVE: To investigate the effects of angiotensin-converting enzyme (ACE) inhibitors and statins (hydroxy-methyl-glutaryl-CoA reductase inhibitors) on inflammatory markers and endothelial functions in patients with rheumatoid arthritis (RA). METHODS: A total of 45 patients with longterm RA were randomized into 3 groups to receive 8 weeks of treatment with placebo (n = 15), simvastatin (20 mg/day, n = 15), or quinapril (10 mg/day, n = 15) as an adjunct to existing antirheumatic drug treatment. Factors with a role in the development of endothelial dysfunction, such as C-reactive protein (CRP), fibrinogen, nitric oxide (NO), and serum cytokine concentrations including interleukin 1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) were measured at baseline and in the posttreatment period. Brachial artery vasodilator responses were assessed by high resolution ultrasound to evaluate endothelial functions. RESULTS: Simvastatin treatment significantly decreased serum CRP and TNF-a [from 14 +/- 6 to 7 +/- 3 mg/l (p = 0.025) and 30 +/- 5 to 16 +/- 4 pg/ml (p = 0.012), respectively], while quinapril had no significant changes in these 2 measures. IL-1beta and IL-6 showed insignificant changes in patients in the 2 drug groups. Endothelium-dependent vasodilatation was improved significantly in the simvastatin group [from 5.3 +/- 1.1% to 8.9 +/- 1.4% (p = 0.025)], while there was no difference in endothelium-independent vasodilatation [9.0 +/- 1.8% to 11.2 +/- 2.5% (p = 0.17)]. The quinapril group showed no significant changes in both types of vasodilation although there was a tendency to an increase in endothelium-dependent vasodilatation [from 6.1 +/- 0.8% to 7.8 +/- 0.7% (p = 0.06)]. Treatment with the 2 drugs had no significant effects on resting arterial diameter. CONCLUSION: We show that simvastatin 20 mg daily improves endothelial function in patients with RA. Its beneficial effect may be attributed to lowering CRP and TNF-alpha concentrations. ACE inhibition with daily 10 mg quinapril was found to have no significant effects on inflammatory markers and endothelial vasodilator response.     

Clinical case review: A method to improve identification of true clinical and radiographic pneumonia in children meeting the World Health Organization definition for pneumonia

Background

In 2001, two hexavalent vaccines were licensed in Italy (Hexavac^®, Infanrix Hexa^®), and since 2002 were extensively used for primary immunization in the first year of life (at 3, 5, 11/12 months of age). In 2005, the market authorization of Hexavac^® was precautionary suspended by EMEA, because of doubts on long-term protection against hepatitis B virus. The objectives of this study were to evaluate the persistence of antibodies to anti-HBs, in children in the third year of life, and to investigate the response to a booster dose of hepatitis B vaccine.

Methods

Participant children were enrolled concomitantly with the offering of anti-polio booster dose, in the third year of life. Anti-HBs titers were determined on capillary blood samples. A booster dose of hepatitis B vaccine was administered to children with anti-HBs titers < 10 mIU/ml, with the monovalent precursor product of the previously received hexavalent vaccine. HBsAb titers were tested again one month after the booster.

Results

Sera from 113 children previously vaccinated with Hexavac^®, and from 124 vaccinated with Infanrix Hexa^® were tested for anti-HBs. Titers were ≥ 10 mIU/ml in 69% and 96% (p < 0,0001) respectively. The proportion of children with titers ≥ 100 mIU/ml did also significantly differ among groups (27% and 78%; p < 0,0001). Post-booster, 93% of children achieved titers ≥ 10 mIU/ml, with no significant difference by vaccine group.

Discussion

Fifteen months after third dose administration, a significant difference in anti-HBs titers was noted in the two vaccine groups considered. Monovalent hepatitis B vaccine administration in 3-year old children induced a proper booster response, confirming that immunologic memory persists in children with anti-HBs titers < 10 mIU/ml. However, long-term persistence of HBV protection after hexavalent vaccines administration should be further evaluated over time.     

Circulating glucocorticoid bioactivity and serum cortisol concentrations in premature infants: the influence of exogenous glucocorticoids and clinical factors

OBJECTIVE: Glucocorticoids are widely used before preterm delivery and in preterm infants may bear serious adverse effects. Better knowledge about the circulating glucocorticoid milieu after glucocorticoid treatment could improve treatment modalities. Therefore, we investigated the influence of exogenous glucocorticoids and clinical factors on serum cortisol (F) levels and circulating glucocorticoid bioactivity (GBA) in preterm infants. DESIGN: Eighty-nine infants (gestational age (GA) 23.6-33.1 weeks at birth) were enrolled in a prospective cohort study in two tertiary neonatal centres. METHODS: Cord, day of birth (D0), fourth day (D4) and 36 weeks postmenstrual age serum F and GBA levels were measured. RESULTS: The cord GBA was 5.8-fold and D0 GBA 2.3-fold higher in the infants exposed to antenatal steroids within 12 h before birth when compared with those unexposed or exposed >7 days before birth (95% CI 3.8-8.6; P<0.0001, and 1.8-3.0; P<0.0001 respectively). In the infants treated with early postnatal dexamethasone, D4 GBA was 1.7-fold (1.3-2.2; P<0.0005) higher when compared with levels in the infants without this treatment. Clinical factors indicating perinatal distress, such as Apgar scores <7 and low GA, were associated with higher cord, D0 and D4 serum F levels. CONCLUSIONS: Both ante- and postnatally administered glucocorticoids increase circulating GBA not attributable to endogenous F. Perinatal distress and preceding glucocorticoid treatment need to be taken into account when circulating glucocorticoid milieu is evaluated in preterm infants. The GBA assay may prove to be a useful instrument in the development of new glucocorticoid treatment strategies.     

Relative roles of inhibin B and sex steroids in the negative feedback regulation of follicle-stimulating hormone in men across the full spectrum of seminiferous epithelium function

CONTEXT AND OBJECTIVE: Our aim was to explore the relative roles of gonadal sex steroids and inhibin B in the regulation of FSH across a spectrum of seminiferous epithelium function. SUBJECTS: The study included three groups: group I, healthy men (n = 31); group II, men with idiopathic hypogonadotropic hypogonadism receiving pulsatile GnRH (n = 12) selected to represent a spectrum of seminiferous tubular development, testicular size, and baseline inhibin B levels; and group III, men with functional anorchia (n = 3) receiving testosterone replacement. DESIGN: Subjects were studied before and after 3 d of acute sex steroid withdrawal. SETTING: The study was conducted at the Mallinckrodt General Clinical Research Center of Massachusetts General Hospital. INTERVENTIONS: Acute biochemical castration was achieved using high-dose ketoconazole (groups I and II) or withdrawal of androgen therapy (group III). MAIN OUTCOME MEASURES: The relationship between FSH and inhibin B in both normal and castrate sex steroid milieu was measured. RESULTS: In both normal and castrate sex steroid milieus, there was a negative relationship between inhibin B and FSH, best described by a logarithmic model. Acute biochemical castration resulted in the most dramatic increases in FSH in men with the lowest baseline inhibin B levels. CONCLUSIONS: We came to the following conclusions: 1) in the human male, inhibin B is the principal gonadal feedback regulator of FSH secretion unless seminiferous tubular function is severely compromised, and a logarithmic model best describes this relationship; and 2) sex steroid inhibition of FSH secretion is most apparent when serum inhibin B levels fall well below the normal range.