Semirigid partial annuloplasty band allows dynamic mitral annular motion and minimizes valvular gradients: an echocardiographic study

BACKGROUND: Traditional mitral annuloplasty devices include both rigid rings, which restrict annular motion, and soft rings and bands, which can locally deform. Conflicting data exist regarding their impact on annular dynamics. We studied mitral annuloplasty with a semirigid partial band and with a nearly complete rigid ring. METHODS: Intraoperative three-dimensional transesophageal echocardiograms (n = 14) and predischarge transthoracic echocardiograms were retrospectively analyzed in patients undergoing mitral valve repair for degenerative disease with either a rigid ring (n = 77) or a semirigid partial band (n = 38). Each transesophageal echocardiogram was analyzed with TomTec three-dimensional software to produce cardiac cycle frame planimetry and to measure device geometry. Actual device sizes provided reference dimensions. Blinded analysis of Doppler data from transthoracic echocardiograms was performed. RESULTS: Validation of the quantitative transesophageal echocardiogram methodology revealed a 1.3% +/- 0.3% (mean +/- standard error of the mean) underestimation of actual linear dimension. With the semirigid partial band, systolic valve orifice area and intertrigonal distance decreased from 6.14 +/- 0.37 to 5.55 +/- 0.24 cm(2) (-9.6%; p = 0.01) and from 2.69 +/- 0.08 to 2.55 +/- 0.13 cm (-5.2%; p = 0.03), respectively. Systolic anterior-posterior distance decreased from 2.1 +/- 0.10 to 1.95 +/- 0.06 cm (-7.1%; p = 0.01) compared with diastole. In contrast, rigid ring orifice area was unchanged (4.12 +/- 0.15 to 4.10 +/- 0.16 cm(2); -0.5%; p = 0.48) during the cardiac cycle. Transthoracic echocardiography revealed significantly lower mitral inflow gradients with semirigid partial band (mean gradients compared with rigid ring, 4.0 +/- 0.3 versus 5.0 +/- 0.3 mm Hg; p = 0.02; peak gradients, 8.9 +/- 0.5 versus 11.1 +/- 0.5 mm Hg; p = 0.01). CONCLUSIONS: Three-dimensional transesophageal echocardiographic measurements of annular dynamics are valid and reliable when discrete annuloplasty devices are present. In contrast to the rigid ring, the semirigid partial band permits more physiologic geometric changes and is associated with lower postoperative mitral valve gradients.     

Insulin treatment reduces pre-prandial plasma ghrelin concentrations in children with type 1 diabetes.

BACKGROUND: Ghrelin is well recognized as a key factor in regulating appetite and energy homeostasis. The aim of the present study is to characterize the plasma ghrelin concentrations in children with type 1 diabetes at the time of diagnosis and to determine the effect of metabolic control after insulin therapy on circulating ghrelin levels. Also, the relationship between the simultaneous blood glucose concentrations and fasting plasma ghrelin concentrations was explored. MATERIAL/METHODS: This prospective study assessed the changes in pre-prandial plasma ghrelin levels after treatment of type 1 diabetes with insulin. Results: The study comprised 19 children with new onset diabetes mellitus. Mean plasma ghrelin levels declined by 29% in diabetic children post insulin treatment (p=0.007). There was a significant correlation between plasma ghrelin and body mass index (BMI) in children with type 1 diabetes at diagnosis (r=-0.54), but not at follow up. The difference in ghrelin at diagnosis and at 3 month follow up demonstrated an inverse relationship to difference in plasma glucose (r=-0.48). CONCLUSIONS: Plasma ghrelin concentrations could be suppressed in untreated type 1 diabetic children by improved glycemic control following insulin replacement.     

Diffusion tensor imaging-based tissue segmentation: validation and application to the developing child and adolescent brain

We present and validate a novel diffusion tensor imaging (DTI) approach for segmenting the human whole-brain into partitions representing grey matter (GM), white matter (WM) and cerebrospinal fluid (CSF). The approach utilizes the contrast among tissue types in the DTI anisotropy vs. diffusivity rotational invariant space. The DTI-based whole-brain GM and WM fractions (GMf and WMf) are contrasted with the fractions obtained from conventional magnetic resonance imaging (cMRI) tissue segmentation (or clustering) methods that utilized dual echo (proton density-weighted (PDw)), and spin-spin relaxation-weighted (T2w) contrast, in addition to spin-lattice relaxation weighted (T1w) contrasts acquired in the same imaging session and covering the same volume. In addition to good correspondence with cMRI estimates of brain volume, the DTI-based segmentation approach accurately depicts expected age vs. WM and GM volume-to-total intracranial brain volume percentage trends on the rapidly developing brains of a cohort of 29 children (6-18 years). This approach promises to extend DTI utility to both micro and macrostructural aspects of tissue organization.     

Hypotonicity-Induced Renin Exocytosis from Juxtaglomerular Cells Requires Aquaporin-1 and Cyclooxygenase-2

The mechanism by which extracellular hypotonicity stimulates release of renin from juxtaglomerular (JG) cells is unknown. We hypothesized that osmotically induced renin release depends on water movement through aquaporin-1 (AQP1) water channels and subsequent prostanoid formation. We recorded membrane capacitance (C_m) by whole-cell patch clamp in single JG cells as an index of exocytosis. Hypotonicity increased C_m significantly and enhanced outward current. Indomethacin, PLA₂ inhibition, and an antagonist of prostaglandin transport impaired the C_m and current responses to hypotonicity. Hypotonicity also increased exocytosis as determined by a decrease in single JG cell quinacrine fluorescence in an indomethacin-sensitive manner. In single JG cells from COX-2^{−/ −} and AQP1^{−/ −} mice, hypotonicity increased neither C_m nor outward current, but 0.1-μM PGE₂ increased both in these cells. A reduction in osmolality enhanced cAMP accumulation in JG cells but not in renin-producing As4.1 cells; only the former had detectable AQP1 expression. Inhibition of protein kinase A blocked the hypotonicity-induced C_m and current response in JG cells. Taken together, our results show that a 5 to 7% decrease in extracellular tonicity leads to AQP1-mediated water influx in JG cells, PLA₂/COX-2-mediated prostaglandin-dependent formation of cAMP, and activation of PKA, which promotes exocytosis of renin.Juxtaglomerular (JG) granular cells in the terminal part of the renal afferent glomerular arterioles are the only cells in the organism that synthesize preprorenin, process it to active renin, and store active renin in mature secretory granules. The rate of renin granule exocytosis determines the level of activation of the renin-angiotensin-aldosterone system. Renin secretion from most^1,2 but not all^3,4 in vitro preparations displays a uniquely high sensitivity to changes in extracellular osmolality such that a moderate reduction in the extracellular osmolality leads to rapid increases in renin secretion. The sensing and transduction events for renin release in response to osmotic perturbations are not known. At the glomerular tuft, the extracellular osmolality may vary depending on sodium chloride (NaCl)transport rate by the adjacent macula densa and thick ascending limb cells, which are relatively water impermeable.^5,6 JG cell capacitance (C_m), an index of cell surface area, increased when extracellular osmolality was decreased by 5 to 10% at the single cell level.⁷ This observation shows exocytotic release of renin in response to decreases in extracellular osmolality.⁷ Introduction of a pipette solution with slightly increased osmolality to the cell cytoplasm is sufficient to initiate exocytosis of renin in JG cells.⁷ This indicates that cell swelling, and not granule swelling, is involved in the response and shows that sensing and transduction of the initial change in osmolality is not dependent on an extracellular receptor for the agent used (e.g., sucrose or mannitol), as shown recently to be the case for succinate.⁴ The estimated number of granules recruited for exocytosis by a hypotonic extracellular challenge corresponded closely to the number that fused after receptor-dependent activation of cAMP formation.⁷ The existing data predict an involvement of water fluxes across the JG cell membrane, but aquaporin water channels have not been demonstrated in JG cells. Marked cell swelling normally initiates a regulatory volume decrease response whereby the cell, through coordinated activation of ion and organic osmolyte efflux, regains cell volume.⁸ A distinct role for phospholipase A2 (PLA₂) and prostaglandin E2(PGE₂) EP2 receptors in swelling-induced activation of regulatory processes in single cells has been demonstrated.⁹ Prostaglandin E₂ and PGI₂ enhance outward current and renin secretion from JG cells.¹⁰ In the study presented here, we hypothesized that JG cells respond to a decrease in extracellular osmolality by water uptake, Cyclooxygenase (COX)-dependent prostaglandin formation and renin release. The hypotheses were tested using single JG cells subjected to whole-cell patch-clamp analysis and primary cultures enriched in JG cells from rats, wild-type mice, and mice with targeted deletions of COX-2 and aquaporin-1 (AQP1).     

Oral vitamin D supplementation reduces the incidence of eucalcemic PTH elevation after surgery for primary hyperparathyroidism

BACKGROUND: As many as 43% of patients will have normocalcemic intact parathyroid hormone (PTH) elevation after undergoing curative parathyroidectomy for primary hyperparathyroidism. This phenomenon may be due in part to an absolute or relative deficiency of vitamin D, which is under-recognized in patients with primary hyperparathyroidism. METHODS: From September 1, 2004, to September 30, 2005, 86 consecutive patients underwent parathyroidectomy for primary sporadic hyperparathyroidism (psHPT). The patients were segregated into 2 groups based on postoperative management. Group 1 was composed of 26 patients who received routine oral calcitriol and calcium carbonate postoperatively. The 60 patients in the second group (group 2) received calcium carbonate postoperatively at the discretion of the primary surgeon. RESULTS: A total of 85 patients (99%) achieved postoperative cure with sustained reduction in serum calcium. Within 30 days postoperatively, mean serum PTH levels normalized in both groups (41 +/- 31 vs 39 +/- 31 pg/ml; P = .91). However, at 1 to 3 months postoperatively, mean serum calcium levels remained similar (9.5 +/- 0.7 vs 9.3 +/- 0.5 mg/dl; P = .39) whereas mean serum PTH levels in groups 1 and 2 were 43 +/- 25 pg/ml and 67 +/- 45 pg/ml (P = .02), respectively. At 4 to 6 months postoperatively, mean PTH was again higher in group 2 (36 +/- 22 vs 67 +/- 35; P = .03), whereas mean serum calcium levels were normal (9.2 +/- 0.8 vs 9.6 +/- 0.4 mg/dl; P = .18). The incidence of postoperative normocalcemic PTH elevation was significantly higher in group 2 at 1 to 3 months (14% vs 39%; P = .04) and at 7 to 12 months (22% vs 83%; P = .04). CONCLUSIONS: Vitamin D supplementation following parathyroidectomy for primary hyperparathyroidism reduces the incidence of postoperative eucalcemic PTH elevation.