Comparison of long-term effect of coronary artery bypass grafting in patients with ischemic cardiomyopathy with viable versus nonviable left ventricular myocardium

In this study, 63% of patients with a substantial amount of viable myocardium showed an increased left ventricular ejection fraction (LVEF) 12 +/- 3 months after coronary artery bypass grafting. In 93% of these patients, increased LVEF persisted at 4.5 +/- 1 years of follow-up. Conversely, in nonviable patients, LVEF did not increase at 12 +/- 3 months or at follow-up of 4.5 +/- 1 years.     

Early identification of patients at risk of developing a persistent back problem: the predictive validity of the Orebro Musculoskeletal Pain Questionnaire

OBJECTIVE: To test the predictive utility of the Orebro Musculoskeletal Pain Screening Questionnaire in identifying patients at risk for developing persistent back pain problems. DESIGN: Prospective, where participants completed the questionnaire and their cases were followed for 6 months to assess outcome with regard to pain, function, and absenteeism due to sickness. PARTICIPANTS: One hundred seven patients, recruited from seven primary care units. RESULTS: Discriminant analyses showed that the items on the questionnaire were significantly related to future problems. For absenteeism due to sickness, 68% of the patients were correctly classified into one of three groups, whereas an even distribution would have produced 33%. The analyses for function correctly classified 81%, and for pain 71%, into one of two groups, compared with a chance level of 50%. A total score analysis demonstrated that a cutoff score of 90 points had a sensitivity of 89% and a specificity of 65% for absenteeism due to sickness, and a sensitivity of 74% and a specificity of 79% for functional ability. CONCLUSIONS: The results underscore that psychological variables are related to outcome 6 months later, and they replicate and extend earlier findings indicating that the Orebro Screening Questionnaire is a clinically reliable and valid instrument. The total score was a relatively good predictor of future absenteeism due to sickness as well as function, but not of pain. The results suggest that the instrument could be of value in isolating patients in need of early interventions and may promote the use of appropriate interventions for patients with psychological risk factors.     

Comparison between serum creatinine and creatinine clearance for the prediction of postoperative mortality in patients undergoing major vascular surgery

BACKGROUND: Poor renal function prior to surgery is associated with increased risk for mortality in patients undergoing major vascular surgery. Traditionally, this function is assessed by serum creatinine concentration (SeCreat). However, SeCreat is also influenced by age, gender and body weight. Hence, creatinine clearance (C(Cr)) is considered to be a better reflection of renal function. This study was undertaken to explore the prognostic value of preoperative calculated Cc, compared to SeCreat for the prediction of postoperative mortality. PATIENTS AND METHODS: The study group comprised 852 consecutive patients who underwent elective major vascular surgery at the Erasmus Medical Center, Rotterdam. Preoperative C(Cr) was calculated based on the Cockroft-Gault equation using preoperative SeCreat, age, body weight and gender. Univariable logistic regression analyses were used to study the relation between preoperative SeCreat, C(Cr) and postoperative mortality. Furthermore, multivariable logistic regression analysis was applied to evaluate the additional predictive value of age, body weight and gender additional to SeCreat. The receiver operating characteristic (ROC) curve was determined to evaluate the predictive power of several regression models for perioperative mortality. RESULTS: Postoperative mortality was 5.9% (50/852) within 30 days of surgery. In a univariable analysis, 10 micromol/l increment of SeCreat were associated with a 20% increased risk of postoperative mortality (OR = 1.2, 95% CI, 1.1-1.3) with an area under the ROC curve of 0.64 (95% CI, 0.56-0.71). If age, gender and body weight were added, the area under the ROC curve increased to 0.70 (95% CI, 0.63-0.77; p < 0.001), indicating that these risk factors had additional prognostic value. Indeed, in a separate regression analysis 10 ml/min decrease in C(Cr) was associated with a 40% increased risk of postoperative mortality (OR = 1.4,95% CI, 1.2-1.5; ROC area: 0.70, 95% CI, 0.63-0.76). ROC curve analysis showed that the cut-off value of 64 ml/min for C(Cr) yielded the highest sensitivity/specificity to predict postoperative mortality. CONCLUSION: Preoperative SeCreat was strongly associated with postoperative mortality, and adding age, gender, and body weight to the model showed improved predictive power indicating that preoperative C(Cr) calculated with these data has additional prognostic value.     

Reduced experimental autoimmune encephalomyelitis after intranasal and oral administration of recombinant lactobacilli expressing myelin antigens

Oral administration of autoantigens is a safe and convenient way to induce peripheral T-cell tolerance in autoimmune diseases like multiple sclerosis (MS). To increase the efficacy of oral tolerance induction and obviate the need for large-scale purification of human myelin proteins, we use genetically modified lactobacilli expressing myelin antigens. A panel of recombinant lactobacilli was constructed producing myelin proteins and peptides, including human and guinea pig myelin basic protein (MBP) and proteolipid protein peptide 139–151 (PLP_139–151). In this study we examined whether these Lactobacillus recombinants are able to induce oral and intranasal tolerance in an animal model for multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Lewis rats received soluble cell extracts of Lactobacillus transformants intranasally three times prior to induction of EAE. For the induction of oral tolerance, rats were fed live transformed lactobacilli for 20 days. Ten days after the first oral administration EAE was induced. Intranasal administration of extracts containing guinea pig MBP (gpMBP) or MBP_72–85 significantly inhibited EAE in Lewis rats. Extracts of control transformants did not reduce EAE. Live lactobacilli expressing guinea pig MBP_72–85 fused to the marker enzyme β-glucuronidase (β-gluc) were also able to significantly reduce disease when administered orally. In conclusion, these experiments provide proof of principle that lactobacilli expressing myelin antigens reduce EAE after mucosal (intranasal and oral) administration. This novel method of mucosal tolerance induction by mucosal administration of recombinant lactobacilli expressing relevant autoantigens could find applications in autoimmune disease in general, such as multiple sclerosis, rheumatoid arthritis and uveitis.     

Levels of certain metals, organochlorine pesticides and dioxins in cord blood, maternal blood, human milk and some commonly used nutrients in the surroundings of the Aral Sea (Karakalpakstan, Republic of Uzbekistan)

Since the 1960s a massive decline in the volume of the Aral Sea has occurred as a result of the diversion of the supplying rivers to cotton irrigation schemes. The contaminated sediment of the former seabed has been disseminated over the surrounding area by strong winds. This deterioration of the ecosystem has created a hazardous situation for the health of approximately 3.5 million people. This pilot study was undertaken to assist Karakalpak health workers in investigating the degree of exposure to metals, persistent organochlorine pesticides (OCPs) and dioxins during the most vulnerable prenatal and postnatal period and to provide guidelines for future research. All subjects came from areas located within 200 km of the southern border of the Aral Sea. Blood was obtained from 18 pregnant women and 28 newborns (cord blood) to determine the levels of metals, lead, cadmium, zinc and selenium and the OCPs alpha-, beta- and gamma-hexachlorocyclohexane (HCH; lindane is the product name of gamma-hexachlorocyclohexane), hexachlorobenzene (HCB), and isomers and metabolites of dichlorodiphenyltrichloroethane (DDT), i.e. op-DDT, pp-DDT, pp-DDE and pp-TDE. Levels of metals were also determined in blood from 28 non-pregnant women. In addition, levels of 17 dioxins were determined in 41 human milk samples and 1batch of formula. Information about possible dietary sources of the fat-soluble OCPs and dioxins was obtained from a pooled sample of butter and from seven cottonseed oil samples. A mass-selective detector coupled to a gas chromatograph equipped with a large volume injector was used to analyse the selected OCPs, whereas the dioxins were determined by gas chromatography with high-resolution mass spectrometry. The levels of metals in cord and maternal blood were consistent with concentrations observed in European countries. Only three women (7%) had lead levels greater than 100 ppb. The most notable pollutants in maternal and cord blood were the OCPs, notably HCB, beta-HCH, pp-DDE and the most toxic dioxin, 2,3,7,8-TCDD, when calculated as TEQs. A similar pattern was observed in human milk: beta-HCH and pp-DDE levels of more than 1,000 ng g(-1) fat were found in 68 and 43% of the subjects, respectively. Levels of 2,3,7,8-TCDD were six times higher than those observed in Western Europe. Traces of pp-DDE were detected in the batch of formula milk. Contaminated animal fat, but not cottonseed oil, is the most likely dietary source of OCPs and dioxins. CONCLUSION: Further epidemiological research is needed to elucidate the health implications of these pollutants on perinatal and maternal health, including lactation. More importantly, an investigation should be initiated to identify the emission sources of persistent organic pollutants in Karakalpakstan and adjacent regions.     

Long-term effects of social stress on antiviral immunity in pigs

Mixing of unfamiliar pigs is common practice in intensive pig husbandry. Since pigs maintain a dominance hierarchy, mixing often leads to vigorous fighting. Apart from the negative impact that fighting has on welfare, there is evidence that the social stress associated with fighting suppresses immune function. In the present experiment, we investigated the impact of mixing on specific long-term immune responses and protection against challenge infection after vaccination with pseudorabies virus (PRV). Specific pathogen-free (SPF) pigs were mixed pairwise with an unfamiliar same-gender conspecific or left undisturbed with a same-gender littermate at 3 days after vaccination with PRV. Half of the pigs were females (gilts) and half were castrated males (barrows). Mixing increased agonistic behavior to the same degree in gilts and barrows. Cortisol concentrations in saliva and catecholamine excretion in urine were increased in mixed pigs, and these effects were independent of dominance status and gender. Subsequently, the effects of mixing, gender, dominance status and interactions between these factors on immune response parameters were studied. The main result was that mixed barrows showed suppressed immune responses after vaccination and increased clinical symptoms after challenge infection compared to control barrows. Mixed gilts however did not differ from control gilts. It also appeared that mixed dominants were more seriously affected than mixed subordinates were. We conclude that, in some pigs, social stress after mixing suppresses the immune response to a viral vaccine and consequently impairs protection against challenge infection.     

Individual prediction of functional recovery after coronary revascularization in patients with ischemic cardiomyopathy: the scar-to-biphasic model

Currently, the prediction of improvement of left ventricular (LV) ejection fraction (EF) after revascularization in patients with ischemic cardiomyopathy relies only on viable myocardium extent, whereas both the amount of viable and scar tissue may be important. A model was developed, based on the amount of viable and nonviable myocardium, to predict functional recovery. Viable and scarred myocardium was defined by dobutamine stress echocardiography (DSE) in 108 consecutive patients. LVEF before and 9 to 12 months after revascularization was assessed by radionuclide ventriculography; an improvement of ≥5% was considered significant. In the 1,089 dysfunctional segments (63%), DSE elicited biphasic response in 216 segments (20%), sustained improvement in 205 (19%), worsening in 43 (4%), and no change in 625 (57%). LVEF improved in 39 patients (36%). Only the numbers of biphasic and scar segments were predictors of improvement or no improvement of LVEF (odds ratio 1.5, 95% confidence interval 1.2 to 1.7, p <0.0001 for biphasic segments; odds ratio 0.8, 95% confidence interval 0.7 to 0.9, p <0.0005 for scarred segments). The sustained improvement and worsening pattern were not predictive of improvement or no improvement. A regression function, based on the number of scar and biphasic segments, showed that the likelihood of recovery was 85% in patients with extensive biphasic tissue and no scars and 11% in patients with extensive scars and no biphasic myocardium. Patients with a mixture of scar and biphasic tissue had an intermediate likelihood of improvement (50%). In patients with ischemic cardiomyopathy and a mixture of viable and nonviable tissue, both numbers of viable and nonviable segments should be considered to accurately predict functional recovery after revascularization.