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.     

Design and synthesis of new 2-aryl, 3-benzyl-(1,3-oxazolidine or 1,3-thiazolidine)-4-ones as selective cyclooxygenase (COX-2) inhibitors

A new series of 2-aryl, 3-benzyl-(1,3-oxazolidine or 1,3-thiazolidine)-4-ones, possessing a methylsulfonyl pharmacophore, were synthesized to evaluate their biological activities as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1 and COX-2 isozyme inhibition studies were performed to acquire structure-activity relationship data with respect to the point that molecular modeling studies showed that designed compounds bind in the primary binding site such that the C-2 para-SO₂Me substituent inserts into the 2° pocket present in COX-2 enzyme. COX-1 and COX-2 inhibition studies showed that all compounds were selective inhibitors of the COX-2 isozyme with IC₅₀ values in the highly potent 0.21 to 0.34 μM range, and COX-2 selectivity indexes in the 222.3 to >476 range. 3-Benzyl-2-(4-methylsulfonylphenyl)-1,3-oxazolidine-4(5H)-one was identified as the most potent (IC₅₀ = 0.21 μM) and selective (S.I. > 476) COX-2 inhibitor among the synthesized compounds. It also was a more selective COX-2 inhibitor than the parent reference compound celecoxib (S.I. > 403).     

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.