Gene expression profile of renal proximal tubules regulated by proteinuria

BACKGROUND: Proximal tubules activated by reabsorption of protein are thought to play significant roles in the progression of kidney diseases. Thus, identification of genes related to proteinuria should provide insights into the pathological process of tubulointerstitial fibrosis. METHOD: Gene expression profiles were constructed by means of direct sequencing procedures to identify genes induced in the mouse kidney proximal tubules (PT) exposed to proteinuria. RESULTS: By comparing the gene expression of control PT to that of disease model PT, the abundantly expressed genes in control PT were down-regulated presumably because of potentially toxic effects of proteinuria. From the more than 1000 up-regulated genes, an immunity related gene, thymic shared antigen-1 (TSA-1), and a novel gene, GS188, were selected for further characterization. The increased expression of TSA-1, a member of the Ly-6 family, and of GS188 in response to proteinuria was confirmed by Northern analysis, immunohistochemistry, in situ hybridization and laser microdissection along with real-time PCR analysis. Full length cloning of GS188 identified it as a family member of LR8 that was reported to express predominantly in fibroblasts. CONCLUSIONS: The gene expression profiles showed that the expression patterns in PT were changed dramatically by proteinuria. The profiles include novel genes that should be further characterized to aid the understanding of the pathophysiology of progressive kidney diseases.     

Propofol Increases Pulmonary Artery Smooth Muscle Myofilament Calcium Sensitivity: Role of Protein Kinase C

Background: Vascular smooth muscle tone is regulated by changes in intracellular free Ca2+ concentration ([Ca2+]i) and myofilament Ca2+ sensitivity. These cellular mechanisms could serve as targets for anesthetic agents that alter vasomotor tone. This study tested the hypothesis that propofol increases myofilament Ca2+ sensitivity in pulmonary artery smooth muscle (PASM) via the protein kinase C (PKC) signaling pathway.

Methods: Canine PASM strips were denuded of endothelium, loaded with fura-2/AM, and suspended in modified Krebs- Ringer's buffer at 37[degrees]C for simultaneous measurement of isometric tension and [Ca2+]i.

Results: The KCl (30 mm) induced monotonic increases in [Ca2+]i and tension. Verapamil, an L-type Ca2+ channel blocker, attenuated KCl-induced increases in [Ca2+]i and tension to an equal extent. In contrast, propofol attenuated KCl-induced increases in [Ca2+]i to a greater extent than concomitant changes in tension and caused an upward shift in the peak tension-[Ca2+]i relation. Increasing extracellular Ca2+ in the presence of 30 mm KCl resulted in similar increases in [Ca2+]i in control and propofol-pretreated strips, whereas concomitant increases in tension were greater during propofol administration. The Ca2+ ionophore, ionomycin (0.1 [mu]m), increased [Ca2+]i to approximately 50% of the value induced by 60 mm KCl. Under these conditions, propofol (10, 100 [mu]m) caused increases in tension equivalent to 11 +/- 2 and 28 +/- 3% of the increases in tension in response to 60 mm KCl, whereas [Ca2+]i was slightly decreased. Similar effects were observed in response to the PKC activator, phorbol 12-myristate 13-acetate (PMA, 1 [mu]m). Specific inhibition of PKC with bisindolylmaleimide I before ionomycin administration decreased the propofol- and PMA-induced increases in tension and abolished the propofol- and PMA-induced decreases in [Ca2+]i. Selective inhibition of Ca2+-dependent PKC isoforms with Go 6976 also attenuated propofol-induced increases in tension.     

Management of adrenal metastasis from hepatocellular carcinoma

Purpose: Although the adrenal gland is a common site of extrahepatic metastasis from hepatocellular carcinoma (HCC), there are no definitive guidelines for the treatment of adrenal metastasis. This study examines the effectiveness of various treatments for this disease. Methods: We retrospectively analyzed 20 patients treated for adrenal metastasis of HCC by adrenalectomy (n = 13), transarterial chemoembolization (TACE), or percutaneous ethanol injection therapy (PEIT) (n = 7). Results: There were no significant differences in cumulative survival rates between patients given adrenalectomy and those given TACE or PEIT, either after completing treatment for primary HCC or after the first treatment for adrenal metastasis. Six of seven patients with tumor thrombi in the inferior vena cava (IVC) from adrenal metastasis underwent adrenalectomy combined with intracaval thrombectomy, five of whom survived for more than 1 year after surgery, and two of whom are still alive without any recurrence more than 3 years after surgery. PEIT showed good results for small adrenal metastasis. Conclusion: These findings suggest that therapeutic modalities should be chosen according to the clinical features of each individual, including the size of the metastatic tumor, whether there is invasion into the IVC, the function of the remaining liver, and the existence of intra- and/or nonadrenal extrahepatic lesions. Furthermore, intracaval tumor thrombectomy could be indicated for patients with IVC thrombus if they are suitable candidates for surgery. Received: July 9, 2001 / Accepted: July 2, 2002 Reprint requests to: Y. Shimahara     

New Pancreatic Duct-Invagination Anastomosis Using UltrasonicDissection for Nonfibrotic Pancreas with a Nondilated Duct

Nonfibrotic pancreases with a nondilated duct are susceptible to pancreatic fistula or leakage following pancreaticoduodenectomy. We developed a novel pancreatic duct-invagination anastomosis using an ultrasonic dissector and applied this technique to 14 consecutive pancreaticoduodenectomies and 1 segmental pancreatectomy for otherwise normal pancreases. With the aid of an ultrasonic dissector, even branch pancreatic ducts were skeletonized, ligated securely, and divided during pancreatic transection. Moreover, the main duct was exposed (> 1 cm) easily by ultrasonic dissection and a small-caliber pancreatic tube was inserted into the duct on the stump. Subsequently, pancreatic duct invagination could be easily done through a 10 G intravenous catheter passed through the gastrointestinal tract. The main duct was anchored to the adjacent serosa, but any pancreatic parenchymal sutures, possibly leading to internal laceration and/or parenchymal ischemia particularly in soft nonfibrotic pancreases, were avoidable during the procedures. All the anastomoses were done within 10 minutes. Only 1 patient (6.7%)developed pancreatic fistula, which resolved spontaneously in 21 days postoperatively. Neither anastomotic leakage nor remnant pancreatitis was seen in this series. Although a prospective, randomized study is needed, this technique may contribute to reduced morbidity after pancreaticoduodenectomy for a nonfibrotic pancreas with a nondilated main duct.     

Anesthesia protocols for early vitrectomy in former preterm infants diagnosed with aggressive posterior retinopathy of prematurity

Aggressive posterior retinopathy of prematurity (ROP) can, if left untreated, rapidly progress to total retinal detachment within 1–2 weeks. Early surgical intervention with vitrectomy has been attempted to treat and prevent further retinal detachment. We investigated the anesthetic management of 29 infants with aggressive posterior ROP undergoing early vitrectomy. Postmenstrual age at surgery ranged from 35 to 47 weeks (median 41). Weight ranged from 1408 to 3478 g (median 1875). All infants underwent general anesthesia with fentanyl and sevoflurane. Mean surgical and anesthetic times were 88.6 and 143.6 min, respectively. In two patients, vitrectomy was postponed for one week due to enteric perforation in one patient and meningitis in the other, because the anticipated perioperative risk was deemed high. There were no intraoperative complications, except in one patient who developed pulmonary edema following upper airway obstruction. All patients survived to be discharged from NICU or transferred to the referring hospital. In all cases, complete or partial retinal reattachment was successfully achieved. Early vitrectomy for aggressive posterior ROP may be effective despite associated perioperative risks. As this condition progresses rapidly, prompt preoperative organization, including anesthetic planning, is important and useful. Anesthesiologists can play an important role in the perioperative management of such high-risk infants.     

Long-term survival and functional recovery after isolated coronary artery bypass grafting in patients with severe left ventricular dysfunction

Objective  Coronary artery bypass grafting (CABG) in patients with left ventricular dysfunction has been considered to be a challenging operation. We assessed the early angiographic and long-term clinical and functional outcomes of patients with poor left ventricular function who underwent isolated CABG. Methods  We retrospectively reviewed the records of 78 patients with a poor left ventricular ejection fraction (35% or less) who underwent isolated CABG between January 1991 and November 2006. The mean age of the patients was 66.1 ± 9.4 years, and their mean New York Heart Association functional class was 3.1 ± 0.8. Their mean end-diastolic left ventricular diameter was 57.4 ± 8.1 mm, and their mean grade of mitral regurgitation was 0.7 ± 1.0. Early postoperative angiograms were performed at 32.5 ± 33.5 days after the operation. Interval echocardiographic data were analyzed, and the long-term survival rate was evaluated. Results  The average number of distal anastomoses per patient was 3.2 ± 1.1. The operative mortality rate was 7.7%. Stroke occurred in 1.3% of patients. The overall patency rates for arterial and venous grafts were 100% and 97.2%, respectively. The left ventricular ejection fraction significantly improved from 28.2% ± 5.1% to 34.4% ± 8.4%. Both the end-diastolic and end-systolic left ventricular dimensions significantly decreased from 57.4 ± 8.1 to 55.1 ± 8.8 mm and from 47.4 ± 8.4 to 45.1 ± 9.7 mm, respectively. The actuarial patient survival rate at 10 years was 73.1%. Conclusion  CABG in patients with left ventricular dysfunction was effective, with favorable early graft patency rates. The long-term outcome was also acceptable, with echocardiographic functional recovery.     

Surgical Resection of Hilar Cholangiocarcinoma: Analysis of Survival and Postoperative Complications

Background Surgery is the only potentially curative treatment for hilar bile duct cancer. This study sought to evaluate the efficacy and feasibility of surgical management of hilar bile duct carcinoma, including radical hepatectomy, at a single institution. Methods We performed a retrospective review of 49 consecutive patients who underwent surgery at our hospital between 1990 and 2003. Results Altogether, 44 of 49 patients underwent radical hepatectomy combined with caudate lobectomy and lymphadenectomy. One and four patients underwent partial hepatectomy or bile duct resection, respectively. No patients underwent preoperative portal vein embolization. The 5-year survival rate was 39.7%, with a median survival time of 3.75 years. The postoperative morbidity and mortality rates were 46.8% and 2.0%, respectively. Cox’s proportional hazard model revealed that lymph node status and the residual tumor factor were independent prognostic factors. Multivariate analysis revealed that preoperative hyperbilirubinemia, postoperative complications, and extended surgical procedures were independently associated with postoperative hyperbilirubinemia. After potentially curative resection, 39.4% of patients suffered from disease recurrence. In 60% of the total cases, the sites of recurrence were distant metastases. Conclusion Surgery, including radical hepatectomy combined with caudate lobectomy and lymph node dissection, is a feasible, effective treatment for hilar bile duct cancer.     

Value of Laparoscopic Appendectomy in Perforated Appendicitis

Background The purpose of this clinical study was to evaluate the efficacy of laparoscopic appendectomy in patients with perforated appendicitis. Methods This study involved a total of 73 consecutive patients who had undergone appendectomy for perforated appendicitis between January 1999 and December 2004. While 39 patients underwent open appendectomy (OA) during the first 3 years, the remaining 34 patients underwent laparoscopic appendectomy (LA) during the last 3 years. Results There was no case of LA converted to OA. No significant difference was found in the operating time between the two groups. Laparoscopic appendectomy was associated with less analgesic use, earlier oral intake restart (LA, 2.6 days; OA, 5.1 days), shorter median hospital stay (LA, 11.7 days; OA, 25.8 days), and lower rate of wound infections (LA, 8.8%; OA, 43.6%). Conclusions These results suggest that LA for perforated appendicitis is a safe procedure that may prove to have significant clinical advantages over conventional surgery.     

Intrathecal injection of epidermal growth factor and fibroblast growth factor 2 promotes proliferation of neural precursor cells in the spinal cords of mice with mutant human SOD1 gene

We investigated three steps of neural precursor cell activation--proliferation, migration, and differentiation--in amyotrophic lateral sclerosis spinal cord treated with intrathecal infusion of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2) into the lumbar spinal cord region of normal and symptomatic transgenic (Tg) mice with a mutant human Cu/Zn superoxide dismutase (SOD1) gene. We observed that 5-bromodeoxyuridine (BrdU) + nestin double-labeled neural precursor cells increased in the spinal cords of Tg mice compared with non-Tg mice, with a much greater increase produced by EGF and FGF2 treatment. The number of BrdU + nestin double-labeled cells was larger than that of BrdU + ionized calcium-binding adapter molecule-1 (Iba1), BrdU + glial fibrillary acidic protein (GFAP), or BrdU + highly polysialylated neural cell adhesion molecule (PSA-NCAM) double-labeled cells, but none expressed neuronal nuclear antigen (NeuN). On further analysis of the gray matter of Tg mice, the number of BrdU + nestin and BrdU + PSA-NCAM double-labeled cells increased more in the ventral horns than the dorsal horns, which was again greatly enhanced by EGF and FGF2 treatment. Because neural precursor cells reside close to the ependyma of central canal, the present study suggests that proliferation and migration of neural precursor cells to the ventral horns is greatly activated in symptomatic Tg mice and is further enhanced by EGF and FGF2 treatment and, furthermore, that the neural precursor cells preferentially differentiate into neuronal precursor cells instead of astrocytes in Tg mice with EGF and FGF2 treatment.