Sternal surgical-site infection following coronary artery bypass graft: prevalence, microbiology, and complications during a 42-month period.

OBJECTIVE: Surgical-site infection (SSI) is a serious and costly complication following coronary artery bypass graft (CABG). We analyzed surgical factors, microbiology, and complications at a 608-bed community teaching hospital to identify opportunities for prevention. METHODS: All patients undergoing CABG procedures from June 1997 through December 2000 were analyzed. Hospital records and postdischarge surveillance data were reviewed for demographics, surgical information, timing and classification of infection, microbiology, and bacteremic events. RESULTS: Of 3,443 patients undergoing CABG, sternal SSI developed in 122 (3.5%); 71 (58.2%) were classified as superficial SSI and 51 (41.8%) as deep SSI. Surgical antimicrobial prophylaxis was employed in all cases. On average, infection occurred 21.5 days (range, 4 to 315) after CABG. Most cases were diagnosed on readmission (59%); 20 cases (16%) were identified by postdischarge surveillance. Microbiological data were positive in 109 (89.3%), with a single pathogen implicated in most (86.2%). Gram-positive cocci were most frequently recovered (81%); gram-negative bacilli (17%), gram-positive bacilli (1%), and yeast (1%) were less common. Staphylococcus aureus was the most frequently isolated pathogen (49%). Bacteremia was noted in 22 instances (18%). It was significantly associated with deep SSI (P =. 002) and identified only in S. aureus cases. CONCLUSIONS: SSI complicated 3.5% of the procedures. S. aureus was implicated in most of the cases and was significantly associated with deep SSI. It was the only pathogen associated with secondary bacteremia. In addition to standard guidelines, targeted methods against S. aureus should help reduce the overall rate of SSI.     

Repetitive, negligible force reaching in rats induces pathological overloading of upper extremity bones.

Work-related repetitive motion disorders are costly. Immunohistochemical changes in bones resulting from repetitive reaching and grasping in 17 rats were examined. After 3-6 weeks, numbers of ED1+ macrophages and osteoclasts increased at periosteal surfaces of sites of muscle and interosseous membrane attachment and metaphyses of reach and nonreach forelimbs. These findings indicate pathological overloading leading to inflammation and subsequent bone resorption. INTRODUCTION: Sixty-five percent of all occupational illnesses in U.S. private industry are attributed to musculoskeletal disorders arising from the performance of repeated motion, yet the precise mechanisms of tissue pathophysiology have yet to be determined for work-related musculoskeletal disorders. This study investigates changes in upper extremity bone tissues resulting from performance of a voluntary highly repetitive, negligible force reaching and grasping task in rats. MATERIALS AND METHODS: Seventeen rats reached an average of 8.3 times/minute for 45-mg food pellets for 2 h/day, 3 days/week for up to 12 weeks. Seven rats served as normal or trained controls. Radius, ulna, humerus, and scapula were collected bilaterally as follows: radius and ulna at 0, 3, 4, 5, 6, and 12 weeks and humerus and scapula at 0, 4, and 6 weeks. Bones were examined for ED1-immunoreactive mononuclear cells and osteoclasts. Double-labeling immunohistochemistry was performed for ED1 (monocyte/macrophage lineage cell marker) and TRACP (osteoclast marker) to confirm that ED1+ multinucleated cells were osteoclasts. Differences in the number of ED1+ cells over time were analyzed by ANOVA. RESULTS: Between 3 and 6 weeks of task performance, the number of ED1+ mononuclear cells and osteoclasts increased significantly at the periosteal surfaces of the distal radius and ulna of the reach and nonreach limbs compared with control rats. These cells also increased at periosteal surfaces of humerus and scapula of both forelimbs by 4-6 weeks. These cellular increases were greatest at muscle attachments and metaphyseal regions, but they were also present at some interosseous membrane attachments. The number of ED1+ cells decreased to control levels in radius and ulna by 12 weeks. CONCLUSIONS: Increases in ED1+ mononuclear cells and osteoclasts indicate that highly repetitive, negligible force reaching causes pathological overloading of bone leading to inflammation and osteolysis of periosteal bone tissues.     

Striatal delivery of CERE-120, an AAV2 vector encoding human neurturin, enhances activity of the dopaminergic nigrostriatal system in aged monkeys.

Neurturin (NTN) is a potent survival factor for midbrain dopaminergic neurons. CERE-120, an adeno-associated virus type 2 (AAV2) vector encoding human NTN (AAV2-NTN), is currently being developed as a potential therapy for Parkinson's disease. This study examined the bioactivity and safety/tolerability of AAV2-NTN in the aged monkey model of nigrostriatal dopamine insufficiency. Aged rhesus monkeys received unilateral injections of AAV2-NTN into the caudate and putamen, with each animal therefore serving as its own control. Robust expression of NTN within the nigrostriatal system was observed 8 months postadministration. (18)F-fluorodopa imaging using positron emission tomography revealed statistically significant increases in (18)F-fluorodopa uptake in the injected striatum compared with the uninjected side at 4 and 8 months. In addition, at 8 months postadministration, a significant enhancement in tyrosine hydroxylase immunoreactive fibers and an increase in the number of tyrosine hydroxylase immunoreactive cells was observed in the AAV2-NTN injected striatum compared with the uninjected side. Robust activation of phosphorylated extracellular signal-regulated kinase immunoreactivity in the substantia nigra was also observed. Histopathological analyses revealed no adverse effects of AAV2-NTN in the brain. Collectively, these results are consistent with the neurotrophic effects of NTN on the dopaminergic nigrostriatal system and extend the growing body of evidence supporting the concept that AAV2-NTN may have therapeutic benefit for Parkinson's disease.     

Nicotine induces calcium spikes in single nerve terminal varicosities: a role for intracellular calcium stores

We have previously shown that a large part of the D-amphetamine-induced release of dopamine in the nucleus accumbens is not associated with an increase in locomotor activity, and that "functional" dopamine release (i.e. release of dopamine associated with locomotor activity) requires the distal facilitation of noradrenergic transmission through alpha1-adrenergic receptors in the prefrontal cortex. To determine the role of monosynaptic or polysynaptic projections from the prefrontal cortex to the nucleus accumbens in these amphetamine responses, either AMPA/kainate (6-cyano-7-nitroquinoxaline-2,3-dione, CNQX, 300microM), N-methyl-D-aspartate (D(-)-2-amino-5-phosphono-pentanoic acid, APV, 500microM) or metabotropic [(+)-alpha-methyl-4-carboxy-phenylglycine, MCPG, 10mM] glutamate receptor antagonists were infused through a dialysis probe in the rat nucleus accumbens. CNQX and MCPG but not APV reduced the "non-functional" release of dopamine evoked by local (3microM) and systemic D-amphetamine (2mg/kg i.p.) treatments. However, the locomotor hyperactivity and functional dopamine release induced by systemic D-amphetamine were abolished by MCPG, but neither by CNQX nor by APV. MCPG treatment also abolished the hyperlocomotor activity and functional dopamine release evoked by bilateral morphine injection into the ventral tegmental area. The dopamine release evoked by this morphine treatment was 16-fold lower than that induced by the systemic D-amphetamine injection, although similar behavioral activations were observed. Altogether, our results further aid the discrimination of functional and non-functional release of dopamine. We suggest that the activation of metabotropic glutamate receptors in the nucleus accumbens is required for functional dopamine release following systemic D-amphetamine injection.     

Interaction of polystyryl radical with copper(II) complexes

The polymerization of styrene initiated by 2,2′-azoisobutyronitrile (AIBN) was studied in N,N-dimethylformamide (DMF) solution at 60°C in the presence of tetrakis(N,N-dimethylformamide)copper(II) perchlorate, and also in the presence of its monoazido copper(II) complex [Cu(DMF)₃N₃]⁺. The monoazido complex in DMF was prepared in situ by mixing solid sodium azide with tetrakis(N,N-dimethylformamide)copper(II) perchlorate in a mole ratio of 1:1. The nature of the complex was established by Job's method. The equilibrium constant K for the reaction [Cu(DMF)₄]²⁺ + N ? [Cu(DMF)₃N₃]⁺ + DMF determined by the limiting logarithmic method was found to be 1,25 · 10⁴l · mol^?1. The presence of [Cu(DMF)₄]²⁺ ions in the polymerization systems caused retardation, but [Cu(DMF)₃N₃]⁺ ions produced well defined induction periods. The rate constants at 60°C for the interaction of polystyryl radical towards [Cu(DMF)₄]²⁺ and [Cu(DMF)₃N₃]⁺ ions were calculated to be 6,6 · 10² and 5,74 · 10⁴ l · mol^?1 · s^?1, respectively.     

Randomized, double-blind, placebo-controlled study of montelukast for treating perennial allergic rhinitis.

BACKGROUND: Perennial allergic rhinitis (PAR) is a persistent allergic inflammation of the upper respiratory tract due to year-round allergen exposure. OBJECTIVE: To evaluate the leukotriene receptor antagonist montelukast for the treatment of PAR. METHODS: Protocol 265 was a 2-arm study performed during the winter. After a placebo run-in period, adults with perennial allergen sensitivity and active symptoms of PAR were randomized to receive 10 mg of montelukast (n=1002) or placebo (n=990) once daily during a 6-week, double-blind, active-treatment period. The primary end point was the daytime nasal symptoms score, defined as the average of scores for nasal congestion, rhinorrhea, and sneezing rated daily by patients. RESULTS: Statistically significant improvements in PAR symptoms were seen in patients treated with montelukast. Their daytime nasal symptoms scores were reduced during treatment compared with those of the placebo group: the difference between treatments in least squares mean change from baseline was -0.08 (95% confidence interval [CI], -0.12 to -0.04; P < .001). Montelukast treatment also improved global evaluations of allergic rhinitis by patients and Rhinoconjunctivitis Quality of Life Questionnaire scores: differences vs the placebo group were -0.15 (95% CI, -0.27 to -0.04; P < .01) and -0.15 (95% CI, -0.24 to -0.06; P < .001), respectively. Other end points that showed statistically significant improvement with montelukast treatment were nighttime symptoms and each of the 4 nasal symptoms (congestion, rhinorrhea, sneezing, and itching). The treatment effects of montelukast were stable and persistent during the entire 6 weeks of treatment. CONCLUSION: Montelukast provided statistically significant relief of PAR symptoms during 6 weeks of treatment.     

Relationship between oxidative stress and embryotoxicity of hydrosalpingeal fluid

BACKGROUND: Oxidative stress mechanisms are involved in the pathophysiology of many reproductive disorders. The objective of this study was to characterize oxidative stress parameters in hydrosalpingeal fluid (HSF) and examine their possible role in early embryo development. METHODS AND RESULTS: HSF was aspirated at laparoscopic salpingectomy in 11 infertile women. Reactive oxygen species (ROS), total (non-enzymatic) antioxidant capacity (TAC) and lipid peroxidation (LPO) were assayed. Two-cell mouse embryos were incubated with 25, 50 or 75% HSF and the blastocyst development rate was observed. ROS was detected in five of 11 (45%) HSF samples with a mean of 4.2 x 10(4) c.p.m. LPO was detected in all samples at a mean (+/- SD) value of 5575.4 +/- 6091.9 micromol/l malonaldehyde. The mean blastocyst development rate at 25, 5+/- 0 and 75% HSF and in the control group was 88.9 +/- 9.4, 65.7 +/- 19.1, 45.7 +/- 5.7 and 96.7% respectively (P < 0.0001). The blastocyst development rate was positively correlated to ROS concentrations (P < 0.02) but was not significantly related to LPO. CONCLUSIONS: The blastocyst development rate decreased with increasing concentrations of HSF. For the first time, the presence of ROS, LPO and TAC activity in human HSF was characterized. A possible role of oxidative stress in the embryotoxicity of HSF is suggested.     

Effect of gossypol in association with chromium protoporphyrin on heme metabolic enzymes

Gossypol prevents the liberation of oxygen from oxyhemoglobin and exerts a hemolytic effect on erythrocytes. In excessive dosages of gossypol, an extreme burden is placed upon the respiratory and circulatory organs owing to the reduced oxygen carrying capacity of blood. Chromium protoporphyrin (CrPP) has been shown to either competitively suppress or to significantly ameliorate a variety of naturally occurring or experimentally induced forms of jaundice in animals and man. In this communication, a novel tissue dependent response to gossypol (50 micromol/kg bw) and gossypol in association with CrPP (50 micromol/kg bw) is described. Our results revealed that gossypol stimulated the hepatic, splenic, and renal delta-aminolevulinic acid synthase (ALA-S) activity, the heme biosynthetic enzyme, and simultaneous administration of CrPP and gossypol synergized the gossypol-mediated increase of ALA-S activity. Gossypol was found to be a potent stimulator of heme oxygenase (HMOX) activity in rat liver and kidney to varying degrees. This tissue response contrasted with that of the spleen, where gossypol decreased the activity of the enzyme. In consonance with the increased hepatic and renal HMOX activity, a marked increase was observed in total serum bilirubin concentration in gossypol treated rats. When rats were given CrPP simultaneously with gossypol, the gossypol mediated increase in hepatic and renal HMOX activity was effectively blocked. Furthermore, the increase in enzymatic activity was accomplished by a decline in the total microsomal protein content on gossypol administration. These findings emphasize the toxic effect of gossypol in eliciting increased heme degradation by stimulating HMOX activity in the liver and the kidney and the potential usefulness of CrPP in experimental and perhaps clinical conditions in which hyperbilirubinemia occurs.