The impact of tubal ectopic pregnancy in Papua New Guinea - a retrospective case review

BACKGROUND: Ectopic pregnancy (EP) is an important cause of morbidity and mortality amongst women of reproductive age. Tubal EP is well described in industrialised countries, but less is known about its impact in low-resource countries, in particular in the South Pacific Region. METHODS: We undertook a retrospective review of women with tubal EP treated at a provincial referral hospital in coastal Papua New Guinea over a period of 56 months. Demographic and clinical variables were obtained from patients’ medical records and analysed. The institutional rate of tubal EP was calculated, and diagnosis and management reviewed. Potential risk factors for tubal EP were identified, and delays contributing to increased morbidity described. RESULTS: A total of 73 women had tubal EP. The institutional rate of tubal EP over the study period was 6.3 per 1,000 deliveries. There were no maternal deaths due to EP. The mean age of women was 31.5+/−5.7 years, 85% were parous, 67% were rural dwellers and 62% had a history of sub-fertility. The most commonly used diagnostic aid was culdocentesis. One third of women had clinical evidence of shock on arrival. All women with tubal EP were managed by open salpingectomy. Tubal rupture was confirmed for 48% of patients and was more common amongst rural dwellers. Forty-three percent of women had macroscopic evidence of pelvic infection. Two-thirds of patients received blood transfusions, and post-operative recovery lasted six days on average. Late presentation, lack of clinical suspicion, and delays with receiving appropriate treatments were observed. CONCLUSIONS: Tubal EP is a common gynaecological emergency in a referral hospital in coastal PNG, and causes significant morbidity, in particular amongst women residing in rural areas. Sexually transmitted infections are likely to represent the most important risk factor for tubal EP in PNG. Interventions to reduce the morbidity due to tubal EP include the prevention, detection and treatment of sexually transmitted infections, identification and reduction of barriers to prompt presentation, increasing health workers’ awareness of ectopic pregnancy, providing pregnancy test kits to rural health centres, and strengthening hospital blood transfusion services, including facilities for autotransfusion

Activation of TrkB with TAM-163 results in opposite effects on body weight in rodents and non-human primates.

Strong genetic data link the Tyrosine kinase receptor B (TrkB) and its major endogenous ligand brain-derived neurotrophic factor (BDNF) to the regulation of energy homeostasis, with loss-of-function mutations in either gene causing severe obesity in both mice and humans. It has previously been reported that peripheral administration of the endogenous TrkB agonist ligand neurotrophin-4 (NT-4) profoundly decreases food intake and body weight in rodents, while paradoxically increasing these same parameters in monkeys. We generated a humanized TrkB agonist antibody, TAM-163, and characterized its therapeutic potential in several models of type 2 diabetes and obesity. In vitro, TAM-163 bound to human and rodent TrkB with high affinity, activated all aspects of the TrkB signaling cascade and induced TrkB internalization and degradation in a manner similar to BDNF. In vivo, peripheral administration of TAM-163 decreased food intake and/or body weight in mice, rats, hamsters, and dogs, but increased food intake and body weight in monkeys. The magnitude of weight change was similar in rodents and non-human primates, occurred at doses where there was no appreciable penetration into deep structures of the brain, and could not be explained by differences in exposures between species. Rather, peripherally administered TAM-163 localized to areas in the hypothalamus and the brain stem located outside the blood-brain barrier in a similar manner between rodents and non-human primates, suggesting differences in neuroanatomy across species. Our data demonstrate that a TrkB agonist antibody, administered peripherally, causes species-dependent effects on body weight similar to the endogenous TrkB ligand NT-4. The possible clinical utility of TrkB agonism in treating weight regulatory disorder, such as obesity or cachexia, will require evaluation in man