Interaction of the leucine-rich repeats of polycystin-1 with extracellular matrix proteins: possible role in cell proliferation.

Polycystin-1, the product of the PKD1 gene, is a membrane-bound multidomain protein with a unique structure and a molecular weight of approximately 460 kD. The purpose of this study is to investigate the binding of the cystein-flanked leucine-rich repeats (LRR) of polycystin-1 to extracellular matrix (ECM) components. These interactions may play a role in normal renal development as well as the pathogenesis of autosomal-dominant polycystic kidney disease (ADPKD). In vitro assays were used to assess the binding of a fusion protein containing the LRR of polycystin-1 and that of affinity purified polycystin-1 to a number of ECM components. The results showed that the LRR modulate the binding of polycystin-1 to collagen I, fibronectin, laminin, and cyst fluid-derived laminin fragments. The addition of the LRR fusion protein to cells in culture resulted in a significant dose-dependent reduction in the rate of proliferation. Cyst fluid-derived laminin fragments had a stimulatory effect on cell proliferation, which was reversed by the LRR fusion protein. These results suggest that the LRR of polycystin-1 act as mediators of the polycystin-1 interaction with the ECM. The observed suppression effect of the LRR on cell proliferation suggests a functional role of the LRR-mediated polycystin-1 involvement in cell-matrix and cell-cell interactions. These interactions may result in the enhanced cell proliferation that is a characteristic feature of ADPKD.     

Syringomatous adenoma of the nipple occurring within a supernumerary breast: a case report

Originally described by Rosen in 1983, syringomatous nipple adenoma (SAN) is a tumor of disputed histogenesis, which can be problematic both diagnostically and therapeutically. ¹ It is a benign primary tumor of breast epithelium with histology similar to that of the syringoma. In the current case, we describe a 40-year-old female with this lesion occurring within a supernumerary breast. This case represents, to our knowledge, the first such reported case, and represents a significant finding as its presence could lend some confusion as to whether or not this represents a benign primary process of breast or a potentially infiltrative tumor of the skin.     

Long and short-term outcomes in patients requiring continuous renal replacement therapy post cardiopulmonary bypass.

OBJECTIVE: The development of acute renal failure following cardiac surgery is a rare but devastating complication with high morbidity and mortality. This study aimed to assess the incidence of acute renal failure necessitating continuous renal replacement therapy (CRRT) in patients who required cardiopulmonary bypass, to determine the factors associated with mortality and to evaluate long-term outcome. METHODS: Patients who underwent cardiac surgery between October 1997 and 2003 and treated with CRRT were included (n=98). Six patients were then excluded (already in established renal failure pre-operatively) and one patient lost to follow-up. A retrospective analysis was carried out. RESULTS: Overall CRRT was used in 2.9% (92/3172). The mean (SD) age of patients was 68 (10) years. Their mean pre-operative creatinine level and duration of cardiopulmonary bypass were 154 (87)micromol/l and 160 (84)min, respectively. Mean duration from surgery to establishment of CRRT was 50 (42)h. Mean creatinine level prior to hospital discharge was 168 (93)micromol/l. Thirty-day mortality was 42%. Significant risk factors for death were complex procedures (odds ratio=9.9), gastro-intestinal complications (OR=7.2), cross-clamp time over 88min (OR=5.9), re-exploration (OR=4.0) and patients age over 75 years (OR=3.3). Actuarial 1 and 5-year survivals (95% CI) were 53 (43, 63) % and 52 (42, 62) %, respectively. Only 2 (2.2%) patients required long term renal support. CONCLUSIONS: Acute renal failure necessitating the use of CRRT is a rare but serious complication post cardiopulmonary bypass. In the long-term, surviving patients are not likely to require further renal support.     

Case series: Combined spinal epidural anesthesia for Cesarean delivery andex utero intrapartum treatment procedure

PURPOSE: To report the use of regional anesthesia and iv nitroglycerin to provide anesthesia and uterine relaxation for three Cesarean deliveries (CD) involving ex utero intrapartum treatment (EXIT) of potentially life-threatening airway obstruction in the newborn. CLINICAL FEATURES: Case 1--a 36-yr-old woman at 38 weeks' gestation was scheduled for an elective CD for fetal skeletal dysplasia and micrognathia. Case 2--a 34-yr-old woman at 35 weeks gestation had a fetal ultrasound revealing fixed neck flexion and micrognathia consistent with fetal arthrogryposis. Case 3--a 27-yr-old woman presented at 38 weeks gestation for CD for severe fetal micrognathia, with mandibular growth below the fifth percentile. For each case, a combined spinal epidural anesthetic was performed with 0.75% bupivacaine, fentanyl and morphine intrathecally followed by placement of a multiorifice epidural catheter. Prior to uterine incision patients received a loading dose followed by an iv infusion of nitroglycerin. Uterine relaxation was sufficient in all cases for delivery of the fetus, and allowed for evaluation by direct laryngoscopy and intubation while maintaining fetal-placental circulation. The surgical procedures were completed without incident. CONCLUSIONS: Anesthesia and uterine relaxation for CD and EXIT procedures can be safely provided with regional anesthesia and iv nitroglycerin.     

MHC IN SYSTEMIC LUPUS ERYTHEMATOSUS: A STUDY ON A KUWAITI POPULATION

HLA alleles were studied in Kuwaiti patients with Systemic lupus erythematosus (SLE). Although significant association of B5, B8, and DR3 has been reported in the literature, the most common phenotype for our patients is A3, DR2 as susceptible alleles and DQ1 as a protective gene.     

Release of Proinflammatory Cytokines During Pediatric Cardiopulmonary Bypass: Heparin-Bonded Versus Nonbonded Oxygenators

Background. Heparin bonding of the cardiopulmonary bypass (CPB) circuit may be associated with a reduced inflammatory response and improved clinical outcome. The relative contribution of a heparin-bonded oxygenator (ie, >80% of circuit surface area) to these effects was assessed in a group of pediatric patients.

Methods. Twenty-one pediatric patients undergoing CPB operations were assigned randomly to receive either a heparin-bonded oxygenator (group H, n = 11) or a nonbonded oxygenator (group C, n = 10) in otherwise nonbonded circuits. The two groups were similar in pathology, age, weight, CPB time, and cross-clamp time. Plasma levels of the cytokines tumor necrosis factor-, interleukin-6, and interleukin-8, as well as terminal complement complex, neutrophils, and elastase, were analyzed before, during, and after CPB.

Results. Significant levels of tumor necrosis factor- were not detected in either group. Plasma levels of all other markers increased during and after CPB compared with baseline. Plasma levels of interleukin-6 peaked in both groups 2 hours after the administration of protamine but remained significantly higher in group C 24 hours after operation. Plasma concentrations of interleukin-8 peaked at similar levels in both groups 30 minutes after protamine administration and returned to baseline thereafter. Levels of terminal complement complex and elastase peaked in both groups 30 minutes after protamine administration. Plasma levels of terminal complement complex were significantly higher at the end of CPB and after protamine administration in group C. Elastase levels were significantly higher 2 and 24 hours after CPB in group C. The ventilation time of patients in group H was significantly lower than that of patients in group C: 10 (range, 3 to 24) versus 22 (range, 7 to 24) hours, respectively (p < 0.01).

Conclusions. The present study confirms the proinflammatory nature of pediatric operations and demonstrates a lessened systemic inflammatory response with the use of heparin-bonded oxygenators. This is achieved without bonding of the entire circuit, which could have significant cost-benefit implications by negating the need for custom-built heparin-bonded circuitry.     

Partially hepatectomized rats: a model for the study of the effect of toxins on the plasma protein profiles of nascent hepatocytes.

A useful framework is proposed for unifying the synthesis of plasma proteins and their degradation by, or release from, liver cells of intact and partially hepatectomized rats, in which synthesis and release of acute-phase plasma proteins occur in synchrony with the internalization and catabolism of plasma and extracellular proteins. The catabolism of proteins and other hepato-intracellular glycoproteins during sepsis or trauma is essential to provide constituent amino acids and carbohydrates for the synthesis of acute-phase plasma proteins. Increases in the plasma levels of acute-phase response proteins in sham-operated rats reached a maximum between 1 and 2 d after mock surgery, and had returned virtually to control levels within 6 d. By contrast, acute-phase proteins in the plasma of partially hepatectomized rats were decreased by 10-20% of their initial values after 24 h. A maximum acute-phase response on d 7 after the operation was characterized by an increase of 181, 445, and 19% for alpha-1-acid glycoprotein, hepatoglobin, and hemopexin, whereas other acute-phase proteins remained below control levels, for example, by 11, 25, and 38% for albumin, transferrin, and prealbumin, respectively. This delayed response suggests that the nascent liver cells had inherited the capacity of the parent cells to respond to inflammatory signal and had synthesized acute-phase plasma proteins. Accordingly, a time frame for the application of toxin to nascent hepatocytes is suggested. An increased activity (300 +/- 50%) for both bound and free neuraminidase in remnant liver tissue 19 h post partial hepatectomy suggested that hepatic regenerating factor(s) were produced in liver tissue via the hepatic bound and/or free neuraminidase-mediated desialylation of humoral substrates. By contrast, circulating levels of lysosomal enzymes alpha-fucosidase and beta-N-acetyl-D-glucosaminidase were increased marginally after 24 h but had returned nearly to control levels after 7 d, suggesting that lysosomal acid hydrolases do not play a major role in regenerative DNA synthesis, mitosis, or in the synthesis of acute-phase plasma proteins.