Cefamandole versus cefonicid prophylaxis in cardiovascular surgery: a prospective study

We randomized 400 patients who were scheduled for an elective cardiovascular operation involving median sternotomy to receive cefamandole nafate or cefonicid in a prospective double-blind study. Three hundred fifty-seven patients were evaluable for prophylactic efficacy. Chest wound and donor site infections and early prosthetic valve endocarditis occurred more frequently with cefonicid (11 patients, 6.3%) than with cefamandole (4 patients, 2.2%) (p = 0.05). Three patients, all in the cefonicid group, required sternal debridement to control postoperative deep wound infections. Twenty-five miscellaneous postoperative infections (urinary tract infection, pneumonia, intravenous site infection, bacteremia, sepsis, Clostridium difficile diarrhea) occurred in 16 patients (9.19%) in the cefonicid group and four in 4 patients (2.19%) in the cefamandole group (p = 0.003). These data indicate that cefamandole is superior to cefonicid in preventing both surgical wound infections and miscellaneous nonsurgical infections after cardiovascular operations.     

Classification of Nursing Interventions for Care of the Integument

The Classification of Nursing Interventions research team at The University of Iowa, College of Nursing is building a taxonomy of nursing interventions that will include all of the direct care treatment activities that nurses perform on behalf of patients. This report describes the study in which 12 nursing interventions and their associated activities for care of the integument were extracted from a large database and validated through a two-round Delphi survey. Using an adaptation of Fehring's model for determining diagnostic content validity of nursing diagnoses, a definition, critical activities, and supporting activities were developed for each of the following interventions: Bathing, Bedrest Care, Hair Care, Nail Care, Oral Health Maintenance, Oral Health Promotion, Oral Health Restoration, Positioning, Pressure Management, Skin Care–Topical Treatments, Skin Surveillance, and Wound Care. Further research is needed to validate supporting activities and to continue classifying interventions and activities that nurses use in treating impaired skin integrity (potential and actual) and altered oral mucous membrane integrity (potential and actual).     

A novel modification of the Thrombelastograph assay, isolating platelet function, correlates with optical platelet aggregation

Flow cytometry, singlet platelet counting, and optical aggregation have been used to monitor clopidogrel and glycoprotein IIb/IIIa (GPIIb/IIIa) platelet antagonists. Optical aggregation is considered the gold standard, but neither it nor flow cytometry is convenient in larger-scale clinical studies or point-of-care systems. Singlet platelet counting, a point-of-care assay correlated with optical platelet aggregation, only provides a measurement of platelet function at a single point in time. The Thrombelastograph is used to assay whole blood for thrombin-generated maximal clot-shear elasticity, referred to as the maximal amplitude (MA). Although platelet dysfunction, thrombocytopenia, and the in vitro effect of strong inhibitors such as IIb/IIIa antagonists can be observed, with thrombin generation milder platelet inhibitors cannot be assessed. We modified the Thromboelastograph assay, using reptilase and factor XIIIa, to form a clot, without thrombin generation, in heparinized whole blood. The resulting clot MA is dependent on added platelet agonists such as ADP or arachidonic acid, is sensitive to platelet antagonists, and provides a continuous measure of platelet function more analogous and better correlated with optical aggregation. This novel modification of the Thromboelastograph assay should prove to be a useful point-of-care whole-blood assay with which to monitor the effects of GPIIb/IIIa, ADP, and thromboxane A(2)-receptor-inhibiting drugs in patients.     

Biochemical and immunological heterogeneity of the Ro ribonucleoprotein particles. Analysis with sera specific for the RohY5 particle.

Anti-Ro autoantibodies found in sera from patients with systemic lupus erythematosus and related diseases precipitate four RNAs (hY1-hY5) from human cell extracts. We identified two patient sera that selectively immunoprecipitated from such extracts the Ro particle containing the hY5 RNA (RohY5 particle). Using cell fractions either enriched in or depleted of RohY5 particles, we have shown that these sera contain autoantibodies that target an antigenic determinant on the 60-kD Ro polypeptide that is expressed only on RohY5 particles and is absent on the Ro particles containing the hY1-hY4 RNAs (RohY1-hY4 particles). In a competitive inhibition assay using a cell fraction enriched in RohY1-hY4 particles but depleted of RohY5 particles, four of six control anti-Ro sera were also shown to contain antibodies reactive with the epitope specific for the RohY5 particle. Thus anti-RohY5 antibodies frequently occur in tandem with anti-Ro antibodies, but are not detected unless inhibition assays are performed. Finally, anti-RohY5 specific sera do not immunoprecipitate any Ro particles from various nonhuman cell lines. In contrast to other autoantibodies in systemic lupus and related diseases that bind conserved regions on conserved polypeptides, this observation suggests that a portion of the anti-Ro response targets a nonconserved epitope on a conserved autoantigen.     

Taurine deficiency damages photoreceptors and retinal ganglion cells in vigabatrin-treated neonatal rats

The anti-epileptic drug vigabatrin induces an irreversible constriction of the visual field, but is still widely used to treat infantile spasms and some forms of epilepsy. We recently reported that vigabatrin-induced cone damage is due to a taurine deficiency. However, optic atrophy and thus retinal ganglion cell degeneration was also reported in children treated for infantile spasms. We here show in neonatal rats treated from postnatal days 4 to 29 that the vigabatrin treatment triggers not only cone photoreceptor damage, disorganisation of the photoreceptor layer and gliosis but also retinal ganglion cell loss. Furthermore, we demonstrate in these neonatal rats that taurine supplementation partially prevents these retinal lesions and in particular the retinal ganglion cell loss. These results provide the first evidence of retinal ganglion cell neuroprotection by taurine. They further confirm that taurine supplementation should be administered with the vigabatrin treatment for infantile spasms or epilepsy.     

THC-methadone and THC-naltrexone interactions on discrimination, antinociception, and locomotion in rats

This study examined cannabinoid-opioid interactions within the same subjects on measures of discrimination, antinociception, horizontal locomotion, and catalepsy. Male Sprague-Dawley rats were trained to discriminate Δ(9)-tetrahydrocannabinol (THC, 3 mg/kg) from vehicle. THC alone (0.32-10 mg/kg) dose-dependently increased THC-appropriate lever responding and decreased response rate. THC alone also produced paw pressure antinociception and decreased locomotor activity, but did not produce catalepsy. Methadone (0.32-5.6 mg/kg) and naltrexone (0.32-3.2 mg/kg) alone produced low THC-appropriate lever responding up to doses that decreased response rate. When combined with THC, methadone (1.0 mg/kg) flattened the THC discrimination curve, but did not affect antinociceptive or motoric effects of THC. Naltrexone did not alter any effects of THC. In rats that were not trained to discriminate THC from vehicle, 1.0 mg/kg methadone did enhance THC antinociception. These results suggest that μ-opioid receptor agonists can disrupt the discriminative stimulus effects of cannabinoids while not significantly altering their antinociceptive or motoric effects, in chronically drug-exposed subjects. Further research is required to determine whether opioid enhancement of cannabinoid antinociception is limited to acute exposure, or simply requires higher doses in chronically drug-exposed subjects.     

Safety of Laparoscopic Ventral Hernia Repair in Octogenarians

Background and Objectives:

The recurrence rate after laparoscopic ventral hernia repair is lower than the rate of recurrence via the open approach in many series. Studies have demonstrated the safety and efficacy of this procedure but have had relatively young patient populations. We present our experience in a significantly older population.

Methods:

A retrospective chart review of all patients 80 to 89 years of age undergoing a laparoscopic ventral hernia repair at our institution from May 2000 to June 2007 was performed. Data collected included demographics, number and type of previous abdominal operations, number of previous hernia repairs, defect and mesh size, postoperative complications, and follow-up.

Results:

Twenty octogenarian patients underwent laparoscopic ventral hernia repair. Nine were men and 11 were women. The mean age was 82 years. Thirteen patients (65%) had one or more associated comorbidities at the time of surgery. Eighteen patients (90%) had undergone a mean of 1.7 prior abdominal operations. Six (30%) patients had undergone a mean of 1.1 previous open hernia repairs; 5 (83%) with mesh. Eight patients (40%) had an additional operative procedure at the time of laparoscopic hernia repair. Ten minor complications occurred in 10 patients (50%). Four major complications occurred in 4 patients (20%). One patient required reoperation for evacuation of hematoma at a trocar site. No patients complained of pain at a transabdominal suture site or persistent seromas by 6 weeks of follow-up. At mean follow-up of 3.1 months, no recurrences occurred and no patients required mesh removal in this series. No deaths occurred.

Conclusion:

Laparoscopic ventral hernia repair is becoming an accepted technique for hernia repair in the United States, with a well-documented low recurrence rate. Our series demonstrates that this approach is equally safe and effective for a significantly older segment of the population.     

PAG mu opioid receptor activation underlies sex differences in morphine antinociception

Given the findings that (1) systemic opioid antinociception varies by estrous stage in females and (2) the magnitude of sex differences in opioid antinociception is negatively correlated with opioid agonist efficacy, we hypothesized that sex differences in the function of the descending pain modulatory system are likely influenced by estrous stage in females and by the number of available opioid receptors therein. The present study tested these hypotheses by (1) comparing antinociception produced by morphine microinjection to the ventral periaqueductal gray (vPAG) in females at different stages of the estrous cycle and (2) examining systemic morphine antinociception in males versus females under conditions of reduced vPAG mu opioid receptor availability. When estrous stage of females was not controlled for (Experiment 1), there was no significant sex difference in tail withdrawal antinociception following morphine microinjection (0.3-10microg), although morphine was more potent in males than females in producing immobility. Experiment 2 showed that intra-vPAG morphine produced less antinociception and immobility in estrus than in diestrus females; that is, only estrus females' response to morphine was lower than that of males. Experiment 3 showed that microinjection of the irreversible mu opioid antagonist beta-funaltrexamine (beta-FNA) into the vPAG shifted the systemic morphine dose-effect curve farther to the right in females than in males. That is, a reduction in available vPAG mu opioid receptors had a greater impact on opioid antinociception in females than in males, suggesting that females have fewer vPAG mu opioid receptors than males. Overall, these data suggest that ovarian hormones and PAG mu opioid receptor density contribute to sex differences in antinociception produced by morphine.     

2006 Curt P. Richter award winner: Social influences on stress responses and health

Both positive and negative social interactions can modulate the hypothalamic-pituitary-adrenal (HPA) axis and influence recovery from injuries and illnesses, such as wounds, stroke, and cardiac arrest. Stress exacerbates neuronal death following stroke and cardiac arrest, and delays cutaneous wound healing, via a common mechanism involving stress-induced increases in corticosterone, acting on glucocorticoid receptors. In contrast, hamsters and mice that form social bonds are buffered against stress and heal cutaneous wounds more quickly than socially isolated animals, presumably because the physical contact experienced by the pairs releases oxytocin, which in turn suppresses the HPA axis and facilitates wound healing. Social housing also decreases stroke-induced neuronal death and improves functional recovery, but the mechanism appears to involve suppressing the inflammatory response that accompanies stroke, rather than alterations in HPA axis activity. An interaction between the HPA axis and immune system determines stroke outcome in neonatally manipulated mice that exhibit life-long dampening of the HPA axis. Taken together, these studies provide support for the detrimental effects of stress and identify potential mechanisms underlying the well-documented clinical observation that social support positively influences human health.