Cardiovascular function during the first 24 hours after off pump coronary artery bypass grafting--a prospective, randomized study

We hypothesized that cardiovascular performance during the first 24 postoperative hours would be better in patients after off pump coronary artery bypass grafting compared to conventional on pump surgery. Fifty-nine patients were randomized to on or off pump coronary artery bypass grafting. Hemodynamic parameters, including cardiac index and systemic vascular resistance index were measured before and at 1, 4, and 20 h after surgery. Troponin T and creatine kinase-MB (CK-MB) were measured before and at 1, 6, and 20 h after surgery. There was no difference in age, sex, ejection fraction or number of grafts between groups. Cardiac index was higher (p=0.05) and systemic vascular resistance index was lower (p=0.007) in the off pump group 1 h after arrival in the intensive care unit. CK-MB and troponin T were significantly lower in the off pump group after 1 h (CK-MB p<0.001, troponin T p<0.001) and after 6 h (CK-MB p=0.02, troponin T p<0.001). After 24 h there was no difference between the two groups. In conclusion, immediately after surgery there was better cardiovascular performance and less release of markers of myocardial damage after off pump coronary surgery. After 24 h all differences were eliminated.     

Cobalt staining of hippocampal neurons mediated by non-desensitizing activation of AMPA but not kainate receptors

Activation of calcium permeable glutamate receptors is likely to be important for neuronal death associated with brain trauma, stroke and neurodegenerative diseases. Cobalt uptake can be used to identify cells containing Ca2+-permeable non-NMDA ionotropic glutamate receptors. However, the relative contribution of AMPA and kainate receptors, and also the role of receptor desensitization on the influx of Co2+, remain to be established. We found that the selective non-desensitizing activation of AMPA receptors was efficient in promoting Co2+ staining. However, the selective activation of kainate receptors, even under non-desensitizing conditions, did not result in Co2+ staining. Taken together, our results show that non-desensitizing stimulation of AMPA, but not of kainate receptors, mediates the influx of Co2+ in cultured rat hippocampal neurons.     

Granulocyte-macrophage colony-stimulating factor treatment before doxorubicin and cyclophosphamide chemotherapy priming in women with early-stage breast cancer.

PURPOSE: To determine if inhibition of stem-cell activity induced by granulocyte-macrophage colony-stimulating factor ([GM-CSF]; Sargramostim; Immunex Corporation, Seattle, WA) withdrawal or priming protects hematopoietic stem cells from the cytotoxic effects of adjuvant chemotherapy for early-stage breast cancer. PATIENTS AND METHODS: Serial blood counts were performed in 20 women with early-stage breast cancer receiving four courses of cyclophosphamide and doxorubicin chemotherapy. By a double-blind, placebo-controlled, balanced randomization, subjects received GM-CSF priming on days 5 to 1 for courses 1 and 3 or courses 2 and 4. RESULTS: Compared with before priming, after priming the times to neutrophil nadir (12.8 +/- 2.5 days v 14.8 +/- 1.5 days, respectively; P =.0001) and platelet nadir (mean +/- SD, 10.1 +/- 1.9 days v 11.1 +/- 2.2 days, P <.05) were shorter, indicating a shift of cytotoxicity to later progenitors. The neutrophil nadir was similar with and without priming (mean +/- SD, 490 +/- 310/microL v 550 +/- 350/microL, respectively; P =.2); however, on day 16 the mean neutrophil count was higher (mean +/- SD, 1030 +/- 580/microL v 690 +/- 370/microL, P =.004), and the proportion of patients with a neutrophil count less than 500/microL was lower after priming than before (six of 35 or 17. 1% v 12 of 34 or 35.3%, respectively; P =.04). The platelet nadir was higher (mean +/- SD, 166,000 +/- 51,000/microL after priming v 151,000 +/- 45,000/microL before priming, P =.007), and the duration of thrombocytopenia, ie, a platelet count less than 150,000/microL, was shorter (1.5 +/- 2.1 days v 2.8 +/- 2.9 days, P =.0025) after priming. Episodes of fever and neutropenia were not observed. CONCLUSIONS: GM-CSF priming from days 5 to 1 before doxorubicin and cyclophosphamide chemotherapy was associated with an earlier neutrophil and platelet nadir. On day 16, a higher mean neutrophil count and a lower proportion of patients with severe (< 500/microL) neutropenia were observed. Beneficial effects on the severity and duration of thrombocytopenia were also noted. These observations support the hypothesis that GM-CSF priming protects hematopoietic progenitors from the cytotoxic effects of chemotherapy.     

Oral and Genital Human Herpesvirus 8 and Human Papillomavirus in heterosexual partners

Background: The purpose of this study was to verify a possible co‐infection of human herpesvirus 8 (HHV‐8) in commonly associated human papillomavirus (HPV) penile lesions and to determine the frequency of detection of these viruses in the oral mucosa of their female counterparts. Methods: Thirty‐one male subjects underwent penile swabs from clinical HPV‐related lesions. Their female counterparts underwent swabs of the vagina, uterine cervix, and oral mucosa. HPV and HHV‐8 detection was performed by polymerase chain reaction using the consensus primers MY11/MY09 and KS1/KS2, respectively. Results: HPV DNA was detected in 31/31 penile lesions. HPV DNA was also detected in 18/31 (58%) female genital brushings and 17/31 (54%) female oral brushings. HHV‐8 DNA was detected in 1/31 (3.2%) male genital brushings and 3/31 (9.6%) female oral mucosa brushings. None of the female genital brushings were HHV‐8 DNA‐infected. Conclusions: Based upon the results of this study, co‐infection between HPV and HHV‐8 in malignant and pre‐malignant penile lesions is an unlikely finding.     

Is there any barrier impairment in sensitive skin?: a quantitative analysis of sensitive skin by mathematical modeling of transepidermal water loss desorption curves

Background/purpose: Sensitive skin is a vague, subjective and difficult to characterize affliction. It affects a large part of the population and is accompanied with great interest by the cosmetic industry. Some studies have suggested that sensitive skin is the result of impaired barrier function, which leads to the exposure of immune system cells and sensitive nerves, resulting in marked cutaneous responses to otherwise harmless stimuli. This study aimed to investigate the cutaneous barrier integrity of individuals with sensitive skin by a novel approach: a plastic occlusion stress test followed by measurement of transepidermal water loss (TEWL) desorption curves. Methods: The study was conducted in volunteers with sensitive skin in the hands and a control group with no sensitivity complaints. A previously developed mathematical model was adjusted to the TEWL data points and two parameters were calculated: dynamic water mass and the evaporation half‐life period. Results: Statistically significant differences have been detected in the parameters obtained in the sensitive skin group, which supports the thesis that individuals with an increased skin susceptibility have impaired barrier function. Conclusion: Whereas in the studies based in basal TEWL measurements only discrete differences were reported, the dynamic approach followed in this study provided unequivocal evidence of barrier impairment. The methodology enabled a more objective characterization of sensitive skin and can potentially be applied to the diagnosis/prediction of sensitivity; as well as the efficacy assessment of cosmetic products that are specifically designed to fulfill the needs of consumers with this skin condition.     

Neurotoxicity of heroin–cocaine combinations in rat cortical neurons

Cocaine and heroin are frequently co-abused by humans, in a combination known as speedball. Recently, chemical interactions between heroin (Her) or its metabolite morphine (Mor) and cocaine (Coc) were described, resulting in the formation of strong adducts. In this work, we evaluated whether combinations of Coc and Her affect the neurotoxicity of these drugs, using rat cortical neurons incubated with Coc, Her, Her followed by Coc (Her + Coc) and Her plus Coc (Her:Coc, 1:1). Neurons exposed to Her, Her + Coc and Her:Coc exhibited a decrease in cell viability, which was more pronounced in neurons exposed to Her and Her + Coc, in comparison with neurons exposed to the mixture (Her:Coc). Cells exposed to the mixture showed increased intracellular calcium and mitochondrial dysfunction, as determined by a decrease in intracellular ATP levels and in mitochondrial membrane potential, displaying both apoptotic and necrotic characteristics. Conversely, a major increase in cytochrome c release, caspase 3-dependent apoptosis, and decreased metabolic neuronal viability were observed upon sequential exposure to Her and Coc. The data show that drug combinations potentiate cortical neurotoxicity and that the mode of co-exposure changes cellular death pathways activated by the drugs, strongly suggesting that chemical interactions occurring in Her:Coc, such as adduct formation, shift cell death mechanisms towards necrosis. Since impairment of the prefrontal cortex is involved in the loss of impulse control observed in drug addicts, the data presented here may contribute to explain the increase in treatment failure observed in speedball abusers.