Low-density lipoprotein particle size decreases during normal pregnancy in association with triglyceride increases

OBJECTIVE: To characterize the changes in low-density lipoprotein (LDL) peak particle diameter (diameter of the predominant LDL subclass) in relation to changes in serum triglyceride concentration during successive stages of normal gestation and postpartum. METHODS: Nonfasting venous blood was obtained longitudinally during and after uncomplicated primiparous pregnancy from 10 nonsmoking women with no history of metabolic disorders. Plasma LDL diameter was determined by nondenaturing polyacrylamide gel electrophoresis. Serum concentrations of total cholesterol, triglyceride, apolipoprotein B, apolipoprotein A-I, and LDL-cholesterol were measured. Gestational changes were analyzed by one-way repeated-measures analysis of variance and the paired multiple comparison Student-Newman-Keuls test. Pearson coefficients were computed for correlation of serum lipids and LDL diameter. RESULTS: Low-density lipoprotein diameter decreased progressively with advancing gestation, evident by 16-20 weeks relative to 5-12 weeks. Seven of 10 cases were subclass pattern B (diameter less than 255 A) by term, indicating that small, dense particles predominated. The average diameter decrease from early to late gestation was 13 A. All subjects reverted to subclass pattern A (diameter 255 A or more) by 6-12 weeks postpartum, indicating prevalence of large, buoyant LDL. Low-density lipoprotein diameter correlated inversely with concentrations of serum triglyceride (r = -.61, P < .0001), apo B (r = -.66, P < .0001), cholesterol (r = -.53, P < .001), LDL cholesterol (r = -.45, P < .005), and apo A-I (r = -.39, P < .02). CONCLUSION: Gestational triglyceride increases are accompanied by progressive decreases in LDL diameter in a majority of cases. These changes undergo reversal postpartum and therefore are transient. Small, dense LDL particles have a number of properties capable of altering vascular function. However, the consequences of the gestational LDL size decrease for maternal and fetal metabolism remain unknown.     

Survival and functional status after resection of recurrent glioblastoma multiforme

OBJECTIVE: To determine the selection factors for and results of second resections performed to treat recurrent glioblastoma multiforme (GM), we studied 301 patients with GM who were treated from the time of diagnosis using two prospective clinical protocols. METHODS: The patients were prospectively followed from the time of diagnosis, using clinical and radiographic criteria after maximal surgical resection and external beam radiotherapy with or without adjuvant chemotherapy. Resection of recurrent GM was performed at the recommendation of the treating clinicians. The results of the second resections were retrospectively reviewed and analyzed using multivariate logistic regression, Kaplan-Meier-Turnbull survival analysis, Cox regression, and propensity score stratification. RESULTS: Forty-six patients underwent second resections during the study period. The actuarial rate of the second resections was 15% of the patients 1 year after diagnosis and 31% 2 years after diagnosis. Younger age (P = 0.01) and more extensive initial resection (P = 0.02), but not Karnofsky Performance Scale (KPS) score at the time of diagnosis or recurrence, predicted a higher chance of selection for reoperation after initial tumor recurrence. Twenty-eight percent of the patients had improved KPS scores after undergoing reoperation, 49% were stable, and 23% had declines in KPS scores of 10 to 30 points. There was no operative mortality. After reoperation, 85% of the patients received chemotherapy, 11% received brachytherapy or underwent stereotactic radiosurgery, and 17% underwent third resections. The median survival period after reoperation was 36 weeks. Higher preoperative KPS scores predicted longer survival periods after reoperation (P = 0.03). Age and interval since diagnosis were not significant prognostic factors. The median high-quality survival period (KPS score, > or =70) was 18 weeks. The median survival period after first tumor progression was 23 weeks for 130 patients treated using the same protocols who did not undergo reoperations. Patients who did undergo reoperations experienced clinically and statistically significantly longer survival periods. However, this was determined to be partially because of selection bias. CONCLUSION: Survival after resection of recurrent GM remains poor despite advances in imaging, operative technique, and adjuvant therapies. High-quality survival after resection of recurrence to treat GM seems to have increased significantly since an earlier report from our institution.     

Threonine 82 in the regulatory chain is important for nucleotide affinity and for the allosteric stabilization of Escherichia coli aspartate transcarbamoylase

Changes in the kinetic properties of voltage-activated sodium currents (I(Na)) were studied in rat retinal ganglion cells during in vivo differentiation. Whole-cell recordings from cells maintained as retinal slices or whole-mounts were examined using the patch-clamp technique in the perforated patch mode. Voltage-clamp recordings revealed significant ontogenetic modifications in key properties of I(Na) and the present study described for the first time the detailed time course of such alterations. I(Na) was first expressed on embryonic day 17/18 (E17/18). Current density increased during development from an average of -81 pA/pF on E17/18 to a maximum of -747pA/pF on postnatal day 10/12 (P10/12). Simultaneously, the activation of I(Na) shifted towards more negative potentials, reflected by a shift in the potential of half-activation from -14.1 mV on E17/18 to - 37.5 mV on P10/12. No significant changes in these parameters were observed after P10/12. Steady-state inactivation shifted first towards more positive potentials, reflected by a shift in the potential of half-inactivation from -51 mV on E17/18 to -38 mV on P3/5, but shifted back towards more negative values thereafter (-44 mV in the adult). The most striking feature of I(Na) in rat RGCs was a transient slowing of I(Na) kinetics that was never described before. Time to peak and decay time constants increased between E20 and P5, resulting in slow and broad sodium currents within a developmental period that is characterized by intensive synaptogenesis in the target structures of retinal ganglion cells and maximum retinal ganglion cell death. Thereafter, time to peak and decay time constants decreased again to values found before E20, resulting in rapid sodium spikes. In conclusion, sodium currents in rat retinal ganglion cells displayed substantial electrophysiological changes during pre- and postnatal development. These changes in the sodium system had different temporal time patterns, indicating that they may play specific roles during the development of the visual system.     

Colon cancer cell vaccine prepared with replication-deficient vaccinia viruses encoding B7.1 and interleukin-2 induce antitumor response in syngeneic mice

The objective of this study was to evaluate the clinical efficacy and cost effectiveness of inpatient and outpatient laparoscopic lumbar diskectomy (LLD) compared with laminectomy (LAM) in the surgical treatment of disabling L5-S1 disk herniation. Sixty-two adults underwent surgery for herniated L5-S1 intervertebral disks (31 LLD and 31 LAM). Operative blood loss (EBL) (milliliters), operative time (ORT) (minutes), hospital stay (LOS), and rehabilitation time to normal activity (REHAB) (days), recurrent symptoms, postoperative morbidity, percent pain free, and hospital patient charges were calculated. Thirty LLD patients (97%) had immediate relief of disk pain. Morbidity after LLD included transient urinary retention (one) and rectus hematoma (one). One LAM patient had a pseudomeningocele. Among patients observed for > or =6 months, with a median follow up time of 34 months, 22 of 25 LLD patients (88%) returned to normal activity, while 12 of the LAM group (52%) were disabled (p = 0.004). Functional outcome was improved by LLD for workers compensation patients followed > or =6 months, with 86% LAM disabled, vs. 10% LLD (p = 0.001). Sixteen LLD patients (52%) and 18 (58%) of the LAM group needed postoperative physical therapy. Four LLD patients recurred; three required reoperation. Four LAM patients had surgery for recurrent disk herniation. ORT was longer for LLD than LAM (210 vs. 158 minutes, median, p < 0.05). EBL and REHAB time were significantly reduced with LLD, vs. LAM. With a median follow-up of 34 months, 58% of LLD and 39% of LAM patients followed > or =6 months were pain free. Outpatient LLD (n = 9) reduced LOS (1 day vs. 2 days and 4 days, p < 0.01) and lowered patient charges ($4,405 vs. $5,723 and $7,192, p < 0.01) compared with inpatient LLD (n = 23) and LAM, respectively. LLD is a safe, cost-effective, minimally invasive alternative to LAM for treating herniated L5-S1 disks. Compared with LAM, LLD reduces EBL, LOS, REHAB time, and patient charges, improves function, and increases long-term pain relief. Cost effectiveness is optimized when LLD is performed as outpatient surgery.     

Propagation of mechanically induced intercellular calcium waves via gap junctions and ATP receptors in rat liver epithelial cells

Mechanical stimulation was used to initiate Ca2+ waves in rat liver epithelial cells in order to ascertain the degree to which gap junctional intercellular communication (GJIC) is involved in communication of Ca2+ to adjacent cells and to assess alternative Ca2+ signaling pathways that may be present between these cells. In both WB-F344 cells, which show a high degree of GJIC, and WB-aB1 cells, which are GJIC deficient, mechanical stimulation of a single cell induced a Ca2+ wave which propagated away from the point of stimulation, across cell borders, to neighboring cells directly or indirectly in contact with the stimulated cell. In addition, the Ca2+ wave was transmitted to nearby isolated cells that exhibited no direct or indirect contact with the stimulated cell. Treatment of cells with 18beta-glycyrrhetinic acid, a compound that has been shown to block GJIC, did not significantly affect propagation of the Ca2+ wave. In contrast, treatment with suramin, a P2-purinergic receptor inhibitor, significantly reduced both the rate and the extent of Ca2+ wave propagation in WB-F344 cells and completely blocked its propagation in WB-aB1 cells. Cotreatment with suramin and glycyrrhetinic acid was found to completely block the mechanically induced Ca2+ wave in both cell lines. These studies indicate that mechanically induced cell injury in rat liver epithelial cells initiates signaling through at least two pathways, involving intercellular communication via gap junctions and extracellular communication via ATP activation of purinergic receptors.     

Glutathione-binding proteins of Setaria digitata: antibody responses in human infected with Wuchereria bancrofti

Glutathione-s-transferase activity was determined in filarial parasites. The activity was detected in adult stages of cattle parasite Setaria digitata. It was absent in other stages of Setaria and also in infective larval stages of Wuchereria bancrofti and Brugia malayi. The activity was enhanced about twenty five fold following purification of adult setaria extracts on glutathione agarose column. Antibody (IgG and IgM) levels to the affinity purified proteins (SdGBP) were detected predominantly (90%) in Wuchereria bancrofti infected individuals compared with normal residents of endemic regions. IgA and IgE responses could not be detected. Filarial sera in contrast to non-filarial caused reduction in the enzymatic activities of Sd GBP. Microfilaraemic sera after diethylcarbamazine treatment resulted in enhanced reduction of enzymatic activity.     

Platelet and neutrophil distributions in pump oxygenator circuits. III. Influence of nitric oxide gas infusion

The authors used quantitative gamma scintigraphy to evaluate the influence of nitric oxide gas on platelet and neutrophil deposition in Cobe Duo microporous oxygenators during cardiopulmonary bypass (CPB). The effects of nitric oxide gas on circulating platelet and neutrophil counts and platelet function also were assessed. Animals were prepared by standard methods. Cells were harvested, labeled (111 In platelet and 99mTc neutrophil), infused, and recirculated. Nitric oxide gas, a guanylate cyclase pathway promoter, was infused int he Duo gas port at 500 ppm (t = 0-60 min), increased to 1,000 (t = 60-80 min), and stopped (final, 10 min). Images were taken at 10-15 min intervals during CPB. Standard isotope image corrections were made. No differences between nitric oxide gas and control experiments were observed for flow, pressure, hematocrit, or replacement volume. Nitric oxide gas infusion significantly (p < 0.05) reduced both platelet adherence to the oxygenator and in vitro platelet aggregation. Neutrophil adhesion tended to be lower, and circulating platelet and neutrophil counts tended to be higher with nitric oxide gas infusion. Results of in vitro aggregometry studies using rabbit platelets indicate that the class V phosphodiesterase inhibitor zaprinast can strongly enhance the inhibitory effects of nitric oxide. The authors conclude nitric oxide gas is a promising platelet sparing agent in the setting of CPB.     

Sepsis outcomes in infants and children with central venous catheters: percutaneous versus surgical insertion

OBJECTIVE: To review the literature on central venous catheters (CVCs) in infants and children. DATA SOURCES: Published surgical, medical, nursing, and nutritional studies from 1968 to the present. STUDY SELECTION: More than 250 studies were reviewed; selection criteria for the 64 studies chosen included age, percutaneous CVC (PCVC) or surgical CVC (SCVC) use, and defined rate of sepsis. DATA EXTRACTION: Included study purpose, sample size and age, indications for total parenteral nutrition, insertion method and sites, number of CVCs, and sepsis outcomes. DATA SYNTHESIS: Yielded weighted mean sepsis rates that were 3.5 times higher for SCVC use in neonatal and/or pediatric populations; subanalyses of homogeneous groups of studies yielded rates that were 2.5 to 3.8 times higher. CONCLUSIONS: Percutaneous CVC insertion should be given primary consideration for neonatal and pediatric intensive-care patients.