Aim:The study aims to review the contemporary presentation, diagnosis and treatment of children with infantile hypertrophic pyloric stenosis (IHPS) at an Australian paediatric tertiary centre. Methods: A retrospective case review of patients with IHPS presenting to our institution between January 2004 and December 2010 was performed. Results were compared with a previous study evaluating two earlier 6-year series of patients treated between January 1984 and November 1995. Results: Of 362 infants presenting over the current 7-year review, 84.8% were male. Mean age of admission fell from 5.9 weeks in the previous study to 5.4 weeks. An 'olive' was palpated on examination in 48%, visible peristalsis seen in 25% and 16% of patients presented with haematemesis. Diagnosis solely on clinical examination fell from 74% to 9% and was associated with a corresponding increase in use of ultrasound from 16% to 91%. The frequency of serum chloride values less than 85 mmol/L declined from 26% to 9%. A variety of open and minimally invasive surgical approaches were used with similar outcomes, although laparoscopic pyloromyotomy was associated with significantly higher rates of wound infection (c 2 = 4.6, P = 0.03). The frequency of major complications remained low at 1%. Conclusion: Contemporary patients with IHPS typically present earlier with a reduction in the incidence of metabolic derangement. Diagnosis based on clinical examination alone appears uncommon, with the majority of suspected cases confirmed by ultrasound. There was no clear difference in overall outcome based on the surgical approach used, although minor variations may reflect our institution's initial experience with laparoscopic pyloromyotomy.
Antibody–drug conjugates (ADCs) have emerged as valuable targeted anticancer therapeutics with at least 11 approved therapies and over 80 advancing through clinical trials. Enediyne DNA-damaging payloads represented by the flagship of this family of antitumor agents, N-acetyl calicheamicin γ1I, have a proven success track record. However, they pose a significant synthetic challenge in the development and optimization of linker drugs. We have recently reported a streamlined total synthesis of uncialamycin, another representative of the enediyne class of compounds, with compelling synthetic accessibility. Here we report the synthesis and evaluation of uncialamycin ADCs featuring a variety of cleavable and noncleavable linkers. We have discovered that uncialamycin ADCs display a strong bystander killing effect and are highly selective and cytotoxic in vitro and in vivo.
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