Theatre of paediatric surgery

In the 50 years since the first edition of this journal, operative paediatric surgery has undergone radical change. Many of the most common instruments are unchanged, both as a testament to their utility and in recognition of past surgeons remembered eponymously. Surrounding that basic core of instruments, theatre has changed radically as new tools and techniques have arisen. Surgeons have come down from their pedestals, recognising surgery as a team sport rather than a solo performance. More than half of the current paediatric surgical trainees are women, a higher proportion than in any other craft group of the Royal Australasian College of Surgeons. The appearance, and rapid development, of laparoscopy is to many observers the most notable change in surgery over the last 50 years. Placed in its context though, it is simply the most prominent example of a frameshift in surgical thinking. The patient as a whole is now the focus, rather than just the disease. Recent developments are as much about minimising harm to normal tissues as they are about extirpating pathology. As a surgical maxim, ‘Primum non nocere’ is even more in evidence in 2015 than it was in 1965.     

Drug-prescribing patterns during pregnancy in the tertiary care hospitals of Pakistan: a cross sectional study

Background

Low birth weight (LBW) is considered as a major multifaceted public health concern. Seventy-two percent of LBW infants are born in Asia. An estimation of 8% LBW infants has been reported for Eastern Mediterranean region including Iran. This study investigated contributory factors of LBW in singleton term births in Tehran, Iran. Tehran is a multicultural metropolitan area and a sample from the general population in Tehran could be regarded as a representative sample of urban population in Iran.

Methods

This was a retrospective study using data from 15 university maternity hospitals in Tehran, Iran. Data on all singleton term births in these hospitals were extracted from case records during a one calendar year. Study variables included: maternal age, maternal educational level, history of LBW deliveries, history of preterm labor, cigarette smoking during pregnancy, number of parities, chronic diseases and residential area (Tehran versus suburbs of Tehran). In order to examine the relationship between LBW and demographic and reproductive variables the adjusted logistic regression analysis was performed.

Results

In all, data for 3734 term pregnancies were extracted. The mean age of women was 25.7 (SD = 5.3) years and 5.2% of term births were LBW. In addition to association between LBW and maternal age, significant risk factors for LBW were: history of LBW deliveries [adjusted odds ratio (OR) = 2.53, 95% confidence interval (CI) = 1.06–6.03], smoking during pregnancy (OR = 4.64, 95% CI = 1.97–10.95) and chronic diseases (OR for hypertension = 3.70, 95% CI = 2.25–6.06, OR for others = 2.04, 95% CI = 1.09–3.83).

Conclusion

The findings indicate that in addition to maternal age, history of LBW deliveries; smoking during pregnancy and chronic diseases are significant determinants of LBW in this population. This is consistent with national and international findings indicating that maternal variables and risk behaviors during pregnancy play important roles on LBW.     

ST6Gal-I expression in ovarian cancer cells promotes an invasive phenotype by altering integrin glycosylation and function

Background

Ovarian adenocarcinoma is not generally discovered in patients until there has been widespread intraperitoneal dissemination, which is why ovarian cancer is the deadliest gynecologic malignancy. Though incompletely understood, the mechanism of peritoneal metastasis relies on primary tumor cells being able to detach themselves from the tumor, escape normal apoptotic pathways while free floating, and adhere to, and eventually invade through, the peritoneal surface. Our laboratory has previously shown that the Golgi glycosyltransferase, ST6Gal-I, mediates the hypersialylation of β₁ integrins in colon adenocarcinoma, which leads to a more metastatic tumor cell phenotype. Interestingly, ST6Gal-I mRNA is known to be upregulated in metastatic ovarian cancer, therefore the goal of the present study was to determine whether ST6Gal-I confers a similarly aggressive phenotype to ovarian tumor cells.

Methods

Three ovarian carcinoma cell lines were screened for ST6Gal-I expression, and two of these, PA-1 and SKOV3, were found to produce ST6Gal-I protein. The third cell line, OV4, lacked endogenous ST6Gal-I. In order to understand the effects of ST6Gal-I on cell behavior, OV4 cells were stably-transduced with ST6Gal-I using a lentiviral vector, and integrin-mediated responses were compared in parental and ST6Gal-I-expressing cells.

Results

Forced expression of ST6Gal-I in OV4 cells, resulting in sialylation of β1 integrins, induced greater cell adhesion to, and migration toward, collagen I. Similarly, ST6Gal-I expressing cells were more invasive through Matrigel.

Conclusion

ST6Gal-I mediated sialylation of β1 integrins in ovarian cancer cells may contribute to peritoneal metastasis by altering tumor cell adhesion and migration through extracellular matrix.     

Availability of Safe Childbirth Supplies in 284 Facilities in Uttar Pradesh,India

Maternal and Child Health Journal - Objectives Vital to implementation of the World Health Organization (WHO) Safe Childbirth Checklist (SCC), designed to improve delivery of 28 essential birth...     

Inhibition of Neu-Induced Mammary Carcinogenesis in Transgenic Mice Expressing ERΔ3, a Dominant Negative Estrogen Receptor α Variant

The estrogen receptor ?? (ER??) splicing variant with an in-frame deletion of exon 3 (ER??3) is frequently expressed in the normal breast, but its influence on tumorigenesis has not been explored. In vitro, ER??3 has dominant negative activity, suggesting it may suppress estrogen stimulation in the breast. ER??3 may inhibit classical signaling on estrogen response element (ERE)-regulated genes as well as activate non-classical pathways at Sp1 and AP-1 sites. Transgenic mice were developed that express mouse ER??3 in all tissues examined, including the mammary gland. To investigate if ER??3 expression affects tumorigenesis, ER??3 mice were crossbred with MMTV-Neu mice. Mammary tumor onset was significantly delayed in ER??3/Neu versus MMTV-Neu females and metastatic incidence and burden was significantly reduced. Consequently, ER??3 expression suppressed tumor development and metastasis in this aggressive model of HER2/Neu-positive breast cancer. To determine if ER ligands with anticancer activity may augment ER??3 protection, the bitransgenic mice were treated with tamoxifen and soy isoflavones starting at age 2?months. Soy protein with isoflavones (181?mg/1,800?kcal) did not affect tumor development in MMTV-Neu or ER??3/Neu mice; however, metastatic progression was not inhibited in soy-treated ER??3/Neu mice, as it was in untreated ER??3/Neu mice. In contrast, tamoxifen (20?mg/1,800?kcal) significantly enhanced tumor prevention in ER??3/Neu versus MMTV-Neu mice (98?% vs. 81?% tumor free). The results in ER??3/Neu mice demonstrate that ER??3 influences estrogen-dependent mammary carcinogenesis and, thus, may be protective in women expressing ER??3 in the breast. However, exposure to different estrogens may augment or block its beneficial effects.     

Subclavian stenting in a hostile aortic arch facilitated by a low-profile brachial artery through-and-through access

Subclavian stenting can be extremely difficult in a hostile type II aortic arch (with acute angulation of the subclavian artery origin) or type III aortic arch. This case illustrates use of a low-profile system to gain through-and-through (flossing) access through the brachial artery to facilitate stenting via the femoral approach. This approach can be useful in patients with small brachial arteries where the risk of complication may be high if a standard vascular sheath was placed for stenting via the brachial approach. This technique also avoids the use of a surgical cut down.     

Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase

A human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA-containing retrovirus was used to infect murine long-term primary bone marrow cultures. High levels of ATase expression were obtained, and colony- forming cells of the granulocyte-macrophage lineage from the cultures transduced with the human ATase retrovirus were three times more resistant to the alkylating agent, N-methyl-N-nitrosourea (MNU), than control cultures. Furthermore, expression of the human ATase protected long-term hematopoiesis, measured as the output of progenitor cells to the nonadherent fraction of the culture, against the cytotoxic effects of repeated exposures to MNU. These results clearly show that a human ATase cDNA-containing retrovirus can be used to infect long-term primary bone marrow cultures and that this attenuates their sensitivity to nitrosoureas.