Increased Intra-abdominal Pressure Induces Acute Kidney Injury in an Experimental Model of Congestive Heart Failure.

BACKGROUND: Congestive heart failure (CHF) entails a complex interaction between the heart and the kidney that represents a clinical entity called cardiorenal syndrome (CRS). One of the mechanisms underlying CRS includes increased intra-abdominal pressure (IAP). We examined the effect of elevated IAP on kidney function in rats with low- and high-output CHF. METHODS AND RESULTS: Rats with compensated and decompensated CHF induced by means of aortocaval fistula, rats with myocardial infraction (MI) induced by means of left anterior descending artery ligation, and sham control rats were subjected to either 10 or 14 mm Hg IAP. Urine flow (V), Na+ excretion (UNaV), glomerular filtration rate (GFR), and renal plasma flow (RPF) were determined. The effects of pretreatment with tadalafil (10 mg/kg orally for 4 days) on the adverse renal effects of IAP were examined in decompensated CHF and MI. Basal V and GFR were significantly lower in rats with decompensated CHF compared with sham control rats. Decompensated CHF rats and MI rats subjected to 10 and 14 mm Hg IAP exhibited more significant declines in V, UNaV, GFR and RPF than compensated and sham controls. Elevated IAP also induced tubular injury, as evidenced by significantly increased absolute urinary excretion of neutrophil gelatinase-associated lipocalin. In addition, in a nonquantitative histologic analysis, elevated IAP was associated with increase in necrosis and cell shedding to the tubule lumens, especially in the decompensated CHF subgroup. Pretreatment of decompensated CHF rats and MI rats with tadalafil ameliorated the adverse renal effects of high IAP. CONCLUSIONS: Elevated IAP contributes to kidney dysfunction in high- and low-cardiac output CHF. IAP induces both hemodynamic alterations and renal tubular dysfunction. These deleterious effects are potentially reversible and can be ameliorated with the use of phosphodiesterase-5 inhibition.

[SHOULD PATIENTS WITH PRIMARY HYPERPARATHYROIDISM AND NEGATIVE IMAGING STUDIES BE REFERRED TO SURGERY?]

INTRODUCTION: Parathyroidectomy is the only curative treatment for primary hyperparathyroidism (PHPT). In cases where imaging fails to demonstrate an adenoma, a bilateral neck exploration (BNE) is performed. Negative imaging is thought to predict surgical failure, and patients with negative imaging are often not referred for surgery. These patients are at risk for disease progression. AIMS: Evaluate the effect of negative imaging on surgical findings and the cure rate in patients with PHPT. METHODS: A total of 133 patients underwent parathyroidectomy for PHPT. Data were retrospectively retrieved including preoperative imaging, surgical findings and results. A comparison was conducted between patients with negative and positive imaging. The main outcome measure was cure. RESULTS: A negative MIBI (methoxy-isobutyl-isonitrile) scan was seen in 30 (22%) patients and a negative US in 46 (34.5%). Patients with negative MIBI scan more commonly underwent BNE compared with patients with a positive scan (53% vs. 25%, respectively, p=0.0046). Patients with negative imaging had a significantly higher rate of multigland disease compared with patients with positive imaging (35% vs. 12%, p=0.004, for the MIBI scan; 27% vs. 12%, p=0.024, for the US, respectively). Overall cure rate was 96%. Highest cure rates were seen in patients with both positive MIBI and US (99% cure rate) and lowest cure rates of 67% in patients with triple negative imaging (MIBI scan, US and 4DCT (Dual computed tomography)) (p=0.003). CONCLUSIONS: Localization of an adenoma in preoperative imaging predicts very high cure rates in patients with PHPT. Negative imaging increases the risk for multigland disease and is associated with lower cure rates.

Negative Fine-Needle Aspiration in Patients with Goiter: Should We Doubt It?

BACKGROUND: Epidemiologic studies demonstrated higher incidence of thyroid cancer in patients with multinodular goiters compared to the general population. The aim of this study was to evaluate the risk of finding significant thyroid cancer in patients undergoing thyroidectomy for presumed benign disease. METHODS: The records of 273 patients operated for indications other than cancer or indeterminate cytology were reviewed and analyzed. RESULTS: 202 (74%) patients had a preoperative fine-needle aspiration (FNA) performed. FNA was benign in 96% of patients and non-diagnostic in 4%. Malignancy was unexpectedly found in 50 (19%) patients. Papillary carcinoma constituted 94% of cancers and 86% of cancers were incidental microcarcinomas. Only 7 (2.6%) patients of the entire cohort had tumors greater than 1 cm, of those only 3 had a previous benign FNA (false-negative rate 1.5%). CONCLUSIONS: The rate of significant thyroid cancer found unexpectedly in resected goiters is extremely low. A negative FNA excludes significant cancer with near certainty.

Parathyroid surgery in the elderly: should minimally invasive surgery be abandoned?

BACKGROUND: Single adenoma is the cause of 80 % of primary hyperparathyroidism (PHPT) resulting in wide acceptance of minimally invasive parathyroidectomy (MIP). The incidence of PHPT increases with age. Little information is available regarding the prevalence of multiglandular disease (MGD) in older patients. METHODS: The records of 537 patients that underwent parathyroid surgery between January 2005 and October 2012 at two endocrine surgery referral centers were retrospectively reviewed. Comparison was performed between patients younger than 65 and older than 65 years of age. Clinical variables included preoperative laboratories and imaging, extent of neck exploration, number of glands excised, and intraoperative parathyroid hormone levels during surgery. RESULTS: There were 374 (70 %) patients in the younger age group (YG) and 163 (30 %) patients in the older age group (OG). The mean age was 50 ± 0.5 and 71 ± 0.4 years, respectively. There was no difference between the groups in terms of gender or laboratory results. MGD was significantly more common in the OG (24 % vs. 12 %; p = 0.001) and similarly MIP was less commonly completed in the OG (49 % vs. 68 %; p < 0.001). Cure rates were comparable between the OG and YG (93 % vs. 95 %; p = 0.27). In the OG, patients with MGD had significantly smaller glands as compared to patients with single adenomas in this group (331 ± 67 vs. 920 ± 97 mg; p = 0.006, respectively). CONCLUSIONS: MGD in PHPT was found to be more prevalent in older patients. Planning a bilateral neck exploration should be considered in older patients, especially when a relatively small gland is suggested by imaging or encountered during surgery.

The use of VivaSight™ single lumen endotracheal tube in morbidly obese patients undergoing laparoscopic sleeve gastrectomy.

BACKGROUND: The population of obese patients is progressively growing and bariatric operations are becoming increasingly common. Morbidly obese patients require special anesthetic care and are often considered to be difficult to ventilate and intubate. The VivaSight™ Single Lumen tube is an endotracheal tube with a camera embedded in its tip. The view from the tip appears continuously on a monitor in the anesthesiologist's vicinity. The aim of this study was to assess the VivaSight™ in comparison with conventional endotracheal tube as an aid in the intubation and surveillance of tube position during surgery of obese patients. METHODS: This is a prospective study of 72 adult obese patients who underwent laparoscopic sleeve gastrectomy. The patients were randomly assigned to be intubated by either the VivaSight™ (40 patients, test group) or a conventional endotracheal tube (32 patients, control group). Data on the patients, the pre-operative airway evaluation, the endotracheal intubation and the post-operative outcome were collected and compared. RESULTS: The Mallampati scores were significantly higher in the test group than in the control group. Endotracheal intubation took 29 ± 10 and 24 ± 8 seconds using the VivaSight™ and a conventional tube respectively (p = 0.02). Three of the patients in the control group, while none of those in the test group, had soft tissue injury (p < 0.05). CONCLUSION: We found the VivaSight™ SL to be helpful in the endotracheal intubation and continuous surveillance of tube position in morbidly obese patients undergoing laparoscopic sleeve gastrectomy.

Phosphodiesterase-5 inhibition attenuates early renal ischemia-reperfusion-induced acute kidney injury: assessment by quantitative measurement of urinary NGAL and KIM-1.

Acute kidney injury (AKI) is a common clinical problem that still lacks effective treatment. Phosphodiesterase-5 (PDE5) inhibitors possess anti-apoptotic and anti-oxidant properties, making it a promising therapy for ischemia-reperfusion (I/R) injury of various organs. The present study evaluated the early nephroprotective effects of Tadalafil, a PDE5 inhibitor, in an experimental model of renal I/R. Sprague-Dawley rats were divided into two groups: vehicle-treated I/R (n = 10), and Tadalafil (10 mg/kg po)-treated I/R group (n = 11). After removal of the right kidney and collection of two baseline urine samples, the left renal artery was clamped for 45 min followed by reperfusion for 60, 120, 180, and 240 min. Functional and histological parameters of the kidneys from the various groups were determined. In the vehicle-treated I/R group, glomerular filtration rate was significantly reduced compared with that in normal kidneys. In addition, the ischemic kidney showed remarkable cast formation, necrosis, and congestion, a consistent pattern of acute tubular necrosis. Furthermore, urinary excretion of NGAL and KIM-1, two novel biomarkers of kidney injury, substantially increased following I/R insult. In contrast, Tadalafil treatment resulted in a significant improvement in kidney function and amelioration of the adverse histological alterations of the ischemic kidney. Noteworthy, the urinary excretion of NGAL and KIM-1 markedly decreased in the Tadalafil-treated I/R group. These findings demonstrate that Tadalafil possesses early nephroprotective effects in rat kidneys subjected to I/R insult. This approach may suggest a prophylactic therapy for patients with ischemic AKI.

Urinary NGAL and KIM-1: biomarkers for assessment of acute ischemic kidney injury following nephron sparing surgery.

PURPOSE: Nephron sparing surgery is considered the treatment of choice in most patients with confined renal cancer. Interrupting renal blood flow is often necessary during such surgery, which can induce significant renal injury. We explored the possibility of using urinary NGAL and KIM-1 excretion as novel biomarkers to assess the extent of acute kidney injury after nephron sparing surgery. MATERIALS AND METHODS: The study group included 27 patients who underwent open nephron sparing surgery for enhancing solid renal tumors. During surgery the renal artery was clamped for between 6 and 47 minutes. Urine samples were collected before surgery, and 1, 3, 8, 24, 48 and 72 hours after renal pedicle clamp removal. Urinary levels of NGAL and KIM-1 were determined. RESULTS: Renal artery clamping induced renal injury, as reflected by increased urinary NGAL and KIM-1 in all participants. These increases in urinary NGAL excretion were evident after 1 hour of renal ischemia and lasted for 72 hours. Urinary NGAL correlated with the serum creatinine increase and ischemia duration. Compared with patients without significantly increased serum creatinine, those with significantly increased serum creatinine after nephron sparing surgery had a greater increase in urinary NGAL but not in KIM-1. CONCLUSIONS: Renal injury severity after nephron sparing surgery could be quantitatively assessed by measuring urinary NGAL and KIM-1.

Acute obstructive jaundice and chronic cirrhosis protect against the adverse renal effects of pneumoperitoneum: role of nitric oxide.

BACKGROUND: Obstructive jaundice and cirrhosis are associated with impaired renal function. Previously we demonstrated that increased intra-abdominal pressure (IAP, pneumoperitoneum) in normal rats induced renal dysfunction. This study investigated the renal effects of pneumoperitoneum in rats with acute jaundice and cirrhotic rats. METHODS: Following a baseline period, rats with obstructive jaundice or cirrhosis induced by acute or chronic bile duct ligation (BDL), respectively, and their sham-controls were subjected to consecutive IAPs of 10 and 14 mmHg for 45 min each. Urine flow (V), Na(+) excretion (UNaV), glomerular filtration rate (GFR), renal plasma flow (RPF), and urinary NO metabolites ([Formula: see text]) and cGMP (UcGMP) were determined. RESULTS: Elevating IAP from 0 to 10 and 14 mmHg in normal rats caused IAP-dependent reductions in V, UNaV, GFR, RPF, [Formula: see text] and UcGMP. Basal renal function and hemodynamics were lower in rats with obstructive jaundice. In contrast to normal rats, application of elevated IAP of 10 and 14 mmHg significantly improved V, UNaV, GFR, RPF, and MAP along with increased [Formula: see text] and preserved UcGMP. Similarly, when identical IAP conditions were applied to cirrhotic rats, no deleterious changes in V, UNaV, GFR or RPF were observed. CONCLUSIONS: Application of pneumoperitoneum to rats with acute BDL improves kidney function and renal hemodynamics. Likewise, increased IAP does not exert adverse renal effects in cirrhotic rats. These effects are distinct from the deleterious renal consequences of increased IAP in normal rats. Perturbations in the generation of NO/cGMP during IAP in normal rats but not in rats with BDL or cirrhosis may contribute to these differences.

[4-dimensional computed tomography for localization of parathyroid adenoma].

INTRODUCTION: In about 85% of patients with primary hyperparathyroidism (pHPT) only a single parathyroid gland is diseased. The operation of choice in this group of patients is minimally invasive parathyroidectomy (MIP). In order to perform an MIP, the diseased gland should be identified prior to surgery. This is not always possible with the routine imaging studies including parathyroid sestamibi scan and ultrasound. Four-dimensional computed tomography (4D-CT) scanning was developed in order to identify an enlarged parathyroid gland. Several characteristics make it possible to identify glands of this type and to differentiate it from other neck nodes. PURPOSE: To evaLuate the accuracy of 4D-CT in the identification of parathyroid adenoma/s in order to perform an MIP. METHODS: A total of 69 patients underwent parathyroidectomy for pHPT during the period July 2010 to June 2012. The 4D-CT was performed on 27 patients. Data were retrospectively extracted from the patients' charts including imaging studies, operative notes, number and LocaLization of glands excised and pathological reports. RESULTS: The 4D-CT was positive for a single adenoma in 26 patients confirmed in surgery. In 4 of those patients, one or two additional glands were found enlarged during surgery. Sixteen patients underwent an MIP, 3 patients had a unilateraL exploration and in 8 cases a biLateraL exploration was performed. The 4D-CT had a sensitivity of 81.4% and a positive predictive value of 100% in this group of patients. CONCLUSIONS: The 4D-CT is another tool for the identification of enlarged parathyroid gLand/s before surgery. Further study is needed to determine its place in the current armamentarium of pre-operative localization studies.

Vasopressin-2 receptor antagonist attenuates the ability of the lungs to clear edema in an experimental model.

In the last two decades, the role of the alveolar active sodium transport was extensively studied and was found to play a crucial role in regulating alveolar fluid clearance (AFC), and thus in keeping the airspaces free of edema. The recent development of highly selective nonpeptide vasopressin-receptor antagonists gives us a rare chance to explore the role of vasopressin in the pathogenesis of lung edema. Therefore, the present study examined the involvement of vasopressin in modulating the ability of the lung to clear edema. Vasopressin enhanced the rate of lung edema clearance by 30% as compared with untreated control rats (from 0.49 ± 0.02 to 0.64 ± 0.02 ml/h), whereas V(2) receptor antagonists significantly decreased the ability of the lung to clear water (from 0.64 ± 0.02 to 0.31 ± 0.06 ml/h; P < 0.0001). In contrast, V(1) receptor antagonist did not change the rate of AFC. The administration of ouabain (a Na,K-ATPase inhibitor) and amiloride (a Na(+) channel blocker) inhibited the stimulatory effects of vasopressin (from 0.64 ± 0.02 to 0.22 ± 0.02 ml/h [P < 0.0001] and from 0.64 ± 0.017 to 0.23 ± 0.02 ml/h [P < 0.0001], respectively). Vasopressin significantly increased Na,K-ATPase protein abundance in the basolateral membranes of the alveolar epithelial cells via V(2) receptor activation. We report a novel role of the vasopressin pathway in AFC. This observation indicates a beneficial role of vasopressin in AFC by up-regulating active sodium transport.

Pneumoperitoneum aggravates renal function in cases of decompensated but not compensated experimental congestive heart failure: role of nitric oxide.

PURPOSE: Congestive heart failure is associated with impaired renal function. Previously we noted that increased intra-abdominal pressure (pneumoperitoneum) in normal rats induced renal dysfunction. In this study we investigated the renal effects of pneumoperitoneum in rats with compensated (urinary Na(+) excretion greater than 1,200 µEq per 24 hours) and decompensated (urinary Na(+) excretion less than 200 µEq per 24 hours) congestive heart failure, and the possible involvement of nitric oxide in these effects. MATERIALS AND METHODS: After a baseline period rats with congestive heart failure induced by aorto-caval fistula and sham operated controls underwent consecutive intra-abdominal pressures of 7, 10 or 14 mm Hg for 45 minutes each. Urinary flow, urinary Na(+) excretion, glomerular filtration rate, renal plasma flow and urinary nitric oxide metabolites were determined. RESULTS: There were no changes in urinary flow, urinary Na(+) excretion, glomerular filtration rate or renal plasma flow during 7 mm Hg insufflation in controls. However, significant decreases in these parameters were observed during 10 and 14 mm Hg in correlation with intra-abdominal pressure. Baseline renal function and hemodynamics were lower in rats with congestive heart failure in correlation with disease severity. Rats with decompensated congestive heart failure that underwent 10 and 14 mm Hg showed aggravated decreases in urinary flow, urinary Na(+) excretion, glomerular filtration rate and renal plasma flow. In contrast, no adverse renal effects were observed in rats with compensated congestive heart failure under identical intra-abdominal pressure conditions. Despite unaltered baseline urinary nitric oxide metabolites in the 2 congestive heart failure subgroups, the decompensated group showed decreased urinary nitric oxide metabolites after 14 mm Hg. Finally, rats with compensated congestive heart failure pretreated with the nitric oxide synthase inhibitor L-NAME showed worse renal function in response to pneumoperitoneum. CONCLUSIONS: Decompensated congestive heart failure renders rats susceptible to the adverse renal effects of pneumoperitoneum, a phenomenon that may involve alterations in the renal nitric oxide system.

[Neutrophil gelatinase-associated lipocalin (NAGL): a novel biomarker for acute kidney injury].

The incidence of both acute and chronic kidney diseases is persistently increasing and is reaching epidemic proportions. Early therapeutic intervention may significantly decrease the morbidity and mortality rates among these patients. However, the lack of early non-invasive biomarkers has hampered our ability to diagnose kidney diseases as early as possible, and subsequently, to initiate timely, effective, and appropriate treatment. Until recently, no biomarker for kidney disease, except for creatinine was available to clinicians in general and nephrologists in particular. Unfortunately, creatinine is an unreliable indicator during acute and chronic changes in kidney function, since serum creatinine concentrations can vary widely with age, gender, muscle mass, muscle metabolism, medications and hydration status. Secondly, serum creatinine concentrations may not change until a significant amount of kidney function (50-60%) has already been lost. In the last few years various specific biomarkers for kidney diseases were discovered and the most reliable representative is neutrophil gelatinase-associated lipocalin (NGAL), which is the focus of this review. Several studies have demonstrated that plasma and urinary NGAL levels increase two hours after the induction of acute kidney injury (AKI) in several clinical situations such as cardiac surgery, radiocontrast nephropathy, kidney transplantation, hemolytic uremic syndrome and critically ill patients in intensive care unit. Serum and urine concentrations of NGAL increase before those of creatinine, making this biomarker a powerful tool for early detection of renal disease, thus hopefully to reduce the high mortality rate among patients with AKI.

Nitric oxide synthase inhibition aggravates the adverse renal effects of high but not low intraabdominal pressure.

BACKGROUND: Previously, the authors demonstrated that an intraabdominal pressure (IAP) of 14 mmHg in normal rats reduced kidney function/hemodynamics. These adverse effects are related to interference with the nitric oxide (NO) system. This study was designed to compare the effects of NO synthase (NOS) inhibition on kidney function/hemodynamics during increases in IAP from 0 mmHg to 7, 10, and 14 mmHg. METHODS: The rats were divided into six groups. After an IAP of 0 (baseline), the first three groups were subjected to increasing IAPs as follows: 7 mmHg (group 1), 10 mmHg (group 2), and 14 mmHg (group 3). Each pressure was applied for 1 h, followed by a deflation period of 60 min (recovery). An additional three groups were pretreated with nitro-L: -arginine methyl ester (L: -NAME), an NOS inhibitor, before pressures of 7 mmHg (group 4), 10 mmHg (group 5) and 14 mmHg (group 6) were applied for 1 h. Urine flow rate (V), Na(+) excretion (U(Na)V), glomerular filtration rate (GFR), and renal plasma flow (RPF), were determined throughout the experiments. RESULTS: There were no significant changes in V, U(Na)V, GFR, or RPF during 7-mmHg insufflation. However, significant reductions in these parameters were observed during 10 and 14 mmHg, with V decreasing from 9.95 + or - 1.34 microl/min to 6.8 + or - 1.1 and 6.1 + or - 0.5 microl/min (p < 0.05) and U(Na)V decreasing from 1.29 + or - 0.28 to 0.43 + or - 0.32 muEq/min (p < 0.05), and 0.39 + or - 0.09 muEq/min (p < 0.05). These alterations in excretory functions were associated with considerable declines in GFR, from 1.98 + or - 0.2 to 1.05 + or - 0.18 ml/min (p < 0.05) and 0.95 + or - 0.06 ml/min (p < 0.05) and RPF from 8.66 + or - 0.62 to 3.94 + or - 0.88 ml/min (p < 0.05) and 3.08 + or - 0.71 ml/min (p < 0.05), respectively. When the animals were pretreated with L: -NAME, the adverse renal effects of an IAP of 14 mmHg, but not 10 mmHg, were substantially aggravated. CONCLUSION: Decreased renal function/perfusion is induced by IAP pressures of 10 and 14 mmHg but not 7 mmHg. Inhibition of NOS aggravates the adverse renal effects of high (14 mmHg) but not low (7 or 10 mmHg) IAP, indicating that NO deficiency may contribute to the renal dysfunction during high IAP.

Impact of Pneumoperitoneum on the Development of Acute Kidney Injury: Comparison Between Normal and Diabetic Rats.

BACKGROUND: Minimally invasive surgery is considered the gold-standard approach for many surgical procedures. However, it requires CO2 insufflation and elevated intra-abdominal pressure (IAP), which may result in adverse pulmonary, cardiovascular, gastrointestinal, and renal changes. The kidneys are highly sensitive to pressure changes, where risk factors such as severe infection, dehydration, older age, and chronic kidney disease may aggravate the likelihood for the development of acute kidney injury (AKI). Unfortunately, the impact of diabetes mellitus on the deleterious effects of elevated IAP-induced AKI was not fully studied so far. The present study was designed to examine the effect of pneumoperitoneum on renal function and the development of AKI in diabetic rats. MATERIALS AND METHODS: Sprague Dawley rats were divided into 2 groups: control (nondiabetic) rats (n=7) and diabetic rats (n=10). A Veress needle was introduced through the supravesical incision where inflating CO2 allowing the IAP to be increased to the desired pressures 7, 10, and 14 mm Hg for 45 minutes each and at the end of the experiment, the pressure was deflated to zero. During each pressure point, hemodynamic parameters were recorded and urine and blood samples were collected for analysis. RESULTS: The baseline values of renal hemodynamic were significantly lower in diabetic rats. There were no major statistically significant changes from baseline in urinary flow, urinary sodium excretion (UNaV), glomerular filtration rate, and renal plasma flow during 7 mm Hg pressure in both groups. When the IAP was further elevated, a significant deterioration of these parameters was recorded. This trend was more pronounced among diabetic rats. When examining urinary neutrophil gelatinase-associated lipocalin, a linear correlation was observed between the IAP and the biomarker level. This correlation was more significant in the diabetic group. CONCLUSION: The present study demonstrated a direct correlation between IAP elevation and the development of AKI. Diabetic rats were more sensitive to the deleterious effect of pneumoperitoneum, where urinary neutrophil gelatinase-associated lipocalin levels may be used as a future biomarker to predict postoperative AKI, especially in patients with diabetes.

Urinary excretion of endothelin receptors ET A and ET B in hypertensive patients and normotensive subjects.

BACKGROUND/AIMS: Endothelin (ET)-1 is produced by most renal cell types. Renal tubular and vascular cells express both the ET receptors ET(A) and ET(B). Since significant amounts of ET-1 of renal origin were detected in human urine, urinary ET-1 has been used as an index for the capacity of renal ET-1 production. Here, we determine the existence of additional components of the intrarenal ET system, namely the ET(A) and ET(B) receptor subtypes, in the urine of normal and hypertensive subjects. METHODS: ET(A) and ET(B) receptors were detected in urine samples that were concentrated by TCA precipitation, Speedvac or ProteoSpin. RESULTS: Analysis of the human urine extracts revealed the existence of approximately 50 and 55 kDa of immunoreactive proteins, corresponding to ET(B) and ET(A), respectively, indicating that intact ET(A) and ET(B) are excreted in the urine of healthy subjects and hypertensive patients. Normotensive and hypertensive subjects had statistically comparable ET(B) excretion normalized to creatinine (0.58 +/- 0.16 vs. 0.83 +/- 0.17 microg/mg creatinine, respectively; p = 0.304). In contrast, ET(A) excretion was higher among hypertensive subjects (0.05 +/- 0.01 vs. 0.11 +/- 0.02 microg/mg creatinine; p = 0.0451). Immunostaining of ET(A) and ET(B) in the human urinary system revealed expression of both receptors, principally in tubular cells (mainly in medullary collecting ducts) and in the bladder urothelium, and ET(A) expression in the peritubular capillaries and arterioles. Urinary ET receptors closely and inversely correlated with indices of urine concentration, suggesting that their shedding is principally affected by urine flow. CONCLUSION: ET receptors are present in human urine, conceivably originating within the urinary system. Their excretion is principally affected by urinary concentration. It remains to be determined whether urinary ET(A)/ET(B) is of physiological/pathophysiological relevance.

Impact of pneumoperitoneum on renal perfusion and excretory function: beneficial effects of nitroglycerine.

BACKGROUND: Increased intra-abdominal pressure (IAP) (pneumoperitoneum) during laparoscopic surgery may result in adverse effects on kidney function. The mechanisms underlying this phenomenon have not been fully determined. OBJECTIVE: The present study was designed to: (1) investigate the effects of incremental increases in IAP on renal function in normal rats and (2) evaluate whether the nitric oxide (NO) system is involved in renal dysfunction characterizing pneumoperitoneum. METHODS: Male rats were organized into two groups. The first group was subjected to IAP of 0 (baseline), 7 or 14 mmHg, over 1 h for each pressure, followed by a deflation period of 60 min (recovery). Two additional groups were pretreated with: (1) non-depressor dose of nitroglycerine (NTG) and (2) nitro-L-arginine-methylester (L-NAME), an NO synthase inhibitor, before applying 14 mmHg for 1 h. Urine flow rate (V), Na+ excretion (U(Na)V), glomerular filtration rate (GFR), renal plasma flow (RPF), and blood pressure were determined throughout the experiments. RESULTS: There were no significant changes in V, U(Na)V, GFR, and RPF during 7 mmHg insufflation. However, significant reductions in these parameters were observed during 14 mmHg: V from 8.49 +/- 0.92 to 6.12 +/- 0.54 microl/min, U(Na)V from 1.29 +/- 0.28 to 0.39 +/- 0.09 microEq/min, and FE(Na) from 0.37 +/- 0.11 to 0.27 +/- 0.04%. These alterations in excretory functions were associated with a considerable decline in GFR from 1.85 +/- 0.09 to 0.88 +/- 0.09 ml/min, p < 0.05, (-46.3 +/- 5.2% from baseline) and RPF from 8.66 +/- 0.62 to 4.33 +/- 0.49 ml/min, p < 0.05, (-51.93 +/- 5.24% from baseline), without a significant change in mean arterial blood pressure (MAP). When the animals were pretreated with NTG, the adverse effects of pneumoperitoneum on V, U(Na)V, GFR, and RPF were substantially improved, suggesting that NO system plays a beneficial counter-regulatory role during laparoscopy. In line with this notion, pretreatment with L-NAME remarkably aggravated pneumoperitoneum-induced renal hypoperfusion and dysfunction. CONCLUSION: Decreased renal perfusion and function are induced by IAP pressure of 14 mmHg. These adverse effects are probably related to interference with the NO system, and could be partially ameliorated by pretreatment with NTG.

Effects of novel vasopressin receptor antagonists on renal function and cardiac hypertrophy in rats with experimental congestive heart failure.

Arginine vasopressin (AVP) plays an important role in renal hemodynamic alterations, water retention, and cardiac remodeling in congestive heart failure (CHF). The present study evaluated the acute and chronic effects of vasopressin V(1a) receptor subtype (V(1a)) and vasopressin V(2) receptor subtype (V(2)) antagonists on renal function and cardiac hypertrophy in rats with CHF. The effects of acute administration of SR 49059 [(2S)1-[(2R,3S)-5-chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxybenzene-sulfonyl)-3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2-carboxamide)] (0.1 mg/kg) and SR 121463B (1-[4-(N-tert-butylcarbamoyl)-2-methoxybenzenesulfonyl]-5-ethoxy-3-spiro-[4-(2-morpholinoethoxy)cyclohexane]indol-2-one, fumarate; equatorial isomer) (0.3 mg/kg), V(1a) and V(2) antagonists, respectively, on renal function, and of chronic treatment (3.0 mg/kg/day for 7 or 28 days, via osmotic minipumps or p.o.), on water excretion and cardiac hypertrophy were studied in rats with aortocaval fistula and control rats. CHF induction increased plasma AVP (12.8 +/- 2.5 versus 32.2 +/- 8.3 pg/ml, p < 0.05). Intravenous bolus injection of SR 121463B to controls produced dramatic diuretic response (from 5.5 +/- 0.8 to 86.3 +/- 21.9 microl/min; p < 0.01). In contrast, administration of SR 49059 did not affect urine flow. Likewise, administration of SR 121463B, but not SR 49059, to rats with CHF significantly increased urinary flow rate from 20.8 +/- 6.4 to 91.6 +/- 26.5 microl/min (p < 0.01). The diuretic effects of SR 121463B were associated with a significant decline in urinary osmolality and insignificant change of Na+ excretion. In line with its acute effects, chronic administration of SR 121463B to CHF rats increased daily urinary volume 2 to 5-fold throughout the treatment period. Both SR 121463B and SR 49059 significantly reduced heart weight in CHF rats when administered for 4 weeks, but not 1 week. These results suggest that V(2) and V(1a) antagonists improve water balance and cardiac hypertrophy in CHF and might be beneficial for the treatment of water retention and cardiac remodeling in CHF.

Primary Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Stomach.

Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) is a tumor of small round cells arising in skeletal tissues. These tumors rarely arise in the stomach. We present a 31-year-old healthy female patient who was admitted to our surgical ward due to upper gastrointestinal hemorrhage. Upper endoscopy revealed a large ulcerated bleeding mass originating from the lesser curvature. Biopsy revealed tumor cell immunoreactivity positive for CD99, vimentin, and Ki67 (an index of proliferation). These findings were compatible with gastric ES/PNET. The fluorescence in situ hybridization analysis result for the EWSR1 gene rearrangement (11: 22 translocation) was positive. The patient refused neoadjuvant treatment and thus underwent an operation during which a mass at the lesser curvature of the stomach was found. The mass was adhering to the pancreatic tail and to the mesentery of the transverse and descending colon. Total gastrectomy, distal pancreatectomy, splenectomy, and left adrenalectomy were done. The patient refused adjuvant treatment. She is free of disease 3 years after surgery.

Induction of cardiac hypertrophy by a controlled reproducible sutureless aortocaval shunt in the mouse.

Much of the understanding about the pathophysiological responses to chronic cardiac overload has been gained by the use of rat and dog models of aortocaval fistula (ACF). The use of a similar model in genetically manipulated mice may further elucidate the molecular mechanisms in these responses. The only reports about ACF in mice to date have applied a needle puncture to create the ACF, which may result in an uncontrolled and irreproducible size of the shunt, and require several weeks to induce the characteristic cardiac changes. In order to obtain a more consistent approach to characterize this mode of cardiac hyperfunction, we present a surgical murine model of ACF that results in rapid progression of the typical systemic and cardiac changes. A sutureless side-to-side infrarenal surgical anastomosis of 0.6-0.8 mm in diameter was created between the abdominal aorta and inferior vena cava in ICR (Institute of Cancer Research) mice. Six to 7 days later, significant cardiac hypertrophy developed. The heart/body weight ratio increased from 0.45 +/- 0.02% in control mice to 0.77 +/- 0.03% in mice with ACF (p < .003). The dry heart weight ratio increased from 0.099 +/- 0.0033% to 0.13 +/- 0.008% (p < .006). The ACF dramatically induced the atrial and ventricular expression of atrial natriuretic factor mRNA, and increased the total cardiac content of endothelin-1 (162.5 +/- 50.6 vs. 83.9 +/- 9.0 pg). Mean arterial pressure in anesthetized mice with ACF decreased from 69.8 +/- 4.9 to 54.8 +/- 5.5 mm Hg (p < .025). Urinary sodium excretion returned to preoperative levels several days following surgery. These results demonstrate that cardiac hypertrophy could be rapidly and reproducibly achieved in mice by the placement of a surgical ACF. This model, when applied in genetically manipulated mice, may be a valuable tool for functional genomic studies about the pathogenesis of cardiac hypertrophy and heart failure.

Minimally invasive surgery for treatment of hyperparathyroidism.

BACKGROUND: Minimal invasive surgery for parathyroidectomy has been introduced in the treatment of hyperparathyroidism. OBJECTIVE: To evaluate the contribution of the sestamibi-SPECT (MIBI) localization, cervical ultrasonography, and intraoperative rapid turbo intact parathormone assay in minimal invasive parathyroidectomy. METHODS: Between August 1999 and March 2004, 146 consecutive hyperthyroid patients were treated using the MIBI and ultrasound for preoperative localization and iPTH measurements for intraoperative assessment. RESULTS: Parathyroid adenoma was detected in 106 patients, primary hyperplasia in 16, secondary hyperplasia in 16, tertiary hyperplasia in 5, and parathyroid carcinoma in 1 patient. Minimal invasive exploration of the neck was performed in 84 of the 106 patients (79.2%) with an adenoma, and in 17 of them this procedure was performed under local cervical block anesthesia in awake patients. Adenoma was correctly diagnosed by MIBI scan in 74% of the patients, and by ultrasound in 61%. The addition of ultrasonography to MIBI increased the accuracy of adenoma detection to 83%. In 2 of the 146 patients (1.4%) iPTH could not be significantly reduced during the initial surgical procedure. Minimal invasive surgery with minimal morbidity, and avoiding bilateral neck exploration, was achieved in 79.2% of patients with a primary solitary adenoma. CONCLUSIONS: Preoperative localizationof the parathyroid gland by MIBI and ultrasound together with intraoperative iPTH measurements resulted in an overall cure rate of 98.6% for the entire series, The addition of ultrasound to the MIBI scan increased the accuracy of adenoma detection.