Beta-blockers for the treatment of problematic hemangiomas

OBJECTIVE:

To examine treatment indications, efficacy and side effects of oral beta-blockers for the treatment of problematic hemangiomas.

METHODS:

A retrospective review of patients with hemangiomas presenting to the Alberta Children’s Hospital Vascular Birthmark Clinic (Calgary, Alberta) between 2009 and 2011 was conducted. The subset of patients treated with oral beta-blockers was further characterized, investigating indication for treatment, response to treatment, time to resolution of indication, duration of treatment, occurrence of rebound growth and side effects of therapy.

RESULTS:

Between 2009 and 2011, 311 new patients with hemangiomas were seen, of whom 105 were treated with oral beta-blockers. Forty-five patients completed beta-blocker treatment while the remainder continue to receive therapy. Indications for treatment were either functional concerns (68.6%) or disfigurement (31.4%). Functional concerns included ulceration (29.5%), periocular location with potential for visual interference (28.6%), airway interference (4.8%), PHACES syndrome (3.8%), auditory interference (0.95%) and visceral location with congestive heart failure (0.95%). The median age at beta-blocker initiation was 3.3 months; median duration of therapy was 10.6 months; and median maximal treatment dose was 1.5 mg/kg/day for propranolol and 1.6 mg/kg/day for atenolol. Ninety-nine patients (94.3%) responded to therapy with size reduction, colour changes, softened texture and/or healing of ulceration. Rebound growth requiring an additional course of therapy was observed in 23 patients. Side effects from beta-blockers included cool extremities (26.7%), irritability (17.1%), lower gastrointestinal upset (14.3%), emesis (11.4%), hypotension (10.5%), poor feeding (7.6%), lethargy (4.8%), bronchospasm (0.95%) and rash (0.95%). Side effects did not result in complete discontinuation of beta-blocker treatment in any case; however, they prompted a switch to a different beta-blocker preparation in some cases. Resolution of the primary indication, requiring a median time of three months, occurred in 87 individuals (82.9%).

CONCLUSIONS:

Treatment of infantile hemangiomas with oral beta-blocker therapy is highly effective and well tolerated, with more than 94% of patients demonstrating a response to treatment and 90% showing resolution of the primary functional indication for treatment.     

Characteristics of a donor population in western Venezuela

To determine the characteristics of blood donors in western Venezuela, we collected data from 1983 to 1985 on 31,320 volunteer donors at the Blood Bank of the State of Zulia in Maracaibo. Fifty-nine percent of the donors were blood group O, 30 percent were group A, 9 percent were group B, and 2 percent were group AB. Most of the donors (93%) were Rh positive. One percent of donors had positive reactions to hepatitis B surface antigen, 3.15 percent for syphilis, 1.43 percent for antibodies to Trypanosoma cruzi, and 0.32 percent to human immunodeficiency virus antibodies. About one-half of the donors were between 18 and 30 years old, and only 10 percent were women. To determine if iron deficiency anemia was a cause for the small size of the female donor pool, we measured serum ferritin in 50 first-time female donors. Ten of these (20%) had serum ferritin values below normal, and the distribution of serum ferritin levels of all 50 was very similar to that reported for frequent donors in Europe and the United States, with a clustering of ferritin values between 10 and 70 ng per ml. The data indicate that blood donors in western Venezuela are markedly different from those in the United States and that iron supplementation may be indicated for female Venezuelan donors.     

Massive antenatal fetomaternal hemorrhage: evidence for long-term survival of fetal red blood cells

BACKGROUND: Massive fetomaternal hemorrhage (FMH) can lead to life-threatening anemia. Quantification based on flow cytometry with anti-hemoglobin F (HbF) is applicable in all cases but underestimation of large fetal bleeds has been reported. A large FMH from an ABO-compatible fetus allows an estimation of the life span of fetal red blood cells (RBCs) in the maternal circulation. CASE REPORT: The mother went to the obstetrician twice antepartum owing to symptoms assumed to be preeclampsia; that, however, was not found. She later delivered by cesarean section owing to diminished fetal movements. No fetal weight gain was observed during the last 2 weeks of pregnancy. STUDY DESIGN AND METHODS: Fetal RBCs were quantified by flow cytometry with anti-HbF, anti-Fy(a), anti-s, and anti-Jk(b) on a regular basis. RESULTS: The infant had anemia at delivery and an FMH was determined to be 314 +/- 17 mL (+/- SD) of whole blood. It is assumed that the two antenatal visits were associated with the FMH. Postpartum follow-up showed that fetal RBCs in the maternal circulation were detectable with anti-HbF up to 119 days. Quantification by flow cytometry based on anti-HbF was in agreement with quantification based on anti-Fy(a), anti-s, and anti-Jk(b), although they were less sensitive. CONCLUSION: ABO-compatible fetal RBCs from an FMH had a life span in the maternal circulation close to that of adult RBCs.     

The effects of endogenous opioids and cortisol on thyrotropin and prolactin secretion in patients with Addison's disease.

This study assessed the controversial role of endogenous opioids and cortisol in the regulation of TSH and PRL secretion in humans. Seven euthyroid male patients with Addison's disease were studied four times, with an interval of 1-3 months, as follows: 1) during normocortisolism [graduated infusion of hydrocortisone, 0.4 mg/kg, over 19.5 h]; 2) normocortisolism and coadministration of naloxone, at 25 microg/kg x h during the last 6.5 h; 3) hypocortisolism (24 h withdrawal of hydrocortisone, followed by 19.5 h saline infusion); and 4) hypocortisolism plus naloxone administration. The TSH and PRL levels were measured every 15 min, from 0800-1530 h. A TRH test was performed at 1300 h and 1400 h (10 microg and 200 microg of TRH, respectively). The mean TSH level increased significantly during hypocortisolism, compared with normocortisolism (1.78 +/- 0.04 vs. 0.84 +/- 0.02 mU/L; P < 0.001). The administration of naloxone suppressed the TSH levels during hypo- and normocortisolism (1.78 +/- 0.04 vs. 1.50 +/- 0.03 and 0.84 +/- 0.02 vs. 0.61 +/- 0.02 mU/L, respectively; P < 0.001). During hypocortisolism, the TSH responses to small and high doses of TRH were significantly higher than during normocortisolism (P < 0.02). Naloxone had no effect on the TSH responses to TRH, neither during hypo- nor during normocortisolism. The mean PRL level increased significantly during hypocortisolism, compared with normocortisolism (5.8 +/- 0.4 vs. 3.6 +/- 0.2 microg/L; P < 0.001), and naloxone induced an increase in PRL levels both during hypo- and normocortisolism (7.1 +/- 0.7 vs. 4.7 +/- 0.5 microg/L, respectively; P < 0.01). The PRL responses to TRH were similar during hypo- and normocortisolism and without any change during opioid receptor blockade. In conclusion, cortisol suppressed basal TSH and PRL secretion and reduced the sensitivity of the thyrotrophs to TRH, without affecting the PRL response to TRH. Our results suggest that endogenous opioids act at the hypothalamic level to stimulate TSH secretion and to suppress the PRL secretion, but these results argue against an essential role of endogenous opioids in the physiological regulation of TSH and PRL secretion in humans.     

Soluble haemoglobin scavenger receptor (sCD163) in patients with suspected community-acquired infections

The aim of our study was to evaluate soluble haemoglobin scavenger receptor (sCD163) as a molecular marker in patients with community-acquired infections. One hundred and ninety-four adult patients admitted to the Department of Internal Medicine, Odense University Hospital, with suspected community-acquired infection were included in a prospective study. Plasma and serum were sampled from all patients on day of admission and sCD163 and interleukin-6 levels were measured. Demographic data, co-morbidity, microbiological aetiology, biochemical parameters, focus of infection, severity score and mortality on day 28 were recorded. Median age was 68 (range 18-92) years. Mortality rate among infected patients on day 28 was 3.8%. sCD163 concentrations (median and range) were: 2.99 mg/l (1.22-12.65) in non-infected patients, 3.62 mg/l (1.59-74.04) (p=0.08) in infected patients without systemic inflammatory response syndrome, 3.2 mg/l (0.54-22.51) (p=0.4) in patients with sepsis, 3.63 mg/l (1.71-28.4) (p=0.01) in patients with severe sepsis, and 4.9 mg/l (2.66-28.4) (p=0.003) in patients with bacteraemia. In this cohort dominated by mild infections, a moderate elevation of sCD163 was observed only in patients with severe sepsis and/or bacteraemia. sCD163 did not discriminate between infected and non-infected patients.     

Prolonged unconjugated hyperbilirubinaemia associated with the haem oxygenase‐1 gene promoter polymorphism

Aim: To elucidate the genetic factors causing hyperbilirubinaemia in prolonged jaundice of the newborns, we investigated whether the HO‐1 gene promoter polymorphism is a cause in unexplained pathological or prolonged jaundice. Methods: Three groups were defined: healthy newborns with no clinical jaundice, newborns hospitalized for jaundice without any identifiable pathological cause and newborns with prolonged jaundice associated with breast milk. Genomic DNA was extracted from the white blood cells and the promoter region of the HO‐1 gene was amplified using PCR and their allelic repeats were determined. Results: We did not detect any significant difference in the allele frequencies between the healthy newborns and the newborns whose serum total bilirubin levels were >12.9 mg/dL. However, the patients with short (<24 GT) dinucleotide repeat in the HO‐1 gene promoter on either allele had significantly higher prolonged unconjugated hyperbilirubinaemia than the healthy newborns. There was no significant difference between the groups 2 and 3. Conclusion: The results indicate that polymorphism of HO‐1 gene promoter region can be an underlying cause of the prolonged unconjugated hyperbilirubinaemia associated with breast milk. In this patient population, short repeat alleles of the HO‐1 gene promoter polymorphism were associated with prolonged jaundice.