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BackgroundWound complications (WC) following cesarean delivery (CD) result in significant morbidity. A randomized trial in 2013, which demonstrated lower WC rates with suture closure compared to staple closure, resulted in a practice change within our academic institution.ObjectiveTo determine the impact of this practice change on WC rates and identify other modifiable risk factors for WC.Study designThis is a retrospective cohort study of all women undergoing CD at the University of California, San Diego between 1 March 2011 and 28 February 2012 (primarily staple) and 1 March 2013 and 28 February 2014 (primarily suture). WC rates were compared between the two time intervals using Chi-square and Student's t-tests. Risk factors (OR, 95%CI) for WC were assessed using multiple logistic regression modeling.ResultsOf 1580 women delivered by CD, rates of WC were higher with staple closure compared to sutures (10.1% versus 4.5%; OR 2.4, 1.4-4.1). Additionally, WC were more likely with vertical skin incisions (OR 3.6, 1.6-8.1), CD for failed labor (OR 2.9, 1.1-7.4) and diabetes (OR 2.1, 1.4-3.9).ConclusionsAfter adjusting for confounders, there were over twofold increased odds of WC with staple closure. Vertical incisions, failed labor and diabetes also contributed to WC. Suture closure appears to decrease the risks of WC post CD.

Achondroplasia is the most common skeletal dysplasia and is associated with serious complications such as foramen magnum stenosis (FMS). This case report describes an infant with achondroplasia who presented with a syndrome of inappropriate antidiuretic hormone secretion (SIADH), secondary to significant FMS and myelocompression. A 2-month-old boy with prenatally diagnosed achondroplasia was referred due to disordered breathing and altered consciousness. On admission, apathy, hypotonus, and hypothermia with typical features of achondroplasia were noticed. Laboratory investigations revealed severe hyponatremia and hypochloridaemia with normal glucose and urea levels. The diagnosis of SIADH was made based on low serum osmolality in the presence of high urine osmolality, along with an elevated copeptin level. An emergency computerized tomography showed a high-grade stenosis at the cranio-cervical junction; subsequent magnetic resonance imaging demonstrated myelocompression. The patient underwent decompression surgery the next day; serum osmolality increased after the operation. Spontaneous breathing after extubation was sufficient whereas tetraplegia persisted despite intensive physiotherapy. Clinicians should be aware of SIADH as a presenting sign of FMS in children with achondroplasia. Further discussion is warranted regarding improving parental education and timing of screening recommendations. [ABSTRACT FROM AUTHOR]

ROMK null mice with a high survival rate and varying severity of hydronephrosis provide a good model to study type II Bartter syndrome pathophysiology (26). During the development of such a colony, we found that more male than female null mice survived, 58.7% vs. 33.3%. To investigate the possible mechanism of this difference, we compared the survival rates, renal functions, degree of hydronephrosis, as well as [PGE.sub.2] and [TXB.sub.2] production between male and female ROMK wild-type and null mice. We observed that female ROMK Bartter's mice exhibited lower GFR (0.37 vs. 0.54 ml x [min.sup.-1] x 100 g [BW.sup.-1], P < 0.05) and higher fractional [Na.sup.+] excretion (0.66% vs. 0.48%, P < 0.05) than male Bartter's. No significant differences in acid-base parameters, urinary [K.sup.+] excretion, and plasma electrolyte concentrations were observed between sexes. In addition, we assessed the liquid retention rate in the kidney to evaluate the extent of hydronephrosis and observed that 67% of male and 90% of female ROMK null mice were hydronephrotic mice. Urinary [PGE.sub.2] excretion was higher in both sexes of ROMK null mice: 1.35 vs. 1.10 ng/24 h in males and 2.90 vs. 0.87 ng/24 h in females. [TXB.sub.2] excretion was higher in female mice in both wild-type and ROMK null mice. The increments of urinary [PGE.sub.2] and [TXB.sub.2] were significantly higher in female null mice than males, 233.33% vs. 22.74% of [PGE.sub.2] and 85.67% vs. 20.36% of [TXB.sub.2]. These data demonstrate a more severe Bartter phenotype in female ROMK null mice, and higher [PGE.sub.2] and [TXB.sub.2] production may be one of the mechanisms of this manifestation. gender difference; ROMK Bartter's; hydronephrosis; renal function

Bartter's syndrome represents a group of hereditary salt- and water-losing renal tubulopathies caused by loss-of-function mutations in proteins mediating or regulating salt transport in the thick ascending limb (TAL) of Henle's loop. Mutations in the ROMK channel cause type II antenatal Bartter's syndrome that presents with maternal polyhydramnios and postnatal life-threatening volume depletion. We have developed a colony of Romk null mice showing a Bartter-like phenotype and with increased survival to adulthood, suggesting the activation of compensatory mechanisms. To test the hypothesis that upregulation of [Na.sup.+]-transporting proteins in segments distal to the TAL contributes to compensation, we studied expression of salt-transporting proteins in ROMK-deficient ([Romk.sup.-/-]) mice. Plasma aldosterone was 40% higher and urinary [PGE.sub.2] excretion was 1.5-fold higher in [Romk.sup.-/-] compared with wild-type littermates. Semiquantitative immunoblotting of kidney homogenates revealed decreased abundances of proximal tubule [Na.sup.+]/[H.sup.+] exchanger (NHE3) and [Na.sup.+]-[P.sub.i] cotransporter (NaPi-IIa) and TAL-specific [Na.sup.+]-[K.sup.+]-2[Cl.sup.-]-cotransporter (NKCC2/BSC1) in [Romk.sup.-/-] mice, while the distal convoluted tubule (DCT)-specific [Na.sup.+]-[Cl.sup.-] cotransporter (NCC/TSC) was markedly increased. The abundance of the [alpha]-,[beta]-, and [gamma]-subunits of the epithelial [Na.sup.+] channel (ENaC) was slightly increased, although only differences for [gamma]-ENaC reached statistical significance. Morphometry revealed a fourfold increase in the fractional volume of DCT but not of connecting tubule (CNT) and collecting duct (CCD). Consistently, CNT and CD of [Romk.sup.-/-] mice revealed no apparent increase in the luminal abundance of the ENaC compared with those of wild-type mice. These data suggest that the loss of ROMK-dependent [Na.sup.+] absorption in the TAL is compensated predominately by upregulation of [Na.sup.+] transport in downstream DCT cells. These adaptive changes in [Romk.sup.-/-] mice may help to limit renal [Na.sup.+] loss, and thereby, contribute to survival of these mice. thick ascending limb of Henle's loop; distal convoluted tubule; thiazide-sensitive NaCl cotransporter; renal outer medulla [K.sup.+] channel; hyperprostaglandin E syndrome

Cantone A, Yang X, Yan Q, Giebisch G, Hebert SC, Wang T. Mouse model of type II Bartter's syndrome. I. Upregulation of thiazide-sensitive Na-Cl cotransport activity. Am J Physiol Renal Physiol 294: F1366-F1372, 2008. First published April 2, 2008; doi:10.1152/ajprenal.00608.2007.l-ROMK-deficient ([Romk.sup.-/-]) mice exhibit polyuria, natriuresis, and kaliuresis similar to individuals with type II Bartter's form of hyperprostaglandin E syndrome (HPS; antenatal Baartter's syndrome). In the present study, we utilized both metabolic and clearance studies to define the contributions of specific distal nephron segments to the renal salt wasting in these mice. The effects of furosemide, hydrochlorothiazide, and benzamil on urinary [Na.sup.+] and [K.sup.+] excretion in both wild-type ([Romk.sup.+/+]) and [Romk.sup.-/-] mice were used to assess and compare salt transport by the [Na.sup.+]-[K.sup.+]-2[Cl.sup.-] cotransporter (NKCC2)-expressing thick ascending limb (TAL), the [Na.sup.+]-[Cl.sup.-] cotransporter (NCC)-expressing distal convoluted tubule (DCT1/DCT2), and the epithelial [Na.sup.+] channel (ENaC)-expressing connecting segment (CNT) and collecting duct (CD), respectively. Whole kidney glomerular filtration rate was reduced by 47% in [Romk.sup.-/-] mice. Furosemide-induced increments in the fractional excretion rate of [Na.sup.+] and [K.sup.+] and absolute excretion of [Na.sup.+] and [K.sup.+] were significantly blunted in [Romk.sup.-/-] mice, consistent with a major salt transport defect in the TAL. In contrast, hydrochlorothiazide produced an exaggerated natriuresis in [Romk.sup.-/-] mice, indicating upregulation of salt absorption by the DCT. Benzamil resulted in a similar increment in absolute Na excretion in both [Romk.sup.-/-] and [Romk.sup.+/+,] indicating no significant upregulation of [Na.sup.+] transport by ENaC in ROMK null mice. Moreover, hydrochlorothiazide increased the fractional [K.sup.+] excretion rate in [Romk.sup.-/-] mice, confirming our recent observation that maxi-K channels contribute to distal [K.sup.+] secretion in the absence of ROMK. ROMK knockout; furosemide; hydrochlorothiazide; benzamil

The renal-specific [Na.sup.+]-[K.sup.+]-[2Cl.sup.-] cotransporter NKCC2 belongs to the SLC12 gene family; it is the target for loop diuretics and the cause of type 1 Bartter's syndrome. Because the NKCC2 sequence contains two putative Nlinked glycosylation sites, one of which is conserved with the renal [Na.sup.+]-[Cl.sup.-] cotransporter in which glycosylation affects thiazide affinity, we assessed the role of glycosylation on NKCC2 functional properties. One (N442Q or N452Q) or both (N442,452Q) N-glycosylation sites were eliminated by site-directed mutagenesis. Wild-type NKCC2 and mutant clones were expressed in Xenopus laevis oocytes and analyzed by [sup.86Rb.sup.+] influx, Western blotting, and confocal microscopy. Inhibition of glycosylation with tunicamycin in wild-type NKCC2-injected oocytes resulted in an 80% reduction of NKCC2 activity. Immunoblot of injected oocytes revealed that glycosylation of NKCC2 was completely prevented in N442A52Q-injected oocytes. Functional activity was reduced by 50% in N442Q- and N452Q injected oocytes and by 80% in oocytes injected with N442,452Q, whereas confocal microscopy of oocytes injected with wild-type or mutant enhanced green fluorescent protein-tagged NKCC2 clones revealed that surface fluorescence intensity was reduced ~20% in single mutants and 50% in the double mutant. Ion transport kinetic analyses revealed no changes in cation affinity and a small increase in [Cl.sup.-] affinity by N442Q and N442,452Q. However, a slight decrease in bumetanide affinity was observed. Our data demonstrate that NKCC2 is glycosylated and suggest that prevention of glycosylation reduces its functional expression by affecting insertion into the plasma membrane and the intrinsic activity of the cotransporter. bumetanide; thick ascending limb; isoforms; salt reabsorption

Gastric acid secretion is activated by two distinct pathways: a neuronal pathway via the vagus nerve and release of acetylcholine and an endocrine pathway involving gastrin and histamine. Recently, we demonstrated that activation of [H.sup.+]-[K.sup.+]-ATPase activity in parietal cells in freshly isolated rat gastric glands is modulated by the calcium-sensing receptor (CaSR). Here, we investigated if the CaSR is functionally expressed in freshly isolated gastric glands from human patients undergoing surgery and if the CaSR is influencing histamine-induced activation of [H.sup.+]-[K.sup.+]ATPase activity. In tissue samples obtained from patients, immunohistochemistry demonstrated the expression in parietal cells of both subunits of gastric [H.sup.+]-[K.sup.+]-ATPase and the CaSR. Functional experiments using the pH-sensitive dye 2',7'-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein and measurement of intracellular pH changes allowed us to estimate the activity of [H.sup.+]-[K.sup.+]-ATPase in single freshly isolated human gastric glands. Under control conditions, [H.sup.+]-[K.sup.+]ATPase activity was stimulated by histamine (100 [micro]M) and inhibited by omeprazole (100 [micro]M). Reduction of the extracellular divalent cation concentration (0 [Mg.sup.2+], 100 [micro]M [Ca.sup.2+]) inactivated the CaSR and reduced histamine-induced activation of [H.sup.+]-[K.sup.+]-ATPase activity. In contrast, activation of the CaSR with the trivalent cation [Gd.sup.3+] caused activation of omeprazole-sensitive [H.sup.+]-[K.sup.+]-ATPase activity even in the absence of histamine and under conditions of low extracellular divalent cations. This stimulation was not due to release of histamine from neighbouring enterochromaffin-like cells as the stimulation persisted in the presence of the [H.sub.2] receptor antagonist cimetidine (100 [micro]M). Furthermore, intracellular calcium measurements with fura-2 and fluo-4 showed that activation of the CaSR by [Gd.sup.3+] led to a sustained increase in intracellular [Ca.sup.2+] even under conditions of low extracellular divalent cations. These experiments demonstrate the presence of a functional CaSR in the human stomach and show that this receptor may modulate the activity of acid-secreting [H.sup.+]-[K.sup.+]ATPase in parietal cells. Furthermore, our results show the viability of freshly isolated human gastric glands and may allow the use of this preparation for experiments investigating the physiological regulation and properties of human gastric glands in vitro. stomach; [H.sup.+]-[K.sup.+]-ATPase; parietal cells